Individual response to antidepressants for depression in adults-a meta-analysis and simulation study.

BACKGROUND: The observation that some patients appear to respond better to antidepressants for depression than others encourages the assumption that the effect of antidepressants differs between individuals and that treatment can be personalized. OBJECTIVE: To compare the outcome variance in patients receiving antidepressants with the outcome variance in patients receiving placebo in randomized controlled trials (RCTs) of adults with major depressive disorder (MDD) and to illustrate, using simulated data, components of variation of RCTs. METHODS: From a dataset comprising 522 RCTs of antidepressants for adult MDD, we selected the placebo-controlled RCTs reporting outcomes on the 17 or 21 item Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Rating Scale and extracted the means and SDs of raw endpoint scores or baseline to endpoint changes scores on eligible depression symptom rating scales. We conducted inverse variance random-effects meta-analysis with the variability ratio (VR), the ratio between the outcome variance in the group of patients receiving antidepressants and the outcome variance in the group receiving placebo, as the primary outcome. An increased variance in the antidepressant group would indicate individual differences in response to antidepressants. RESULTS: We analysed 222 RCTs that investigated 19 different antidepressants compared with placebo in 345 comparisons, comprising a total of 61144 adults with an MDD diagnosis. Across all comparisons, the VR for raw endpoint scores was 0.98 (95% CI 0.96 to 1.00, I2 = 0%) and 1.00 (95% CI 0.99 to 1.02, I2 = 0%) for baseline-to-endpoint change scores. CONCLUSION: Based on these data, we cannot reject the null hypothesis of equal variances in the antidepressant group and the placebo group. Given that RCTs cannot provide direct evidence for individual treatment effects, it may be most reasonable to assume that the average effect of antidepressants applies also to the individual patient.

Transcranial Magnetic Stimulation for Positive Symptoms in Schizophrenia: A Systematic Review.

Transcranial magnetic stimulation (TMS) has been proposed as a potential treatment add-on for positive symptoms in schizophrenia. To summarize the current evidence for its efficacy, we reviewed clinical trials from the last 20 years that investigated TMS for positive symptoms. We performed a search on the PubMed database for clinical trials that used TMS for the treatment of positive symptoms published in peer-reviewed journals. We excluded reviews, case reports, and opinion papers. Of the 30 studies included, the majority (n = 25) investigated auditory verbal hallucinations. Twelve studies found evidence for a positive treatment effect of TMS on positive symptoms, while 18 did not find enough evidence to conclude that TMS is effective for positive symptoms. However, the small sample size of the majority of studies is a limiting factor for the reliability of previous findings. In conclusion, evidence for an effect of TMS on positive symptoms was mixed. Since most of the studies were performed in patients with auditory verbal hallucinations, further research of TMS for other positive symptoms including thought disorder and delusions is warranted.

Evaluation of Differences in Individual Treatment Response in Schizophrenia Spectrum Disorders: A Meta-analysis.

Importance: An assumption among clinicians and researchers is that patients with schizophrenia vary considerably in their response to antipsychotic drugs in randomized clinical trials (RCTs). Objective: To evaluate the overall variation in individual treatment response from random variation by comparing the variability between treatment and control groups. Data Sources: Cochrane Schizophrenia, MEDLINE/PubMed, Embase, PsycINFO, Cochrane CENTRAL, BIOSIS Previews, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform from January 1, 1955, to December 31, 2016. Study Selection: Double-blind, placebo-controlled, RCTs of adults with a diagnosis of schizophrenia spectrum disorders and prescription for licensed antipsychotic drugs. Data Extraction and Synthesis: Means and SDs of the Positive and Negative Syndrome Scale pretreatment and posttreatment outcome difference scores were extracted. Data quality and validity were ensured by following the PRISMA guidelines. Main Outcomes and Measures: The outcome measure was the overall variability ratio of treatment to control in a meta-analysis across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. A personal element of response was hypothesized to be reflected by a substantial overall increase in variability in the treatment group compared with the control group. Results: An RCT was simulated, comprising 30 patients with schizophrenia randomized to either the treatment or the control group. The different components of variation in RCTs were illustrated with simulated data. In addition, we assessed the variability ratio in 52 RCTs involving 15 360 patients with a schizophrenia or schizoaffective diagnosis. The variability was slightly lower in the treatment compared with the control group (variability ratio = 0.97; 95% CI, 0.95-0.99; P = .01). Conclusions and Relevance: In this study, no evidence was found in RCTs that antipsychotic drugs increased the outcome variance, suggesting no personal element of response to treatment but instead indicating that the variance was slightly lower in the treatment group than in the control group; although the study cannot rule out that subsets of patients respond differently to treatment, it suggests that the average treatment effect is a reasonable assumption for the individual patient.

Formal thought disorder is related to aberrations in language-related white matter tracts in patients with schizophrenia.

This study examined the hypothesis that a fronto-temporal disconnection in the language network underpins formal thought disorder (FTD) in schizophrenia. Forty-nine patients with a schizophrenia spectrum disorder (27 with mild FTD, 22 with severe FTD) and 26 healthy controls (HC) were included. Overall psychopathology and FTD were assessed by the Positive and Negative Syndrome Scale and the Thought, Language, and Communication scale, respectively. White matter (WM) microstructure was analysed using Tract-Based Spatial Statistics. In patients, severity of overall FTD (TLC Sum Score) was predicted by decreased fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF), and severity of negative FTD (TLC Emptiness subscale) was predicted by increased FA in the left SLF and arcuate fasciculus (AF). Notably, these results were no longer significant after correction for multiple comparisons. Compared with HC, patients showed lower FA in all the investigated language-related WM tracts as well as across the whole WM skeleton. No difference in FA was found between patients with severe and patients with mild FTD. Our results are compatible with earlier studies reporting impairments in widely spread WM tracts including those related to language processing in patients with schizophrenia.

Quality of life after paediatric ischaemic stroke.

AIM: Paediatric arterial ischaemic stroke can lead to reduced quality of life (QoL). It is important to identify predictors of QoL to support recovery. We examined long-term QoL after arterial ischaemic stroke concerning different variables. METHOD: Children registered in the Swiss Neuropediatric Stroke Registry and suffering from arterial ischaemic stroke between 2000 and 2008 were included. Two years post-stroke, assessments included intelligence quotient tests for cognitive impairment and modified Rankin Scale (mRS) for neurological impairment; 5 years post-stroke, the Kidscreen-27 was used for QoL, DSM-IV criteria screening was used for attention deficits, and the ABILHAND-Kids was used for manual motor skills. Age at stroke, sex, socioeconomic status, lesion characteristics, neuropsychological and motor outcome, and mRS were correlated with QoL measures. RESULTS: Seventy children were examined (49 males, 21 females; mean age 7y 2wks). Age at stroke, sex, socioeconomic status, and lesion characteristics did not influence QoL; IQ below average and attention deficits partially influenced QoL. The highest predictive value for QoL was found for manual motor impairment (p=0.002) and mRS scores (p=0.013). Combined motor, cognitive, and attention impairment negatively affected QoL (p=0.001). INTERPRETATION: Neurological and cognitive impairments after paediatric arterial ischaemic stroke negatively influence QoL. Children with motor and neurological problems, as well as those with combined motor, cognitive, and attention problems, are at higher risk for low QoL.