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Objective: To quantify the risk of hip fracture, thromboembolism, stroke, myocardial infarction, pneumonia and sudden cardiac death associated with exposure to antipsychotics. Methods: Systematic searches were conducted in Medline, Embase and PsycINFO from inception until 30/07/2018 for systematic reviews of observational studies. AMSTAR‐2 was used for the quality assessment of systematic reviews, while the strength of associations was measured using GRADE and quantitative umbrella review criteria (URC). Results: Sixty‐eight observational studies from six systematic reviews were included. The association between antipsychotic exposure and pneumonia was the strongest [URC = class I; GRADE = low quality; odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.62–2.09; participants = 28 726; age = 76.2 ± 12.3 years], followed by the association with hip fracture (URC = class II; GRADE = low quality; OR = 1.57, 95% CI = 1.42–1.74; participants = 5 288 118; age = 55.4 ± 12.5 years), and thromboembolism (URC = class II; GRADE = very low quality; OR = 1.55, 95% CI = 1.31–1.83; participants = 31 417 175; age = 55.5 ± 3.2 years). The association was weak for stroke (URC = class III; GRADE = very low quality; OR = 1.45, 95% CI = 1.24–1.70; participants = 65 700; age = 68.7 ± 13.8 years), sudden cardiac death (URC = class III; GRADE = very low quality; OR = 2.24, 95% CI = 1.45–3.46; participants = 77 488; age = 52.2 ± 6.2 years) and myocardial infarction (URC = class III; GRADE = very low quality; OR = 2.21, 95% CI = 1.41–3.46; participants = 399 868; age = 74.1 ± 9.3 years). Conclusion: The most robust results were found for the risk of pneumonia, followed by the risk of hip fracture and thromboembolism. For stroke, sudden cardiac death and myocardial infarction, the strength of association was weak. The observational nature of the primary studies may represent a source of bias. [ABSTRACT FROM AUTHOR]

Objective The aim of the present systematic review and meta-analysis was to evaluate the impact of physical exercise on cognitive symptoms in depressed adult patients. Methods Systematic literature search was performed in Web of Science™ and CINAHL from inception to August 2016. Two reviewers independently selected randomized trials evaluating the effect of exercise on cognitive functions in patients with a validated diagnosis of depression. Outcome measures included global cognition and different cognitive domains (speed of processing, attention/vigilance, working memory, verbal and visual memory, and reasoning). Results Eight trials met inclusion criteria (637 patients). A fixed-effects model showed absence of beneficial effect on global cognition (Hedges' g = 0.07, 95% CI −0.08 to 0.24, I2 = 0%) as well as on specific cognitive domains. Sensitivity analyses did not show an impact of exercise in studies with shorter intervention duration compared to longer trials (between group heterogeneity Q = 3.564, d f = 1, P = 0.059), single session per week compared to multiple sessions ( Q = 2.691, d f = 1, P = 0.101) and low exercise intensity compared with moderate/high intensity ( Q = 2.952, d f = 1, P = 0.086). Conclusion Our meta-analysis did not observe a substantial benefit of physical exercise on cognitive symptoms in depression. [ABSTRACT FROM AUTHOR]

Objective This study aimed at investigating whether dose is a mediator of treatment effect in fluoxetine-randomized trials. Specifically, we investigated whether dose was higher in trials in which the aim was to demonstrate fluoxetine efficacy in comparison with older antidepressants and lower in trials in which the aim was to demonstrate a new drug's efficacy against fluoxetine. Method We applied the model developed by Baron and Kenny to investigate the mediational role of drug dose on treatment effect. We included all randomized controlled trials comparing fluoxetine with other antidepressants as monotherapy in the acute-phase treatment of unipolar major depression. Results A total of 173 studies were included. In 76 comparisons (44%), fluoxetine was the experimental antidepressant. A metaregression analysis indicated that after adjusting for possible confounders, studies where fluoxetine was the experimental agent were associated with a significant advantage for fluoxetine. However, the Baron and Kenny model revealed no mediational role of drug dose in influencing treatment effect. Conclusion The outcome of fluoxetine-randomized trials changed according to whether this drug was used as a new compound or as a reference. This finding cannot be attributed to antidepressants dose, as dose failed to emerge as mediator of treatment effect in the Baron and Kenny approach. [ABSTRACT FROM AUTHOR]

