May 2009

Treating Fibromyalgia
Antidepressants offer some relief for sufferers of fibromyalgia.

Donepezil in Schizophrenia?
A recent report suggests donepezil (Aricept) does not appear to benefit cognitive symptoms of schizophrenia.

Second-Generation Antipsychotics and the Risk of Cardiac Death
Second-generation antipsychotics produce about the same level of cardiac risks as first-generation agents.

Preventing Dementia
Higher levels of education, mentally challenging work, and moderate coffee consumption may protect against Alzheimer’s disease, but Ginkgo biloba does not.

In Brief
Mixed Results for Modafinil as an Adjunct in Schizophrenia; Memantine Not Efficacious as an Adjunct in Schizophrenia

Donepezil in Schizophrenia?

May 2009

Well over half of patients with schizophrenia experience cognitive impairment, often before other symptoms develop.1 Historically, dopamine has received most of the attention as the neurotransmitter underlying schizophrenia symptoms. But acetylcholine is involved in many cognitive functions, and some studies suggest abnormalities in cholinergic pathways in patients with this disorder.

Acetylcholinesterase inhibitors increase synaptic levels of cholinergic activity, both nicotinic and muscarinic. A cholinesterase inhibitor commonly employed to treat dementia is donepezil (Aricept). Results from studies of donepezil to treat schizophrenia have been mixed.

Akhondzadeh and others in Iran conducted a 12-week, double-blind study of donepezil (funded by Tehran University of Medical Sciences) in 30 patients, aged 22 to 44 years, with chronic schizophrenia.1 After 8 weeks of treatment with a stable dose of risperidone (Risperdal and others), subjects were randomly assigned to receive donepezil, 10 mg/day, or placebo in addition to risperidone, 4 to 6 mg/day.

Cognitive performance on a variety of neurocognitive tasks showed no benefit from adjunctive donepezil compared with placebo. However, patients taking donepezil had significantly greater improvement in negative symptoms of schizophrenia.

Such a small trial is vulnerable to what statisticians call a “type II” error—failing to find a benefit when one actually exists. By the same token, taking all studies of donepezil in schizophrenia into consideration, there does not appear to be a strong signal of benefit for cognitive symptoms. Whether donepezil has anything to offer for the negative or any other symptoms of schizophrenia remains to be elucidated by future research.

1Akhondzadeh S, Gerami M, Noroozian M, Karamghadiri N, Ghoreishi A, Abbasi SH, Rezazadeh SA: A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1810-1815.