Category Archives: Research

Chaos, Migraine, and Evolution

Lawrence Robbins, MD


Migraine often results in disability and diminished quality of life. Despite this, our species remains particularly vulnerable to migraine. Why is this so?  Evolution may provide answers. The study of evolution and disease is not simply an academic exercise. In studying the history of our species, and those that preceded us, we may be able to develop safer and more effective treatments. We ignore evolution at our peril.

Chaos theory is a subset of nonlinear dynamics. Nature has been able to utilize chaotic dynamics in the brain, heart, and elsewhere (Korn, & Faure, 2003). Chaotic dynamics provide advantages over stochastic (random) or reductive (simple, linear) systems. Neurons and neuron clusters effectively utilize chaos. One hallmark of chaos is the extreme sensitivity to initial conditions (Bird, 2003). This leads to the classic butterfly effect, where a tiny perturbation in the beginning results in enormous changes down the line. Initial conditions played a significant role in the development of Homo sapiens (Bird, 2003). If we travelled back in time, and changed even the tiniest initial traits, today’s human would appear significantly different. 

Chaotic dynamics may play several roles in migraine pathophysiology. For instance, a tiny initial change in blood flow, such as occurs due to a patent foramen ovale (PFO), could eventually lead to the initiation of a migraine. The complex electrical wiring of the brain involves chaotic dynamics (Korn et al., 2003).  Chaos, migraine, and evolution are intimately interwoven. This paper outlines some of their connections. 


Chaos is a math-based subset of non-linear dynamics. Chaos improves the adaptability, efficiency, and versatility of neuronal systems.  A number of biological systems are governed somewhat by chaotic dynamics.  These systems include the ion flow and electrical activity of the brain, the beating of the heart, blood glucose levels, and glycolysis. Several studies have demonstrated chaos at the cellular level in the brain (Schweighofer, Doya, et al., 2004). By evaluating the flow of ions through the energy barriers of the channel protein, maps reveal the chaotic controls. Algorithms and numerical solutions have been constructed revealing when the transition to chaotic dynamics occurs (Landau, Sompolinsky, 2018). Characteristics of chaotic systems include, most importantly, an exquisite sensitivity to initial conditions.  Chaos is deterministic and predictable solely from one point to the next, but not beyond that point. The initial conditions are then reset after each point.

When compared to reductive or stochastic systems, chaotic systems save energy and are more adaptable.  Chaotic dynamics are involved in governing cortical spreading depression (CSD) (Pietrobon, Moskowitz, 2014). Chaos has been demonstrated to play a role in K+, Ca+, and Na+ movements. The flow of ions about the cell has been determined to be a combination of randomness, reductive(linear) movements, and chaotic processes. A small initial change in K+ efflux, or Ca+ influx, will result in a large effect downstream. Clusters of neurons, as well as single neurons, fire in a variety of patterns. These range from regular oscillating patterns to bursts, and everything in between. Neuronal systems undergo transitions that carry them between diverse states (Vreeswijk, Sompolinsky, 1998). Chaotic dynamics partially govern both individual neurons, as well as groups of neurons.


Tiny CNS perturbations may be brought about by the usual migraine triggers such as weather, stress, or hormonal changes. Through chaotic dynamics this may result in plasma protein extravasation (PPE) and cortical spreading depression, both of which are vital processes in the pathophysiology of migraine (Kernick, 2005). Medications affecting CSD may influence the neuronal membrane through chaotic controls. A small number of patients with patent foramen ovale (PFO) have experienced resolution of their migraines after PFO closure. The usual explanation for the PFO induction of migraine is via microemboli. It is also possible that chaotic dynamics play a role.  A small change in blood flow downstream (the heart) may induce a significant change in CNS dynamics upstream.

Chronic migraine pathophysiology involves wind-up and central sensitization(CS) . These are possibly controlled by chaotic dynamics. Thalamic recruitment involved in expansion of the pain area is likely governed by chaotic dynamics. Thalamic-cortical circuits involve chaotic dynamics. The pathological shift of homeostasis observed in chronic CS, with a loss of brainstem inhibition, may actually reflect a loss of chaotic control (Vreeswijk,et al.,1998). This is similar to the loss of control in the heart, resulting in arrhythmia.  The brainstem periaqueductal grey (PAG)—important in migraine—has been shown to be under chaotic control thru P/Q- type Ca+ channels. Migraine physiology incorporates a combination of genetic and environmental factors.  Trigger factors that affect migraine include stress, weather, and hormonal   changes.   These may affect the delicate balance between interneuronal nonlinear, reductive, and stochastic dynamics.  This may lead to chronic migraine. When a system is forced or stressed, nonlinear dynamics may be affected. 

New onset daily persistent headache (NDPH) may result from a perturbation of neuronal dynamics. Emotional, infectious, or other stresses may influence the delicate balance between nonlinear dynamics and stochastic or reductive dynamics. This could lead to chronic head pain.

Calcium and sodium efflux occur with CSD. Potassium and P/Q calcium channels are also involved. This complex system is unlikely to be governed primarily by random or linear kinetics. Chaotic controls have been demonstrated to be involved with these ionic movements (Pietrobon, et al., 2014). Chaotic dynamics could explain some of the properties of CSD. The initiation of CSD may be brought about by a miniscule change in potassium levels. This tiny effect may activate receptors and result in a large change downstream. The result is CSD and oligemia. With the potassium efflux partially under chaotic control, the chaos probably helps to regulate the increased cortical hyperactivity inherent in the brain of some migraineurs.

The trigeminal nucleus caudalis, vital in migraine pathophysiology, may be activated by a tiny initial stimulus. Through chaotic dynamics, this may result in the release of pro-inflammatory peptides and a release of glutamate. CSD leads to increased plasma protein extravasation. Only chaotic dynamics may explain how this may be possible. The medications that affect CSD (amitriptyline, topiramate, sodium valproate) may influence chaotic dynamics via membrane effects. When nonlinear dynamics are involved, it possibly takes less drug to produce an effect. The periaqueductal gray matter is involved in a number of CNS processes, including migraine. There is evidence that the periaqueductal gray is partially controlled by chaotic dynamics (Schweighofer, et al., 2004).

The loss of chaotic dynamics may lead to a pathological shift of homeostasis. The loss of brainstem inhibitory activity may actually reflect a lessening of chaotic control, eventually leading to a migraine. Similar loss of chaotic dynamics may explain certain arrhythmias and epileptic seizures.

The primary excitatory neurotransmitter in the brain is glutamate.  Along with calcium, glutamate is crucial in the feedback process. Glutamate is directly involved in bi-directional communications between neurons and astrocytes. It is likely that glutamate feedback processes are critical in the generation of complex bursting oscillations in astrocytes. These glutamate-mediated events are involved in migraine, epilepsy, and memory storage. The control of this feedback process may be partially enacted through chaotic dynamics. The cascade of magnesium binding to N-methyl-D-aspartate (NMDA) in the periphery about the brain, with subsequent calcium influx, is very sensitive to minute initial changes (Kernick, 2005).  This cascade is important in peripheral sensitization, which leads to migraine attacks. These magnesium and NMDA effects may be under chaotic control.

Brain-derived neurotrophic factor (BDNF) is a neurotropin that modulates neuronal membrane excitability. BDNF was used in one study to affect hippocampal neurons (Fujisawa, Yamada, Nishiyama, Ikegaya, 2004). Chaotic dynamics partially govern patterns of electrical activity in hippocampal neurons. The hippocampal electrical system is a deterministic one with a few degrees of freedom. Neuronal chaos may be sensitive to change by the application of small amounts of materials, such as BDNF, that influence temporal spiking. The application of BDNF to cultured hippocampal neurons enhanced spike timing and resulted in stereotyped firing patterns. It was felt that BDNF influenced chaos through effects on membrane levels of sodium (Fujisawa, et al., 2004).  BDNF enhanced membrane conductance and thus stabilized the membrane. The application of BDNF affected the switching between periodic and aperiodic neuronal oscillations. BDNF has been linked to modulation of neuroplasticity. The BDNF application decreased irregularity of firing patterns by modulating neuronal outputs as well as inputs. The result was a BDNF-induced chaos stabilization. This was the first experiment to demonstrate a pharmacological stabilization of chaos at the neuronal level (Fujisawa, et al., 2004).


Chaos and evolution are intimately interconnected. There is a chaotic (non-linear) connection between phenotype and genotype. This complex relationship is constantly in flux. A single mutation may be inconsequential, or it may result in enormous changes that are unpredictable. This is typical for a non-linear system. With these unpredictable mutations, iterations over thousands of generations will usually result in evolutionary changes (McKee, 2000). It is debatable as to how much the environment plays a role, versus genetic changes that are generated internally.

The unpredictability of evolution is typical of non-linear systems. Most discussions of evolution predictors focus on random, stochastic processes (mutations, genetic drift, random environmental changes). A reductive system would behave in a much more orderly, predictable manner. However, these fixed reductive systems are limited, and non-linear dynamics allows for enhanced evolutionary adaptability. The behavior of evolutionary systems is extremely sensitive to initial conditions. This was demonstrated during the quaternary period. At the beginning of each interglacial, the initial circumstances determined the outcome of that period. Between interglacials there were differences that were unpredictable, due to the non-linear nature of the system (Bird, 2003).

Non-linear dynamics lead to a system that is not scaled. The tree of life is fractal, and follows non-linear dynamics. The branches of the tree are continuously being split, resulting in evolutionary changes.  If we travelled back 5 million years, and re-started the human evolutionary process, the result would be dramatically different. This is the nature of a non-linear system. A simpler stochastic reductive system would be predictable but limited. It has been demonstrated that, when many traits interact, chaotic dynamics may govern phenotypic evolution.   Ancient species in human evolution, such as Australopithecus and Homo habilis, may have diverged due to chaotic dynamics (McCann, Yodzis, 1994).

Natural selection utilizes chaotic dynamics, chance, and coincidence (McKee, 2000). Natural selection does not invent, it tends to mosey along and tinker. The chance mutation must be coincidentally beneficial because of some environmental change.  For instance, if our ancestors needed robust teeth due to changing climactic conditions, those who happened to have larger teeth would have prevailed. Chaotic dynamics oversees chance and coincidence in the evolutionary process.


 Examining evolutionary systems in relation to disease is much more than an academic exercise. The evolutionary history will give us a complete picture of a disease. Understanding the evolutionary foundation may help us in developing safe and effective treatments.

Illness can be considered through two frameworks: 1. a proximate view, and 2. an evolutionary lens. The proximate view considers the nuts and bolts of a disease: pathophysiology, treatment, biochemistry, etc. It’s vitally important to also consider the disease process using an evolutionary viewpoint (Perlman, 2013). One essential question is: “why have migraines persisted, and why are humans still so susceptible to migraine?” The proximate lens says that migraine is a physical trait that involves multiple physiologic systems. The evolutionary framework begs the question: “why does our DNA code for migraine?”

There are physiological trade-offs that permeate evolution. While sickle cell disease is devastating, the sickle cell gene does also protect against malaria. Cystic fibrosis also involves serious trade-offs. Heterozygotes for cystic fibrosis were less likely to suffer dehydration from illnesses such as cholera. Genes exist to propagate themselves, sometimes to the detriment of the organism (the “selfish gene”)(Dawkins, 2013). This is also the story of migraine. Evolutionary benefits from migraine are possible (Loder, 2002).  It is also possible that our species simply continues to be vulnerable to migraine, and the evolutionary benefits are few. There are multiple genes involved in migraine, and evolution does not easily remove “bad genes”(Loder, 2002).

 It’s likely that migraines in humans increased as a result of our migration to more northern latitudes (Vigano, Manica, Di Piero, Leonardi, 2019).  Low vitamin D levels may help explain the increase in prevalence of migraine farther north (Prakash, 2010). The TRPM8 gene involves a receptor that plays a part in cold sensation and thermoregulation. TRPM8 (the “T” variation) is also linked to an increased risk for migraine (Dussor, Cao, 2016).  People who carry the “T” variation are better adapted to cold environments, and this adaptation likely improved their survival and reproductive success. Migraine may have been a negative consequence from this cold adaptation: another trade-off. The TRPM8 and latitudinal studies were the first to link migraine, evolution, natural selection, and geography (Vigano, et al., 2019).

The reasons why migraine persists are varied. While there is no epidemiological data from past millenia, the prevalence of migraine may be increasing. An increased sensitivity to light, smells, and sound could be beneficial under certain conditions. Migraine may be advantageous in combating certain infections (Loder, 2002). This may occur through an enhanced immune response, or by an increase in blood flow. Only a small percentage of people never experience headache (7% of men, and 1% of women), signaling that there may be some evolutionary advantage of headache.

