Prediction of Early Antidepressant Efficacy in Patients with Major Depressive Disorder Based on Multidimensional Features of rs-fMRI and P11 Gene DNA Methylation: Prédiction de l'efficacité précoce d'un antidépresseur chez des patients souffrant du trouble dépressif majeur d'après les caractéristiques multidimensionnelles de la méthylation de l'ADN du gène P11 et de la IRMf-rs.

OBJECTIVE: This study established a machine learning model based on the multidimensional data of resting-state functional activity of the brain and P11 gene DNA methylation to predict the early efficacy of antidepressant treatment in patients with major depressive disorder (MDD). METHODS: A total of 98 Han Chinese MDD were analysed in this study. Patients were divided into 51 responders and 47 nonresponders according to whether the Hamilton Depression Rating Scale-17 items (HAMD-17) reduction rate was ≥50% after 2 weeks of antidepressant treatment. At baseline, the Illumina HiSeq Platform was used to detect the methylation of 74 CpG sites of the P11 gene in peripheral blood samples. Resting-state functional magnetic resonance imaging (rs-fMRI) scan detected the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in 116 brain regions. The least absolute shrinkage and selection operator analysis method was used to perform feature reduction and feature selection. Four typical machine learning methods were used to establish support vector machine (SVM), random forest (RF), Naïve Bayes (NB), and logistic regression (LR) prediction models based on different combinations of functional activity of the brain, P11 gene DNA methylation and clinical/demographic features after screening. RESULTS: The SVM model based on ALFF, ReHo, FC, P11 methylation, and clinical/demographic features showed the best performance, with 95.92% predictive accuracy and 0.9967 area under the receiver operating characteristic curve, which was better than RF, NB, and LR models. CONCLUSION: The multidimensional data features combining rs-fMRI, DNA methylation, and clinical/demographic features can predict the early antidepressant efficacy in MDD.

A Randomized Evaluation of MoodFX, a Patient-Centred e-Health Tool to Support Outcome Measurement for Depression: Une évaluation randomisée de MoodFX, un outil de santé en ligne centré sur le patient pour soutenir la mesure du résultat dans la dépression.

BACKGROUND: e-Health tools using validated questionnaires to assess outcomes may facilitate measurement-based care for psychiatric disorders. MoodFX was created as a free online symptom tracker to support patients for outcome measurement in their depression treatment. We conducted a pilot randomized evaluation to examine its usability, and clinical utility. METHODS: Patients presenting with a major depressive episode (within a major depressive or bipolar disorder) were randomly assigned to receive either MoodFX or a health information website as the intervention and control condition, respectively, with follow-up assessment surveys conducted online at baseline, 8 weeks and 6 months. The primary usability outcomes included the percentage of patients with self-reported use of MoodFX 3 or more times during follow up (indicating minimally adequate usage) and usability measures based on the System Usability Scale (SUS). Secondary clinical outcomes included the Quick Inventory of Depressive Symptomatology, Self-Rated (QIDS-SR) and Patient Health Questionnaire (PHQ-9). RESULTS: Forty-nine participants were randomized (24 to MoodFX and 25 to the control condition). Of the 23 participants randomized to MoodFX who completed the user survey, 18 (78%) used MoodFX 3 or more times over the 6 months of the study. The mean SUS score of 72.7 (65th-69th percentile) represents good usability. Compared to the control group, the MoodFX group had significantly better improvement on QIDS-SR and PHQ-9 scores, with large effect sizes and higher response rates at 6 months. There were no differences between conditions on other secondary outcomes such as functioning and quality of life. CONCLUSION: MoodFX demonstrated good usability and was associated with reduction in depressive symptoms. This pilot study supports the use of digital tools in depression treatment.

E-health tools may be useful for measuring and tracking symptoms and other outcomes during treatment for depression. This study is a randomized evaluation of MoodFX, a free web-based app that helps patients track their symptoms using validated questionnaires, and also offers depression information and self-management tips. A total of 49 participants with clinical depression were randomized to using MoodFX or a health information website, for 6 months. In a survey, the participants that used MoodFX found it easy and useful to use. In addition, the participants that used MoodFX had greater improvement in depressive symptoms after 6 months, compared to those who used the health information website. These results suggest that MoodFX may be a useful tool to monitor outcomes and support depression treatment.

Management strategies for antidepressant-related sexual dysfunction.

