Antipsychotic augmentation with modafinil or armodafinil for negative symptoms of schizophrenia: Systematic review and meta-analysis of randomized controlled trials

Journal of Psychiatric Research

Volumn 60, Issue , 2015, Pages 14-21

  Andrade, Chittaranjan ^a   Kisely, Steve ^b   Monteiro, Ingrid ^a   Rao, Sanjay ^c  

^a NATIONAL INSTITUTE OF MENTAL HEALTH AND NEUROSCIENCES   (India)

^b UNIVERSITY OF QUEENSLAND   (Australia)

^c DALHOUSIE UNIVERSITY   (Canada)

Author keywords

Armodafinil; Augmentation; Modafinil; Negative symptoms; Positive symptoms; Schizophrenia

Indexed keywords

ARMODAFINIL; MODAFINIL; PLACEBO; BENZHYDRYL DERIVATIVE; NEUROLEPTIC AGENT; WAKEFULNESS PROMOTING AGENT;

ARTICLE; DEPRESSION; DIZZINESS; DRUG EFFECT; DRUG INDUCED HEADACHE; FATIGUE; HUMAN; INSOMNIA; META ANALYSIS; NAUSEA; NEGATIVE SYNDROME; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POSITIVE SYNDROME; PSYCHOPHARMACOTHERAPY; RANDOMIZED CONTROLLED TRIAL (TOPIC); SEXUAL DYSFUNCTION; SHORT COURSE THERAPY; SYSTEMATIC REVIEW; ADULT; COGNITION; DRUG EFFECTS; FEMALE; MALE; MIDDLE AGED; PATHOPHYSIOLOGY; SCHIZOPHRENIA; SLEEP STAGE;

ADULT; ANTIPSYCHOTIC AGENTS; BENZHYDRYL COMPOUNDS; COGNITION; FATIGUE; FEMALE; HUMANS; MALE; MIDDLE AGED; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SCHIZOPHRENIA; SLEEP STAGES; WAKEFULNESS-PROMOTING AGENTS;

EID: 84919331031     PISSN: 00223956     EISSN: 18791379     Source Type: Journal    
DOI: 10.1016/j.jpsychires.2014.09.013     Document Type: Article

References (35)