Certain genes that result in harmless “quirks” in one environment can have deadly outcomes in other venues. Our modern environment certainly contributes to migraine frequency. The environment has radically changed, after millions of years of evolution (Cochran, Harpending, 2009).  For the vast majority of human history, we were primarily hunting and gathering. Recently, only 10 to 12 thousand years ago, societies in Southwest Asia (the fertile crescent) began to cultivate plants and domesticate animals. Many factors may contribute to increased migraine frequency: changes in culture, living circumstances, agriculture and diet, environmental toxins, densely packed populations, infections (particularly viral), harsh indoor lighting, loud speakers, poor sleep, and increased stress (Loder, 2002).  When modern hunter-gatherer societies switch to our “western diet,” they suffer from heart disease and an increase in cancer (Milton, 2000).  One of many examples where a changing environment has an impact on disease involves the genes for heart disease. These genes may not have been particularly detrimental for Stone Age humans, due to short lifespans. But as lifespans have been significantly lengthened, these genes have become threatening. Phenotypic and adaptive plasticity are significant factors in humans adapting to the changing environment (Perlman, 2013).

While migraine is three times more common in women than in men, the evolutionary explanation for this is unclear. Men generally did most of the hunting and gathering, for which migraine could pose disadvantages. For child care, food preparation, and homekeeping, migraine may possibly offer small evolutionary advantages. Migraine commonly decreases during pregnancy, providing an evolutionary incentive for more pregnancies.

It’s likely that migraine only afflicts the human species. Our ancient human brainstem has obstacles in coping with a cortex that is recently enlarged. With excessive afferent input, our brainstem may be overwhelmed. Having higher cortical functions not found in other primates may contribute to our continued vulnerability to migraine.   

Migraine may function as a defense mechanism against excessive stress, noise, or light (Loder, 2002).  The elevated sense of smell may serve as a defense from toxins or viruses entering the CNS. Vomiting may help to remove toxins. Women migraineurs probably have a lower prevalence of type 2 diabetes, compared to those without migraine (Fagherazzi, El Fatouhi, Fournier, et al., 2019).  An activation of the trigeminal nuclear complex could be protective (Loder, 2002).  If migraine offers protections for an individual, then that individual’s genes may be propagated more successfully. If an ancestral human experienced 100 migraines during a year, and just one of those migraines protected the person from harm, the trade-off would have been worthwhile. In an evolutionary framework, the cost of migraine may be inexpensive.

There is a difference between a defense and a defect. Coughing is a defense, but becoming blue from hypoxia is not. We want to retain our natural defenses. The calcitonin gene-related peptide (CGRP) associated with migraine may be advantageous under stress (Kee, 2018). CGRP has existed in a variety of species for hundreds of millions of years. CGRP plays various roles in the body, some positive, some harmful (Kee, Kodji, Brain, 2018). Under stress, CGRP is beneficial for our cerebrovascular and cardiovascular systems. Disrupting this natural defense, as happens with our CGRP monoclonal antibodies that prevent migraine, may be harmful.  The CGRP story is one example of the danger in ignoring the evolutionary importance of a compound.       

Natural selection is dependent on reproduction. After the reproductive years, a particular trait could very well become detrimental, but that does not affect gene propagation. In order to understand a trait (or disease) such as migraine, we must consider all of the evolutionary processes. These include genetic drift, mutations, migration, non-random mating, and natural selection (Perlman, 2013). Sometimes, natural selection produces opposing effects, resulting in a heightened vulnerability to disease.

 It’s imperative to not only view individuals through an evolutionary lens, but to also consider the phylogeny of the species (Perlman, 2013). The relationships between humans have morphed in the past 12,000 years (Cochran, et al., 2009).  One primary factor driving phylogenetic changes is the increase in population density, resulting in most humans living in significantly smaller spaces. Culture, which influences our state of disease or health, may also contribute to an increase in headache prevalence.

Headache and pain are adaptive responses. Being still, or in bed, may help repair damaged tissues. Incomplete or inadequate natural selection is often cited as the cause for our flaws or disease, but it is more likely that many illnesses are the result of compromises and/or design flaws (Nesse, Williams, 2012).  For example, our esophagus crosses our trachea. Because of this, our airway must inconveniently be closed every time that we swallow, to prevent choking. Allergies, atherosclerosis, nearsightedness, and nausea in pregnancy are similar examples stemming from evolutionary compromises and design flaws (Nesse, 2005, 2012).

Another important evolutionary concept to consider is intrinsic vulnerability (Nesse, 2011). Different species have various levels of vulnerability to certain diseases. Humans mature rather slowly, with infrequent reproduction. This is a factor regarding enhanced vulnerability of our species to certain diseases. It’s difficult for us to rid ourselves of genes that cause harm. Migraine involves a multitude of factors and genes, and it’s not likely that natural selection would be capable of eliminating migraine.

To more wholly understand migraine, we should venture beyond the proximate and physiologic processes. The evolutionary foundations of migraine are vitally important to study. Examining migraine under an evolutionary lens may help us in evaluating the safety of new treatments, such as the CGRP monoclonal antibodies. We must pay attention to evolution.


Chaos, migraine, and evolution are intertwined. Chaotic dynamics are vital within the central nervous system. Chaos is important at the ionic, neuronal, and neuronal cluster levels. Chaos may be involved in the generation of CSD. Sensitization and wind-up, crucial components of migraine, probably incorporate chaotic dynamics.

Evolution and natural selection involve chaos, chance, and coincidence. The evolutionary result of thousands of generations depends exquisitely upon initial conditions, characteristic of chaotic dynamics.

For myriad reasons, our species remains remarkably vulnerable to migraine. To understand migraine, we have to look farther than simple physiologic and proximate processes. We cannot truly understand migraine without examining the evolutionary underpinnings. The safety of new migraine treatments should be evaluated under an evolutionary lens.


Bird, R. (2003). Chaos and Life: complexity and order in evolution and thought. NY,NY: Columbia University Press.

Cochran G, Harpending H (2009). The 10,000 Year Explosion: How civilization accelerated human evolution. NY,NY: Basic Books.

Dawkins,R.  (2016). The Selfish Gene. Oxford, UK: Oxford University Press.

Dussor G, Cao,Y-Q. (2016). TRPM8 and migraine. Headache, 56, 1406-1417.

Fagherazzi G, El Fatouhi D, Fournier A. (2019). Associations between migraine and type 2 diabetes in women: findings from the E3N cohort study. JAMA, 76, 257-263.

Fujisawa S, Yamada M, Nishiyama N, Ikegaya N. (2004). BDNF boosts spike fidelity in chaotic neural oscillations. Biophysics J, 86, 1820-1828.

Kee Z, Kodji X, Brain SD. (2018). The role of calcitonin gene related peptide (CGRP) in neurogenic vasodilation and its cardioprotective effects. Frontiers in Physiology, 9, 1249.

Kernick D. (2005). Migraine—new perspectives from chaos theory. Cephalalgia, 25, 561-566.

Korn H, Faure P. (2003). Is there chaos in the brain? C.R. Biologies, 326, 787-840.

Landau ID, Sompolinsky H. (2018). Coherent chaos in a recurrent neural network with structured connectivity. Computational Biology, Retrieved May 20, 2020 from

Loder E. (2002). What is the evolutionary advantage of migraine? Cephalalgia, 22, 624-632.

McCann K, Yodzis P. (1994). Non-linear dynamics and population disappearances. The American Naturalist, 144, 873-879.

McKee, J (2000). The Riddled Chain: chance, coincidence, and chaos in human evolution. Piscataway,NJ: Rutgers University Press.

Milton K. (2000). Hunter-gatherer diets: a different perspective. The American Journal of Clinical Nutrition, 71, 665-667.

Nesse,RM. (2005). Maladaptation and natural selection. The Quarterly Review of Biology, 80, 62-70.

Nesse,RM. (2011). Ten questions for evolutionary studies of disease vulnerability. Evolution Applications, 4, 264-277.

Nesse,RM, Williams GC. (2012). Why We Get Sick: the new science of Darwinian medicine. New York, New York: Vintage Books.

Perlman R. (2013). Evolution and Medicine. Oxford, UK: Oxford University Press.

Pietrobon D, Moskowitz MA. (2014). Chaos and commotion in the wake of cortical spreading depression and spreading depolarizations. Nature Review Neuroscience, 15, 379-393.

Schweighofer N, Doya K, et al. (2004). Chaos may enhance transmission in the inferior olive. Proceedings of the National Academy of Science, 101, 4655-4660.

Vigano A, Manica A, Di Piero V, Leonardi M. (2019). Did going north give us migraine? An evolutionary approach on understanding latitudinal differences in migraine epidemiology. Headache, 59, 632-634.

Vreeswijk C, Sompolinsky H. (1998). Chaos in neuronal networks with balanced excitatory and inhibitory activity. Science, 274, 1724-1726.

Update on Gepants: New Abortives for Migraine

Lawrence Robbins,M.D.

Gepants are small molecule calcitonin gene-related peptide (CGRP) receptor antagonists. The preventive CGRP monoclonal antibodies(Aimovig, Emgality, Ajovy) are large molecules, delivered once per month as a SQ injection. Seven gepants have been developed since 2004. (1) Telcagepant was extensively studied, but withdrawn due to hepatotoxicity concerns. CGRP has many effects throughout the body. CGRP triggers a cascade of inflammatory mediators that feed into the trigeminovascular system. By blocking CGRP, the gepants stop the process prior to inflammation.

Regarding migraine, CGRP is an inflammatory compound. They will initially be utilized as migraine abortives, but eventually they will also be used to prevent migraine. The gepants may be helpful for 3 groups of migraineurs. They will be prescribed for a number of patients who found triptans (sumatriptan, rizatriptan, zolmitriptan, etc.) to be ineffective. In addition, gepants will be used for certain patients who cannot tolerate triptans. Finally, for those patients with significant cardiac or cerebrovascular risk factors, the gepants may be relatively safe, since they do not constrict cardiac or cranial arteries. While efficacy is modest, these are well tolerated medications.

The first gepant to come to market will be ubrogepant. Almost 2,700 patients participated in the ubrogepant ACHIEVE studies. (2,3) The doses have ranged from 25mg to 100mg. The t-max is 0.7 to 1.5 hours. Approximately 20% of patients who used the 50mg dose were pain free after 2 hours. While 25mg and 100mg tablets of ubrogepant were evaluated, it is likely that 50mg will be the primary dose. Ubrogepant was well tolerated, with 2% to 5% of patients reporting nausea, somnolence, dry mouth, dizziness, or upper respiratory tract infections. No serious adverse events were reported. The safety and tolerability were also explored in a 52 week extension study. Few adverse events, and no hepatotoxicity was reported. The effect of ubrogepant on the patient’s most bothersome migraine symptom was evaluated 2 hours post-dose. 39% of those treated with ubrogepant reported that their worst migraine symptom was resolved. The therapeutic gain for ubrogegepant (active drug vs. placebo) is relatively low, 6.4%-9.4%. In comparison, the therapeutic gain for sumatriptan is 16%-21%.

Rimegepant is another gepant, in development for abortive and preventive use. The dose is 75mg, with a t-max of 2 hours. In the 2 main trials, 19.4% of patients achieved pain freedom at 2 hours. (4) 37% of patients reported freedom from their most bothersome symptom. As with ubrogepant, no significant liver toxicity was reported. Adverse events were low, with nausea being reported by 1.4% of patients. The therapeutic gain for rimegepant is 5% to 7.6%.

A third gepant, atogepant, is currently being studied.

The gepants will be a useful alternative to triptans. Many patients find triptans to be ineffective. Some migraineurs cannot tolerate the adverse effects of the triptans. For certain patients with cardiovascular risk factors, triptans may not be completely safe. Gepants will be considered in these clinical settings. The initial (2 hour) efficacy rates are fairly low, but it appears that gepants may become more effective over 2 to 8 hours. During the trials, these were fairly well tolerated medications. It will take at least several years before we are able to accurately assess the true adverse effect profile of the gepants.


1. Olesen J, Diener H-C, Husstedt IW et al Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. 2004. N Eng J Med 350:1104-1110.

