[Advance directives in perinatal psychiatry: A parenting aid for women with bipolar disorder?] / Directives anticipées en psychiatrie périnatale : une aide à la parentalité pour les femmes ayant un trouble bipolaire ?

Advance directives in psychiatry (ADP) allow patients to anticipate their requests for care. Their purpose is to promote the acceptation of care, prevent relapses and maintain the autonomy of people with severe and persistent disorders such as bipolar disorder (BD). The risk of relapse is particularly high during the perinatal period. ADPs could be a tool to facilitate care pathway and so maintain mood stability for women with BD during the perinatal period and provide good conditions for child development.

Nitric Oxide Synthase activity in major depressive episodes before and after antidepressant treatment: Results of a large case-control treatment study.

BACKGROUND: Nitric oxide synthase (NOS) activity, an enzyme potentially involved in the major depressive episodes (MDE), could be indirectly measured by the L-Citrulline/L-Arginine ratio (L-Cit/L-Arg). The aim of this study was: (1) to compare the NOS activity of patients with a MDE to that of healthy controls (HC); (2) to assess its change after antidepressant treatment. METHODS: A total of 460 patients with a current MDE in a context of major depressive disorder (MDD) were compared to 895 HC for NOS activity (L-Cit/L-Arg plasma ratio). L-Arg and L-Cit plasma levels were measured using a MS-based liquid chromatography method. Depressed patients were assessed at baseline, and after 3 and 6 months of antidepressant treatment for depression severity and clinical response. RESULTS: Depressed patients had a lower NOS activity than HC at baseline [0.31 ± 0.09 v. 0.38 ± 0.12; 95% confidence interval (CI) -0.084 to -0.062, p < 0.0001]. Lower NOS activity at baseline predicted a higher response rate [odds ratio (OR) = 29.20; 95% CI 1.58-536.37; p = 0.023]. NOS activity in depressed patients increased significantly up to 0.34 ± 0.08 after antidepressant treatment (Est = 0.0034; 95% CI 0.0002-0.0067; p = 0.03). CONCLUSIONS: Depressed patients have a decreased NOS activity that improves after antidepressant treatment and predicts drug response. NOS activity may be a promising biomarker for MDE in a context of MDD.

[Efficacy and tolerance of PDE-5 in the treatment of erectile dysfunction in schizophrenic patients: A literature review]. / Efficacité et tolérance des IPDE-5 dans le traitement de la dysfonction érectile chez le patient schizophrène : une revue de la littérature.

INTRODUCTION: Sexual dysfunction is an important public health problem in men and is associated with reduced quality of life. It is more common in patients with schizophrenia. It is well-established that antipsychotic drugs cause sexual dysfunction with consequences on the quality of life of patients, adherence to treatment, and public health costs. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are indicated for the management of erectile dysfunction. However, there is little information on such treatment in schizophrenic patients. This literature review aimed to summarize the current data on the efficacy and tolerability of PDE-5 inhibitors in the erectile dysfunction in schizophrenic patients. MATERIAL AND METHODS: PubMed, PsycInfo and Cochrane databases were searched for studies published until August 2014. RESULTS: Only 6 studies met the inclusion criteria. Three were randomized, double-blind, cross-over, placebo-controlled trials and three were open studies. Various scales were used to measure erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, quality of life and intensity of schizophrenic symptoms. In the 3 randomized studies (one with sildenafil 25-50 mg, one with lodenafil carbonate 80 mg/j and the last one with tadalafil 10 mg), the rate of participants who completed the trial was high (around 95 %). All three included patients with schizophrenia or schizophrenia spectrum disorders. Patients reported significant improvement on sexual dysfunction. However, no statistical difference was reported between lodenafil and placebo, on different scales, suggesting a very important placebo effect in patients with schizophrenia. All three found a good tolerance of PDE-5 inhibitors. Side effects were rare and were mainly nasal congestion, headaches, nausea and dizziness. There were no major side effects or drug interactions. Considering the 3 open studies, 2 involved sildenafil and one tadalafil. All concluded in improved erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, and even the quality of life when it was studied. However, very few patients were included. DISCUSSION: Little data are available on the use of PDE5 inhibitors in schizophrenic patients. The 6 studies included few patients which reduces the power and the scope of their conclusions. There is also an important bias due to the use of self-questionnaires. The methodologies of the studies differ in many aspects which limits the comparability. Inclusion and exclusion criteria, drugs used and scales varied among the studies. However, the management of erectile disorder seems to be a consistent target in an integrative approach for the overall well-being of schizophrenic patients. PDE-5 inhibitors appear to be safe and could improve erectile function in schizophrenic patients. CONCLUSION: In total, the current data suggest efficiency and good tolerance of the use of PDE-5 inhibitors in schizophrenic patients with erectile dysfunction. However, further studies focusing on PDE-5 inhibitors are needed to more deeply assess their efficacy and safety in patients with schizophrenia.

