G. Cerveri

Clinical outcome and tolerability of sertraline in major depression: A study with plasma levels

Sertraline (SRT) has been shown to be an effective antidepressant in extensive clinical trial programs but data on plasma concentrations regarding clinical outcome and tolerability are lacking. Twenty-one out-patients of both sexes, with mean age of 50.23 years (S.D. = 17.37), affected by major depressive disorder, recurrent (Diagnostic and Statistical Manual of Mental Disorder--IV, DSM-IV), were treated with 25-150 mg of SRT once a day (mean=66.26 mg, S.D.=30.50) for 30 days. Clinical evaluation was assessed at baseline (T0), after 15 days (T15), and then after 30 days (T30). Plasma samples for SRT level determination were collected at T30. Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scale for Depression (HRS-D), and Hamilton Rating Scale for Anxiety (HRS-A) showed a significant improvement during the study (P<.01 vs. T0). The most commonly reported side effects were nausea (19%), cephalalgia (9.5%), dry mouth (9.5%), decreased libido (9.5%), tremor (4.7%), and tachycardia (4.7%). SRT plasma levels ranged from 2.82 to 112.20 ng/ml (mean=40.42 ng/ml, S.D.=26.93). No correlation between SRT plasma levels and clinical improvement or side effects were observed. Drug plasma level determination does not seem be strictly necessary from a clinical point of view but further research seems advisable in patients at risk like elderly and during long-term studies.

Clinical outcome and tolerability of duloxetine in the treatment of major depressive disorder: A 12-week study with plasma levels

Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor that has been recently approved for the treatment of major depressive disorder (MDD). However, little is known about the relationship between DLX plasma levels and clinical response. The aims of this open-label study were 1) to assess clinical outcome and tolerability of DLX by means of clinician and patient assessments and 2) to evaluate the value of plasma DLX levels as predictors of clinical response and tolerability. This was a naturalistic, open-label study of 45 outpatients affected with MDD (16 men and 29 women), who received DLX at doses of 30—120 mg/day and were evaluated at baseline (T0) and after 2, 4 and 12 weeks (T1—3). The assessments included the Hamilton Rating Scales for Depression (HRSD) and Anxiety (HRSA), Clinical Global Impression-Severity (CGI-S), Beck’s Depression Inventory (BDI) and a mood visual analogue scale (VAS). Compared with T0, there were significant improvements in HRSD at T1, T2 and T3 (P < 0.001), in HRSA, CGI-S and the self-administered BDI at T2 and T3 (P < 0.001), and in the VAS scores shown at T3 (P = 0.01). DLX treatment was safe and well tolerated. Plasma DLX levels at T2 ranged from 5 to 135 ng/mL (mean ± SD = 53.56 ± 39.45) and correlated almost significantly with the DLX dose (r = 0.35; P = 0.069). There was a significant curvilinear quadratic relationship between the improvement of HRSA scores and plasma DLX levels (R2 = 0.27; P = 0.02). The incidence of anxiety or irritability was associated with the highest plasma levels. Our findings suggest that monitoring plasma DLX levels may be helpful in predicting better treatment responses and tolerability. The present data seem to suggest an optimal anxiolytic efficacy of DLX at intermediate plasma levels.

The risk of new-onset diabetes in antidepressant users – A systematic review and meta-analysis

Background Antidepressant Drugs (ADs) are among the most commonly prescribed medications in developed countries. The available epidemiological evidence suggests an association between AD use and higher risk of developing type 2 diabetes mellitus. However, some methodological issues make the interpretation of these results difficult. Moreover, very recent studies provided conflicting results. Given the high prevalence of both diabetes and AD use in many countries, clarifying whether this association is causal is of extreme relevance for the public health. The aim of the present study is to provide an up-to-date evaluation of the evidence in support of a causal role of ADs in inducing diabetes. Methods and findings A systematic literature search was conducted to identify relevant studies in MEDLINE (PubMed), PsycINFO, and International Pharmaceutical Abstracts (IPA) through 31st December 2016. Only studies assessing the incidence of new-onset diabetes in subjects treated with ADs were included. Results were pooled using a random-effects meta-analysis. Moreover, we extensively reviewed the role of the different sources of bias that have been proposed to explain the association between AD and diabetes. Twenty studies met the inclusion criteria. In the meta-analysis, the association between AD use and diabetes was still evident after the inclusion of the recent negative studies [pooled relative risk = 1.27, 95% confidence interval (CI), 1.19–1.35; p<0.001]. None of the biases proposed by previous authors seemed able to fully explain the observed association. Conclusions This updated meta-analysis confirms the association between AD use and incident diabetes. It still remains a matter of debate whether single ADs exert a different effect on the risk of diabetes. Given the possible heterogeneity, we suggest that a classification of ADs according to their pharmacological profiles could be useful in better elucidating the nature of this association.

