Translating the Evidence on Atypical Depression Into Clinical Practice

Although the introduction of selective serotonin reuptake inhibitors ushered in an era of relative comfort among clinicians in treating major depressive disorder (MDD), no one antidepressant is appropriate for all patients with depression. In patients with atypical symptoms, efficacy of therapeutic agents may be greatest for monoamine oxidase inhibitors (MAOIs). The first-generation MAOIs such as phenelzine and isocarboxazid were largely nonselective inhibitors of both subtypes of MAO, MAO_A and MAO_B. These medications carried with them dietary restrictions, medication restrictions, a need for titration, and a substantial side effect burden, including weight gain, cardiovascular effects (i.e., hypertension and hypotension), and sexual side effects. The second-generation MAOI selegiline is selective for MAO_B at oral doses of up to 10 mg/day. At higher doses, selegiline loses selectivity and inhibits both MAO_A and MAO_B. Because the antidepressant effects of selegiline occur with the higher doses that impact tyramine pressor effects, an ideal formulation would optimize dose while minimizing adverse effects of MAO_A inhibition in the gastrointestinal mucosa. Efforts in this direction led to formulation of the selegiline transdermal system (STS). The most common side effects are irritation at the patch site and insomnia. Drugs to be avoided with the STS include some pain medications, antidepressants, muscle relaxants, and any form of sympathomimetic amines, which include amphetamines, cold products with pseudoephedrine, phenylephrine, phenylpropanolamine, ephedrine, and stimulant-containing weight-reduction agents. Although no tyramine-restricted diet is required for the 6-mg/24-hour patch, a restricted diet is recommended for the higher-dose patches to reduce the risk of hypertensive crisis.