Efficacy and tolerability of antipsychotic polypharmacy for schizophrenia spectrum disorders. A systematic review and meta-analysis of individual patient data.

BACKGROUND: Antipsychotic polypharmacy (APP) is frequently prescribed for schizophrenia-spectrum disorders. Despite the inconsistent findings on efficacy, APP may be beneficial for subgroups of psychotic patients. This meta-analysis of individual patient data investigated moderators of efficacy and tolerability of APP in adult patients with schizophrenia-spectrum disorders. DESIGN: We searched PubMed, EMBASE, and the Cochrane Central Register of Randomized Trials until September 1, 2022, for randomized controlled trials comparing APP with antipsychotic monotherapy. We estimated the effects with a one-stage approach for patient-level moderators and a two-stage approach for study-level moderators, using (generalized) linear mixed-effects models. Primary outcome was treatment response, defined as a reduction of 25 % or more in the Positive and Negative Syndrome Scale (PANSS) score. Secondary outcomes were study discontinuation, and changes from baseline on the PANSS total score, its positive and negative symptom subscale scores, the Clinical Global Impressions Scale (CGI), and adverse effects. RESULTS: We obtained individual patient data from 10 studies (602 patients; 31 % of all possible patients) and included 599 patients in our analysis. A higher baseline PANSS total score increased the chance of a response to APP (OR = 1.41, 95 % CI 1.02; 1.94, p = 0.037 per 10-point increase in baseline PANSS total), mainly driven by baseline positive symptoms. The same applied to changes on the PANSS positive symptom subscale and the CGI severity scale. Extrapyramidal side effects increased significantly where first and second-generation antipsychotics were co-prescribed. Study discontinuation was comparable between both treatment arms. CONCLUSIONS: APP was effective in severely psychotic patients with high baseline PANSS total scores and predominantly positive symptoms. This effect must be weighed against potential adverse effects.

Choroidal structural analysis in ultra-high risk and first-episode psychosis.

Both structural and functional alterations in the retina and the choroid of the eye, as parts of the central nervous system, have been shown in psychotic disorders, especially in schizophrenia. In addition, genetic and imaging studies indicate vascular and angiogenesis anomalies in the psychosis spectrum disorders. In this ocular imaging study, choroidal structure and vascularity were investigated using enhanced depth imaging (EDI) optical coherence tomography (OCT) in first-episode psychosis (FEP), ultra-high risk for psychosis (UHR-P), and age- and gender- matched healthy controls (HCs). There were no significant differences between groups in central choroidal thickness, stromal choroidal area (SCA), luminal choroidal area (LCA) and total subfoveal choroidal area. The LCA/SCA ratio (p<0.001) and the choroidal vascularity index (CVI) (p<0.001) were significantly different between FEP, UHR-P and HCs. CVI and LCA/SCA ratio were significantly higher in patients with FEP compared to help-seeking youth at UHR-P. CVI and LCA/SCA ratio were not different between UHR-P and HCs. However, CVI was higher in UHR-P compared to HCs after excluding the outliers for the sensitivity analysis (p = 0.002). Current findings suggest that choroidal thickness is normal, but there are abnormalities in choroidal microvasculature in prodromal and first-episode psychosis. Further longitudinal studies are needed to investigate oculomics, especially CVI, as a promising biomarker for the prediction of conversion to psychosis in individuals at clinical high-risk.

[Do general practitioners diagnose and treat patients with alcohol use problems?]. / Pratisyen Hekimler Alkol Kullanim Sorunlari Olan Hastalari Taniyor ve Tedavi Ediyorlar Mi?

AIM: To determine the primary health care working general practitioners' knowledge, attitude and behavior towards alcohol use disorders. METHOD: In this descriptive and cross-sectional study 135 general practitioners (GPs) completed the questionnaire. RESULTS: Pre and post graduate education on alcohol use disorders is low (25.4 % and 11.7% respectively). Most of the GPs do not know the levels of risky alcohol use, screening tests, and biochemical markers. The mean knowledge score is 6.67+/-1.70. Most GPs think that alcohol use disorders are not an important issue in primary health care (57%), they do not have time to deal with patients' alcohol problems (74.1%), it is difficult to diagnose risky alcohol users without clear symptoms (91.1%), patients do not follow advice on alcohol use (85.2%), and physicians themselves are tolerant towards alcohol (71.1%). Half of the GPs reported that they find it difficult to talk about alcohol use with patients and think that patients may be angered by alcohol consumption questions. Mean attitude score is 4.44+/-2.15. Most of the GPs reported that they would ask questions about alcohol use to their patients (91.7%) and declare that the patients' problems were related to alcohol (90.2%). More than half of them reported that they would refer the patient to a specialist or an alcohol treatment center (58.5%). The mean behavior score is 5.96+/-1.46. CONCLUSION: In our country it is clear that more education and support for GPs is needed due to their important role in intervention for alcohol use problems.

A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety.

BACKGROUND: Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine. The purpose of this study was to carry out a placebo-controlled, randomized, double-blind trial of the efficacy, safety, and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine. METHOD: In this 6-week double-blind study, 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were randomly assigned to risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale, the Clinical Global Impressions-Severity of Illness scale, the Global Assessment of Functioning scale, and the Quality of Life Scale. A variety of safety and tolerability measures were also obtained. Data were collected between November 2001 and July 2003. RESULTS: Significant improvement was noted in both groups on a variety of measures of psychopathology, but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure, the PANSS positive symptom subscale. There were no significant differences between the treatment groups regarding extrapyramidal symptoms, weight gain, vital signs, serum clozapine levels, and QTc interval. The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation. The patients treated with risperidone developed significant increases in plasma prolactin levels. CONCLUSION: Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period.