If one of the SSRI or tricyclic and related drugs given in full doses for 4 to 6 weeks does not produce the desired effect, or as often happens, the patient is intolerant of the given drug, an alternative group, for example, an MAO inhibitor, may be tried. In one of the many new “effectiveness” trials sponsored by the National Institutes of Mental Health, as distinguished from “efficacy” in randomized trials, failure of citalopram to accomplish remission of depression, by changing to bupropion, sertraline, or venlafaxine was successful in 25 percent of cases (Rush et al). After discontinuing SSRIs, there must be a drug-free interval of 1 to 2 weeks before instituting an MAO inhibitor in order not to provoke a serotonin syndrome. Some studies suggest that MAO inhibitors are superior in depression with atypical features such as increased appetite. Phenelzine, isocarboxazid, and tranylcypromine are in this category, of which the first is said to be the least likely to produce serious side effects. The usual starting dose is 15 mg tid, which is gradually increased as needed to a maximum of 45 mg tid. The most serious risk of MAO inhibitors is the occurrence of a hypertensive crisis; consequently, these drugs should be dispensed with caution in patients with hypertension and with cardiovascular or cerebrovascular disease. Patients taking these drugs should avoid foods with a high tyramine content (aged cheese, many pickled foods, chicken liver, beer, wines, yeast extract) as well as medications containing sympathomimetic agents or l-dopa (decongestants, amphetamines, caffeine) and the aforementioned serotonin agonists. The use of the MAOI (monoamine oxidase inhibitor)-B drugs for Parkinson disease (see Chap. 38) is also interdicted.
Supplementation of antidepressants with the administration of an antiepileptic medication as a “mood stabilizer” is a popular approach with many psychiatrists. Valproate or gabapentin are used, but also used are carbamazepine or phenytoin. There are few credible studies by which to judge the value of this strategy, but these drugs may provide some additional benefit, if only as antianxiety agents. More persuasive are the data suggesting that antiepileptic drugs are useful in treatment of the manic state.
Because many depressed patients are responsive to one of the tricyclic drugs, MAO inhibitors, or serotonin agonists but not to all of them, the clinician is greatly aided by information regarding which of these drugs has been helpful in past episodes. As mentioned, response to antidepressant drugs is not expected for several weeks. Treatment, if successful, should be continued for 6 to 9 months and generally combined with some type of psychotherapy. The premature discontinuation of medications is a major source of relapse. The dosage of medication may then be reduced slowly over a period of weeks. Rapid reduction may result in withdrawal symptoms (nausea, vomiting, malaise, and muscular pains). If depressive symptoms recur upon withdrawal, the effective dose should be gradually reinstituted. Mann (2005) provides a thorough review of the medical treatment of depression; the side effects of each are given in tabular form and adapted for Table 48-3.