Antidepressant-related sexual dysfunction is one of the most frequently met adverse effects for individuals suffering from major depressive disorder. When primary prevention by non-pharmacological measures fails, empirical coping strategies might be proposed. In this article, we present a brief overview of pharmacological strategies for antidepressant-related sexual dysfunction, considering antidepressants and conceivable corrective medications. We suggest dividing these strategies into three groups: (1) tapering (dose reduction, therapeutic window or short-term treatment interruption); (2) maintenance (focusing on spontaneous remission); (3) optimizing treatment (substitution for another antidepressant or addition of treatments to correct sexual side effects). Whichever strategy is selected, we encourage the clinician to propose the most adequate therapeutic option for the patient, while considering the efficacy and overall tolerance of the current antidepressant strategy, the affected phase of sexuality and patient preferences and gender. This summary is limited to antidepressant treatments and correctors marketed in France and aimed at a clinician reading to help manage patients suffering from antidepressant-induced sexual dysfunction.

[Premenstrual dysphoric disorder (PMDD): Drug and psychotherapeutique management, a literature review]. / Trouble dysphorique prémenstruel : prises en charge médicamenteuses et psychothérapeutiques, une revue de littérature.

INTRODUCTION: Premenstrual Dysphoric Disorder (PMDD) was first recognised in July 2013 in the DSM-5 after a long journey to identify its existence. It was not until 1983 that the US National Institute of Mental Health determined research criteria for the study of PMS. In 1994, the term "premenstrual dysphoric disorder" (PMDD) replaced this term in the 4th edition of the Diagnostic System Manual (DSM). It was listed in the section "Mood Disorder Not Otherwise Specified" and remained under consideration until the DSM-5, in which it appeared in the depressive disorders section. The legitimisation of the psychiatric diagnosis as well as the determination of clear symptomatology criteria in 2013 opened up possibilities for management, development of clinical, pathophysiological, therapeutic and psychotherapeutic studies. This disabling disorder can affect personal, social, family and professional life. In 2019, the ICD-11 in turn introduced the diagnosis of premenstrual dysphoric disorder, which solidifies the recognition of the disorder. OBJECTIVE: (I) to review the existing treatments, both medicinal and psychotherapeutic, and (II) to review their effectiveness. At the end of this work we will formulate recommendations for the management of these patients. METHODOLOGY: A bibliographic search was carried out from 7 June 2021 to 7 July2021 on the databases (bases de données) Psychinfo APA, Scopus, PubMed, as well as the bases de données of the Cochrane organisation and the recommendation documents of the Haute Autorité de la santé. After an initial selection based on keywords, the full text of all articles were read to arrive at the final selection of 32 articles. RESULTS: Antidepressants and Cognitive Behavioural Therapies (CBT) appear to be the most commonly recommended treatments for PMDD. Other research shows the effectiveness of oral contraceptives including drospirenone. Selective serotonin reuptake inhibitors (SSRIs) were identified as an effective treatment for PMDD. These data are consistent with the current etiological hypothesis of PMDD which has a negative impact of natural hormonal fluctuations on certain neurotransmitters. CBT showed positive results in reducing the functional impact of PMDD. DISCUSSION: Selective serotonin reuptake inhibitor (SSRI) antidepressants were reported to be first-line treatments for PMDD (sertraline 50-150 mg/d, fluoxetine 10-20 mg/d, escitalopram 10-20 mg/d, paroxetine 12.5-25 mg/d). Drospirenone (EE 3 mg and EE 20 mg/d 24 days of hormonal pills, 4 days inactive) appears to have been a first or second line treatment depending on the articles. Current results clearly point to the effectiveness of CBT in helping to reduce: functional impairment, depressed mood, feelings of hopelessness, anxiety, mood swings, sensitivity, irritability, insomnia, conflict with others, impact of premenstrual symptoms on daily life, intensity of symptoms experienced, and symptom handicap. CBTs could also become a first-line treatment if there were to be more evidence of their effectiveness. In the future, it would seem useful to offer a psychotherapeutic treatment that can be reproduced and to multiply research with a high level of scientific comparability in order to clarify the place of CBT in the management of PMDD. Research on the etiopathology of the disorder and the optimal drug regimen is still ongoing. There is a need to develop appropriate psychotherapeutic techniques to support and accompany these patients. CONCLUSION: In order to better evaluate treatments for PMDD, there is a need to homogenise studies on the subject at several levels: design, treatment doses, psychotherapeutic techniques, and evaluation measures. At present, some studies include both premenstrual syndrome (PMS) and PMDD patients. PMS and PMDD do not include the same symptoms, nor the same severity and potentially the same aetiology in the patients studied. In order to propose rigorous research that evaluates the effectiveness of treatments for PMDD and to properly support people with both these disorders, it seems essential to distinguish the two conditions. The role of the health practitioner is to be able to identify PMDD by differentiating it from other clinically related disorders. The patient must then be accompanied to make a choice of treatment adapted to her symptoms, their severity, her history, her plans for procreation, contraindications and her preferences. In 2021, the French National Authority for Health did not offer any guidelines or recommendations for the management of premenstrual dysphoric disorder. There is a need to develop research in France.