5-HTTLPR and gender differences in affective disorders: A systematic review.

BACKGROUND: Serotonin transporter-linked polymorphic region (5-HTTLPR) variants have been extensively studied in psychiatric disorders. Although gender effects have been reported, they have not been comprehensively reviewed. The aim of our study was to summarize literature findings on 5-HTTLPR and gender differences in affective disorders. METHODS: A systematic search of PubMed, ISI Web of Knowledge, and PsycINFO databases was performed for dates until January 2015. The included articles (n=78) analyzed the association between 5-HTTLPR and affective spectrum disorders, taking into account gender. The quality of each study was assessed through STROBE and CONSORT. RESULTS: 5-HTTLPR modulation of affective disorders varied by gender. The S allele (or SS genotype) seemed to be differently associated with an increased risk of depression, depressive symptoms, anxiety traits and symptoms, and symptoms of internalizing behavior among women and an increased risk of aggressiveness, conduct disorder and symptom counts of externalizing behavior among men. Moreover, the presence of stressful life events reinforced the association. Interestingly, these differences seemed to begin with adolescence and were not consistent among the elderly, suggesting a plausible role of hormonal fluctuations. LIMITATIONS: The review is limited by the small number of included papers, due to the paucity of information in the literature regarding 5-HTTLPR and gender. CONCLUSIONS: 5-HTTLPR variants may exert a differential modulation on a number of features depending on gender. Further studies are needed to more deeply investigate the effect of 5-HTTLPR×gender on the modulation of affective disorders.

Post-partum depressive symptoms and medically assisted conception: a systematic review and meta-analysis.

