Clinical correlates of paliperidone palmitate and aripiprazole monohydrate prescription for subjects with schizophrenia-spectrum disorders: findings from the STAR Network Depot Study.

This study, based on the 'Servizi Territoriali Associati per la Ricerca' (STAR) Network Depot Study nationwide baseline data, explored whether individual symptoms severity and clusters might influence the prescription of paliperidone palmitate 1-month (PP1M) vs. aripiprazole monohydrate. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology and relevant symptoms clusters. Drug Attitude Inventory, 10 items, was used to test attitude towards medications. Adherence to treatments was rated according to the Kemp seven-point scale. We assessed for eligibility 451 individuals and, among them, we included 195 subjects (n = 117 who started PPM1 and n = 78 aripiprazole monohydrate). Individuals were comparable in terms of age, gender, treatment years, recent hospitalizations, previous long-acting injectable antipsychotic treatments, additional oral treatments, attitude toward drugs, medication adherence, and alcohol/substance-related comorbidities. Subjects starting PP1M presented higher BPRS overall (P = 0.009), positive (P = 0.015), and negative (P = 0.010) symptom scores compared to subjects starting aripiprazole monohydrate. Results were confirmed by appropriate regression models and propensity score matching analysis. No differences were found comparing the other BPRS subscale scores: affect, resistance, and activation. Clinicians may be more prone to prescribe PPM1, rather than aripiprazole monohydrate, to subjects showing higher overall symptom severity, including positive and negative symptoms. No additional clinical factors influenced prescribing attitudes in our sample.

Adjunctive second-generation antipsychotics for specific symptom domains of schizophrenia resistant to clozapine: A meta-analysis.

A fair amount of subjects with schizophrenia do not respond to clozapine and are defined 'ultra-resistant'. In this systematic review and meta-analysis, we tested the efficacy of adjunctive second-generation antipsychotics (SGAs) for main symptom domains (positive, negative, and depressive symptoms) in individuals with clozapine-resistant schizophrenia. We searched main electronic databases till December 2017. We included twelve double-blind, randomized, placebo-controlled trials (RCTs), evaluating the efficacy of SGAs for clozapine non/partial responders. We did not find any difference between SGAs and placebo (standardized mean difference, SMD = -0.21; p = 0.170; I2 = 68.0%) in improving positive symptoms. The effect size varied according to RCT duration (p = 0.025) and assessment methods (p = 0.016). Low-moderate effects of SGAs on both negative (SMD = -0.38; p = 0.005; I2 = 62.7%) and depressive symptoms (SMD = -0.35; p = 0.003; I2 = 4.9%), were estimated. In sum, our meta-analysis highlights the lack of efficacy of SGAs as add-on treatment for positive symptoms in clozapine-resistant schizophrenia. A small benefit of SGAs was estimated for both negative and depressive symptoms. Further RCTs are needed to establish efficacy and tolerability of SGAs or other augmentation strategies for different symptoms of clozapine-resistant schizophrenia.

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.

Engagement in the Overdose RIsk InfOrmatioN (ORION) e-Health Tool for Opioid Overdose Prevention and Self-Efficacy: A Preliminary Study.

Increasing awareness of, and information about, overdose risk is an appropriate approach in risk reduction. e-Health technology in substance use disorders is an opportunity to support behavioral changes related to public health concerns. The present study aimed to evaluate the short-term impact of an innovative e-health psychoeducational software, the Overdose RIsk InfOrmatioN (ORION) tool. The ORION programme provided relevant information to opioid-dependent individuals about the risk of suffering a drug overdose as a result of high risky and dysfunctional behaviors. Seven aggregate risk factors were identified through a systematic review and their outputs included in a risk estimation model. We recruited 194 opioid-dependent treatment-seeking individuals from the United Kingdom, Germany, Italy, and Denmark. All participants were given at study entry, and after their use of the software, the General Self-Efficacy (GSE) Scale. We found comparable pre- and post-ORION administration mean GSE scores (SD), 28.49 (5.50) and 28.32 (5.90), respectively (p = 0.297). However, there was an inverse correlation between the number of risk factors and reported levels of self-efficacy (p < 0.001). ORION was able to identify individuals who are most in need of reducing their modifiable risk factors with appropriate interventions. However, a one-shot e-health tool cannot influence complex domains such as self-efficacy unless this is used with other effective interventions. Nonetheless, the ORION tool is unique in its style and content of delivery, that is translating risks combination into a clear estimation, and will need further development such as (a) integration in smartphone-based e-health apps and (b) testing in other high-risk populations.

Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients.

Recent reports show that, in patients treated with finasteride for male pattern hair loss, persistent side effects including sexual side effects, depression, anxiety and cognitive complaints may occur. We here explored the psychiatric and andrological features of patients affected by post-finasteride syndrome (PFS) and verified whether the cerebrospinal fluid (CSF) and plasma levels of neuroactive steroids (i.e., important regulators of nervous function) are modified. We found that eight out of sixteen PFS male patients considered suffered from a DSM-IV major depressive disorder (MDD). In addition, all PFS patients showed erectile dysfunction (ED); in particular, ten patients showed a severe and six a mild-moderate ED. We also reported abnormal somatosensory evoked potentials of the pudendal nerve in PFS patients with severe ED, the first objective evidence of a neuropathy involving peripheral neurogenic control of erection. Testicular volume by ultrasonography was normal in PFS patients. Data obtained on neuroactive steroid levels also indicate interesting features. Indeed, decreased levels of pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone), dihydrotestosterone and 17beta-estradiol and increased levels of dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol were observed in CSF of PFS patients. Neuroactive steroid levels were also altered in plasma of PFS patients, however these changes did not reflect exactly what occurs in CSF. Finally, finasteride did not only affect, as expected, the levels of 5alpha-reduced metabolites of progesterone and testosterone, but also the further metabolites and precursors suggesting that this drug has broad consequence on neuroactive steroid levels of PFS patients.

Area-Level Deprivation and Adverse Consequences in People With Substance Use Disorders: Findings From the Psychiatric and Addictive Dual Disorder in Italy (PADDI) Study.

BACKGROUND: Environmental factors may operate with individual ones to influence the risk of substance use. Research has focused on severe adverse consequences influenced by contextual variables. However, the literature on community level factors influencing substance use behaviors is relatively limited across Europe so far. OBJECTIVE: We capitalized on data from a National survey, exploring individual and contextual characteristics, to study adverse consequences among people with substance use disorders. METHODS: The impact of area-level deprivation on nonfatal overdose, hepatitis C or B infections, and major involvement with the criminal justice system, was explored. Logistic regression models with cluster-robust errors, modeling subject-level and area-level effects, were used. RESULTS: Living in deprived and intermediate areas, as compared with affluent ones, was associated with greater likelihood of both nonfatal overdose and jail sentences longer than 6 months, though not of active viral hepatitis. CONCLUSIONS: Area-level deprivation may play an important role in determining adverse consequences in people with substance use disorders, also after controlling for individual-level characteristics. More research is needed to understand the aspects of social and physical environments that matter for drug outcomes before effective policy and research interventions can be developed.

Association between depression and neuropathy in people with type 2 diabetes: a meta-analysis.

OBJECTIVE: Depression and neuropathy are frequent complications of type 2 diabetes. The current meta-analysis aimed to estimate the association between depression and neuropathy in subjects with type 2 diabetes. METHODS: We systematically searched electronic databases for articles published up to February 2015, providing data on the association between depression and neuropathy in individuals with type 2 diabetes. No language restrictions were applied. The meta-analysis generated random-effect odds ratios with 95% confidence intervals (95% CI). Risk of publication bias and heterogeneity were estimated using the Egger test and I(2) index, respectively. Leave-one-out analysis was performed. Data were analysed using stata. RESULTS: Thirteen studies were included in the meta-analysis. Data on the association between depression and neuropathy were available for 3898 individuals with type 2 diabetes. Pooled analysis showed an association between depression and neuropathy, with an odds ratio of 2.01 (95% CI: 1.60-2.54; p < 0.001). There was no risk of publication bias (p = 0.064), and heterogeneity was moderate (I(2) = 44.5%). Leave-one-out analysis confirmed consistency of the findings. The association appeared partly influenced by age, because studies selecting older people (sample mean age > 65 years) showed a slightly higher estimate for the association. CONCLUSIONS: We found an association between depression and neuropathy among people with type 2 diabetes. Because of the cross-sectional nature of included studies, the relationship between these two conditions might be bidirectional. Further research exploring factors that might moderate or mediate this association is needed. Targeted interventions for comorbid depression and neuropathy should be implemented in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.