2. Allergan Announces Positive Top Line Phase 3 Clinical Trial for Ubrogepant- an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine. Available at

3. Allergan Announces Second Positive Phase 3 Clinical Trial for Ubrogepant- an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine. Available at

4. Biohaven Announces Successful Achievement of Both Co-Primary regulatory Endpoints in Two Pivotal Phase 3 Trials of Rimegepant an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine Available at

Personality and Pain: Which Came First?

James N. Weisberg, PhD

This article is adapted from a chapter in a soon to be published text:
Weisberg, J.N., Paul, C. & Twyner, C. Personality and Personality Disorders in Chronic Pain.  In Incayawar, M., Clark, M. & Maldonado-Bouchard, S. (Eds.). Overlapping Pain and Psychiatric Syndromes-Global Perspectives. New York, NY: Oxford University Press

Chronic pain is a significant health care issue at epidemic proportions in the United States1 and there is a high incidence of both clinical psychiatric disorders2,3 and personality disorders (PD) in the chronic pain population.4 This article will briefly summarize some of the important points pertaining to the prevalence and interplay between personality disorders and chronic pain.

Personality and Pain

The relationship between personality and pain can easily be traced to ancient Greece. More recently, in the late 19th century psychodynamic theorists discussed the connection between emotional factors and the experience of chronic pain.5 George Engel maintained that, while physical pain may result from underlying pathophysiology, the interpretation of pain is a psychological phenomenon and also noted that certain diagnoses, including Depression, Hysteria and Hypochondriasis were relatively common in people experiencing chronic pain.6 In an attempt to further characterize personality characteristics, the use of Minnesota Multiphasic Personality Inventory (MMPI)7 and its successors (MMPI-2, MMPI-2-RF) led to a plethora of research seeking to use psychometric tests quantify these early theorists, help predict treatment outcome from multidisciplinary treatment8, spine surgery9, spinal cord  stimulators10as well as  and pain-related disability11.  However, despite the hundreds of studies using the MMPI and its successors, there continues to be controversy regarding the applicability and appropriateness of in the chronic pain population.12,13

A number of other psychological inventories have been used in an attempt to describe and characterize individuals with chronic pain and to predict treatment outcomes. Some, but not all of these measures include the NEO Personality Inventory (Neuroticism-Extroversion-Openness Personality Inventory-NEO-PI) and its revisions,14-16 the Millon Clinical Multiaxial Inventory and subsequent revisions (MCMI; MCMI-IV)17,18 and the Temperament and Character Inventory (TCI).19

While psychological inventories have investigated different personality characteristics as they relate to pain, relatively few studies have investigated personality disorders in chronic pain. 

Personality Disorders and Chronic Pain

Whereas personality refers to the constellation of non-pathological characteristics in an individual’s patterns of thought, emotion, and behavior the DSM defines a personality disorder as “an enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture, is pervasive and inflexible, has an onset in adolescence or early adulthood, is stable over time, and leads to distress or impairment.”20 Thus, the essential difference between a trait and disorder is the degree of distress and disruption caused.

Personality and personality disorders are likely the combination of biological, developmental, and environmental factors that become impacted by state-dependent variables such as mood and anxiety. The Diathesis-Stress model purports that individuals have underlying genetic vulnerabilities and possibly early life experiences that interact with stressors the individual encounters later in life.21  Depending on the nature of the stressors and the individual’s ability to cope with such stressors, the underlying vulnerability may or may not become expressed as a disease process. The diathesis-stress model was first applied to explain schizophrenia21 and depression.22  It has also been applied to the development of chronic back pain23 and the development of depression in chronic pain patients.2 Similarly, this model has been proposed to apply to personality disorders in chronic pain patients.24 Thus, combined with underlying traits and situational stressors brought on by chronic pain, an individual’s underlying personality traits and characteristics may become magnified to the extent the individual meets criteria for a personality disorder.

Epidemiology of Personality Disorders:

In its most recent edition, the American Psychiatric Association cites data from a national epidemiologic survey suggesting approximately 15% of US adults meet criteria for at least one personality disorder.25 A large epidemiological study found prevalence estimates for the different clusters suggest 5.7% for disorders in Cluster A (Paranoid, Schizotypal and Schizoid Personality Disorder), 1.5% for disorders in Cluster B (Histrionic, Narcissistic and Borderline Personality disorders),  6.0% for disorders in Cluster C (Avoidant, Dependent, Obsessive-Compulsive Personality Disorders), and 9.1% for any personality disorder, indicating frequent co-occurrence of disorders from different clusters.26

To date, approximately 15 studies have investigated the prevalence of personality disorders in chronic pain.  Some of the more seminal studies are highlighted here.  The first published study using a semi-structured interview to diagnose DSM-III personality disorders in chronic pain found 37% of their sample met criteria for at least one personality disorder with the most common diagnoses being histrionic PD (14%), dependent PD (12%) and borderline PD  (7%).27  Fishbain et al,28 using a semi-structured interview to diagnosis both DSM-III axis I and Axis II disorders, found 59% of their chronic pain sample met criteria for a personality disorder with most common diagnoses being dependent PD (17%), Passive-Aggressive PD (15%) and histrionic PD (12%).   Weisberg et al29 used a combination of clinical interview, treatment notes and both patient and family self-report measures to assess personality disorders in 55 chronic pain patients who were evaluated and treated at a comprehensive outpatient pain management program. They found that 31% met criteria for at least one PD and an additional 27% met criteria for PD-NOS which is used when an individual meets incomplete criteria for two or more personality disorders.  Similar to other studies, the most common diagnoses were borderline PD (13%) and dependent PD (11%).  These researchers suggest that obtaining longitudinal information from both the patient and an individual with a longstanding relationship with the patient might provide a more thorough assessment of the impact of state factors such as mood, anxiety, and stress on the presentation of personality.29 More recently, Conrad et al30 found that 41% of their chronic pain sample met criteria for a personality disorder diagnoses compared to 7% of their control group.  Most common were Borderline PD (11%) and paranoid PD (12%). The authors found clinical disorders, such as depression at a equally high rate, lending more credence to the importance of assessing personality in context of state factors.

In summary, the relatively few studies that have investigated personality disorders in various samples of patiens with  chronic pain have found prevalence rates from 31% to over 80%. However, as has been noted by previous researchers, due to a variety of factors including state-dependent variables, stressors unique to chronic pain, genetic and developmental influences and other known and unknown factors, significant caution must be used when making a personality disorder diagnosis in the individuals with chronic pain.  In addition, knowing premorbid functioning is crucial in understanding the multifactorial nature of the observed behavior.  Nontheless, the presence of a personality disorder increases the liklihood of co-morbid conditions, such as substance misuse and abuse and makes treatment of chronic pain that much more challenging to the pain clinician.

The Nexus of Personality Disorders in Chronic Pain and Substance Use Disorders:

There has also been a paucity of research on the interaction between personality disorders and substance use disorders in chronic pain.  One study investigated psychological comorbidities, including personality disorders, in chronic pain sufferers presenting to either a university emergency department or an urgent care clinic requesting opioids.31 Pertinent results demonstrated 18% likely had a personality disorder diagnosis and found that personality disorder was significantly related to opioid abuse.31 A recent study found the incidence of personality disorders to be 52% in those with co-occurring chronic pain and substance use disorders.32 The most common personality disorder was antisocial PD (22%) followed by avoidant PD (19%) and paranoid PD (16%). Although there is little literature on this topic, both of these studies suggest that personality disorders may be a moderating variable in the incidence of substance use disorders in persons with chronic pain.                                                                                                                                         

Treatment of Personality Disorders in Chronic Pain

While working with people living with either chronic pain or personality disorders can prove to be daunting to the clinician separately, working with those with the co-morbid diagnoses of both personality disorders and chronic pain can pose unique challenges and opportunities in regard to treatment. Although maladaptive behaviors are, by definition, problematic in a variety of settings, legitimate concerns may be disregarded as secondary to the manifestations of personality disorders or simply attributed to being “difficult.”

The need for the pain clinician to screen for personality disorders is rooted in the understanding that the manifestations of a personality disorder in a person living with chronic pain can be exacerbated or unmasked by the individual’s pain condition according to the diathesis-stress model.24  In addition, the need for vigilance and awareness with these conditions is considerable as these patients are at higher risk for various adverse outcomes, including substance use disorders. 31 Attempting to detangle the personality disorder from the chronic pain state with the goal of treating one or the other may be difficult at best.

Cognitive-Behavioral Therapy for chronic pain (CBT-CP) has been well documented in the literature to be one of the most effective treatments for chronic pain.33-35 Acceptance and Commitment Therapy (ACT)36, has been shown to benefit patients with personality disorders that had failed in previous treatment with significant improvements in personality pathology and quality of life.37 ACT for chronic pain has also been effective at decreasing pain intensity, anxiety, and disability38 The use of CBT-CP and ACT may be a potential avenue for treatment, but research designed to investigate these interventions among people with coexisting chronic pain and personality disorders is lacking.

Dialectical Behavior Therapy (DBT), a current mainstay of treatment of borderline personality disorder, focuses on the development of coping skills with the ultimate goal of improving emotional regulation and control.39 However, as with other therapeutic modalities, there is minimal evidence for treatment for DBT in those with chronic pain and comorbid personality disorders.

Given the common elements between Cognitive-Behavioral Therapy and Dialectical Behavior Therapy, it stands to reason that a hybrid model combining elements of both CBT-CP with DBT might be a highly successful approach to maximizing treatment potential in patients with co-morbid chronic pain and personality disorders, especially borderline personality disorder.


In summary, it is important to assess patients not just for depression, anxiety and other clinical psychiatric disorders, but for personality traits and disorders in order to better understand the impact personality may have on the expression of their pain perception, medication use and coping styles.  Understanding the role personality disorders may play in the complexities of chronic pain should result in the tailoring of multimodal treatments for chronic pain that emphasize non-opioid medical management, cognitive-behavioral and physical therapies.


