Modafinil for clozapine-treated schizophrenia patients: A double-blind, placebo-controlled pilot trial

Journal of Clinical Psychiatry

Volumn 70, Issue 12, 2009, Pages 1674-1680

  Freudenreich, Oliver ^a,b,c   Henderson, David C ^a,b   Macklin, Eric A ^b,d   Evins, A Eden ^a,b   Fan, Xiaoduo ^a,b   Cather, Cori ^a,b   Walsh, Jared P ^a,b   Goff, Donald C ^a,b  

^a Freedom Trail Clinic   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE; MODAFINIL;

ABDOMINAL PAIN; ADULT; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; COGNITIVE DEFECT; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEPRESSION; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; HEADACHE; HUMAN; MALE; NEGATIVE SYNDROME; OUTCOME ASSESSMENT; PILOT STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SCHIZOPHRENIA; STOMACH PAIN; SYMPTOM; WAKEFULNESS;

ADOLESCENT; ADULT; ANTIPSYCHOTIC AGENTS; BENZHYDRYL COMPOUNDS; CENTRAL NERVOUS SYSTEM STIMULANTS; CLOZAPINE; COGNITION DISORDERS; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FATIGUE; FEMALE; HUMANS; MALE; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; PILOT PROJECTS; PLACEBOS; PSYCHOTIC DISORDERS; SCHIZOPHRENIA; SCHIZOPHRENIC PSYCHOLOGY; TREATMENT OUTCOME; WAKEFULNESS;

EID: 74549156560     PISSN: 01606689     EISSN: None     Source Type: Journal    
DOI: 10.4088/JCP.08m04683     Document Type: Article

References (45)

