Moclobemide and amitriptyline, alone or in combination, in therapy resistant depression

Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines

“…The rationale behind combining antidepressants is to broaden pharmacological action in the hope that multiple actions will be of benefit. The combination of a TCA with an MAOI was used historically for treatment-resistant depression, but there is a lack of controlled evidence for benefit and the potential for dangerous interactions (Lader, 1983); however, a small RCT combining amitriptyline and moclobemide did find greater efficacy than amitriptyline alone (Tanghe et al, 1997). The most common antidepressant combinations reported are (1) an SSRI with mirtazapine, reboxetine, bupropion or a TCA, (2) mirtazapine with a TCA or venlafaxine and (3) mianserin with a TCA or SSRI (Rojo et al, 2005).…”

Combining antidepressants: a review of evidence

“…There is a potential for synergism with the combination of dual reuptake inhibition from a TCA and monoamine oxidase inhibition from a monoamine oxidase A enzyme reversible inhibitor. One small RCT (n = 58) (Tanghe 1997), one open-label trial (n = 14) (König 1997) and a short report (n = 18) have published on this combination (Steinberg 1994). The RCT showed a non-specific trend towards faster onset of action in the combination group (amitriptyline and moclobemide), but also reported increased agitation.…”

“…Agitation and inner restlessness were the most commonly described adverse events when combining TCAs and moclobemide. Hypomanic switches were reported in the RCT group of inpatients with treatment-resistant major depression (Tanghe 1997). Hypertensive crises may occur, especially in patients with pre-existing hypertension (König 1997).…”