Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: A meta‐analysis of randomized controlled trials

Abstract

Objective The aim of this study was to evaluate the efficacy and safety of the dopaminergic‐enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. Methods A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP‐I) or bipolar II (BP‐II) depression. Data for response/remission and all‐cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. Results Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP‐I patients and one modafinil study included both bipolar subtypes with limited heterogeneity (I2 = 34%, P = .19; I2 = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01‐1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10‐1.73; P = .005). All‐cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89‐1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39‐2.5; P = .98; RR, 1.02; 95% CI, 0.37‐2.85; P = .97). Conclusion This narrower scope meta‐analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic‐enhancing agents are encouraged.

Psychological Climacteric Symptoms and Attitudes toward Menopause among Emirati Women

“…Likewise, treating menopausal fatigue with armodafinil was associated with improvement in depressive symptoms, insomnia, cognitive function, and total scores of the MENQOL scale [23]. In the meantime, a current meta-analysis revealed that use of armodafinil as an adjunctive treatment for depressive and bipolar disorders improves responsiveness to antidepressants [51]. Altogether, fatigue experienced by peri-and postmenopausal women may alter psychological wellbeing, and proper management of fatigue may be essential to prevent the development of chronic fatigue syndrome and mood disorders.…”

The Treatment of Bipolar Depression: Current Status and Future Perspectives

“…However, in two further doubleblind RCTs of adjunctive armodafinil in bipolar I depression, although armodafinil reduced depressive symptoms to a greater extent than placebo, it did not separate from placebo in the primary efficacy outcomes in either study [72,73]. A recent meta-analysis combining these studies found that compared with placebo, augmentation with modafinil or armodafinil was associated with significantly greater treatment response and remission, encouraging further studies that delineate subtypes of bipolar depression responsive to these novel dopamine enhancing agents [68].…”

“…The wakefulness-promoting agent modafinil and its longer lasting R-enantiomer (armodafinil) both act to inhibit dopamine-reuptake and have a potential adjunctive role in bipolar depression [68]. One placebo-controlled trial examining adjunctive modafinil at doses of 100 mg-200 mg/day in bipolar depression found significantly greater improvement in depressive symptoms in the modafinil group at week 2, maintained through to week 6 [69].…”

Adjunctive treatment with psychostimulants and stimulant-like drugs for resistant bipolar depression: a systematic review and meta-analysis

“…Moreover, we also replicated the results of a more recent meta-analysis showing that, compared to placebo, augmentation with modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression was associated with significantly greater rates of treatment response, with the all-cause discontinuation not differing from placebo and no evidence of mood switch or suicide attempts on MoArm treatment. 72 Based on the above, in addition to using psychostimulants in comorbid ADHD and BD, it seems that using psychostimulants (and stimulant-like drugs) as an add-on to standard treatment in resistant bipolar depression may well have a place in clinical practice, not only in in-patients but in out-patients as well. Improvement in the symptoms of resistant bipolar depression translates into improvement in patient quality of life, decreased carer and family burden, lower cost for the health service and fewer lost days at work.…”