1. Buchanan RW, Breier A, Kirckpatrick B, et al. Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. Am J Psychiatry. 1998;155(6):751-760. PubM ed
2. Bilder RM, Goldman RS, Volavka J, et al. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Am J Psychiatry. 2002;159(6):1018-1028. PubMed doi:10.1176/appi.ajp.159.6.1018
3. Milev P, Ho BC, Andreasen NC. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am J Psychiatry. 2005;162(3):495-506. PubMed doi:10.1176/appi.ajp.162.3.495
4. Rosenheck R, Leslie D, Keefe R, et al. Barriers to employment for people with schizophrenia. Am J Psychiatry. 2006;163(3):411-417. PubMed doi:10.1176/appi.ajp.163.3.411
5. Safferman A, Lieberman JA, Kane JM, et al. Update on the clinical efficacy and side effects of clozapine. Schizophr Bull. 1991;17(2):247-261. PubMed
6. Burke M, Sebastian CS. Treatment of clozapine sedation. (letter) Am J Psychiatry. 1993;150(12):1900-1901. PubMed
7. Curran C, Byrappa N, McBride A. Stimulant psychosis: systematic review. Br J Psychiatry. 2004;185:196-204. PubMed doi:10.1192/bjp.185.3.196
8. Richard ML, Liskow BI, Perry PJ. Recent psychostimulant use in hospitalized schizophrenics. J Clin Psychiatry. 1985;46(3):79-83. PubMed
9. Valentino RM, Foldvary-Schaefer N. Modafinil in the treatment of excessive daytime sleepiness. Cleve Clin J Med. 2007;74(8):561-566, 568-571. PubMed doi:10.3949/ccjm.74.8.561
10. Scammell TE, Estabrooke IV, McCarthy MT, et al. Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci. 2000;20(22):8620-8628. PubMed
11. Roth T, Schwartz JR, Hirshkowitz M, et al. Evaluation of the safety of modafinil for treatment of excessive sleepiness. J Clin Sleep Med. 2007;3(6):595-602. PubMed
12. Turner DC, Clark I, Pomarol-Clotet E, et al. Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia. Neuropsychopharmacology. 2004;29(7):1363-1373. PubMed doi:10.1038/sj.npp.1300457
13. Sevy S, Rosenthal MH, Alvir J, et al. Double-blind, placebo-controlled study of modafinil for fatigue and cognition in schizophrenia patients treated with psychotropic medications. J Clin Psychiatry. 2005;66(7):839-843. PubMed
14. Pierre JM, Peloian JH, Wirshing DA, et al. A randomized, double-blind, placebo-controlled trial of modafinil for negative symptoms in schizophrenia. J Clin Psychiatry. 2007;68(5):705-710. PubMed
15. Krupp LB, LaRocca NG, Muir-Nash J, et al. The Fatigue Severity Scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121-1123. PubMed
16. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
17. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545. PubMed
18. Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-276. PubMed
19. Andreasen NC. Negative symptoms in schizophrenia: definition and reliability. Arch Gen Psychiatry. 1982;39(7):784-788. PubMed
20. Andreasen NC. Scale for the Assessment of Negative Symptoms (SANS). Iowa City, IA: University of Iowa; 1983.
21. Heinrichs DW, Hanlon TE, Carpenter WT Jr. The quality of life scale: an instrument for rating the schizophrenic deficit syndrome. Schizophr Bull. 1984;10(3):388-398. PubMed
22. Levine J, Schooler NR. SAFTEE: a technique for the systematic assessment of side effects in clinical trials. Psychopharmacol Bull. 1986;22(2):343-381. PubMed
23. Blair J, Spreen O. Predicting premorbid IQ: a revision of the national adult reading test. Clin Neuropsychol. 1989;3(2):129-136. doi:10.1080/13854048908403285
24. Nuechterlein KH, et al. Developmental processes in schizophrenic disorders: Longitudinal studies of vulnerability and stress. Schizophr Bull. 1992;18(3):387-425. PubMed
25. Benedict RHB, Schretlen D, Groninger L, et al. The Hopkins Verbal Learning Test - Revised. Clin Neuropsychol. 1998;12(1):43-55.
26. Wechsler D. Wechsler Adult Intelligence Scale, 3rd ed. (WAIS-III). San Antonio, TX: The Psychological Corporation; 1997.
27. Heaton R. Wisconsin Card Sorting Test Manual. Odessa, FL: Psychological Assessment Resources, Inc.; 1990.
28. Benton A, Hamsher K. Multilingual Aphasia Examination (Manual Revised). Iowa City: University of Iowa; 1978.
29. Hommel G. A comparison of two modified Bonferroni procedures. Biometrika. 1989;75(2):383-386. doi:10.1093/biomet/75.2.383
30. Spence SA, Green RD, Wilkinson ID, et al. Modafinil modulates anterior cingulate function in chronic schizophrenia. Br J Psychiatry. 2005;187:55-61. PubMed doi:10.1192/bjp.187.1.55
31. Hunter MD, Ganesan V, Wilkinson ID, et al. Impact of modafinil on prefrontal executive function in schizophrenia. Am J Psychiatry. 2006;163(12):2184-2186. PubMed doi:10.1176/appi.ajp.163.12.2184
32. Makela EH, Miller K, Cutlip WD. Three case reports of modafinil use in treating sedation induced by antipsychotic medications. J Clin Psychiatry. 2003;64(4):485-486. PubMed
33. Parnas AS, Weber M, Richardson R. Effects of multiple exposures to D-cycloserine on extinction of conditioned fear in rats. Neurobiol Learn Mem. 2005;83(3):224-231. PubMed doi:10.1016/j.nlm.2005.01.001
34. Schwartz JRL, Hirshkowitz M, Erman MK, et al. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea: a 12-week, open-label study. Chest. 2003;124(6):2192-2199. PubMed doi:10.1378/chest.124.6.2192
35. Provigil [package insert]. West Chester, PA: Cephalon; 2008.
36. Mariani JJ, Hart CL. Psychosis associated with modafinil and shift work. (letter) Am J Psychiatry. 2005;162(10):1983. PubMed doi:10.1176/appi.ajp. 162.10.1983
37. Narendran R, Young CM, Valenti AM, et al. Is psychosis exacerbated by modafinil? (letter) Arch Gen Psychiatry. 2002;59(3):292-293. PubMed doi:10.1001/archpsyc.59.3.292
38. Robertson P, DeCory HH, Madan A, et al. In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000;28(6):664-671. PubMed
39. Robertson P Jr, Hellriegel ET. Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-137. PubMed doi:10.2165/00003088-200342020-00002
40. Robertson P Jr, Hellriegel ET, Arora S, et al. Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clin Pharmacol Ther. 2002;71(1):46-56. PubMed doi:10.1067/mcp.2002.121217
41. Spina E, de Leon J. Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol. 2007;100(1):4-22. PubMed doi:10.1111/j.1742-7843.2007.00017.x
42. Dequardo JR. Modafinil-associated clozapine toxicity (comment on Am J Psychiatry 2001;158:970). Am J Psychiatry. 2002;159(7):1243-1244. PubMed doi:10.1176/appi.ajp.159.7.1243-a
43. Chetty M, Murray M. CYP-mediated clozapine interactions: how predictable are they? Curr Drug Metab. 2007;8(4):307-313. PubMed doi:10.2174/ 138920007780655469
44. Farrow TF, Hunter MD, Haque R, et al. Modafinil and unconstrained motor activity in schizophrenia: double-blind crossover placebo-controlled trial. Br J Psychiatry. 2006;189:461-462. PubMed doi:10.1192/bjp.bp.105.017335
45. Henderson DC, Louie PM, Koul P, et al. Modafinil-associated weight loss in a clozapine-treated schizoaffective disorder patient. Ann Clin Psychiatry. 2005;17(2):95-97. PubMed doi:10.1080/10401230590932407