Cognitive dysfunctions in schizophrenia: potential benefits of cholinesterase inhibitor adjunctive therapy

In schizophrenia, cognitive dysfunctions commonly affect attention, memory and executive function, interfere with functional outcome and remain difficult to treat. Previous studies have implicated the cholinergic system in cognitive functioning. In Alzheimer's disease, cholinergic agonists have shown modest clinical benefits on cognitive and behavioural symptoms. Impaired cholinergic activity might also be involved in schizophrenia. Hence the role of cholinesterase inhibitors (ChEI) as adjunctive therapy is under study. We aimed to review the literature and evaluate the overall effectiveness of ChEI adjunctive therapy for the management of cognitive dysfunctions in schizophrenia.

We conducted a computer-based search using PubMed (up to February 15, 2006) and ISI Web of Science (conference proceeding abstracts from January 2003 to December 2005) databases. We used the search terms "schizophrenia," "cognition or memory" and "tacrine or donepezil or rivastigmine or galantamine." Studies included were critically analyzed for allocation, blindness, duration and study design, demographic data, and clinical and neuropsychological outcome assessments. We excluded studies that involved patients with psychiatric disorders other than schizophrenia-spectrum or if they involved animals or molecular investigations. We also excluded conference proceeding abstracts with no explicit neuropsychological battery and/or results.

Data on ChEI as adjunctive therapy for the cognitive impairments in schizophrenia are sparse and so far derived from small samples and mostly open uncontrolled studies. ChEI's potential in long-term management has barely been documented and remains to be fully explored.

There is insufficient evidence on whether ChEI should be used for the treatment of cognitive dysfunctions in schizophrenia. Nevertheless, further studies with appropriate trial designs and outcome measures in homogenous schizophrenia populations are warranted.