  1. Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC)2011.
  2. Banks SM, Kerns RD. Explaining the high rates of depression in chronic pain: A diathesis-stress framework. Psychological bulletin. 1996;119(1):95-110.
  3. McWilliams LA, Cox BJ, Enns MW. Mood and anxiety disorders associated with chronic pain: an examination in a nationally representative sample. Pain. 2003;106(1-2):127-133.
  4. Weisberg JN. Personality and personality disorders in chronic pain. Curr Rev Pain. 2000;4(1):60-70.
  5. Breuer J, Freud S. Studies on hysteria. Original work published 1893-1895 ed. New York, NY: Basic Books; 1957.
  6. Engel GL. Psychogenic pain and pain-prone patient. Am J Med. 1959;26(6):899-918.
  7. Hathaway SR, McKinley J. Minnesota Multiphasic Personality Inventory. Minneapolis, MN: University of Minnesota Press; 1943.
  8. Kleinke CL, Spangler AS, Jr. Predicting treatment outcome of chronic back pain patients in a multidisciplinary pain clinic: methodological issues and treatment implications. Pain. 1988;33(1):41-48.
  9. Block AR, Ohnmeiss DD, Guyer RD, Rashbaum RF, Hochschuler SH. The use of presurgical psychological screening to predict the outcome of spine surgery. The Spine Journal. 2001;1(4):274-282.
  10. Block AR, Marek RJ, Ben-Porath YS, Kukal D. Associations Between Pre-Implant Psychosocial Factors and Spinal Cord Stimulation Outcome: Evaluation Using the MMPI-2-RF. Assessment. 2017;24(1):60-70.
  11. Gatchel RJ, Polatin PB, Mayer TG. The dominant role of psychosocial risk factors in the development of chronic low back pain disability. Spine. 1995;20(24):2702-2709.
  12. Fishbain D, Cole B, Cutler R, Lewis J, Rosomoff H, Rosomoff R. Chronic pain and the measurement of personality: Do states influence traits? Pain Medicine. 2006;7(6):509-529.
  13. Turk DC, Fernandez E. Personality assessment and the minnesota multiphasic personality inventory in chronic pain: underdeveloped and overexposed. Pain Forum. 1995;4(2):104-107.
  14. Costa PT, McCrae RR. The NEO Personality Inventory Manual. Orlando, FL: Psychological Assessment Resources; 1985.
  15. Costa PT, McCrae RR. Revised NEO Personality Inventory (NEO–PI–R) and NEO Five-Factor Inventory (NEO–FFI) professional manual. Odessa, FL: Psychological Assessment Resources; 1992.
  16. McCrae RR, Costa PT, Jr., Martin TA. The NEO-PI-3: a more readable revised NEO Personality Inventory. J Pers Assess. 2005;84(3):261-270.
  17. Millon T. Millon Clinical Multiaxial Inventory. Minneapolis, MN: National Computer Systems; 1977.
  18. Millon T, Grossman S, Millon C. Millon Clinical Multiaxial Inventory-IV: MCMI-IV. Bloomington: NCS Pearson; 2015.
  19. Cloninger C, Svrakic, DM., Przybeck, TR. A psychobiological model of temperment and character. Archives of general psychiatry. 1993;50:975-990.
  20. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. Washington, D.C.: Author; 2013.
  21. Meehl PE. Schizotaxia, schizotypy, schizophrenia. American Psychologist. 1962;17:827-838.
  22. Monroe SM, Simons AD. Diathesis-stress theories in the context of life stress research: implications for the depressive disorders. Psychological bulletin. 1991;110(3):406-425.
  23. Flor H, Turk DC. Etiological theories and treatments for chronic back pain. I. Somatic models and interventions. Pain. 1984;19(2):105-121.
  24. Weisberg JN, Keefe FJ. Personality disorders in the chronic pain population: Basic concepts, empirical findings, and clinical implications. Pain Forum. 1997;6(1):1-9.
  25. Grant BF, Hasin DS, Stinson FS, et al. Prevalence, correlates, and disability of personality disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. J Clin Psychiatry. 2004;65(7):948-958.
  26. Lenzenweger MF, Lane MC, Loranger AW, Kessler RC. DSM-IV personality disorders in the National Comorbidity Survey Replication. Biological psychiatry. 2007;62(6):553-564.
  27. Reich J, Tupin JP, Abramowitz SI. Psychiatric diagnosis of chronic pain patients. Am J Psychiatry. 1983;140(11):1495-1498.
  28. Fishbain DA, Goldberg M, Meagher BR, Steele R, Rosomoff H. Male and female chronic pain patients categorized by DSM-III psychiatric diagnostic criteria. Pain. 1986;26(2):181-197.
  29. Weisberg JN, Gallagher RM, Gorin A. Personality disorder in chronic pain: A longitudinal approach to validation of diagnosis. Paper presented at: 15th Annual Scientific Meeting of the American Pain Society; November 1996, 1996; Washington, DC.
  30. Conrad R, Schilling G, Bausch C, et al. Temperament and character personality profiles and personality disorders in chronic pain patients. Pain. 2007;133(1-3):197-209.
  31. Wilsey BL, Fishman SM, Tsodikov A, Ogden C, Symreng I, Ernst A. Psychological comorbidities predicting prescription opioid abuse among patients in chronic pain presenting to the emergency department. Pain Medicine. 2008;9(8):1107-1117.
  32. Barry DT, Cutter CJ, Beitel M, Kerns RD, Liong C, Schottenfeld RS. Psychiatric Disorders Among Patients Seeking Treatment for Co-Occurring Chronic Pain and Opioid Use Disorder. J Clin Psychiatry. 2016;77(10):1413-1419.
  33. Majeed MH, Sudak DM. Cognitive Behavioral Therapy for Chronic Pain-One Therapeutic Approach for the Opioid Epidemic. J Psychiatr Pract. 2017;23(6):409-414.
  34. Ehde DM, Dillworth TM, Turner JA. Cognitive-behavioral therapy for individuals with chronic pain: efficacy, innovations, and directions for research. Am Psychol. 2014;69(2):153-166.
  35. Knoerl R, Lavoie Smith EM, Weisberg J. Chronic Pain and Cognitive Behavioral Therapy: An Integrative Review. West J Nurs Res. 2016;38(5):596-628.
  36. Cederberg JT, Cernvall M, Dahl J, von Essen L, Ljungman G. Acceptance as a Mediator for Change in Acceptance and Commitment Therapy for Persons with Chronic Pain? Int J Behav Med. 2016;23(1):21-29.
  37. Chakhssi F, Janssen W, Pol SM, van Dreumel M, Westerhof GJ. Acceptance and commitment therapy group-treatment for non-responsive patients with personality disorders: An exploratory study. Personality and mental health. 2015;9(4):345-356.
  38. McCracken LM. Learning to live with the pain: Acceptance of pain predicts adjustment in persons with chronic pain. Pain. 1998;74(1):21-27.
  39. Wilks CR, Korslund KE, Harned MS, Linehan MM. Dialectical behavior therapy and domains of functioning over two years. Behaviour research and therapy. 2016;77:162-169.



Disparities in Pain and Pain Care: Combating Bias in Practice

Jennifer L. DelVentura, Ph.D., ABPP
Jennifer L. Steiner, Ph.D., ABPP

In a post in a previous issue of this newsletter, titled “Gender disparities in Pain and Pain Care,” we explored the evidence that women are not only at higher risk for pain and pain conditions but that their pain appears to be underestimated and, in some cases, undertreated compared with men’s pain. Similar patterns are evident in diagnosis and treatment of pain in racial/ethnic/SES minority patients, ranging from differences in prevalence and severity of pain in these groups to differential access to resources and pain care.

While there are many factors operating at different levels (community, institutional/systemic, familial/social, individual) contributing to these disparities, the impact of provider biases on pain care is of particular interest for us, as clinicians.  Biases are ubiquitous, often unconscious, and a normal part of human cognition, but they are not innocuous.  They may even be inconsistent with conscious beliefs—e.g., one may deny having negative beliefs about minority groups, but still evidence presence of unconscious biases in decision-making.  But importantly, with awareness and effort biases are malleable.  It is our task as ethical, caring providers to strive to minimize the impact of harmful biases on patient care.   

Using measurement tools normed for minority populations

One approach to reducing impact of biases involves using pain assessment tools normed for minority patient populations.  Even seemingly unbiased tools may be interpreted and rated differently by minority groups.  Take for example the widely-used numerical pain rating scale with verbal anchors (e.g., “moderate,” “severe” or “worst pain imaginable”) to describe pain intensity.  While these scales appear bias-free, their use rests on the assumption that we all interpret pain descriptors in the same way.  Yet this may not be true, as is demonstrated in a study by Campbell and colleagues[1], comparing pain ratings to thermal stimuli in men vs. women and white vs. black participants.  Findings indicated that when using a generic numerical pain rating scale, women and black participants rated the stimuli as significantly more painful than their counterparts.  However, when participants were allowed to individualize the rating scale by moving the verbal anchors to reflect their subjective interpretation of pain, group differences in pain ratings were no longer significant[1] suggesting group differences in how these anchors were interpreted, perhaps attributable to culture, socialization, or other factors.

The Campbell et al [1] study points to the need for measures modified for or normed to different populations.  Indeed, a few measures with such norms do exist.  For example, for psychologists, the MMPI-II-RF and Millon Behavioral Medicine Diagnostic [2], offer a multitude of specific patient group norms divided by gender (but not ethnicity).  Additionally, several behavioral measures of functioning that are commonly used by physical therapists now have more extensive norms for different populations. The unipedal stance (UPST) now has norms for age and gender [3] and several other common tests such as the timed up-and-go test and single limb stance test have established significant differences based on age [4-6].  However, most measures lack norms specific to race/ethnicity, and thus this remains an important area of development for the field of pain management.  Because such minority group norms are not widely available, it is crucial to be aware of the inherent limitations of our commonly used measures.

Provider-level strategies for managing bias

But what else can providers do to reduce impact of bias on patient care?  Social psychology research offers valuable insights into strategies for addressing biases in our work.  Based on this research, Burgess and colleagues [7] put forth a multi-step, evidence-based framework for addressing biases in healthcare, parts of which we will briefly summarize here.

First, fostering providers’ internal motivation for change is foundational to this model and involves bringing awareness to the presence of biases in our work.  This can be done using techniques like the implicit association test (IAT, [8, 9], a measure of response latency that evaluates the strength of an association between pairs of contrasting concepts and is believed to tap into implicit connections between concepts in the brain. The IAT takes advantage of the brain’s inherent tendency to pair concepts together in service of faster processing, the more closely two concepts are linked together for an individual, the faster the person should be able to respond when one component of the pair is activated in the brain. It is a computer-administered task that has been used to highlight unconscious biases or preferences for people that belong to particular social groups (race, gender, religion., etc.), however, it is important to note that there is some debate as to what the IAT actually measures, and whether implicit bias is correlated with explicit bias and/or explicit behavior [10, 11]. Nevertheless, completing an IAT for a number of variables, i.e. gender, race, size, etc. (at[1] may offer some insight into our own associations and may inform self-reflection.

To give an example of what such an exercise might look like we invite you to consider the following sentences (adapted from the group exercise described in Holm et al., 2017) and count how many are true for you:

  • I can feel confident that others feel that I am qualified upon first impression.
  • I can speak in a roomful of medical providers and feel that I am heard.
  • My age adds to my credibility.
  • When I report pain or physical symptoms to my doctor, I can feel confident that my race or gender identification will not work against me.
  • When I report pain or physical symptoms to my doctor, I can feel confident that others will take them seriously and not assume I am motivated by secondary gain.
  • I can feel confident that if a family member requires hospital or emergency treatment they would be treated with dignity and respect even if they don’t mention my connection with the hospital.

Consider what you notice here.  How many feel true for you? And how might this reflect privilege (or lack thereof) in a healthcare environment? The intention here is not to blame or shame individuals who carry privilege, but rather to consider how this privilege might impact our experience and the quality of care we receive [7, 12].

Now, we invite you to bring to mind a patient or acquaintance with minority group affiliations (race, gender, age, SES). Then with this patient in mind, read through and consider these sentences again from this person’s perspective.  How many of these might feel true to this person?  And in turn, how might this impact actual or perceived care?  The answers and experience might be rather different in this case, and may be uncomfortable for us to consider.  Indeed, it is common for exercises like the above to elicit some negative emotions and internal discomfort (e.g., cognitive dissonance).  However, when elicited in a safe, nonjudging environment, these negative emotions can serve to motivate behavior change.  

Other strategies and considerations for providers

Other steps in the Burgess et al [7] model include increasing contact and comfort with minority groups, and facilitating perspective-taking and empathy for minority group patients—e.g., imagining situations from the patient’s perspective.  However, empathy can suffer due to stress, burnout, and time (e.g., over the course of one’s career).  Even when great strides have been made in reducing the impact of biases and increasing awareness of one’s biases, as creatures of habit we tend to regress back into old patterns if not careful.  Thus, self-care and becoming attuned to our own needs is vital to reducing bias in our work.  It is important that providers practice recognizing signs of burn-out within themselves and routinely re-assess for potential biases. At a systems level, this perhaps highlights the need for greater resources, i.e. advocating for lighter patient caseloads, more time with patients, more time for education (such as seminars or experiential trainings) of this nature both during graduate-level training and at the post-licensure level, and more.

All considered, it is important to note that perfection is neither expected nor realistic in efforts to reduce negative impacts of biases.  Rather, we should strive to reduce biases through practice of empathy, perspective-taking, awareness, and seeing patients as individuals rather than through the lens of group membership.


  1. Campbell, T.S., et al., Relationship of ethnicity, gender, and ambulatory blood pressure to pain sensitivity: Effects of individualized pain rating scales. The Journal of Pain, 2004. 5(3): p. 183.
  2. Millon, T., et al., Millon Behavioral Medicine Diagnostic. 2001, Minneapolis, MN: NCS Assessments.
  3. Springer, B.A., et al., Normative values for the unipedal stance test with eyes open and closed. J Geriatr Phys Ther, 2007. 30(1): p. 8-15.
  4. Hirano, K., et al., Impact of low back pain, knee pain, and timed up-and-go test on quality of life in community-living people. J Orthop Sci, 2014. 19(1): p. 164-71.
  5. Bohannon, R., Single limb stance times: a descriptive meta-analysis of data from indivdiuals at least 60 years of age. . Topics in Geriatric Rehabilitation, 2006. 22(1): p. 70-77.
  6. Steffen, T.M., T.A. Hacker, and L. Mollinger, Age- and gender-related test performance in community-dwelling elderly people: Six-Minute Walk Test, Berg Balance Scale, Timed Up & Go Test, and gait speeds. Phys Ther, 2002. 82(2): p. 128-37.
  7. Burgess, D., et al., Reducing racial bias among health care providers: lessons from social-cognitive psychology. J Gen Intern Med, 2007. 22(6): p. 882-7.
  8. Greenwald, A.G., D.E. McGhee, and J.L. Schwartz, Measuring individual differences in implicit cognition: the implicit association test. J Pers Soc Psychol, 1998. 74(6): p. 1464-80.
  9. Nosek, B.A., A.G. Greenwald, and M.R. Banaji, Understanding and using the Implicit Association Test: II. Method variables and construct validity. Pers Soc Psychol Bull, 2005. 31(2): p. 166-80.
  10. Lane, K.A., et al., Understanding and using the implicit association test: IV. Implicit Measures of Attitudes, 2007: p. 59-102.
  11. Hofmann, W., et al., A meta-analysis on the correlation between the implicit association test and explicit self-report measures. Pers Soc Psychol Bull, 2005. 31(10): p. 1369-85.
  12. Holm, A.L., et al., Recognizing Privilege and Bias: An Interactive Exercise to Expand Health Care Providers’ Personal Awareness. Acad Med, 2017. 92(3): p. 360-364.

