No abstract

Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The effect of TMS vs. sham on negative symptoms in each study was quantified by the standardized mean difference (SMD, Cohen’s d) with 95% confidence intervals (95%CI) and pooled across studies using an inverse variance random effects model. We identified 57 studies with a total of 2633 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD = 0.41, 95%CI: 0.26; 0.56, p-value < 0.001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex and using a stimulation frequency >1 Hz was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters are yet to be established.

Background: The six-item Positive and Negative Syndrome Scale (PANSS-6) is a measure of the severity of core symptoms of schizophrenia, which can be administered via the brief Simplified Negative and Positive Symptoms Interview (SNAPSI). A recent study has confirmed the validity of PANSS-6 ratings as derived by SNAPSI (PANSS-6SNAPSI) among inpatients with schizophrenia. Aims: We aimed to test the validity of PANSS-6SNAPSI among outpatients with schizophrenia using PANSS-6 ratings extracted from the 30-item PANSS-30 as derived by the Structured Clinical Interview for the Positive and Negative Syndrome Scale (PANSS-6SCI-PANSS) as a gold standard reference. Methods: PANSS-6SNAPSI and PANSS-6SCI-PANSS ratings were obtained at two time points by independent raters with established inter-rater reliability. Agreement between PANSS-6SNAPSI and PANSS-6SCI-PANSS ratings was estimated via intra-class coefficients (ICCs) and responsiveness over time was quantified using Spearman’s rank correlation coefficients. Post hoc “leave-one-out” analyses were carried out, in which each rater in turn was excluded from the ICC calculations. Results: Seventy-three outpatients with schizophrenia participated in the study (mean age: 38.3 years; 56% males). The ICC for PANSS-6SNAPSI versus PANSS-6SCI-PANSS was 0.67 [95%CI = 0.56–0.76] and the Spearman’s rank correlation coefficient for responsiveness was 0.40 ( p = 0.004). When data from a specific outlying rater were excluded, the ICC for PANSS-6SNAPSI versus PANSS-6SCI-PANSS was 0.75 [95% CI = 0.63–0.83] and the Spearman’s rank correlation coefficient for responsiveness was 0.55 ( p = 0.018). Conclusions: We found PANSS-6SNAPSI ratings to have acceptable clinical validity, suggesting that PANSS-6SNAPSI can be used for both inpatients and outpatients with schizophrenia.

Several trials have shown preliminary evidence for the efficacy of Transcranial Magnetic Stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The standardized mean difference (SMD, Cohen’s d) with 95% confidence intervals (CI) was calculated for each study (TMS vs. sham) and pooled across studies using an inverse variance random effects model. We identified 56 studies with a total of 2550 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD=0.37, 95%CI: 0.23; 0.52, p-value <0.00001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex, using a stimulation frequency >1 Hz, and a stimulation intensity at or above the motor threshold, was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters have yet to be resolved.