Objective The integration of new treatments into the market and routine clinical practice should be dependent on robustness of evidence from randomised controlled trials ( RCTs). We assessed study designs of long-term studies for bipolar disorder of all second-generation antipsychotics ( SGAs) submitted to the Food and Drug Administration ( FDA) and the completeness of evidence submitted to the regulatory agency. Method Systematic review of double-blind RCTs comparing SGAs with placebo or active drugs in adults. FDA website and electronic databases were searched until July 2013. Results Six placebo-controlled trials comparing aripiprazole, olanzapine, quetiapine and ziprasidone were found in the FDA website. Electronic searches found four additional RCTs about aripiprazole, olanzapine or quetiapine. All RCTs (either submitted to FDA or not) selected patients who responded to acute treatment to increase the treatment effect observed in the long-term phase ( enrichment design). By contrast, in the prescribing information sheets for all SGAs, the reported indication was 'maintenance treatment of bipolar disorder'. Conclusion Extrapolation of results from enrichment studies to the more general population of patients should be carried out cautiously because average treatment benefits are likely to be less in unselected patients. Clear guidance for regulatory submission of RCTs is needed. [ABSTRACT FROM AUTHOR]

Background National and regional authorities in Scotland have introduced multiple measures to appreciably enhance prescribing efficiency for the proton pump inhibitors ( PPIs), statins and renin-angiotensin inhibitor drugs. Generic oral risperidone recently became available in Scotland; however, schizophrenia is a complex disease with advice from respected authorities suggesting that treatment should be individualised. Aims To assess (i) changes in atypical antipsychotic drug ( AAP) utilisation and expenditure following the availability of oral generic risperidone in Scotland; (ii) to determine (a) current INN prescribing rates for risperidone following generic availability and (b) decrease in expenditure/ DDD for generic risperidone; (iii) to suggest additional measures that could possibly be introduced in Scotland to further enhance prescribing of generic AAPs; and (iv) to provide guidance to NHS Scotland as well as other European authorities on the implications. Methods Retrospective observational study and an interrupted time series design. Results No appreciable change in the utilisation patterns of risperidone pre- and postgeneric availability. Appreciable INN prescribing averaged 93-98% of total oral risperidone. Generic risperidone was 84% below prepatent loss prices by study end, reducing annual expenditure for oral risperidone in 2010 by GB£3.19mn compared with prepatent loss situation. However, overall expenditure on AAPs increased by 42% from 2005 to 2010. Discussion As expected, there was no change in utilisation patterns for risperidone, although potential to influence prescribing patterns. Continued high INN prescribing suggests no problems with generic risperidone in practice. Costs will start to decrease as more AAPs lose their patents (olanzapine and quetiapine). There is the possibility to accelerate this reduction through educational activities. Conclusion There is potential to realise some savings with generic AAPs. However, this is limited by the complexity of the disease area. Any measures introduced must aim at increasing the prescribing of generic AAPs first line in suitable patients. [ABSTRACT FROM AUTHOR]

Objective: To ascertain the existence of an excess of avoidable mortality among psychiatric patients in an area with a community-based system of care, to identify predictors of higher risk of avoidable mortality and to provide some possible indication to reduce avoidable mortality in modern psychiatric services. Method: All patients with an ICD-10 psychiatric diagnosis, living in a catchment area of about 75 000 inhabitants, seeking care in 1982–2001 were included ( n = 6956). Mortality and causes of death were ascertained using linkage procedures with other local health databases. Standardized mortality ratios (SMRs) were calculated for each avoidable cause of death. Results: The observed number of deaths for those causes considered avoidable by the European Community was four times greater than the expected ( P < 0.01). SMR was higher for deaths preventable with adequate health promotion policies than for those preventable with appropriate health care. Males, alcohol/drug addicted and young patients have the highest avoidable SMRs. Conclusion: These findings urgently call for the implementation of health promotion and preventive programs targeted to psychiatric patients. Moreover, mental health services should improve the capacity to manage medical health problems of their patients. [ABSTRACT FROM AUTHOR]

