Oral scopolamine augmentation for major depression

Major depressive disorder (MDD) is a chronic, recurrent and devastating mental illness affecting approximately 16% of individuals in the USA in their lifetime. Selective serotonin reuptake inhibitors are the most widely prescribed and standard antidepressants in the treatment of MDD. The reason for such antidepressants being the first-trial antidepressant treatment choice has mainly come from proven efficacy, florid experience, and improved tolerability and safety compared with older antidepressants. However, currently available evidence from placebo-controlled or large practical clinical trials have demonstrated that the efficacy of such modern antidepressants is still limited to MDD patients in full remission as well as functional recovery in clinical practice. Almost 70% of MDD patients fail to remit after initial antidepressant treatment, and the risks to relapse and recurrence dramatically increase with further treatment steps. Thus, clinicians conclude that they have to make a proper and timely decision in management of their MDD patients in clinical practice, depicting that better understanding regarding diverse treatment strategies are not optional but mandatory for difficult-to-treat patients with MDD. Among different treatment strategies, augmentation with current antidepressant is attractive since it does not need any delay in switching to a different antidepressants, prevents loss of efficacy from previous antidepressants, enhances the efficacy of initial antidepressants or produces a synergistic effect with current antidepressants. Recently, Khajavi et al. investigated the efficacy and safety of oral scopolamine (anticholinergic agent) augmentation in moderate-to-severe MDD in a randomized, double-blind, placebo-controlled clinical trial (randomized controlled trial). This article summarizes the study background, methods and important results. Clinical implications, related practical issues, major pitfalls and future research direction are also presented.