[Antidepressive agents and hypertension: A case/no-case study in French pharmacovigilance database]. / Antidépresseurs et hypertension artérielle : étude cas /non-cas dans la base nationale de pharmacovigilance.

INTRODUCTION: Drug-induced hypertension was described with several pharmacological classes. The association between hypertension and antidepressant drugs (AD) is controversial. The objective of this study was to evaluate the link between hypertension and ADs. MATERIALS AND METHODS: A retrospective disproportionality analysis from observations consecutively reported to the French pharmacovigilance database between 1985 and 2020 was performed. The relationship between the suspected ADs and the occurrence of hypertension was assessed by calculating the reporting odds ratio (ROR) in a case/non-case design. A negative (paracetamol) and a positive (celecoxib) control were used to validated this disproportionality method. RESULTS: We compared 6725 cases (including 464 AD-related cases) to 789,483 non-cases (including 56,440 AD-related cases). The reporting of hypertension was significantly associated with serotonin/norepinephrine reuptake inhibitors (SNRI) (ROR 1.43, 95 % CI 1.26-1.64) and monoamine oxidase inhibitors (MAOI) (ROR 6.41, 95 % CI 4.25-9.67) but not with other ADs classes. Concerning ADs analyzed independently of their AD class, a significant signal was observed with many SNRIs (duloxetin, milnacipran and venlafaxin) and with all MAOIs (moclobemide, iproniazide) (ROR between 2.04 and 17.93) but not with others ADs. The ROR value of positive (celecoxib) and negative (paracetamol) controls were ROR=1.53; IC95 %=1.04-2.26 and ROR=0.72; IC95 %=0.65-0.80, respectively. CONCLUSION: We found a significant association between development or worsening of hypertension and SNRIs and MAOIs but not with others ADs, in this study performed in real conditions of life. It is therefore advisable to remain cautious when prescribing ADs and to check systematically for hypertension.

[Use of antidepressants in unipolar depression in the elderly]. / L'utilisation des antidépresseurs dans l'épisode dépressif caractérisé unipolaire du sujet âgé.