Hallucinatory disorder: Preliminary data for a clinical diagnostic proposal

Introduction. Chronic hallucinatory psychosis is a psychopathological profile reported in French literature but not included in the current Anglo‐American psychiatric classifications. We compared a group of patients with a clinical picture related to this syndrome to a group of patients with schizophrenia in order to evaluate the possibility of characterising hallucinatory disorder as a diagnostic entity. Methods. Nine patients with a clinical profile related to chronic hallucinatory psychosis were compared to a group of nine patients with schizophrenia. All of the patients were clinically evaluated using the measures: SCID‐P, GAF, BPRS, PANSS, SAPS, SANS, HRS‐A, HRS‐D, CDSS, MMSE, and CGI. Results. Analysis of the clinical rating scales characterised schizophrenia as comprising three dimensions (positive, negative, and disorganised symptoms), each of which contributes differently to the psychopathological profile of individual patients. However, the patients with hallucinatory disorder seemed to be mainly characterised by auditory verbal hallucinations, with relative sparing of the other functions typically altered in patients with schizophrenia. Conclusions. The significant differences between the patients in the two groups seem to support the hypothesis that hallucinatory disorder may be considered as being a separate nosographic entity, in which the clinical picture is dominated by the experience of auditory verbal hallucinations.

Gabapentin and the Prophylaxis of Bipolar Disorders in Patients Intolerant to Lithium.

ObjectiveGabapentin (GBP) is a new anticonvulsant drug that has shown efficacy in the treatment of epilepsy, several neurological disorders (pain syndromes, acquired nystagmus, Huntington’s chorea, amyotrophic lateral sclerosis), and more recently in the treatment of bipolar disorders. The aim of this preliminary study was to assess the efficacy of GBP as a mood stabiliser in bipolar disorders. The adverse events of GBP were also evaluated.Patients and Methods21 outpatients, 13 females and 8 males (mean age ± SD: 51.90 ± 11.51 years) affected by bipolar disorder (BD), in partial remission (DSM IV) and intolerant to lithium, were treated with GBP at a dose ranging from 300 to 2400 mg/day (mean ± SD: 1010.86 ± 268.55mg; 13.81 ± 4.21 mg/kg) for 1 year. Clinical assessments were performed with the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HRS-D), the Hamilton Rating Scale for Anxiety (HRS-A) and the Manic Rating Scale (MRS) at baseline (T0), after 15 days (T0.5), after 30 days (T1), and then every month for 12 months.ResultsMean HRS-D, HRS-A and MRS scores did not show any significant variation during the study. Only one patient showed a clinical relapse. The most frequent adverse events reported by patients were dizziness (1%), dry mouth (1%) and sedation (0.5%). There was a significant negative correlation between GBP dosage (mg/kg) and HRS-A score. Mean leucocyte and neutrophil counts showed a significant increase during the study.ConclusionsThese preliminary data show potential efficacy and good tolerability of GBP in the prophylaxis of BD, but double-blind studies are required.

Quality of life, mental health status and service utilization in a sample of outpatients from a mental health service in northern Italy

A positive correlation between BPRS total score and the number of RS per year (r=.325; p=0.009) was found. No correlations were found between BPRS total score and number of accesses per year to the CMHS. Only Environment domain score of the WHOQOLBREF correlated with BPRS total score (r=.-0.258; p=0.040). No correlations were found between WHOQOL-BREF domains score and BPRS depression score, number of accesses to the CMHS or number of RS. After splitting the sample in two groups (psychotic disorders: PD, non psychotic disorders: NPD), PD subjects were shown to have greater BPRS total scores that NPD subjects (50.5±15.4 vs 38.9±12.2; p=0.005), while the latter group showed higher BPRS depression scores ( 1.64±1.0 vs 1.16±0.4; p=0.005). NPD subjects were more likely to attend a RP (40.9% vs 7.7%; p=0.001). The MANCOVA analysis showed that PD subjects showed higher self-rated QOL in all WHQOLBREF domains but Social one (Physical: F=6.668, p=0.012; Psychological: F=6.743, p=0.012; Environment: F=6.635, p=0.013) controlling for BPRS total and depressive score and attendance to RP (Table 1). P.3.b.044 Quality of life, mental health status and service utilization in a sample of outpatients from a mental health service in northern Italy