STUDY QUESTION: Does medically assisted conception increase the risk of post-partum depressive symptoms? SUMMARY ANSWER: Our literature review and meta-analysis showed no increased risk of post-partum depressive symptoms in women after medically assisted conception. WHAT IS KNOWN ALREADY: Women who conceive with medically assisted conception, which can be considered as a stressful life event, could face an increased risk of depressive symptoms. However, no previous meta-analysis has been performed on the association between medically assisted conception and post-partum depressive symptoms. STUDY DESIGN, SIZE, DURATION: A systematic review with electronic searches of PubMed, ISI Web of Knowledge and PsycINFO databases up to December 2014 was conducted to identify articles evaluating post-partum depressive symptoms in women who had benefited from medically assisted conception compared with those with a spontaneous pregnancy. Meta-analyses were also performed on clinically significant post-partum depressive symptoms according to PRISMA guidelines. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 569 references, 492 were excluded on title, 42 on abstract and 17 others on full-text. Therefore, 18 studies were included in the review and 8 in the meta-analysis (2451 women) on clinically significant post-partum depressive symptoms after medically assisted conception compared with a spontaneous pregnancy. A sensitivity meta-analysis on assisted reproductive technologies and spontaneous pregnancy (6 studies, 1773 women) was also performed. The quality of the studies included in the meta-analyses was evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology Statement for observational research. The data were pooled using RevMan software by the Cochrane Collaboration. Heterogeneity between studies was assessed from the results of the χ(2) and I(2) statistics. Biases were assessed with funnel plots and Egger's test. A fixed effects model was used for the meta-analyses because of the low level of heterogeneity between the studies. MAIN RESULTS AND THE ROLE OF CHANCE: The systematic review of studies examining post-partum depressive symptoms after medically assisted conception compared with spontaneous pregnancy is not in favor of an association. Our meta-analysis on clinically significant post-partum depressive symptoms showed no significant difference between women who used medically assisted conception and those with spontaneous pregnancy: odds ratio (OR) = 0.93 (0.67-1.31), Z = 0.40, P = 0.69. The sensitivity meta-analysis reported no significant difference either: OR = 1.04 (0.71-1.52), Z = 0.18, P = 0.86. LIMITATIONS, REASONS FOR CAUTION: The literature on post-partum depressive symptoms and medically assisted conception is sparse. Only eight studies were available for our meta-analysis taking into account the rates of clinically significant post-partum depressive symptoms after medically assisted conception. However, the quality of the studies was high and the heterogeneity between trials was not significant. Whilst post-partum anxiety is more prevalent than depressive states and they can co-occur, it was not considered in these review and meta-analyses. In addition, other risk factors, such as maternal age, socio-demographic data or obstetric factors, are important for the assessment of post-partum depressive symptoms. Our review reported that several of these confounding risk factors were, however, analyzed and controlled for in the studies. WIDER IMPLICATIONS OF THE FINDINGS: Our literature review and meta-analyses showed no increased risk of post-partum depressive symptoms in women after medically assisted conception. Even if the rates of depressive symptoms are the same in the medically assisted conception population as among controls, the risk factors could be different. Though medically assisted conception can be considered as a stressful life event, these women have also lower prevalence of the usual risks. Professionals should also be careful to screen for prenatal and post-partum depressive symptoms, as with all pregnant women. Further studies are needed to clarify the specific features of post-partum depressive symptoms in this population.

Response to CYP2D6 substrate antidepressants is predicted by a CYP2D6 composite phenotype based on genotype and comedications with CYP2D6 inhibitors.

The cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of most antidepressants. Comedication with a potent CYP2D6 inhibitor can convert patients with extensive metabolizer (EM) or ultra-rapid metabolizer (UM) genotypes into poor metabolizer (PM) phenotypes. Since comedication is frequent in depressed patients treated with antidepressants, we investigated the effect of the CYP2D6 composite phenotype on antidepressant efficacy, taking into account both the CYP2D6 genotype and comedication with CYP2D6 inhibitors. 87 Caucasian in patients with a major depressive episode were prospectively treated with flexible doses of antidepressant monotherapy as well as comedications and genotyped for the major CYP2D6 alleles (CYP2D6*3 rs35742686, *4 rs3892097, *5 del, *6 rs5030655, and *2xN). They were classified for CYP2D6 composite phenotype and assessed for antidepressant response after 4 weeks. In terms of genotypes (g), 6 subjects were UMg, 6 PMg, and 75 EMg. Ten patients were coprescribed a CYP2D6 inhibitor, resulting in the following composite phenotypes (cp): 5 UMcp, 16 PMcp, and 66 EMcp. Whereas none of the CYP2D6 genotypes were significantly associated with antidepressant response, UMcp had a lower antidepressant response than PMcp or EMcp (respectively: 39.0 ± 17.9, 50.0 ± 26.0, and 61.6 ± 23.4, p = 0.02). Despite small sample size, this study suggests that a CYP2D6 composite phenotype, taking into account both genotype and comedications with CYP2D6 inhibitors, could predict CYP2D6 substrate antidepressants response. Thus, to optimize antidepressant response, CYP2D6 genotype could be performed and comedications with CYP2D6 inhibitors should be avoided, when prescribing CYP2D6 substrate antidepressants.