[1] is run by a non-profit organization and collects the data for scientific purposes.

[2] The Cultural and Linguistic Competence Health Practitioner Assessment (CLCHPA) through the Georgetown University National Center for Cultural Competence can be found at  Please note that the assessment and website are temporarily out of service for revisions

Personality Disorders: Recognition and Management in a Pain Clinic

by Larry Robins, MD


Patients with moderate-to-severe personality disorders (PD) Are frequently seen in medical practices. It is increasingly important to recognize, limit and manage those with aggressive types of PD.  Likewise, it is crucial to recognize those who fit the bipolar spectrum. In particular, the mild end of the spectrum is often missed. The clinical stakes for missing bipolar are enormous, as these patients tend to bounce from antidepressant to antidepressant, with predictably poor results.  This article delves into recognition and management of patients whose pain treatment is complicated by psychological concerns.

Personality Disorders at a Clinic

Consider the following scenario: a 28 year old man, Bill, presents to the pain clinic with severe low back pain.  He seems angry on the first visit and is very demanding with the front office staff.  Bill tells the staff he is mistrustful of physicians.  He openly states to the doctor, “I will go back to work when you give me the right amount of drugs that help take away my pain.” Bill is upset with his last two health providers.

Over the next few months, the clinic staff bends over backwards for Bill, even though at times he is verbally abusive to the staff with a sense of entitlement.  This is demonstrated in instances such as when he calls and tells the staff: “I want to talk to Dr. Smith NOW, put me through!”  The staff, out of fear, jumps and does what he orders.  His behavior is manipulative. The physician feels as though he is in a subservient position, trying to appease Bill and end the confrontations.

When the physician recommends that Bill be evaluated by a psychotherapist, Bill laughs at the idea and refuses. Suddenly, after nine months of treatment, Bill is suddenly blaming the physician and clinic for all of his difficulties including his pain, obesity, and sexual dysfunction.  Bill threatens to sue the clinic and reports the doctor to the state regulatory office.  What happened here?

Bill was subsequently diagnosed with a paranoid personality disorder.  The clinic employees did not recognize him as having that diagnosis and failed to set limits on Bill’s behavior.  The disruptions in the usual activities of the clinic, the increased stress on the staff, and the monopolization of clinician time are difficult to quantify.  In the remainder of this article features of personality disorders that should help with identification are discussed. Optimal care and management of the disorder begins with recognition.

Approximately 10-12% of people in the general population have features of a personality disorder.1 There are a number of personality disorders, and some are more serious and difficult to treat than others.  In general, characteristics of personality disorders include: lack of insight, poor response to psychotherapy or other therapeutic interventions, difficulty with attachments and trust, a sense of entitlement, and chaotic relationships and distress with family, friends and co-workers.  Comorbid personality disorder with substance abuse is common.

Personality disorders range from mild to very severe and patients with such disorders may take on different roles, including victim, rescuer or persecutor.  When the persecutor role is assumed, the person who is the target may be in danger. Seeing a therapist for a long period of time, perhaps 5-7 years, can help to some degree.  However, goals and expectations must be limited.  Considering the plasticity of the brain is important, as some people can improve naturally over time, particularly among younger patients.   The following section describes some of the more severe personality disorder types.  However, many people do not fit neatly into any of these single categories, because they have features of two or three different personality disorders.

Paranoid Personality Disorder.  People who are diagnosed with paranoid personality disorder tends to be non-trusting, suspicious, related to seeing the world as dangerous. They may seem secretive and reluctant to confide in others.  In relationships, they view themselves as being constantly mistreated, doubt the loyalty of everybody around them, and believe they are being exploited or harmed.  Patients diagnosed with this disorder bear severe grudges against others, often, become angry easily and have a sense of entitlement.  People with paranoid personality disorders can become violent and dangerous, with many spree killers being diagnosed with paranoid personalities.  Several notorious world leaders, including Joseph Stalin and Saddam Hussein, were most likely paranoid personalities.2

Antisocial Personality Disorder.  People diagnosed with antisocial personality disorder characteristically have no regard for the rights of others.  In demeanor, they tend to be irritable, impulsive, and exploitative.  They tend to, see themselves as better or superior, and can be very opportunistic in getting what they want.  People with this disorder   have characteristics of being deceitful, stealing from people around them, and often having trouble with the law.  They frequently engage in fraudulent activities and may be successful as scam artists.  For example, a person with this disorder may take on the role of financial savior for a church, then end up stealing everything from the church.  Generally, people with this disorder have no remorse for their actions. Conduct disorder in a child often morphs into antisocial personality disorder.  Examples include fictional character Tony Soprano on the television show, and, in real life, the mafia’s “Dapper Don,” John Gotti.2

Borderline Personality Disorder (BPD).  Characteristics of people with borderline personality disorder are instability of mood, poor self-image, pervasive abandonment fears, identity disturbance and major boundary issues.  People with borderline personality disorders usually demonstrate impulsiveness, and very quick shifts from depression to anxiety to irritability.  They usually have chronic feelings of emptiness or severe loneliness, plus anger volatile tempers and even suicidal behavior. Under stress, they can become somewhat paranoid.  Coexisting problems with substance abuse or other addictive behaviors may occur, as well as sleep disorders with severe insomnia.  People with severe borderline personality disorders will react with high drama and create chaos for everybody around them.  They tend to have a split world view, which is, they see people as wonderful or terrible, with nothing in between. Borderline personality disorders can vary from mild to severe, nd become better or worse over time. Suicide becomes more likely as patients age into their upper twenties and thirties.3 Suicide is also more common within a week of discharge from a psychiatric unit. Examples of people reportedly diagnosed with borderline personality disorder include Adolph Hitler, Marilyn Monroe, and Glenn Close’s character Alex, in the movie, “Fatal Attraction.” 

Narcissistic Personality Disorder.  Narcissistic personality disorder is less common than those previously discussed and is typified by a personality in which the person sees him or herself as superior to others.  People with this personality have characteristics of grandiosity, being vain, requiring admiration, lacking empathy, having a deep sense of entitlement, having strong belief of self-importance and acting to support those feelings of self-importance.  They characteristically have behaviors which are envious, arrogant, exploitative, and can be very angry.  Examples might include General George Patton, Nicole Kidman’s character in the movie, “To Die For,” Michael Douglas’ character, Gordon Gekko, in the movie, “Wall Street.”2

There are a number of other personality disorders which are not as dangerous for the people around them or for health care providers.  Even though PD characteristics may seem extreme, they are often overlooked, and health care clinics may react by reacting to and treating these patients in a dysfunctional manner.  The difficulties begin with not recognizing the personality disorder.

Pain and Personality Disorders

One  study on people with borderline personality (BPD) concluded that BPD comorbidity with migraine is associated with increased disability from the headaches.4  In addition, in that study  those people diagnosed with BPD, were more severely affected by headaches; more inclined to be refractory to treatment; had increase in medication overuse headache; headaches were more pervasive; there was a higher degree of depression; , more unscheduled visits for acute headache treatment; and less chance of adequate response of headache medications..4

Another study indicated the incidence of BPD was increased in migraineurs.5 My recent study of 1000 migraineurs indicated that 5.5% of patients had a moderate or severe personality disorder.6 There is ample evidence that transformed migraine is associated with more prevalent psychopathology, including personality disorder, than is episodic migraine.  BPD can be considered the mental health equivalent of chronic pain.  In my experience, the two most important prognostic indicators for those with PD are impulsivity and substance abuse.

Treatment for those with PD necessitates a caring, but stern, approach.  Limits must be set on clinician contact, including telephone calls. Abuse of staff should not be tolerated.  Referral to other health care providers, particularly mental health professionals, should be suggested.  Psychotherapists and psychiatrists who are experienced with this population are vital if the patient is to be adequately managed.  Many of the PD patients do not do well with traditional, insight-oriented therapy treatment, but are better managed long-term with dialectical behavioral approach.  For a therapy to be beneficial, it must be consistent and long-term.  A psychoeducational approach may also help.  Unfortunately, even with encouragement and support many PD patients will not continue in therapy. Therapeutic goals for the PD patient are relatively modest.

It is easy to become drawn into the drama surrounding patients with PDs, particularly those with BPD.  The patient with BPD may grant the clinician power, but then subvert the therapy.  An example of this would be, “Doctor, you are the greatest, only you can help me.  These headaches ruin my life, ….and I know that nothing is going to work!”  Some clinicians are able to manage working with these patients without becoming involved in the drama and countertransference, but most do not do well working with them.  If there are signs of a dangerous PD (i.e. abuse and anger being demonstrated), during the first visit or phone call to the clinic), rather than becoming enmeshed in the relationship, is better to refer the patient to someone experienced in working with patients with PD.

There are risks inherent in caring for people who are diagnosed with personality disorders. As compared to the general population, those with BPD are at increased risk for suicide, particularly as they progress into middle age.  Identifiable risk factors for suicide among BPD patients include repeated hospitalizations (i.e. five or more), a recent psychiatric hospitalization, and, among adolescents, birth trauma.3 Certain types of PD (i.e. paranoid, narcissistic, antisocial and borderline) are more likely to become angry and vengeful with health care providers working with them; resorting to lawsuits or writing letters to the departments of regulation.  Violence may be threatened.  A patient with PD often presents as a victim, and then rapidly flips into the role of persecutor.  Anger among these patients becomes intently focused, creating a stressful environment for healthcare workers.  Setting limits and keeping careful documentation are important in these situations.

It does take a village to help a patient with a personality disorder, just as it does to adequately treat those with severe pain. It is important to recruit other clinicians, such as mental health providers, physical therapists, biofeedback therapists, etc., to aid in the treatment.

While there are no specific medications indicated for those with PD, the Axis I symptoms are more amenable to pharmacotherapy. Medications, though limited, may be beneficial for the impulsivity, aggression, self-mutilation, anxiety and depression components of PD.7   Antidepressants, mood stabilizers, and antipsychotics may ameliorate symptoms.  Some of these medications may also lessen headache pain as well.  PD patients with severe, chronic pain present additional challenges for treatment. It is important to limit and closely monitor addictive medications.  Particularly with BPD, opioids and benzodiazepines are best avoided.  The diagnosis of a moderate or severe personality disorder alters both goals and approach for pain management.


For patient care, it has become increasingly important to recognize those patients whose psychiatric problems complicate their treatment in a pain clinic. Patients with a personality disorder are more likely to abuse drugs, file lawsuits, or display abusive behavior toward the staff.  With personality disorders, setting limits is vital. 

Treating patients with chronic pain can be complex and challenging enough.  When their patients who live with chronic pain also have psychological comorbidities, it is vital that the psychopathology be effectively attended to, as well as the pain. 


