title: Antipsychotic augmentation with modafinil or armodafinil for negative symptoms of schizophrenia: systematic review and meta-analysis of randomized controlled trials.
abstract: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of modafinil or armodafinil (ar/mod) augmentation in schizophrenia. We searched PubMed, clinical trial registries, reference lists, and other sources for parallel group, placebo-controlled RCTs. Our primary outcome variable was the effect of ar/mod on negative symptom outcomes. Eight RCTs (pooled N = 372; median duration, 8 weeks) met our selection criteria. Ar/mod (200 mg/day) significantly attenuated negative symptom ratings (6 RCTs; N = 322; standardized mean difference [SMD], -0.26; 95% CI, -0.48 to -0.04). This finding remained similar in all but one sensitivity analysis - when the only RCT in acutely ill patients was excluded, the outcome was no longer statistically significant (SMD, -0.17; 95% CI, -0.51 to 0.06). The absolute advantage for ar/mod was small: just 0.27 points on the PANSS-N (6 RCTs). Ar/mod attenuated total psychopathology ratings (7 RCTs; N = 342; SMD, -0.23; 95% CI, -0.45 to -0.02) but did not influence positive symptom ratings (5 RCTs; N = 302; mean difference, -0.58; 95% CI, -1.71 to 0.55). Although data were limited, cognition, fatigue, daytime drowsiness, adverse events, and drop out rates did not differ significantly between ar/mod and placebo groups. Fixed and random effects models yielded similar results. There was no heterogeneity in all but one analysis. Publication bias could not be tested. We conclude that ar/mod (200 mg/day) is safe and well tolerated in the short-term treatment of schizophrenia. Ar/mod reduces negative symptoms with a small effect size; the absolute advantage is also small, and the advantage disappears when chronically ill patients or those with high negative symptom burden are treated. Ar/mod does not benefit or worsen other symptom dimensions in schizophrenia.
authors.affiliation: Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India. Electronic address: andradec@gmail.com.
authors.forename: Chittaranjan
authors.initials: C
authors.lastname: Andrade
authors.affiliation: School of Medicine, The University of Queensland, Level 4, Building 1, Princess Alexandra Hospital, Ipswich Road, Woolloongabba QLD 4102, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Kisely
authors.affiliation: National Institute of Mental Health and Neurosciences, Bangalore 560 029, India.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Monteiro
authors.affiliation: Dalhousie University, 5909 Veterans' Memorial Lane, 8th Floor, Abbie J. Lane Memorial Building, QEII Health Sciences Centre, Halifax, NS B3H 2E2, Canada.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rao
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D005221:Fatigue / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D012894:Sleep Stages / Q000187:drug effects; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
keywords: Armodafinil; Augmentation; Modafinil; Negative symptoms; Positive symptoms; Schizophrenia