1. Andrade C. Modafinil and armodafinil in schizophrenia. JClin Psychiatry 2012, 73:e1062-e1064.
2. Arbabi M., Bagheri M., Rezaei F., Ahmadi-Abhari S.A., Tabrizi M., Khalighi-Sigaroudi F., et al. Aplacebo-controlled study of the modafinil added to risperidone in chronic schizophrenia. Psychopharmacol (Berl) 2012, 220:591-598.
3. Bobo W.V., Woodward N.D., Sim M.Y., Jayathilake K., Meltzer H.Y. The effect of adjunctive armodafinil on cognitive performance and psychopathology in antipsychotic-treated patients with schizophrenia/schizoaffective disorder: a randomized, double-blind, placebo-controlled trial. Schizophr Res 2011, 130:106-113.
4. Buchanan R.W. Persistent negative symptoms in schizophrenia: an overview. Schizophr Bull 2007, 33:1013-1022.
5. Chue P., Lalonde J.K. Addressing the unmet needs of patients with persistent negative symptoms of schizophrenia: emerging pharmacological treatment options. Neuropsychiatr Dis Treat 2014, 10:777-789.
6. de Saint Hilaire Z., Orosco M., Rouch C., Blanc G., Nicolaidis S. Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats. Neuroreport 2001 Nov 16, 12:3533-3537.
7. Federici M., Latagliata E.C., Rizzo F.R., Ledonne A., Gu H.H., Romigi A., et al. Electrophysiological and amperometric evidence that modafinil blocks the dopamine uptake transporter to induce behavioral activation. Neuroscience 2013, 252:118-124.
8. Freudenreich O., Henderson D.C., Macklin E.A., Evins A.E., Fan X., Cather C., et al. Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial. JClin Psychiatry 2009, 70:1674-1680.
9. Hanson E., Healey K., Wolf D., Kohler C. Assessment of pharmacotherapy for negative symptoms of schizophrenia. Curr Psychiatry Rep 2010, 12:563-571.
10. Cochrane Handbook for systematic reviews of interventions version 5.1.0 [updated March 2011] 2011, The Cochrane Collaboration, Available from, Last accessed 07.06.14. http://www.cochrane-handbook.org, J.P.T. Higgins, S. Green (Eds.).
11. Jablensky A. Epidemiology of schizophrenia. New Oxford textbook of psychiatry 2009, 540-553. Oxford University Press, Oxford. 2nd ed. M.G. Gelder, N.C. Andreasen, J. Lopez-Ibor, J.R. Geddes (Eds.).
12. Kane J.M., Yang R., Youakim J.M. Adjunctive armodafinil for negative symptoms in adults with schizophrenia: a double-blind, placebo-controlled study. Schizophr Res 2012, 135:116-122.
13. Kane J.M., D'Souza D.C., Patkar A.A., Youakim J.M., Tiller J.M., Yang R., et al. Armodafinil as adjunctive therapy in adults with cognitive deficits associated with schizophrenia: a 4-week, double-blind, placebo-controlled study. JClin Psychiatry 2010, 71:1475-1481.
14. Kishi T., Iwata N. NMDA receptor antagonists interventions in schizophrenia: meta-analysis of randomized, placebo-controlled trials. JPsychiatr Res 2013, 47:1143-1149.
15. Kishi T., Mukai T., Matsuda Y., Iwata N. Selective serotonin 3 receptor antagonist treatment for schizophrenia: meta-analysis and systematic review. Neuromolecular Med 2014, 16:61-69.
16. Lepage M., Bodnar M., Bowie C.R. Neurocognition: clinical and functional outcomes in schizophrenia. Can J Psychiatry 2014, 59:5-12.
17. Lindenmayer J.P., Nasrallah H., Pucci M., James S., Citrome L. Asystematic review of psychostimulant treatment of negative symptoms of schizophrenia: challenges and therapeutic opportunities. Schizophr Res 2013, 147:241-252.
18. Lohr J.B., Liu L., Caligiuri M.P., Kash T.P., May T.A., Murphy J.D., et al. Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study. Schizophr Res 2013, 150:289-296.
19. Marder S.R., Alphs L., Anghelescu I.G., Arango C., Barnes T.R., Caers I., et al. Issues and perspectives in designing clinical trials for negative symptoms in schizophrenia. Schizophr Res 2013, 150:328-333.
20. McKeage K., Plosker G.L. Amisulpride: a review of its use in the management of schizophrenia. CNS Drugs 2004, 18:933-956.
21. Mereu M., Bonci A., Newman A.H., Tanda G. The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders. Psychopharmacol (Berl) 2013, 229:415-444.
22. Millier A., Schmidt U., Angermeyer M.C., Chauhan D., Murthy V., Toumi M., et al. Humanistic burden in schizophrenia: a literature review. JPsychiatr Res 2014, 54C:85-93.
23. Minzenberg M.J., Carter C.S. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology 2008, 33:1477-1502.
24. Moher D., Liberati A., Tetzlaff J., Altman D.G., PRISMA Group Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009, 339:b2535.
25. Murphy B.P., Chung Y.C., Park T.W., McGorry P.D. Pharmacological treatment of primary negative symptoms in schizophrenia: a systematic review. Schizophr Res 2006, 88:5-25.
26. Nishino S., Okuro M. Armodafinil for excessive daytime sleepiness. Drugs Today (Barc) 2008, 44:395-414.
27. Pierre J.M., Peloian J.H., Wirshing D.A., Wirshing W.C., Marder S.R. Arandomized, double-blind, placebo-controlled trial of modafinil for negative symptoms in schizophrenia. JClin Psychiatry 2007, 68:705-710.
28. Scoriels L., Jones P.B., Sahakian B.J. Modafinil effects on cognition and emotion in schizophrenia and its neurochemical modulation in the brain. Neuropharmacology 2013, 64:168-184.
29. Sevy S., Rosenthal M.H., Alvir J., Meyer S., Visweswaraiah H., Gunduz-Bruce H., et al. Double-blind, placebo-controlled study of modafinil for fatigue and cognition in schizophrenia patients treated with psychotropic medications. JClin Psychiatry 2005, 66:839-843.
30. Shamsi S., Lau A., Lencz T., Burdick K.E., DeRosse P., Brenner R., et al. Cognitive and symptomatic predictors of functional disability in schizophrenia. Schizophr Res 2011, 126:257-264.
31. Sienaert P., Lambrichts L., Dols A., De Fruyt J. Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review. Bipolar Disord 2013, 15:61-69.
32. Singh S.P., Singh V., Kar N., Chan K. Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. Br J Psychiatry 2010, 197:174-179.
33. Tandon R., DeQuardo J.R., Goodson J., Mann N.A., Greden J.F. Effect of anticholinergics on positive and negative symptoms in schizophrenia. Psychopharmacol Bull 1992, 28:297-302.
34. Tsang H.W., Leung A.Y., Chung R.C., Bell M., Cheung W.M. Review on vocational predictors: a systematic review of predictors of vocational outcomes among individuals with schizophrenia: an update since 1998. Aust N. Z J Psychiatry 2010, 44:495-504.
35. Volkow N.D., Fowler J.S., Logan J., Alexoff D., Zhu W., Telang F., et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. JAMA 2009, 301:1148-1154.