  1. Lester G. Personality Disorders in Social Work and Health Care. Nashville: Cross Country University Press; 2002:28-79.
  2. Lester G. Borderline Personality Disorder. Treatment and Management That Works. Nashville: Cross Country University Press; 2005:24-25.
  3. Lester G. Borderline Personality Disorder. Treatment and Management That Works. Nashville: Cross Country University Press; 2005:15-19.
  4. Rothrock J, et al. Borderline Personality Disorder and Migraine. Headache. 2007; 47:22-26.
  5. Hegarty AM. The prevalence of migraine in borderline personality disorder. Headache.1993;33:271.
  6. Robbins L. The prevalence of personality in migraineurs. US Neurological Disease, 2007, Vol.4, Issue I.
  7. Lester G. Borderline Personality Disorder. Treatment and Management That Works. Nashville: Cross Country University Press; 2005:88-91.
  8. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition. Washington D.C. American Psychiatric Association: 1994.
  9. Akiskal HS. Classification, diagnosis and boundaries of bipolar disorders. Bipolar Disorder.  Edited by Maj M, Akiskal H, Lopez-Ibor J et al.  London, Wiley, 2002, pp 1-52.
  10. Merikangas KR, et al. Comorbidity of migraine and psychiatric disorders.  Neurol Clin. 1997;15:115-123
  11. Baskin SM, et al. Mood and anxiety disorders in chronic headache. Headache. 2006;46(suppl 3):S76-S87.
  12. Robbins L. Bipolar spectrum in Migraine, Cluster and Chronic Tension Headache. US Neurological Disease, 2007, Vol. 3, Issue II.
  13. McIntyre RS, et al. The prevalence and impact of migraine headache in bipolar disorder: Results from the Canadian community health survey. Headache. 2006;46:973-982.
  14. Low NC, et al. Prevalence, clinical correlates and treatment of migraine in bipolar disorder. Headache. 2003;64:53-59.
  15. El-Mallakh, et al. Antidepressants in bipolar depression, in El-Mallakh R, Ghaem S. Bipolar Depression. Washington DC, American Psychiatric Publishing, Inc.; pp149-153.
  16. Calabrese J, et al. A randomized, double-blind, placebo-controlled trail of quetiapine in the treatment of bipolar I or II depression. AM J Psychiatry. 2005;162:1351-1360.

Medication Overuse Headache: Inaccurate and Overdiagnosed

by Larry Robbins, MD

Medication overuse headache (MOH) is very frequently diagnosed; however, the MOH diagnosis is often overused. Patients are labeled as having MOH when what they actually suffer from are refractory headaches, without medication overuse (MO).   Current diagnostic criteria for MOH only require abortive medication use on 10 or 15 days of each month (depending upon the medication). 1 No evidence is needed showing that the abortive actually causes an increase in headache. MO often occurs among people with frequent headaches.  However, MO does not necessarily lead to developing increased headaches. Diagnosing MOH is not an easy task, and requires a careful assessment of the patient’s medication and headache history.  As the abortive medication was used more frequently, the headaches (usually migraines) should have also escalated in a true MOH situation. In addition, after the offending medication was withdrawn, headaches should have receded. The epidemiologic studies of MOH may not be valid, since they do not differentiate MO from MOH.

A number of years ago all abortives, including nonsteroidal anti-inflammatories (NSAIDS), were implicated in MOH. We now realize that certain medications (NSAIDS and triptans) are less likely to cause MOH than others. Opioids and butalbital compounds are the worst offenders. Although simple NSAIDS usually do not contribute to MOH, they continue to be included in the MOH criteria.

Patients often are given the label of MOH simply because they admit to regularly consuming over-the-counter analgesics or a triptan. Many patients who frequently use these medications do not suffer from MOH. There are a number of variables, including genetics, age, type of drug, etc., that help to explain why one patient suffers from MOH, while the next does not.

For many patients with frequent headaches, behavioral techniques and preventive medications (including Botox) are inadequate. Our current preventives often provide little relief, and frequently cause unacceptable side effects. We do not have any preventives that were initially developed for headache, except for the Calcitonin gene-related peptide-inhibitor  (CGRPinhibitor) injections, which will be available later in 2018.  One long-term study indicated that only about half of migraineurs found any preventive helpful for longer than 6 months. 2, 3  Declining efficacy and increased side effects often lead to discontinuation of the preventive.

Many physicians are quick to blame the patient for causing MOH. The patients are told that they are suffering from MOH due to a particular medication, even though

  1. they have only been taking that medication for a short time, 
  2. the headaches did not increase once they began the medication,
  3. medication withdrawal did not lead to a lessening of the headaches.

Physicians often instruct the patient to only use the abortive 2 days per week. The patient usually responds, “that’s fine, but what do I do the other 5 days? I have to function.” Many headache specialists and neurologists maintain a rigid posture, refusing to allow more than a bare minimum of abortive medication.  The patient either suffers or seeks help elsewhere.

Much of what is written about MO and MOH is confusing, with little basis in fact. These are arbitrary terms, without scientific validation. Of course, we must try to minimize the use of abortives. Patients on frequent abortive medication should be withdrawn for a period of time,  (easier said than done). However, many refractory patients would have zero quality of life without their (frequently used) abortives.

The current criteria conflates MO with MOH. As a result, the term MOH is wildly over-diagnosed.  This is concerning because an inaccurate label of MOH may harm the patient. Patients with the MOH diagnosis often are denied the only medication that is helpful for them.  Two alternatives seem reasonable.  We could re-define MOH, using scientifically validated criteria.  Alternatively, we could drop the term MOH altogether.  

Of course, treating those who do have MOH is never easy. Patients are reluctant to give up their abortive, whether it is Excedrin®, a triptan, or an opioid. If we can convince the person their headaches may improve via minimizing the abortive, we sometimes may succeed. There are various strategies for withdrawal.  Sometimes it “takes a village” to treat a patient with severe headaches, and we recruit other “villagers” to assist in the process. These may be physical therapists, psychotherapists, biofeedback specialists, etc.  In the long-term, at least half of those with MOH do revert back to overuse of their . 4


  1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808.
  2. Robbins,L. We Need Better Preventative Medications(Letter). Headache: The Journal of Head and Face Pain. 2001; 41(6): 611-612.
  3. Robbins,L. Efficacy of Preventive Medications for Chronic Daily Headache. Headache Quarterly. 1999; 10(3):135-139.
  4. L.  Letter in Headache, June 2001, Vol. 41, No. 6, pp. 611-612.

Migraine Treatment: A Comprehensive Guide

Migraine is a very common and disabling illness. Picking an agent that is best for each individual patient requires considering the patient’s history, lifestyle, comorbid conditions, and individual preferences.

Migraine headaches are a common cause of disability in the United States, affecting approximately 27 million American adults, or 17.1% of women and 5.6% of men. To help better define migraines, the term classical migraine has been replaced with migraine with aura and non-classical migraine is now referred to as migraine without aura. Chronic migraine, which affects 3.2 million Americans (2%), is defined as having migraine symptoms for at least 15 days per month, lasting at least 4 hours, and for longer than 3 months in duration. This is in contrast to episodic migraine, which causes symptoms on less than 15 days per month. Current treatment for chronic migraine is divided into acute, abortive agents (analgesics, triptans, ergots, etc.) and medications that will prevent migraine onset.

This review will highlight the current definitions of migraines as well as treatment options.

Migraine Characteristics
A recurring headache that is of moderate or severe intensity, and is triggered by migraine-precipitating factors, usually is considered to be migraine. Precipitating factors can include stress, certain foods, weather changes, smoke, hunger, fatigue, hormones, and so on. Migraine without aura is a chronic idiopathic headache disorder with attacks lasting 4 to 72 hours. Status migrainosis applies to migraine headaches that exceed 72 hours. Migraine features often include a unilateral location and a throbbing or pulsating nature to the pain. There may be associated nausea, photophobia, phonophobia, or dizziness. Further characteristics include a positive relationship with menses, decreased frequency during pregnancy, increased pain with physical activity, and history of migraine in first-degree relatives. It has been reported by 70 to 75% of migraine patients that they have a first-degree relative with a history of migraines.

Patients who suffer from migraines often have colder hands and feet compared with controls, and the prevalence of motion sickness is much higher in migraine patients. Although most patients will not have all of these characteristics, there are certain diagnostic criteria that have been established by the International Headache Society for the definite diagnosis of migraine. Distinguishing a milder migraine without aura from a moderate or severe tension headache may be difficult, and it is not surprising when “pure” migraine medications are effective for severe tension-type headaches.

Recurrent, repeated attacks of throbbing or severely aching headache are generally regarded as migraine, whether or not the patient has nausea, dizziness, photophobia, or phonophobia. The patient’s history is used to make the diagnosis of migraine. Physical examination and magnetic resonance imaging (MRI) or computed tomography (CT) scans are helpful only in ruling out organic pathology. Recent-onset headaches need to be investigated with an MRI scan to rule out other organic disorders, particularly brain tumors. In addition to physical exam and imaging, a check of intraocular pressure (IOP) may be warranted. With new-onset headaches, an eye exam is always warranted.

Although the pain is unilateral in 50% of migraine patients, the entire head often becomes involved. The pain may be in the facial or the cervical areas, and often will shift sides from one occurrence to another. Most patients, however, suffer the severe pain on one favored side from attack to attack.

The typical migraine patient suffers one to five attacks in a month, but many patients average less than one (episodic) or more than 10 per month (chronic). The attack frequency varies with the seasons, and many patients can identify a time of year when their headaches increase significantly. Patients with chronic migraine may have 15 days a month of headache, and many even have 30 days/month, 24/7.

The pain of the migraine often follows a bell-shaped curve, with a gradual ascent, a peak for a number of hours, and then a slow decline. Occasionally, the pain may be at its peak within minutes of onset. Many patients with migraine suffer some degree of nausea during the attack, and some experience vomiting as well. The nausea often is mild, and some patients are not bothered by it. Many patients state that the headache is lessened after they vomit. Diarrhea may occur, and is usually mild to moderate. The presence of diarrhea renders the use of rectal suppositories impossible.

Lightheadedness often accompanies the migraine, and syncope may occur. Most patients become sensitive to bright lights, sounds, and/or odors. Between migraine attacks, many patients retain the photophobia, and it is common for migraine patients to wear sunglasses most of the time. Sensitivity to bright lights is a distinctive migraine characteristic.

Pallor of the face is common during a migraine; flushing may occur as well, but is seen less often. Patients do complain of feeling excessively hot or cold during an attack, and the skin temperature may increase or decrease on the side with pain. Patients with migraines often experience tenderness of the scalp that may linger for hours or days after the migraine pain has ceased. This tenderness may actually occur during the prodrome of the migraine. Both vascular and muscular factors contribute to the scalp tenderness. Autonomic disturbances are relatively common, such as pupillary miosis or dilation, rhinorrhea, eye tearing, and nasal stuffiness. These also are symptoms of cluster headache, including the sharp pain about one eye or temple.

Alterations of mood are seen with many patients before, during, and after migraine attacks. Patients are usually anxious, tired, or depressed. They often feel “washed out” after an attack, but a calm or even an euphoric state occasionally is seen as a postdrome to the migraine. Rarely, euphoria or exhilaration may precede a migraine.

Weight gain due to fluid retention may occur, and begins prior to the onset of the migraine. At some point during the migraine, patients may experience polyuria. The weight gain is usually less than 4 lb., and is transient.

Visual Disturbances
Approximately 20% of patients experience visual neurologic disturbances preceding or during the migraine; these auras may be as disturbing to the patient as the migraine pain itself. The visual symptoms usually last 15 to 20 minutes, and most often will be followed by the migraine headache. Most migraine sufferers experience the same aura with each migraine, but occasionally one person may have several types of auras. “The light of a flashbulb going off,” is the description many patients give to describe their aura. The visual hallucinations seen most often consist of spots, stars, lines (often wavy), color splashes, and waves resembling heat waves. The images may seem to shimmer, sparkle, or flicker. These visual occurrences are referred to as photopsia.

Fortification spectra are seen much less often than photopsia. They usually begin with a decrease in vision and visual hallucinations that are unformed. Within minutes, a paracentral scotoma becomes evident and this assumes a crescent shape, usually with zigzags. There often is associated shimmering, sparkling, or flickering at the edges of the scotoma.
Patients may experience a “graying out” of their vision, or a “white out” may occur. Some patients suffer complete visual loss, usually for some minutes. Photopsia may be experienced at the same time as the gray out, white out, or visual loss.

Miscellaneous Neurologic Symptoms
Numbness or tingling (paresthesias) commonly are experienced by patients as part of the migraine. These are experienced most often in one hand and forearm, but may be felt in the face, periorally, or in both arms and legs. Like the visual disturbances, they often last only minutes preceding the pain, but the numbness may continue for hours, and at times the paresthesias are severe. The sensory disturbances usually increase slowly over 15 to 25 minutes, differentiating them from the more rapid pace seen in epilepsy.

Paralysis of the limbs may occur, but this is rare. This is occasionally seen as a familial autosomal dominant trait, and the term familial hemiplegic migraine is applied to this form. With the weakness, aphasia or slurred speech may also occur, and sensory disturbances are seen ipsilateral to the weakness. Vertigo and/or dizziness are often experienced during migraine, and may be disabling. “Migraine associated vertigo” has become a common diagnosis. At times, the dizziness is more disabling to patients than the other symptoms. Ataxia may occur, but is not common. Rarely, multiple symptoms of brain stem dysfunction occur, with the term basilar migraine being applied to this type of syndrome. The attack usually begins with visual disturbances (most often photopsia), followed by ataxia, vertigo, paresthesias, and other brain stem symptoms. These severe neurologic symptoms usually abate after 15 to 30 minutes, and are followed by a headache. This type of migraine often stops over months or years, and the patient is simply left with migraine headaches without neurologic dysfunction.

