T Kishi, T Ikuta, K Oya, S Matsunaga, Y Matsuda and N Iwata,
The international journal of neuropsychopharmacology, May 2018 14
We conducted a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials of anti-dementia drugs plus antipsychotics (ADD+AP) for schizophrenia.Primary outcomes of efficacy and safety included improving overall symptoms (Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores) and all-cause discontinuation, respectively. Other outcomes included psychopathology subscales (positive, negative, general, and anxiety/depressive symptoms), cognitive function (attention/vigilance, reasoning/problem solving, social cognition, speed of processing, verbal learning, visual learning, working memory, and cognitive control/executive function), Mini-Mental State Examination (MMSE) scores, treatment discontinuation due to adverse events and inefficacy, and individual adverse events. We evaluated the effect size using a random effects model.We identified 37 studies (n=1,574): 14 donepezil-based (n=568), 10 galantamine-based (n=371), 4 rivastigmine-based (n=146), and 9 memantine-based (n=489) studies. Pooled ADD+AP treatments were superior to placebo+AP in improving the overall symptoms (24 studies, 1,069 patients: standardized mean difference [SMD]=-0.34, 95% confidence interval [CI]=-0.61 to -0.08, P=0.01), negative symptoms (24 studies, 1,077 patients: SMD=-0.62, 95% CI=-0.92 to -0.32, Pcorrected=0.00018), and MMSE scores (7 studies, 225 patients: SMD=-0.79, 95% CI=-1.23 to -0.34, P=0.0006). No significant differences were found between ADD+AP and placebo+AP regarding other outcomes.Although the results suggest that ADD+AP treatment improves negative symptoms and MMSE scores in schizophrenia patients, they possibly were influenced by a small-study effect and some bias. However, it was not superior to placebo+AP in improving composite cognitive test score, which more systematically evaluates cognitive impairment than the MMSE score. Overall, ADD+AP treatment was well tolerated.