The efficacy of computerized cognitive drill and practice training for patients with a schizophrenia-spectrum disorder: A meta-analysis.

BACKGROUND: Computerized methods for improving cognitive functioning in schizophrenia have gained popularity during the past decades. Therefore, this study evaluates the available evidence for the efficacy of computerized cognitive drill and practice training for patients with schizophrenia-spectrum disorders. METHODS: A systematic search was carried out using PubMed, Embase, Cochrane Database of Systematic Reviews, and PsycINFO. A meta-analysis was performed to compare cognitive drill and practice training in patients with a schizophrenia-spectrum disorder with non-cognitively oriented control conditions. The primary outcome was cognitive functioning. Secondary outcome measures included psychotic symptoms, depressive symptoms, and functional outcomes. Effect sizes (ES) for all included studies were calculated as Hedges' g. RESULTS: 24 studies were included with 1262 patients in total. Compared to a control condition, patients receiving computerized cognitive drill and practice training showed significantly more improvement on attention (ES = 0.31, p = 0.001), working memory (ES = 0.38, p < 0.001), positive symptoms (ES = 0.31, p = 0.003), and depressive symptoms (ES = 0.37, p = 0.002). Small, marginally significant effect sizes were found for processing speed, verbal and visual learning and memory, and verbal fluency. However, significant effects on functional outcomes and social cognition were absent. DISCUSSION: The current study showed evidence for the efficacy of computerized cognitive drill and practice training in patients with schizophrenia-spectrum disorders. However, the absence of effects on social cognition and functional outcomes questions the generalization of treatment effects. Together, these results stimulate further development of computerized training programs for schizophrenia that not only improve cognitive functioning, but also generalize cognitive improvement to functional outcomes.

Efficacy of different types of cognitive enhancers for patients with schizophrenia: a meta-analysis.

Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and is, therefore, a treatment target in itself. Yet, literature on efficacy of different pharmaco-therapeutic options is inconsistent. This quantitative review provides an overview of studies that investigated potential cognitive enhancers in schizophrenia. We included pharmacological agents, which target different neurotransmitter systems and evaluated their efficacy on overall cognitive functioning and seven separate cognitive domains. In total, 93 studies with 5630 patients were included. Cognitive enhancers, when combined across all different neurotransmitter systems, which act on a large number of different mechanisms, showed a significant (yet small) positive effect size of 0.10 (k = 51, p = 0.023; 95% CI = 0.01 to 0.18) on overall cognition. Cognitive enhancers were not superior to placebo for separate cognitive domains. When analyzing each neurotransmitter system separately, agents acting predominantly on the glutamatergic system showed a small significant effect on overall cognition (k = 29, Hedges' g = 0.19, p = 0.01), as well as on working memory (k = 20, Hedges' g = 0.13, p = 0.04). A sub-analysis of cholinesterase inhibitors (ChEI) showed a small effect on working memory (k = 6, Hedges' g = 0.26, p = 0.03). Other sub-analyses were positively nonsignificant, which may partly be due to the low number of studies we could include per neurotransmitter system. Overall, this meta-analysis showed few favorable effects of cognitive enhancers for patients with schizophrenia, partly due to lack of power. There is a lack of studies involving agents acting on other than glutamatergic and cholinergic systems, especially of those targeting the dopaminergic system.

The effect of raloxifene augmentation in men and women with a schizophrenia spectrum disorder: a systematic review and meta-analysis.

Recognizing the robust sex differences in schizophrenia prevalence, the selective estrogen receptor modulator (SERM) raloxifene is a likely candidate for augmentation therapy in this disorder. Therefore, a systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Randomized controlled trials investigating the effect of raloxifene in schizophrenia spectrum disorders were included in the quantitative analyses. Outcome measures were psychotic symptom severity, depression, and cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random-effects model was used to compute overall weighted effect sizes in Hedges' g. Nine studies were included, investigating 561 patients with a schizophrenia spectrum disorder. Raloxifene was superior to placebo in improving total symptom severity (N = 482; Hedge's g = .57, p = 0.009), as well as positive (N = 561; Hedge's g = 0.32, p = 0.02), negative (N = 561; Hedge's g = 0.40, p = 0.02), and general (N = 526; Hedge's g = 0.46, p = 0.01) subscales, as measured by the Positive and Negative Syndrome Scale. No significant effects were found for comorbid depression and cognitive functioning. Altogether, these results confirm the potential of raloxifene augmentation in the treatment of schizophrenia.