Workup for Migraine
As noted, when patients present with a long history of typical migraine attacks, and the headaches are essentially unchanged, scans of the head usually are not absolutely necessary. Whether to do any testing at all depends on the physician’s clinical suspicion of organic pathology. Sound clinical judgment, based on patient history and a physical exam, is crucial in deciding who needs which exam.

In addition to the MRI and CT scan, tests that are sometimes useful for diagnosis of headache include lumbar puncture, IOP testing, CT scan of the sinuses, and blood tests. A magnetic resonance angiogram (MRA) allows the detection of most intracranial aneurysms.

The problems that need to be excluded in a patient with new-onset migraine include sinus disease, meningitis, glaucoma, brain tumor, arteritis, subarachnoid hemorrhage, idiopathic intracranial hypertension( or low pressure headache, which is positional in nature: basically almost gone when the patient lies down), hydrocephalus, pheochromocytoma, stroke or transient ischemic attack, internal carotid artery dissection, and systemic illness.

Headache Triggers
With migraine and chronic daily headache sufferers, avoidance of triggers should be emphasized. The most common triggers are stress (both during and after stress), weather changes, perimenstruation, missing meals, bright lights or sunlight, under- and oversleeping, food sensitivity, perfume, cigarette smoke, exercise, and sexual activity. Some foods can be headache triggers, but foods tend to be overemphasized. In general, headache patients do better with regular schedules, eating three or more meals per day and going to bed and awaking at the same time every day. Many patients state that “I can tell the weather with my head”. Barometric changes and storms are typical weather culprits, but some patients do poorly on bright “sun-glare” days.

Regarding stress as a trigger, it is not so much extreme stress, but daily hassles that increase headaches. When patients are faced with overwhelming daily stress, particularly when they are not sleeping well at night, headaches can be much worse the next day.

Psychotherapy is extremely useful for many headache patients with regard to stress management, coping, life issues, family-of-origin issues, and so on. Although psychotherapy may be recommended, it is crucial to legitimize the headaches as a physical condition; headaches are not a “psychological” problem, but rather a physical one that stress may exacerbate. Once one inherits the brain chemistry for headache, these triggers come into play; without the inherited genetics, most people may have stress/weather changes/hormonal changes, but not experience a headache.

Managing stress with exercise, yoga/Pilates/meditation, etc., often will reduce the frequency of headaches. The ideal would be for the patient to take a class weekly, then do the stretches and breathing for 10 minutes a day. Patients may experience some relief from associated neck or back pain. Relaxation techniques such as biofeedback, deep breathing, and imaging also may be helpful for daily headache patients, particularly when stress is a factor.

Many migraine patients have accompanying neck pain and physical therapy may help; acupuncture or chiropractic treatments occasionally help. Certain physical therapists “specialize” in head and neck pain. Massage may be effective, but the relief is often short-lived. Temporomandibular disorder (TMD), with clenching and/or bruxing, may exacerbate migraine; with TMD, physical therapy, a bite splint, and/or Botox may help. It often “takes a village” to help a person with pain, and we recruit other “villagers”, such as physical therapists or psychotherapists.

Caffeine Use
Although caffeine can help headaches, overuse may increase headaches. Whether in coffee, caffeine pills, or combination analgesics, patients must limit total caffeine intake. The maximum amount of caffeine taken each day varies from person to person, depending on sleep patterns, presence of anxiety, and sensitivity to possible rebound headaches. In general, caffeine should be limited to no more than 150 or 200 mg a day. Some migraineurs do well by completely decaffeinating themselves; it often is worthwhile to try this approach.

Foods to Avoid
As noted, food sensitivities are not that common. Patients tend to focus on the foods, as they are a tangible trigger that one can control (as opposed to weather, for example). However, most people are sensitive to only two or three types of food in the diet. If a particular food is going to cause a headache, it usually will occur within 3 hours of eating.

Medications: Abortives
The most common first-line treatment for migraines includes triptans. More than 200 million patients worldwide have used triptans. The most effective way to use triptans is to take them early in the headache—the earlier a patient takes these agents the better the effect. Sumatriptan is an extremely effective migraine-abortive medication with minimal side effects. It is effective for approximately 70% of patients and is the gold standard in abortive headache treatment. The usual dose is one tablet every 3 hours, as needed; maximum dose, two tablets per day. However, clinicians do need to limit triptan use (ideally, 3 days per week) to avoid rebound headaches or medication overuse headache (MOH). See section on rebound/MOH.

Triptans are helpful for moderate as well as more severe migraines. Certain patients tolerate one of the triptans better than another, and it is worthwhile to try several in an individual patient. Triptans are an excellent choice for migraine patients who are not at risk for coronary artery disease (CAD). Patients in their 50s or 60s can use these drugs, but they should be prescribed cautiously, and only in those patients who have been screened for CAD. Over the 23 years that triptans have been available, serious side effects have been few; they appear to be much safer than was previously thought in 1993.

For patients who cannot tolerate triptans, there are a number of other effective non-triptan first-line approaches, including diclofenac potassium powder(Cambia), Excedrin Migraine, naproxen, ketorolac(po/IM/nasal:”Sprix nasal spray”), ibuprofen, and Prodrin (similar to Midrin, but without the sedative). We often combine 2 first-line approaches (a triptan and a non-steroidal anti-inflammatory drug (NSAID) combination, for instance).

In general, drugs containing ergotamine (also called ergots) are effective second-line therapy for migraines. They were the first anti-migraine drugs available, but they have many side effects, and at most, should be used only 2 days per week. Dihydroergotamine (DHE) is the safest ergot derivative. DHE is primarily a “venoconstrictor”, with little arterial effects. This renders it very unlikely to cause cardiac problems. Indeed, since its introduction in 1945, DHE has been remarkably safe. Intravenous DHE is a very effective migraine-abortive agent administered in the office or emergency room. Availability and cost of DHE have been a problem. Nasal (Migranal Nasal Spray) and inhaled forms of DHE (soon to be released) have been found to be safe and effective as well. Barbiturates and opioids have been studied and are effective, but because of the risk for addiction, should be used sparingly. For severe prolonged migraines, corticosteroids (oral, IV, or intramuscular) often are effective. It is important to use low doses of steroids, for only 1 to 3 days per month.

Many patients have 3 to 6 abortives on their shelf: triptan, NSAIDs, Excedrin, an anti-nausea med, and a painkiller (opioid/butalbital). They use each in different situations, for different types and degrees of headache.

A new therapy has emerged, transcranial magnetic stimulation(TMS). The patient uses a hand held device applied to the back of the head, for an acute migraine attack. The first TMS approved(in Dec., 2013) is the Spring TMS. The official indication is migraine with aura. Studies have been positive on TMS devices over a number of years. Time will tell as to the efficacy. The low-dose home TMS appears to be very safe. People rent the unit, and use 3 or 4 pulses twice daily, as a preventive. TMS may also be used abortively, but preventive use is the most promising.

Miscellaneous Approaches

Muscle relaxants (carisoprodol, diazepam) or tranquilizers (clonazepam, alprazolam) occasionally are useful, primarily to aid in sleeping. Intravenous sodium valproate (Depacon) is safe and can be effective. The atypical antipsychotics, such as olanzapine (Zyprexa) or quetiapine (Seroquel), occasionally may be useful on an as-needed basis. In the emergency room, IV administration of antiemetic agents such as prochlorperazine (Compazine, others) or metoclopramide (Reglan) may be useful. Certain preventive medications, such as valproic acid (Depakote), topiramate (Topamax), and also amitriptyline, may be useful on an as-needed basis, utilizing low doses every 4 to 6 hours. The antihistamine diphenhydramine is occasionally useful when administered intramuscularly. At times, patients may have injections for home use: ketorolac, orphenadrine, sumatriptan, diphenhydramine, promethazine, etc.

Medication Overuse Headache(MOH)
Much is written about MOH, with many patients diagnosed with this condition. Often a patient will be overusing abortive meds (medication overuse), but not be suffering “rebound/withdrawal” headaches (medication overuse, but NOT medication overuse headache). Up until recently, all NSAIDS were lumped under “meds that cause MOH”, and this simply is not true. For some patients, opioids, butalbital, and high caffeine containing meds cause MOH. Triptans are occasionally implicated as well. However, for most patients with chronic migraine, they have daily(or near-daily) headaches, the preventives may not be effective, and they use abortives in an attempt to get through the day.

There are more questions in the area of MOH than we have answers. The pathophysiology of MOH is unclear. Some patients will have MOH from 2 Excedrin daily, while others do not suffer from MOH consuming 8 per day. When patients are using frequent abortives, we often withdraw them from that abortive, push preventives, and attempt to minimize analgesics. However, for many chronic migraine sufferers, the preventives are not very effective. For those sufferers, abortives allow them to live with a reasonable quality of life.

Preventive Medications
There is no algorithm to determine who is to go on preventive headache medication. The number of monthly headaches is one factor, along with comorbidities. Patients have to be willing to take daily medication (many do not want any daily meds). There is no absolute rule that applies to headache treatment. For a patient with two headaches a month that are severe, prolonged, and not relieved by drugs, preventive medicine might be used. On the other hand, for the person who has five headaches a month, but can obtain relief from Excedrin or a triptan, preventive medicine may not be optimal. The choice of who qualifies for medication depends on the patient’s age, medical and psychiatric comorbidities, and frequency and severity of the migraine, as well as the patient’s preference. Comorbidities often determine which preventive meds are used. If a patient has HTN, a med for blood pressure will be used. When patients concurrently suffer with anxiety or depression, various antidepressants are utilized for the headache and mood disorder. We want to minimize meds, and treating 2 conditions with one medication is ideal.

In using medication, a realistic goal is to decrease the headache severity by 40% to 70%, not to completely eliminate the headaches. It is wonderful when the headaches are 90% improved, but the idea is also to minimize medication. “Clinical meaningful pain relief” is usually around a 30% improvement. Most patients need to be willing to settle for moderate improvement. Preventives may take 3 to 6 weeks to work, and “educated guesswork” often is used to find the best approach for each patient. In the long run, preventive medications are effective for approximately 50% of patients. The other 50% scramble with various abortives.

As noted, patients should play an active role in medication choice. Preventive medications should be selected depending on the patient’s comorbidities, GI system, medication sensitivities, and the like. Fatigue and/or weight gain are major reasons why patients abandon a preventive medication. Headache patients commonly complain of fatigue, and tend to give up on medications that increase tiredness. A patient’s occupation also may guide the caregiver away from certain medications; for example, an accountant may not be able to tolerate the memory problems associated with topiramate. Side effects are possible with any medication; the patient must be prepared to endure mild side effects in order to achieve results.

First-line Preventive Medications for Migraine

Botulinum Toxin A
Botulinum toxin A (Botox) has been studied extensively in patients with migraines. Nearly 4 million people have had botulinum toxin A injections for headache. Botulinum toxin A has been found to significantly improve quality of life and reduce headache impact.4 Botox is the only botlinum toxin A FDA-approved for treatment of chronic migraine. It is relatively safe and only takes a few minutes to inject. One set of injections may decrease headaches for 1 to 3 months. There also is a cumulative benefit, where the headaches continue to improve over 1 year of injections. Botox may be safer than many of the medications that are used for headache. Botox does not cause the “annoying” side effects that are commonly encountered with preventives.

Natural Supplements and Herbs
Feverfew, Petadolex (butterbur), and magnesium oxide have all proven effective in double-blind studies as migraine preventives. Of these, Petadolex has been the most effective.
Petadolex is a purified form of the herb butterbur and is made of extracted plant certified by the German Health Authority. The herb preparation is commonly used in Europe, and has been found to be successful in preventing migraines in several well-designed blind studies. The usual dose is 100mg. per day, and many increase this to 150mg. daily(all at once, or in 2 divided doses). Earlier concerns about carcinogenesis with this family of herbs have decreased with the use of Petadolex. Patients have occasionally experienced GI upset or a bad taste in the mouth, but Petadolex is usually well tolerated. It is prudent to stop it every three months or so. Petadolex is available by calling 1-888-301-1084, through, or at

Magnesium helps many systems in the body to function, especially the muscles and nerves. It has been shown that magnesium levels in the brain of migraine patients tend to be lower than normal. Magnesium oxide is used as a supplement to maintain adequate magnesium in the body. A dose of 400 or 500 mg per day can be used as a preventive; tablets are found in most pharmacies. However, mild GI side effects may limit use. There are also drug interactions that may occur; as always, consult your physician. There are tablets, as well as powdered versions available.