Barbui C, Ciuna A, Nosé M, Patten SB, Stegagno M, Burti L, Amaddeo F, Tansella M. Off-label and non-classical prescriptions of antipsychotic agents in ordinary in-patient practice. Acta Psychiatr Scand 2004: 109: 275–278. © Blackwell Munksgaard 2004. To estimate the proportion of off-label prescriptions of antipsychotics (APs) in ordinary in-patient practice. From the South-Verona Psychiatric Case Register all admissions to the in-patient unit during 2001–02 were extracted. Prescriptions of APs were defined off-label when dispensed outside the licensed indications. In addition, the proportion of ‘non-classical prescriptions’ was calculated. During the 2 years surveyed AP agents were prescribed in 311 cases. Nearly 50% of second-generation AP prescriptions were for an off-label indication. In contrast, <15% of first-generation AP prescriptions were for an off-label indication. About 30% of first- and second-generation agents were prescribed for a non-classical indication. Approved labels for second-generation AP agents cover a much narrower range of indications than any of the first-generation agents, and this explains the higher proportion of off-label prescriptions. In contrast, the everyday use of first- and second-generation APs cover a similar range of clinical indications. [ABSTRACT FROM AUTHOR]

Objective: Investigate the relationship of various domains of quality of life (QoL) with socio-demographics, clinical and social characteristics, service use and satisfaction in a representative sample of patients in contact with the South-Verona community mental health service. Method: Measures included: Lancashire Quality of Life Profile (LQOLP), demographics, diagnosis and service utilization data from the Case Register, Brief Psychiatric Rating Scale (BPRS), Disability Assessment Schedule (DAS), Global Assessment of Functioning (GAF) and Verona Service Satisfaction Scale (VSSS). Analyses were conducted using a block-stratified multiple regression model. Results: Demographics, diagnosis, psychopathology, disability, functioning and service use together explained different amounts of variance in each LQOLP domain, but always less than 14%. VSSS explained more variance than any other indicator in health (13.1%), social relations (12.1%), leisure/participation (9.1%), and general wellbeing (9.0%). Conclusion: Different domains of QoL are predicted by different indicators. In some important domains, self-perceived satisfactory and effective care might have an impact on the QoL of patients. [ABSTRACT FROM AUTHOR]

Objective: To assess the postpartum depression (PPD) risk in women with postpartum hemorrhage (PPH) and moderators., Methods: We identified observational studies of PPD rates in women with versus without PPH in Embase/Medline/PsychInfo/Cinhail in 09/2022. Study quality was evaluated using the Newcastle-Ottawa-Scale. Our primary outcome was the odds ratio (OR, 95% confidence intervals [95%CI]) of PPD in women with versus without PPH. Meta-regression analyses included the effects of age, body mass index, marital status, education, history of depression/anxiety, preeclampsia, antenatal anemia and C-section; subgroup analyses were based on PPH and PPD assessment methods, samples with versus without history of depression/anxiety, from low-/middle- versus high-income countries. We performed sensitivity analyses after excluding poor-quality studies, cross-sectional studies and sequentially each study., Results: One, five and three studies were rated as good-, fair- and poor-quality respectively. In nine studies (k = 10 cohorts, n = 934,432), women with PPH were at increased PPD risk compared to women without PPH (OR = 1.28, 95% CI = 1.13 to 1.44, p < 0.001), with substantial heterogeneity (I 2  = 98.9%). Higher PPH-related PPD ORs were estimated in samples with versus without history of depression/anxiety or antidepressant exposure (OR = 1.37, 95%CI = 1.18 to 1.60, k = 6, n = 55,212, versus 1.06, 95%CI = 1.04 to 1.09, k = 3, n = 879,220, p < 0.001) and in cohorts from low-/middle- versus high-income countries (OR = 1.49, 95%CI = 1.37 to 1.61, k = 4, n = 9197, versus 1.13, 95%CI = 1.04 to 1.23, k = 6, n = 925,235, p < 0.001). After excluding low-quality studies the PPD OR dropped (1.14, 95%CI = 1.02 to 1.29, k = 6, n = 929,671, p = 0.02)., Conclusions: Women with PPH had increased PPD risk amplified by history of depression/anxiety, whereas more data from low-/middle-income countries are required., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Objective: This study was conducted to investigate whether the quality of antidepressant drug trials has improved during the last 40 years., Method: A sample of 314 randomized clinical trials published between 1962 and 1998 was analysed., Results: From 1962 to 1970 the median number of patients per trial was 56 (range 24-137), from 1971 to 1980 was 50 (10-211) and from 1981 to 1990 was 51 (20-314). In the last 8 years the median sample size increased to 100 patients (20-1002). Trials had a median duration of 4 weeks in the first two decades of publication, and a median duration of 6 weeks in the following two decades. Patient selection criteria have become increasingly sophisticated and the median number of efficacy measures increased in the last 4 decades from 1 to 4., Conclusion: Stringent selection criteria and sophisticated outcome assessment tend to exclude typical patients from randomized controlled trials and made it more difficult to follow many patients in the long term.