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.
OBJECTIVE
To examine the efficacy and safety of modafinil on parkinsonism and excessive daytime sleepiness (EDS), as well as on negative symptoms and cognitive abilities in patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) in a randomized double-blind placebo-controlled 8-week study.


METHODS
Twenty-four male patients, who were aged 20-63 years and on stable dose of second generation antipsychotic medications and with a negative symptom score of ≥ 20 on the Positive and Negative Syndrome Scale (PANSS), were randomized into either the modafinil (n=12) or placebo (n=12) group. The modafinil group received flexible does of modafinil 50-200mg/day. Primary measurements were the Simpson-Angus Scale (SAS) for extrapyramidal side effects (EPS), the Epworth Sleepiness Scale (ESS), the PANSS and a neuropsychological (NP) test battery. Data were collected on Days 0, 14, 28, 42 and 56 for rating scales, and on Days 0, 28 and 56 for NP tests.


RESULTS
Mixed model analyses showed a significant group-x-time interaction for total SAS scores (P<0.006), with scores decreasing in the modafinil group but remaining the same in the placebo group. There were no significant group-x-time interactions for scores of ESS (total), PANSS (total, positive and negative), and NP tests (composite and domains) (all P's>0.5). No significant adverse events were observed.


CONCLUSIONS
The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. Further studies in larger samples and with longer study time are needed to test/confirm the beneficial effects of modafinil on motor function.
Department of Psychiatry, University of California, San Diego (UCSD), La Jolla, CA, USA; Psychiatry Service, VA San Diego Healthcare System, San Diego, CA, USA; VA Center of Excellence for Stress and Mental Health, San Diego, CA, USA. Electronic address: jlohr@ucsd.edu.
James B
JB
Lohr
Lianqi
L
Liu
Michael P
MP
Caligiuri
Taylor P
TP
Kash
Todd A
TA
May
Jody Delapena
JD
Murphy
Sonia
S
Ancoli-Israel
D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D011618:Psychotic Disorders / Q000188:drug therapy; D012559:Schizophrenia / Q000188:drug therapy; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use*; D055815:Young Adult
D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
Cognition; Excessive daytime sleepiness; Modafinil; Negative symptoms; Parkinsonism; Schizophrenia