Lack of efficacy of moclobemide or imipramine in the treatment of recurrent brief depression: results from an exploratory randomized, double-blind, placebo-controlled treatment study David S. Baldwin a,d , Mary Green b and Stuart A. Montgomery c ‘Recurrent brief depression’ (RBD) is a common, distressing and impairing depressive disorder for which there is no current proven pharmacological or psychological treatment. This multicentre, randomized, fixed-dose, parallel-group, placebo-controlled study of the reversible inhibitor of monoamine oxidase moclobemide (450 mg/day) and the tricyclic antidepressant imipramine (150 mg/day) evaluated the potential efficacy of active medication, when compared with placebo, in patients with recurrent brief depression, recruited in the mid-1990s. After a 2–4-week single-blind placebo run-in period, a total of 35 patients were randomized to receive double-blind medication for 4 months, but only 16 completed the active treatment period. An intention-to-treat analysis of the 34 evaluable patients found no evidence for the efficacy of moclobemide or imipramine, when compared with placebo, in significantly reducing the severity, duration or frequency of depressive episodes. A total of 28 patients experienced at least one adverse event, and four patients engaged in nonfatal self- harm. Limitations of the study include the small sample size and the high rate of participant withdrawal. The lack of efficacy of these antidepressant drugs and the previous finding of the lack of efficacy of the selective serotonin reuptake inhibitor fluoxetine together indicate that medications other than antidepressant drugs should be investigated as potential treatments for what remains a common, distressing and potentially hazardous condition. Int Clin Psychopharmacol 29:339–343 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. International Clinical Psychopharmacology 2014, 29:339–343 Keywords: imipramine, moclobemide, placebo, recurrent brief depression a Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, b Department of Psychiatry, Northwick Park Hospital, Middlesex, c Imperial College School of Medicine, London, UK and d Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa Correspondence to David S. Baldwin, University Department of Psychiatry, College Keep, 4-12 Terminus Terrace, Southampton SO14 3DT, UK Tel: + 44 2380 718 520; fax: + 44 2380 718 532; e-mail: dsb1@soton.ac.uk Received 15 January 2014 Accepted 7 April 2014 Introduction Recurrent brief depression (RBD) is a recognizable medical condition with no currently recognized medical treatment. The findings of epidemiological and clinical studies show that many (∼7%) individuals are affected by short-lived (‘brief’, lasting less than 2 weeks) but highly recurrent episodes of typically severe and markedly impairing depressive symptoms (Angst and Dobler- Mikola, 1985; Montgomery et al., 1990; Maier et al., 1994; Weiller et al., 1994; Carta et al., 2003; Pezawas et al., 2003). The lifetime risk of suicidal behaviour in indivi- duals with this pattern of depressive episodes is similar to that seen in major depression; the risk being even greater in those with both brief and extended depressive epi- sodes, where ∼ 30% of individuals had attempted suicide by the age of 28 years (Angst et al., 1990). The diagnosis of ‘recurrent brief episode’ is included within the ‘other recurrent mood (affective) disorders’ grouping of the tenth edition of the International Classification of Diseases (World Health Organization, 1992). The diag- nosis of ‘recurrent brief depressive disorder’ was included within the group of ‘depressive disorders not otherwise specified’ in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. – text revision (DSM-IV-TR) (American Psychiatric Association, 2000). In the DSM-5 (American Psychiatric Association, 2013), RBD is placed within the group ‘other specified depressive disorder’: to meet the diagnosis, depressive episodes must be characterized by at least five symptoms and must be associated with functional impairment, but should last less than 14 days. This lack of progress in placing a diagnosis of RBD more firmly within the psychiatric nomenclature may in part stem from the absence of an established pharmacological or psychological treatment. Case reports and small case series suggest that patients with RBD may benefit from treatment with nimodipine (Pazzaglia et al., 1993), tra- nylcypromine (Joffe, 1996), mirtazapine (Stamenkovic et al., 1998), lithium (Corominas et al., 1998), fluoxetine (Stamenkovic et al., 2001), reboxetine (Pezawas et al., 2002), lamotrigine (Ravindran and Ravindran, 2007) and olanzapine (De la Fuente, 2008). However, the only large randomized placebo-controlled trial, of the selective serotonin reuptake inhibitor fluoxetine in patients with RBD and repeated suicide attempts, found no evidence of efficacy (Montgomery et al., 1994), and treatment studies with paroxetine have also yielded disappointing Original article 339 0268-1315 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/YIC.0000000000000042 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.