Feverfew has been demonstrated to be mildly effective in some patients for prevention of migraine headache. Feverfew can cause a mild increased tendency toward bleeding, and should be discontinued two weeks prior to any surgery. The problem with many herbal supplements is quality control. The amount of parthenolide (the active ingredient in feverfew) varies widely from farm to farm; certain farms consistently have better quality than others. The usual dose is 2 capsules each morning; there is a liquid form available. Patients occasionally will be allergic to feverfew, and it should not be used during pregnancy. Miscellaneous herbs/supplements have been used, particularly vitamin B2. CoQ10 and fish oil have also been studied. These occasionally help, but are less effective than Petadolex.

Topiramate is an effective migraine preventive, without the weight gain commonly encountered with the other meds. While usually fairly well tolerated, common side effects include memory difficulties(“spaciness”), and tingling. In higher doses, topiramate increases the risk for kidney stones. Topiramate does decrease appetite, leading to weight loss for some patients. This anorexic effect tends to disappear after several months. The usual dose is 50 to 100mg daily, but some do well on as little as 25mg.. The dose may be pushed to 300 or 400mg. per day, in the absence of significant side effects. Topiramate is primarily used for migraine prevention, but has also been utilized for cluster and tension headache as well. Topiramate may cause a metabolic acidosis, with lower bicarbonate levels(and increased chloride). The acidosis may lead to the tingling, which sometimes is alleviated by increasing potassium-containing fruits/vegetables(or adding potassium).

Valproate, or divalproex sodium, (Depakote) is a long-time staple, popular for migraine prevention. It is usually well tolerated in the lower doses used for headaches, however, the generic may not be as effective. Liver functions need to be monitored in the beginning of treatment. Valproate also is one of the primary mood stabilizers for bipolar disorder. Oral Depakote ER (500 mg) is an excellent once-daily, long-acting agent. As with most preventives, valproate needs 4 to 6 weeks to become effective.

The β-blocker propranolol also is FDA-approved as a preventive agent for migraines. Long-acting oral propranolol (Inderal), for example, is very useful in combination with the tricyclic antidepressant amitriptyline. Dosage begins with the long-acting agent given at 60 mg per day, and is usually kept between 60 and 120 mg per day. Lower doses are sometimes effective, such as 20 mg twice a day of propranolol. Other β-blockers also are effective, such as metoprolol (Toprol XL) and atenolol. Some of these are easier to work with than propranolol because they are scored tablets, and metoprolol and atenolol have fewer respiratory effects. Depression may occur. β-blockers are useful for those migraine patients with concurrent hypertension, tachycardia, mitral valve prolapse, and panic/anxiety disorders. Bystolic (nebivolol) is another β-blocker that may be helpful for the prevention of headaches, and has fewer respiratory side effects than other agents. Bystolic probably has the least amount of side effects among the β-blockers.

As noted, amitriptyline is an effective, inexpensive agent that is useful for the prevention of daily headaches and insomnia. As a preventative agent, amitriptyline is prescribed at low doses and taken at night. Sedation, weight gain, dry mouth, and constipation are common side effects. Other tricyclic antidepressants such as doxepin and protriptyline can be effective for migraine. Nortriptyline is similar to amitriptyline, with somewhat fewer side effects. These also are used for daily tension-type headaches. Protriptyline is one of the few older antidepressants that does not cause weight gain. However, anticholinergic side effects are increased with protriptyline; protriptyline is more effective for tension headache than for migraine. Although selective serotonin reuptake inhibitors (SSRIs) are used, they are more effective for anxiety and depression than for migraine.

Naproxen is a very useful agent for the treatment of daily headaches, as well as for younger women suffering from menstrual migraine. Naproxen is nonsedating, but frequently causes GI upset or pain. Effective as an abortive, it may be combined with other first-line preventive medications. Other NSAIDs can similarly be used for migraine prevention. As with all anti-inflammatories, GI side effects increase as people age, and therefore NSAIDs are used more often in the younger population. Blood tests are needed to monitor liver and kidney function.

Second-line Migraine Preventive Therapy

There are a number of second-line migraine treatments. The anti-seizure medication gabapentin has been demonstrated to be mildly useful in migraine and tension headache prophylaxis. In a large study on migraine, doses averaged approximately 2,400 mg per day, but lower doses are usually prescribed. Some patients do well with very low doses (200 or 300 mg per day). Sedation and dizziness may be a problem; however, gabapentin does not appear to cause end-organ damage, and weight gain is relatively minimal. Gabapentin can be used as an adjunct to other first-line preventive medications. A newer drug, pregabalin (Lyrica), has a similar mechanism of action to gabapentin. Lyrica is fairly safe, but sedation and weight gain often occur.

A safe, non-addicting muscle relaxant, tizanidine is useful for migraine and chronic daily headache. Tizanidine may be used on an as-needed basis for milder headaches, or for neck or back pain. Cyclobenzaprine (10 mg) is helpful for sleeping, and helps some with migraine and chronic daily headache.

There have been a number of studies on the efficacy of using angiotensin receptor blockers (ARB) and the angiotensin-converting enzyme inhibitors (ACE’s) for the prevention of migraine. ARBs are preferred because of minimal side effects. Examples include losartan (Cozaar) and candesartan (Atacand). These may be useful for the patient with hypertension and migraine. Side effects include dizziness, among others, but they are usually well tolerated, with no sedation or weight gain.

Similar to the ARB’s, the calcium channel antagonists have been utilized for migraine prevention. Verapamil ER (extended release) is the most commonly used form, with doses ranging from 120mg daily up to 360mg. per day. Verapamil is probably more effective as a cluster headache preventive.

Polypharmacy is common in migraine prevention. Two first-line medications often are used together and the combination of two preventives can be more effective than a single drug alone. For example, valproate often is combined with an antidepressant. Amitriptyline may be combined with propranolol(or other β-blockers), particularly if the tachycardia of the amitriptyline needs to be offset by a β-blocker; this combination is commonly used for “mixed” headaches (migraine plus chronic daily headache.) NSAIDs may be combined with most of the other first-line preventive medications. Thus, naproxen often is given with amitriptyline, propranolol, or verapamil. Naproxen is employed simultaneously as preventive and abortive medication. Polypharmacy commonly is employed when significant comorbidities (anxiety, depression, hypertension, etc.) are present. Unfortunately, polypharmacy brings the risk of increased side effects.

Venlafaxine (Effexor XR) is an excellent antidepressant, occasionally helpful for the prevention of migraine. Used primarily as an SSRI at lower doses; at higher doses (100-150 mg) norepinephrine also is increased. In fact, antidepressants with dual mechanisms (serotonin and norepinephrine) are more effective for pain and headache. Another similar medication is duloxetine(Cymbalta), with typical doses being 30mg to 60mg daily. Cymbalta has several pain indications, but is probably more effective for moods than for headache.

Migraine is a common and disabling illness. Outside of meds, it is important for migraineurs to watch their headache triggers, and exercise regularly. Physical therapy and/or psychotherapy may be of help (“it takes a village”). There is no good algorithm for determining which medication is best. Each patient is unique, and comorbidities drive where we go with treatment. The goal is to decrease head pain, while minimizing medications. NOTE: This is an updated version of an article that appeared in the July, 2014 issue of Practical Pain Management.


Lipton RB et al on behalf of the AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343-349.
Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders. 2nd ed. Oxford, England: Blackwell Publishing; 2003.
Gardner KL. Genetics of migraine: an update. Headache. 2006;46(suppl 1):S19-S24.
Lipton RB, Varon SF, Grosbert B, et al. Onabotulinumtoxin A improves quality of life and reduces impact of chronic migraine. Neurology. 2011;77(15):1465-1472.
Mathew NT, Rapoport A, Saper J, Magnus L, et al. Efficacy of gabapentin in migraine prophylaxis. Headache. 2001;41(2):119-128.
Robbins L. Robbins Headache Clinic.

Innovation: Opioid Substance Use Disorder

by Ann Quinlan-Colwell, PhD, RN-BC, DAAPM

During 2014, patients were admitted more frequently with diagnoses of soft tissue abscesses, epidural abscesses, and endocarditis. Two common denominators, among many of these patients, were a history of self-administering opioids intravenously and now needing intravenous (IV) antibiotics for prolonged periods of time. This combination posed a challenge for health care providers who believed that it was not prudent or safe to discharge patients with a port or peripherally inserted catheter (PICC) line for IV access when the patient was known to abuse opioids intravenously.  Thus, the patients with these dual diagnoses -serious infections requiring IV antibiotics and substance use disorder- were admitted to the hospital for administration of IV antibiotics for six to twelve weeks. 

Two additional concerns arose. Many providers believed that it was important to control pain and to work with these patients, encouraging them to work toward sobriety.  In many instances this was reasonable and opportune since some of the very ill and scared patients demonstrated greater motivation to seriously consider abstinence and sobriety.  The providers consulted the Pain Management Clinical Nurse Specialists (CNS) to help control the patients’ pain while minimizing opioids and then wean the opioids to discontinuation whenever possible.      

Two cardiovascular surgeons who saw the patients with endocarditis invited a team to meet to address how to best work with the patients with endocarditis resulting from IV substance use (IVSU).  The initial group included the cardiovascular surgeons, infectious disease (ID) physician, cardiology administrator, cardiology nurse administrator, behavioral health administrator, substance abuse counselor, pharmacist, social worker, case manager and pain management CNS.  An addictionologist and community provider of buprenorphine were consulted.

Since patients were also being admitted for non-cardiac infections resulting from IVSU, the team expanded to coordinate with the medical center Code Outreach physicians.  Code Outreach is the established process through which the medical center coordinated interdisciplinary care of patients who were frequently evaluated in the emergency department (ED) and/or admitted.  Eventually, the Code Outreach team assumed primary oversight for interventions, patient care, and group activities. 

The intervention and group is now known as the Code Outreach Special Team or “COST”.  It consists of the two Code Outreach physicians, a pharmacist, the substance abuse counsellors, pain management CNSs, case management, cardiac nurse coordinator and one social worker (MSW). This MSW follows all the patients who are admitted to receive long term IV antibiotics to treat infections resulting from IVSU. Each patient in this category is reviewed weekly by the COST.  At the weekly meetings, the patients’ condition, challenges, pain management, progress toward goals, discharge needs/plans as well as the barriers to achieving these are discussed.  The plan of care is amended as needed. A template was developed for an individualized COST note to be created during the meeting and entered into the electronic medical record for the patient. This COST note is available to all professionals providing care and working with the patient. 

Each of the patients is also individually followed at least weekly by the pain management CNS, substance abuse counsellors and MSW.  The team, especially the MSW, works closely with methadone maintenance programs and providers of buprenorphine in the community to identify resources to connect with the patient prior to discharge.  While hospitalized, the substance abuse counsellors, MSW and pain management CNS work with the patients to encourage and support sobriety.  Recently, the team has located an Alcoholic Anonymous/Narcotics Anonymous group to conduct meetings for this group of patients while hospitalized. 

The pain management CNS works with the patients to control their acute pain which generally requires some opioids as part of a multi-modal analgesic plan of care (MMA-APOC).  As resolution of the acute infection resolves, the focus changes to weaning opioids and progressing to a non-opioid MMA-APOC.  Patients are encouraged to learn non-pharmacologic ways to control pain including square breathing, relaxation, distraction, and exercise.  The medical center Healing Arts Network are consulted for patients to learn tai chi and/or yoga and receive massage. 

Future plans include:

  • the MSW being dedicated full time to working with these patients
  • securing a room for the AA/NA meetings
  • identifying a physician to initiate prescription of buprenorphine for interested patients
  • developing a care plan or care trajectory that provides for consistency with room for individual care
  • educating all medical center staff about the COST, clinical note and care plan
  • increase funding for Healing Arts Network to increase support of non-pharmacologic interventions and education
  • increase interactions with community treatment and behavioral health providers and facilities
  • increase interaction and expand work with families of patients followed by the COST
  • collect and analyze data to determine effectiveness of COST activities
  • obtain grant funding to improve and formalize the COST and increase resources

The dedication and work of the member of the Code Outreach Special Team is acknowledged.