Prophylaxis

Discussing prevention of relapse or recurrence of major depression is beyond the scope of this paper but is clearly important. Long-term use of antidepressants is sometimes necessary particularly if patients have two or more episodes. Compliance becomes absolutely necessary, but side effects often cause patients to stop taking medications. Tricyclics and, to a lesser degree, traditional monoamine oxidase inhibitors (MAOIs) have many side effects because they act on the muscarinic, α₁-adrenergic, and histamine H₁ receptors. If an antidepressant is effective, the side effects can be managed.

The new antidepressants have become the agents of choice because they have fewer side effects. Sexual dysfunction is the most common reason for noncompliance and unfortunately is a relatively frequent problem with all antidepressants. Moclobemide and nefazodone seem to have the fewest sexual side effects.

For long-term therapy, doses that were effective for the acute episode should be continued. Clinical experience suggests a need for lifelong maintenance on antidepressants for patients older than 50 years at the time of first episode, for patients 40 years or older who have had two episodes, or for all patients with three or more episodes. If an antidepressant is discontinued, it should be withdrawn very gradually and signs of recurring depression monitored. Long-term use of lithium for prophylaxis of both bipolar disorder and major depression has also been shown to be very effective. There is a very high rate of attempted suicide among patients with major depression following lithium discontinuation.

Conclusion

Treatment-resistant depression is a relative term and depends on how far a physician is willing to go in treating a particular patient. Appropriate use of antidepressants can relieve symptoms in at least two thirds of cases. Drug combinations, electroconvulsive therapy (ECT), and augmentation strategies can, if vigorously applied, reduce the proportion of patients truly treatment resistant to about 7%. Considering the morbidity and mortality associated with depression, a vigorous approach to therapy is worthwhile. Long-term maintenance, once success is achieved, is essential.

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