Newport Beach Neurologists

Antidepressants

1. TRICYCLIC ANTIDEPRESSANTS (TCAs)
   

   Antidepressants, particularly the tricyclic antidepressants, are widely used in the prophylaxis of migraine and tension-type headache. Amitriptyline (Elavil), in dosages ranging from 10 to 200 mg. a day, is probably the most commonly used TCA. Other drugs are also used.

   MECHANISM OF ACTION
   

   The biological basis for its mechanism of action includes "turning off" the generators in the brain stem which create the migraine signal. The antidepressant effect adds to the clinical benefit, even though the anti-migraine effect of amitriptyline has been shown to be independent of the antidepressant effect. It is important to state that the drug may be extremely beneficial in the treatment of some of the least depressed patients. In this regard, many patients become a little paranoid when they hear their doctors placing them on "antidepressant medicine" for their migraines. In no way does this imply that "the problem is all in the mind." Amitriptyline and the tricyclic antidepressants have potent pain relieving effects even in "normal people." If neurologists had discovered these drugs first, they would have been known as pain killers, and then psychiatrists would have had to explain to their patients why they are putting them on a pain medicine for depression!

   TCAs are particularly effective in patients with frequent migraine attacks, migraine with medication overuse, migraine with insomnia, migraine with tension-type headache thrown in the mix, chronic daily headache, and migraine with depression. Combinations of TCAs, particularly amitriptyline, with beta blockers is a very practical way of treating patients with frequent headache, particularly those associated with depression, stress, anxiety, and sleep problems.

   SIDE EFFECTS
   

   TCAs have been associated with anticholinergic effects, such as dry mouth, blurred vision, constipation, urinary retention, and disturbance of the heart rhythm. Several of these agents cause sedation and postural hypotension. In general, these agents should be avoided in patients with cardiac arrhythmias or prostate hypertrophy. They should also be avoided in patients with certain types of glaucoma. Weight gain and sexual dysfunction may also be problems for patients taking TCAs.

   There are quite a number of tricyclic antidepressant drugs, and the physician may select one or other of these agents, depending upon the clinical scenario. Medications such as imipramine, desipramine, and nortriptyline may be selected in an individual case over amitriptyline if the side effects of the former are too intolerable.

2. SELECTIVE SEROTONIN RE-UPTAKE INHIBITORS (SSRIs)
   

   In general, the newer antidepressant drugs are not as effective in the prevention of "pure migraine." However, SSRIs are extensively used in patients with chronic migraine, particularly if there is a coincidental depression.

   SIDE EFFECTS
   

   The side effect profile of these newer antidepressants is different from the older TCAs. Fluoxetine (Prozac) and sertraline (Zoloft) may cause agitation, insomnia, weight loss, sexual dysfunction, and nausea.

   Several other antidepressants have "mixed" effects on neuro-transmitters in the brain, affecting not only serotonin, but other forms of neuro-transmitters. These drugs include: venlafaxine (Effexor), nefazodone (Serzone), and buproprion (Wellbutrin). These are newer antidepressant drugs which can also be very effective in the chronic headache patient.

3. MONOAMINE OXIDASE INHIBITORS (MAOIs)
   

   There are other classes of antidepressants, such as the monoamine oxidase inhibitors (MAOIs), which are occasionally used in the very difficult patient. Because of their multiple side effects, these medications are rarely used except by the most specialized of headache clinics.

   CONCLUSIONS
   

   Antidepressants are very useful in patients with coexisting migraine and tension-type headache. The choice of antidepressant depends upon the patient's tolerance. Amitriptyline is the "gold standard" because of proven efficacy in clinical studies. However, the sedative and "drying" side effects of this drug are often troublesome. If a patient experiences unpleasant side effects with one antidepressant, treatment with one that has a different side effect profile may be tried. Frequently, these side effects will subside with continued treatment.

   The role of the newer antidepressants in the treatment of migraine has yet to be determined. However, these drugs appear to offer a distinct advantage in those patients with chronic headache, as well as those who have coexistent migraine and depression.

   Antidepressant agents can be used successfully in conjunction with other drugs in migraine prophylaxis. Beta blockers or calcium channel blockers may be combined with antidepressant drugs in a therapeutic regimen.

   As with any other preventative medicine, patients must be constantly reassured that achieving a therapeutic effect may take several weeks. It must also be repeatedly stressed that because the patient has been placed on an antidepressant medication, it does not mean the problem is "psychological." These drugs have a potent effect on migraine quite independent of their antidepressant effects.