Chiara Gastaldon

Benzodiazepines and risk of dementia: true association or reverse causation?

According to a recently published population study conducted in France, exposure to benzodiazepines may be associated with an approximately 50% increase in the risk of dementia in the elderly. However, the clinical interpretation of this finding raised some concerns. A causal link between benzodiazepine use and diagnosis of dementia may be real, but it is nevertheless possible that the increased risk might be due to other confounding factors. In this article, the main strengths and weaknesses of this study are briefly analysed, including the possibility of reverse causation. Implications for research and current practice are discussed.

New EMA report on paliperidone 3-month injections: taking clinical and policy decisions without an adequate evidence base

Three-month long-acting paliperidone is a new, recently marketed, formulation of paliperidone, characterised by the longest available dosing interval among long-acting antipsychotics. The clinical profile of 3-month long-acting paliperidone was recently summarised by the European Medicines Agency (EMA) in a public assessment report, released in April 2016. In this commentary, the main strengths and limitations of the EMA assessment report were appraised and discussed, in order to highlight possible implications for clinical practice, future research and regulatory practices for drug approval.

Focused psychosocial interventions for children in low-resource humanitarian settings : a systematic review and individual participant data meta-analysis

BACKGROUND Results from studies evaluating the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in humanitarian settings in low-income and middle-income countries have been inconsistent, showing varying results by setting and subgroup (eg, age or gender). We aimed to assess the effectiveness of these interventions, and to explore which children are likely to benefit most. METHODS We did a systematic review and meta-analysis of individual participant data (IPD) from 3143 children recruited to 11 randomised controlled trials of focused psychosocial support interventions versus waiting list. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, PsycArticles, Web of Science, and the main local low-income and middle-income countries (LMICs) databases according to the list of databases relevant to LMIC developed collaboratively by Cochrane and WHO Library, up to November, 2016. We included randomised controlled trials that assessed the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in LMICs, compared with waiting lists (eg, inactive controls). We excluded quasi-randomised trials, studies that did not focus on psychosocial support interventions, and studies that compared two active interventions without control conditions. We requested anonymised data from each trial for each of the prespecified variables for each child who was randomly assigned. The main outcomes considered were continuous scores in post-traumatic stress disorder (PTSD) symptoms, depressive symptoms, and anxiety symptoms assessed with rating scales administered immediately (0-4 weeks) after the intervention. We harmonised all individual items from rating scales using item response theory methods. This study is registered with PROSPERO, number CRD42013006960. FINDINGS We identified a beneficial effect of focused psychosocial support interventions on PTSD symptoms (standardised mean difference [SMD] -0·33, 95% CI -0·52 to -0·14) that was maintained at follow-up (-0·21, -0·42 to -0·01). We also identified benefits at the endpoint for functional impairment (-0·29, -0·43 to -0·15) and for strengths: coping (-0·22, -0·43 to -0·02), hope (-0·29, -0·48 to -0·09), and social support (-0·27, -0·52 to -0·02). In IPD meta-analyses focused on age, gender, displacement status, region, and household size we found a stronger improvement in PTSD symptoms in children aged 15-18 years (-0·43, -0·63 to -0·23), in non-displaced children (-0·40, -0·52 to -0·27), and in children living in smaller households (<6 members; -0·27, -0·42 to -0·11). INTERPRETATION Overall, focused psychosocial interventions are effective in reducing PTSD and functional impairment, and in increasing hope, coping, and social support. Future studies should focus on strengthening interventions for younger children, displaced children, and children living in larger households. FUNDING European Commission FP7th Framework Programme for Research (Marie Curie International Outgoing Fellowship) and the National Institute on Aging.

Drug dose as mediator of treatment effect in antidepressant drug trials: the case of fluoxetine

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 drugs efficacy against fluoxetine.

Antipsychotic drug exposure and risk of myocardial infarction.

Patients experiencing psychoses and in need of antipsychotic agents may be exposed to a higher risk of myocardial infarction (MI) than the general population. As there have been no randomised studies investigating this association, a recent systematic review and meta-analysis included all observational studies that compared the incidence of MI among patients receiving antipsychotics v. no treatment. It found nine studies and calculated that the odds (risk) for developing MI were 1.88-fold higher in antipsychotic users compared with individuals who had not taken antipsychotic drugs. In this commentary, the results of this systematic review are discussed in view of their clinical implications for everyday clinical practice.

Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy

Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network “Depot” Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. Results Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. Discussion LAIs’ prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs.

Antipsychotic combinations in schizophrenia

In the treatment of resistant schizophrenia, a number of meta-analyses attempted to quantify the efficacy and tolerability of antipsychotic (AP) polypharmacy v. monotherapy with contradictory results. Recently, a systematic review and meta-analysis of randomised controlled trials investigated the efficacy and tolerability of AP combination v. monotherapy in schizophrenia. It included 31 studies: 21 double-blind (considered high-quality studies) and 10 open-label (considered low-quality studies). The meta-analysis showed that, overall, the combination of two APs was more effective than monotherapy in terms of symptom reduction (standardised mean difference (SMD) = -0.53, 95% confidence interval (CI) -0.87 to -0.19); however, this result was confirmed only in the subgroup of low-quality studies. Negative symptoms improved when combining a D2 antagonist with a D2 partial agonist (SMD = -0.41, 95% CI -0.79 to -0.03) both in double-blind and open-label studies. In the present commentary, the results of this systematic review are critically discussed in terms of their clinical and research implications.