Combining antidepressants: a review of evidence

Abstract

SummarySequenced (stepped) treatment approaches are widely endorsed in the management of depression. Combining antidepressants is a recognised step for those failing to respond to monotherapy. Despite the limited evidence base, this strategy is widely used by clinicians in practice. Not every combination used clinically has a sound neuropharmacological rationale and the use of such combinations may increase the side-effect burden without any additional advantage to the patient. Efficacy of various antidepressant combinations along with the data on side-effect profile and toxicity of such combined treatments are reviewed here. The different combinations are considered by each class of antidepressant available in the UK.

Homer1/mGluR5 Activity Moderates Vulnerability to Chronic Social Stress

“…Thus, although CTEP did not reverse the stress-induced molecular profile, it showed therapeutic value in behavioral parameters. These results strengthen the idea of combining different antidepressant treatments to maximize therapeutic efficacy (Connolly and Thase, 2011;Palaniyappan et al, 2009). Indeed, CTEP may serve as a basis for future antidepressants that specifically target the glutamate system, as its pharmacokinetic properties are significantly improved from previous mGluR5 antagonists such as MPEP and MTEP (Lindemann et al, 2011;Anderson et al, 2003;Busse et al, 2004).…”

SNRI‐NaSSA combination therapy for treatment‐resistant depression

“…As a 5HT-receptor antagonist, it has been claimed that mirtazapine will not cause serotonin syndrome at any dose but such a view has been recently challenged. 8 The precise mechanism of action of mirtazapine is uncertain but it is thought to increase central noradrenergic and serotonergic neurotransmission. Mirtazapine acts on both serotonin and noradrenaline, but not through reuptake inhibition.…”

Author's reply

“…In Palaniyappan et al's (2009) useful article, the sideeffects of combination treatments neatly follow the description of each combination, but none men tions bleeding. Abnormal bleeding with selective serotonin reuptake inhibitors (SSRIs) has been studied and reviewed.…”