Augmentation of phenelzine with aripiprazole and quetiapine in a treatment-resistant patient with psychotic unipolar depression: case report and literature review

Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA-MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA-MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA-MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.