A concise guide to monoamine oxidase inhibitors: How to avoid drug interactions

Initiation of an MAOI is always based on whether the patient can reliably follow the basic dietary advice (see “A concise guide to monoamine inhibitors,” Current Psychiatry. December 2017, p. 14-23,47,A), and they agree to check with their clinician before starting new medications. Titration of MAOIs should be based on tolerability; orthostasis is the primary dose-limiting adverse effect associated with rapid titration or higher dosages. This may be especially true in older patients with poor vasomotor tone, or those on α1-adrenergic antagonists or other agents that may induce orthostatic effects. The rapid titration schedules present in certain package inserts (eg, phenelzine²³) should not be followed.

The orthostasis management strategy is similar to that employed for clozapine: minimize the use of concurrent α1-adrenergic antagonists, lower the doses of antihypertensives as much as possible, and encourage adequate fluid intake. For patients with ongoing orthostasis and without a history of congestive heart failure, consider using the potent mineralocorticoid fludrocortisone starting at 0.1 mg/d, and titrating every 10 to 14 days if needed to a maximum of 0.3 mg/d.²⁴ Older literature noted weight gain, peripheral edema, and sexual dysfunction as common adverse effects. Research on the most recently studied MAOI, selegiline transdermal, reported rates of these adverse effects as follows: weight gain: 2.1% for selegiline transdermal vs 2.4% for placebo; all forms of sexual dysfunction: 0 to 1% for selegiline transdermal vs 0 to 0.4% for placebo.²⁵

Augmentation options for patients taking MAOIs

For depressed patients who do not achieve remission of symptoms from MAOI therapy, augmentation options should be sought, as patients who respond but fail to remit are at increased risk of relapse.²⁶ Lithium augmentation is one of the more common strategies, with abundant data supporting its use.^27,28 Case reports dating back >12 years describe the concurrent use of bupropion and MAOIs.^12,29 A recent review of augmentation of MAOIs with second-generation antipsychotics found multiple positive reports for most agents, including aripiprazole, with the sole exception of ziprasidone, a moderate SNRI for which cases of SS have been reported.¹¹ As of November 2017, there are no case reports for asenapine, lurasidone, brexpiprazole, or cariprazine. Triiodothyronine is often a neglected strategy, but older case reports of combined treatment with MAOIs found no obvious concerns beyond those related to the use of thyroid hormone.^30,31