Аспирин снижает риск депрессии у людей с повышенным уровнем гомоцистеина

High total plasma homocysteine (tHcy) is associated with increased risk of cardiovascular events and depression. Consumption of B-vitamins (B6, B9 and B12) reduces tHcy by about 15%, but has equivocal effects on these health outcomes, suggesting that this relationship is either not causal or is confounded by other factors. The results of recent randomized trials suggest that antiplatelet therapy may confound these associations. This cross-sectional study assessed 3687 men aged 69–87 years for history of clinically significant depression (Geriatric Depression Scale 15 items 7) or a recorded diagnosis of depression in the Western Australian Data Linkage System, and collected information on the use of aspirin, B-vitamins and antidepressant medication, along with age, education, living arrangements, smoking history and medical comorbidity as assessed by the Charlson index. Participants donated a blood sample for the measurement of tHcy, and concentrations15 μmol l−1 were considered high. Five hundred and thirteen (13.9%) men showed evidence of depression, and of those 31.4% had high tHcy, 41.5% were using aspirin, 6.8% were consuming B-vitamins. Multivariate logistic regression showed that high tHcy was associated with increased odds of depression (odds ratio (OR)=1.60, 95% confidence interval (CI)=1.20–2.14), as was the use of B-vitamins (OR=1.95, 95% CI=1.21–3.13). There was a significant interaction between high tHcy and aspirin use (OR=0.57, 95% CI=0.36–0.91), but not between high tHcy and B-vitamin use (OR=0.80, 95% CI=0.26–2.46). The analyses were adjusted for smoking status, Charlson index and use of antidepressants. The results of this study indicate that older men with high tHcy who use aspirin have lower risk of depression, and suggest that antiplatelet therapy may be an effective preventive or management strategy for these cases. Randomized trials are required to confirm the antidepressant effect of aspirin in people with high tHcy.

Aspirin decreases the risk of depression in older men with high plasma homocysteine

Допамин и шизофрения

In this meta-analysis, Howes and colleagues studied the nature of dopaminergic dysfunction in schizophrenia. Data were gathered in vivo in 618 patients with schizophrenia and 606 controls using PET or single-photon emission CT. A highly significant elevation in presynaptic dopaminergic function was observed in patients with schizophrenia, with a large effect size but no alterations in dopamine transporter availability. There was a small elevation in D(2/3) receptor availability, but this was not evident in drug-naive patients and was influenced by the imaging approach used.

 The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment

In the current study, Demjaha and colleagues examined striatal dopamine synthesis capacity in 12 treatment-resistant and 12 treatment-responsive schizophrenia subjects, as well as in 12 healthy controls. They found that dopamine synthesis capacity was elevated in the treatment-responsive subjects, but not in the treatment-resistant subjects or in healthy controls. The elevation was most prominent in the associative and limbic striatal subdivisions.

 News Brief: Normal Dopamine Synthesis Capacity in Treatment-Resistant Schizophrenia

Редкая генетическая аномалия как фактор риска развития шизофрении

Approximately 30 percent of people with a genetic disorder known as 22q11 deletion syndrome develop schizophrenia, making it one of the strongest risk factors for the disease.

 Rare genetic disorder points to molecules that may play role in schizophrenia

Современные лекарственные стратегии лечения алкоголизма

γ-Hydroxybutyrate (GHB), anticonvulsants, and α2-agonists have been studied as stand-alone or adjunctive agents in the treatment of alcohol withdrawal syndrome. Although these medications are promising for mild to moderate alcohol withdrawal syndrome, there is a dearth of information about their ability to prevent or treat complicated alcohol withdrawal.

Alcohol Disorders: Practical Tips From New Research

Целесообразность применения монотерапии кветиапином для лечения депрессии

Background

Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect.

Objectives

This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD). Only the randomized controlled trials (RCTs) comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012.

Data sources

MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression.

Study eligible criteria, participants and interventions

Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i) depression severity, ii) response rate, iii) overall discontinuation rate, or iv) discontinuation rate due to adverse events. No language restriction was applied.

Study appraisal and synthesis methods

All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were computed by using a random effect model.

Results

A total of 1497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR). The pooled mean change scores of the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) of the quetiapine-treated group were higher than those of the placebo-treated group with the WMDs (95%CI) of -3.37 (-3.95, -2.79) and -2.46 (-3.47, -1.45), respectively. All studies defined the response and remission as >= 50% reduction of the MADRS total score and the MADRS total score of <=8 at endpoint, respectively. The overall response and remission rates were significantly greater in the quetiapine-treated group with RRs (95%CIs) of 1.44 (1.26, 1.64) and 1.37 (1.12, 1.68), respectively. The pooled discontinuation rate was not significantly different between groups with an RR (95%CI) of 1.16 (0.97, 1.39). The pooled discontinuation rate due to adverse event was greater in the quetiapine group with an RR (95%CI) of 2.90 (1.87, 4.48). With respect to sleep time, the pooled mean change Pittsburgh Sleep Quality Index (PSQI) scores of the quetiapine-treated group was also significantly higher than that of the placebo-treated group [WMD (95%CI) of -1.21 (-1.81, -0.61)].

Limitations

Variety of quetiapine XR doses and the small number of RCTs were key limitations of this meta-analysis.

Conclusions

Based on the limited evidence obtained from three RCTs, quetiapine XR is effective for adult patients with MDD. The high dropout rate due to adverse events suggests that some MDD patients may not be able to tolerate quetiapine XR. Due to the balance of its efficacy benefit and risk of side effects, as the overall discontinuation rate shown, the acceptability of this agent is not more than placebo. These results should be viewed as the very preliminary one. Further studies in this area are warranted.

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

 

Отсутствие долгосрочной противотревожной эффективности потенцирования кветиапином в предварительном исследовании

Background

Comorbid anxiety symptoms,in patients with a primary anxiety disorder or a mood disorder, leads to poor patient outcomes and burdens the healthcare system. This pilot study evaluated the feasibility of extended-release quetiapine fumarate (quetiapine XR) for the treatment of patients with either a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms compared to a placebo, as an adjunct to antidepressant therapy.

Methods

Thirty-nine patients with a diagnosis of a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms were enrolled in this study. Patients with a stable dose of antidepressant therapy were randomized according to a 2:1 probability of receiving either quetiapine XR or a placebo adjunctive treatment for 8 weeks. The efficacy was assessed by the Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impression of severity (CGI-S) score at baseline, week 1, 4, and 8.

Results

A total of 35 patients were included in this intention-to treat (ITT) population for the efficacy analysis (quetiapine XR: 22 patients; placebo: 13 patients). At week 4, statistically significant differences were observed on both the HAM-A score (p = 0.003) and the CGI-S score (p = 0.025), favouring the quetiapine XR (-13.00 +/- 4.14) compared to placebo (-6.63 +/- 5.42). However, no statistically significant difference was observed between the two groups with regard to changes from the baseline to week 8 on the HAM-A score (p = 0.332) or the CGI-S score (p = 0.833).

Conclusions

Augmentation of antidepressant treatment with quetiapine XR did not result in clinical improvement according to the outcome measure of anxiety using the HAM-A and CGI-S scores at week 8, among the patients with either a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms. However, treatment with quetiapine XR as an adjunct to antidepressant therapy appeared to provide a short-term benefit at 4 weeks. Further study is needed with a larger sample size, randomized controlled design and control of the dosage prescribed.

 Quetiapine fumarate augmentation for patients with a primary anxiety disorder or a mood disorder: a pilot study