Cognitive effects of adjunctive 24-weeks Rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind investigation

Schizophr Res. 2006 Jul;85(1-3):73-83. doi: 10.1016/j.schres.2006.03.037. Epub 2006 Jun 21.


Cognitive impairment has the greatest impact on illness outcome in schizophrenia. The most significant challenge in schizophrenia therapeutics, thus, is to develop an efficacious treatment for cognitive impairments. Acetylcholinesterase inhibitors, such as Physostigmine and Rivastigmine, are considered effective treatments for cognitive decline in Alzheimer's Disease, where the loss of cholinergic neurons is thought to be responsible for various cognitive deficits. The current study investigated the cognitive effects of Rivastigmine given as an add-on therapy to antipsychotic-treated schizophrenia patients in a placebo-controlled double-blind design. The study initially involved 40 patients, of which 21 patients (11 assigned to Rivastigmine and 10 assigned to placebo) agreed to continued participation, remained on the study drug, and underwent assessment of executive functioning, verbal skills, verbal and spatial working memory, attention and psychomotor speed on three occasions: (i) at baseline, and then (ii) after 12 weeks and (iii) 24 weeks of treatment with placebo or Rivastigmine. The results failed to reveal significant improvement on any cognitive measure with Rivastigmine treatment, compared with the placebo treatment. Some cognitive variables showed significant practice effects in both the placebo and Rivastigmine groups. No effects were noted in symptoms or side effects ratings. The beneficial cognitive effects of Rivastigmine seen in an open-label preliminary study are not substantiated by this study. Future studies should investigate the effects of other procholinergic drugs, such as Galantamine, which also act on the nicotine receptors and may produce stronger cognitive effects in schizophrenia.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / epidemiology*
  • Double-Blind Method
  • Female
  • Ganglionic Stimulants / pharmacology
  • Ganglionic Stimulants / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Nicotine / pharmacology
  • Nicotine / therapeutic use
  • Phenylcarbamates / pharmacology
  • Phenylcarbamates / therapeutic use*
  • Physostigmine / pharmacology
  • Physostigmine / therapeutic use
  • Psychomotor Performance / drug effects
  • Rivastigmine
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology*
  • Severity of Illness Index
  • Verbal Behavior / drug effects


  • Antipsychotic Agents
  • Cholinesterase Inhibitors
  • Ganglionic Stimulants
  • Phenylcarbamates
  • Nicotine
  • Physostigmine
  • Rivastigmine