Neurology and Psychiatry (combined) Cases

Lawrence Robbins, M.D., Associate Professor of Neurology, Chicago Medical School

Case #1: Bipolar, Migraine, Chronic Daily Headache (CDH), IBS

Caitlin (28 y.o.) has had depression since age 14, finally diagnosed at age 26 as the mild end of the bipolar spectrum (Other Specified Bipolar and Related Disorder: 296.89)
Her depression is in remission on quetiapine (50mg) and lamotrigine (100mg).
Caitlin has had moderate CDH She also experiences severe migraines twice per week for 8 years. She has significant occipital and neck pain.
Work-up is negative.
She takes 6 Excedrin per day.
Caitlin also has moderate IBS-D.

Case #1 Comments

There are many factors that go into our decision with any particular patient. I term this “deconstructing the art of headache medicine”. We use many “inputs” into our decision as to the “top 10” list of what’s appropriate for the patient. There are 2 main buckets: 1. What to do outside of medication, and 2. Medications

ADDITIONAL HISTORY that would be helpful with Caitlin:
Her medication history regarding headaches, severity of the headaches, sleep status, how does the IBS impact her, social and work life, financial/insurance (for instance, could she afford Botox?),
Other comorbidities (psych, medical, central sensitization syndromes), sensitivity to meds, what has she done outside of meds (yoga, meditation, psychotherapy,), is she on vitamin D…
How well are the current drugs helping
Her weight status
Her headache triggers (top 3 = stress, weather, hormones)
Where do the headaches hurt (anterior, posterior)
In addition to her Excedrin (65mg caffeine each), how much other caffeine?
FH of response to meds (if mom had migraines, what worked or did not work): this brings in “placebo by proxy”, and “nocebo by proxy”, both very real and important.
Does she have features of a personality disorder?
Is she chronically tired? …fatigue is a very common comorbidity in headache patients.
Is she willing to take additional headache meds, or try Botox?: …the decisions are a partnership, does she just want natural meds??
Is she in MOH (she has MO — medication overuse, — but is it really MOH, medication overuse headache? These are often conflated, and MOH is overdiagnosed )
Is she exercising, has she had PT (for occipital headaches or neck pain), or psychotherapy?
Acceptance, catastrophizing, resilience: important constructs in treating chronic pain and psychiatric conditions
Her level of functioning; is she socially isolated, how is her support system?

CONSIDERATIONS FOR TREATMENT:

2 buckets: 1. outside of meds, and 2. meds
- Outside of meds:
  - Enhance self-efficacy (basically, doing something OTHER than relying on meds): psychotherapy, PT (if posterior headaches or significant neck pain), exercise, meditation, yoga/Pilates, massage, watching triggers, biofeedback, mindfulness
  - Improve acceptance of a chronic illness (this is not easy)
  - Assess level of resilience: resilience is complex, involving genetics (long arms of the serotonin transporter gene=good, short arms=bad) and also resilience is determined by the 1^st 15 years of life, modelling, psychiatric conditions, etc.
MEDS: KEEP DOSES LOW
- Meds/other treatments for Caitlin: does she need or want daily preventives? If so, consider the various PREVENTIVES: Petadolex (natural): maybe the most effective natural preventive, (not as effective as beta blockers, but less SE’s), topiramate (if weight is an issue, and she can afford (job-wise) to be a little spacy — however, topiramate CAN decompensate moods. With most of our tablets, only 22% or so find these effective for the long-term.
- In a male, we would consider valproate (Depakote ER). Tizanidine at night (particularly if insomnia), beta blockers (if HR is increased, or has POTS, and weight/fatigue not an issue, and she can tolerate beta blockers. It is controversial as to whether they do or do not exacerbate depression); ARBs (losartan, candesartan) often work, with less side effects (ARBs are not quite as effective as beta blockers)… and verapamil (but causes constipation). We would also consider the GEPANTS: Nurtec and Quilipta. These have been fairly effective and reasonably well tolerated.
- Botox is safe, and is effective for 63% of pts… Our best preventive, but expensive…about 45% of patients given Botox continue for the long-term, which is an excellent retention rate for a migraine preventive.
- CGRP monoclonal antibody injections (once per month) are a possibility, but there are many side effects (both serious and non-serious). These are very effective for many patients. However, as of September 2023, there have been over 71,000 reports to the FDA of adverse events, with 10,000+ serious reports.
- SPG block (sphenopalatine ganglion block) with lidocaine (for anterior pain), or other nerve blocks (particularly occipital), or trigger point injections…may be done at home as well as in the office.
- For men with bipolar and headaches, without weight issues, valproate is a consideration. We occasionally will use valproate in women, but only in unusual circumstances. Unfortunately, lamotrigine (one of the best meds for bipolar) does not usually help migraines (nor do oxcarbazepine or gabapentin)
- Although we try very much to avoid them, occasional patients with bipolar can tolerate antidepressants. With Caitlin, a tricyclic (low dose) could help the headache and sleep, as well as her IBS-D. If weight is an issue, consider protriptyline (however, protriptyline causes strong anticholinergic SE’s), or desipramine (a milder tricyclic). Among the tricyclics, amitriptyline or nortriptyline are the usual ones. Nortriptyline (a metabolite of amitriptyline) is less effective than amitriptyline but better tolerated. Nortriptyline is a capsule. Tablets allow for easier titration.
- For those who are tired, concentration problems, weight issues, : stimulants (low doses) more often help the headaches than exacerbate them. Even without ADHD, we use stimulants as adjuncts. Modafinil/armodafinil are excellent for fatigue (and cheap on GoodRx). Unfortunately, unlike the stimulants, modafinil or armodafinil DO NOT help headaches. They have minimal effect on ADHD.
- For overusers of caffeine, we sometimes substitute stimulants (low doses). We try and limit caffeine to 150 or 200mg per day at most. Some patients are on more than 1000mg daily.

