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.