Rivastigmine treatment as an add-on to antipsychotics in patients with schizophrenia and cognitive deficits.
OBJECTIVE
Although new atypical antipsychotic agents have been found to improve overall cognitive function in patients with schizophrenia (SZ), some aspects of memory, attention and executive functions still remain impaired. Acetylcholinesterase (AChE) inhibitors, such as rivastigmine, have been shown to improve cognition in other disorders, particularly Alzheimer's disease. Dysfunctions in cholinergic systems, especially in the prefrontal cortex, have been identified in SZ, suggesting that cholinesterase inhibitors may be effective in treating cognitive deficits in this disease.


METHODS
Using a randomized crossover design, we assessed SZ patients with stable symptoms and poor cognitive functioning. Fifty-eight patients with memory deficits, according to subjective complaints or based on clinicians' observations, were assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS). Only 24 of these subjects met the inclusion criteria. Twenty patients took part in the study (four dropped out). All subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for SZ were maintained on their current antipsychotic medication (18 atypicals and two typicals) and were randomly assigned to treatment with rivastigmine. Dosage was a function of tolerability, beginning at 3 mg/day and progressively increasing to 9 mg/day. Subjects were given the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and 3 and 6 months.


RESULTS
The results revealed no significant improvement in any of the cognitive variables investigated following rivastigmine treatment and symptom severity scores remained unchanged over all recorded time periods.


CONCLUSIONS
Rivastigmine treatment did not appear to enhance cognition in SZ patients with important cognitive impairments. This finding needs to be interpreted with care and requires substantiation with larger sample size studies with patients treated with cognitive enhancer for longer periods.
Chouinard
Sylvie
S
Department of Psychiatry, Fernand-Seguin Research Centre, Louis-Hippolyte Lafontaine Hospital, Montreal, Quebec, Canada.
Stip
Emmanuel
E
Poulin
Julie
J
Melun
Jean-Pierre
JP
Godbout
Roger
R
Guillem
François
F
Cohen
Henri
H
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D003072:Cognition Disorders / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D048448:Phenylcarbamates / Q000008:administration & dosage*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D000068836:Rivastigmine; D012559:Schizophrenia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D000068836:Rivastigmine