Monoamine oxidase inhibitors should typically be avoided in initial or early treatment of depression due to tolerability issues, drug interactions, and dietary restrictions to avoid hypertensive crisis. MAOIs are generally not recommended to be used with SSRIs, SNRIs, or TCAs, and typically require a “washout” period from other antidepressants (Table 4). One review found that MAOI treatment had advantage over TCA treatment for patients with early-stage treatment-resistant depression, though this advantage decreased as the number of failed antidepressant trials increased.12 One MAOI, selegiline, is available in a transdermal patch, and the 6-mg patch does not require dietary restriction.
Esketamine (intranasal) is FDA-approved for treatment-resistant depression (failure of response after at least 2 antidepressant trials with adequate dose and duration) in conjunction with an oral antidepressant. In clinical studies, a significant response was noted after 1 week of treatment.13 Esketamine requires an induction period of twice-weekly doses of 56 or 84 mg, with maintenance doses every 1 to 2 weeks. Each dosage administration requires monitoring for at least 2 hours by a health care professional at a certified treatment center. Esketamine’s indication was recently expanded to include treatment of patients with major depressive disorder with suicidal ideation or behavior.
Stimulants such as amphetamines, methylphenidate, or modafinil have been effective in open studies for augmentation in depression.14 However, no stimulant is FDA-approved for the treatment of depression. In addition to other adverse effects, these medications are controlled substances and carry risk of misuse, and their use may not be appropriate for all patients.