Migraine – Treatment

There is good evidence, backed up by experience, that tricyclic antidepressants work well as prophylaxis for migraine. In my experience clomipramine, used carefully, is noticeably superior to other drugs. Some tricyclic antidepressants are 5-HT 2A blockers; this is may also be a putative mechanism of action of methysergide, cyproheptadine and chlorpromazine (which are all potent 2A blockers). MAOIs may also be effective, as may Lithium. SSRIs probably work, but there is little good controlled-trial evidence for this as yet, although they are being used widely.

Clomipramine is a much more powerful serotonin reuptake inhibitor than amitriptyline. The fact that selective serotonin reuptake inhibitors are proving useful in migraine suggests that it is this property of clomipramine that is responsible for its effect (not one of its many other actions, eg 5-HT 2A blockade). Because it is a more powerful serotonin reuptake inhibitor than amitriptyline it would be expected to be of superior efficacy to amitriptyline and therefor may be the preferred tricyclic antidepressant drug for Migraine: it is puzzling (and illogical) that it has not been more widely used. There are only 2 poor quality trials using clomipramine in Migraine over the last 35 years!

This may be largely an accident of history (ie for marketing reasons clomipramine was promoted as an anti-obsessional drug, although it is a potent antidepressant). Neurologists have tended to use ‘antidepressant’ tricyclic antidepressants and therefor perhaps have left clomipramine out.

Note a recent review concerning the use of pethidine in migraine. It argues (correctly, in my opinion) that pethidine should not be used in migraine.

The repeated* use of narcotic analgesics for Migraine in primary care practice may now be sufficiently distant from accepted good practice to excite adverse comment.

* repeated use could be defined as more than six times per year or escalating need over a shorter time.

I suggest the adoption of the policy that if patients, or their doctor, feel the pain is sufficiently severe to require pethidine (or other narcotics) then they are best managed in hospital. A review of prophylaxis and specialist advice may also be useful.

Our current understanding of migraine suggests it is characterised by three major patho-physiological features:– dopaminergic hypersensitivity, inflammation, and relatively “low” 5-HT levels.

Clinically, blocking dopamine receptors, reducing inflammation, and / or stimulating 5-HT receptors appear to be effective approaches in many migraineurs. However these approaches, individually, do not always provide complete relief. Combination treatment may be more effective (but take care with SSRIs + NSAIDs because of possible GI side effects). Ibuprofen is probably the least GI toxic choice. One would expect the new COX 2 inhibitors to work.

A recent survey showed propranolol, amitriptyline and verapamil are the three preferred migraine prophylactic drugs by both neurologists and GPs in the USA.

The current literature suggests the following ranking for anti-migraine drugs. Note that efficacy, as measured by reduction of headache frequency, is modest, being about 50% at best. (there are many other similarities between migraine and depression)

Most effective:– TCAs, methysergide, beta-blockers, MAOIs, sodium valproate

Of lesser efficacy:– verapamil, SSRIs, naproxen

My view is that clomipramine is the most effective drug, but the least used. It may be the drug of choice when anxiety or depression are co-morbid, which is frequently.

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