Abortives for Caitlin’s headaches: We need to decrease the Excedrin (and slowly taper caffeine: keep caffeine less than 200mg per day). Sometimes we take 4 weeks to taper down on caffeine. We would consider an nsaid for the milder head pain (celecoxib or meloxicam = easier on the stomach)…and consider muscle relaxants. For her migraines, we first try migraine-specific meds; triptans or CGRP abortives (abortive gepants: Ubrelvy, Nurtec)
- Triptans: sumatriptan = the strongest, but slightly more side effects. PO/NS/Injection. The tabs, 50 and 100mg (usually use 100) are inexpensive
  - Sumatriptan…the nasal spray tastes terrible; Tosymra is a form of the nasal spray, more effective and better tolerated than the generic sumatriptan… and the generic 6mg injection is very effective; there is a 3mg easy to use (epipen), Zembrace.
  - Rizatriptan = effective, inexpensive; can use in kids (officially indicated down to age 7, and we sometimes use lower doses even at age 5 or 6)
  - Naratriptan = mild, kinder gentler triptan, less of the triptan side effects; Frovatriptan is very similar to naratriptan
- Zolmitriptan nasal spray (generic) = very effective; 2.5 and 5mg, can use down to age 12.
- We can combine abortives (such as nsaids and triptans)
- Gepants (Ubrelvy and Nurtec ODT) are newer; they have been very good, with very few side effects (occasional nausea); branded and more expensive (until generic is out) but the co-pay cards work well. Reyvow (lasmiditan) is also a different abortive ( a “ditan”); Reyvow is occasionally helpful. Reyvow may cause diiness or fatigue. All 3 of these new ones do not affect the heart.
- DHE = effective, a venoconstrictor (not arterial; so it is safer than the usual ergots), out since 1946…Migranal NS (out as generic) is safe, somewhat effective but stuffs the nose. The newer nasal spray Trudhesa is a better form. Injections = more effective, but painful and expensive; pt. has to draw them up
- Second line abortives; Cambia (powdered diclofenac): effective, and may combine with triptans or gepants.
- Analgesics: butalbital (Fiorinal, Fioricet, Phrenilin: these are potentially addicting; all are slightly different); may be useful for some patients, and also for the elderly (try ½ tab). Useful if one cannot use triptans or others (or no effect); overuse often leads to rebound
- Opioids are a last resort: limit doses and amounts. Opioids are occasionally useful. Check prescription monitoring program (PMP) (ideally each visit if on controlled substances)
- Sometimes valproate, amitriptyline, quetiapine, olanzapine are helpful on an “as needed” basis; if patients happen to be taking these regularly, you can often prescribe them also “as needed”…if nothing else they are sedating
- Steroids (low doses of Prednisone, dexamethasone) are helpful for long, severe migraines… limit (usually) to 60mg of Prednisone in a month; often used for severe menstrual migraine. If the patient has not been on a steroid for at least 12 days you do not usually have to taper…
- Antiemetics: ginger, ondansentron (non-sedating); if no help, then promethazine, prochlorperazine, metoclopramide; occasionally suppository or injection.
- With refractory pain: catastrophizing, acceptance, resilience are important concepts.

Refractory headache:
- Outside of meds for refractory: important to address PT/psychotherapy/meditation/exercise etc…
- Meds: Ketamine (I prefer the nasal spray, low dose, at home: essentially microdosing), CGRP monoclonals (effective but many side effects), Botox (our best preventive: effective and safe)
- Stimulants, daily triptans, ONB and SPG blocks
- MAOIs (underused at this point)
- Opioids…last resort… occasionally work, if patients fulfill certain criteria
- Low Dose Naltrexone (LDN): safe, low cost…may help moods also, well tolerated (need to have LDN compounded: info on lowdosenaltrexone.org)
- Memantine (occasionally helps)
- Put in chart your thoughts on other possibilities; the first visit is the best time to list possibilities: when the patient calls in a month, and you or your partners look at the chart, it is important to have meds or approaches that you can just “plug in”. You cannot recreate all of your initial thoughts with each visit.
- You can number other possibilities “increase topiramate = #1, gepants #2”
- Make sure meds that should NOT be used with her are noted such as “Do NOT use antidepressants” or “NO addicting drugs”

NOTE: this case has been amended: it was originally published in the book Clinical Pearls (2^nd edition), 2022 (by Lawrence Robbins, M.D. and Mahta Amidi, M.D.)

Case #2 will be in the next SPS Newsletter