OBJECTIVE: To study the ageing-related pharmacological modifications about major depressive episodes in the elderly and their impact on the efficiency and tolerability of antidepressants. METHODS: Research through Pubmed and the Cochrane Database of Systematic Reviews, using the following keywords "antidepressant" ; "treatment"; "late life depression"; "elderly"; up until July 2021. RESULTS: Antidepressants were found to be more efficient than a placebo in the elderly's response to and remission from major depressive episodes. Some depressive episode subtypes seem to be less responsive to antidepressants, such as depressive episodes of vascular origin, for which treating cardiovascular risk factors by statins, angiotensin receptor blockers or calcium channel blockers seems relevant. Two other depressive episode subtypes were highlighted : post-stroke depressive episodes and those induced by major neurocognitive disorders. Antidepressants showed an efficient response in the first case but not in the second. Even though antidepressants are known to stimulate cognitive performances in animals, as yet there is not sufficient evidence to prove they indeed improve cognitive functions, or reduce the risk of developing a neurocognitive disorder, or decelerate the cognitive decline in major neurocognitive disorders in humans. Ageing creates pharmacodynamical changes that increase older people's vulnerability to the side effects of antidepressants. Moreover, age-related pharmacokinetic modifications can also change every step in a drug's transformation process in the body, which leads to a high probability of having adverse effects. Since most antidepressants are eliminated using the P450 cytochrome system, their dosage must be adapted to changes of the P450 system. Somatic comorbidities can, in themselves, influence the pharmacokinetics of antidepressants. Many antidepressants interact with the P450 cytochrome and the P-GP protein, which puts them at a high risk of drug interactions. There is no proven efficiency difference between antidepressant classes. Some antidepressant adverse effects can be of particular importance in the elderly, like the risk of bleeding, cardiovascular episodes, hyponatremia, falling and fractures, anticholinergic effects, extrapyramidal syndrome, epilepsy, liver disease and death. Selective serotonin reuptake inhibitors have an indication as the first line of treatment, avoiding paroxetine and fluoxetine. Serotonin and norepinephrine re-uptake inhibitors are relevant if the patient presents psychomotor retardation or pain, while keeping in mind to check blood pressure. Tricyclics and monoamine oxidase inhibitors should be avoided because of their anticholinergic effects. Bupropion can be prescribed if the patient has extreme fatigue. Mirtazapine is useful when the patient presents sleep or appetite disturbance. Several molecules can be used in the case of drug-resistant depression, such as associating aripiprazole with small-dosage antidepressants, or electroconvulsive therapy, or repetitive Transcranial Magnetic Stimulation (rTMS). Ketamine and psychostimulants seem to have antidepressant effects, but complementary studies are needed to conclude. CONCLUSIONS: Unipolar major depressive episodes in the elderly are frequent and their medicinal treatment has specific features. Knowing the specificities of antidepressant use in the elderly allows to optimize its efficiency and to limit the risk of inappropriate prescription leading to harmful adverse effects.

Evolution of sexual functioning of men through treated and untreated depression.

OBJECTIVES: Depression as well as a treatment by antidepressant are factors that may interfere with sexuality. Due to this complex relationship between depression, antidepressant and sexuality, it is difficult to incontestably establish the exclusive accountability of a treatment or of a psychiatric disorder on sexual dysfunctions. The main purpose of the SADD (for Sexuality, Anti-Depressant and Depression) study is to evaluate sexual dysfunctions in depressed men treated with antidepressant or not. METHODS: Participants of this transversal, observational study were men aged over 18 years old, suffering from unipolar major depressive disorder and treated by a psychiatrist, with or without antidepressant. Assessment of sexual functioning through three times: euthymia (before depression), untreated depression and treated depression if applicable was performed based on the ASEX scale. RESULTS: Seventy patients were included. Eight percent of euthymic patients presented a sexual dysfunction (average score on the ASEX=12.4) whereas 56% of untreated patients presented a sexual dysfunction (average total score on the ASEX=17.7) and 62% (34/55) of patients treated with antidepressant (average total score on ASEX=18.5) (P<0.001). Sexual functioning of men receiving treatment is not significantly different to that among men not receiving any antidepressant, even if patients treated with antidepressant reported that they had a better mood than those untreated. CONCLUSIONS: Our results reveal a high prevalence of sexual dysfunction within the framework of major depressive disorder and its treatment and underlines the complex relationship between major depressive disorder, antidepressant and sexuality.

[Antidepressive agents and hyponatremia: A literature review and a case/non-case study in the French Pharmacovigilance database]. / Antidépresseurs et hyponatrémie : revue de littérature et analyse cas/non-cas dans la base nationale de pharmacovigilance française.

OBJECTIVE: Most antidepressants have been associated with a risk of hyponatremia in the literature. This effect is not always reported in monographs. The aim of our study was to clarify the difference of increased risk of hyponatremia among various antidepressants. METHODS: Retrospective study of such cases/non-cases from observations recorded in the French national pharmacovigilance between 01/01/2004 and 31/12/2013. We studied all antidepressants marketed in 2014 in France, with a positive control (haloperidol) and a negative one (amoxicillin). The association between exposure to a given drug and the occurrence of an adverse event was estimated by calculating the reporting odds ratio (ROR). His confidence interval (CI) was calculated with the method of Woolf, with an alpha risk of 5%. The disproportionality is defined by an ROR>1, the 95% CI did not include the value 1. RESULTS: Between 2004 and 2013, 3397 cases of hyponatremia were. All antidepressants were associated with hyponatremia among these cases, with the exception of: milnacipran, amoxapine, dosulepine, doxepine, trimipramine, iproniazide. The effect was predominant for the class of selective inhibitors of serotonin reuptake (SSRIs), inhibitors of serotonin reuptake and noradrenaline (SNRIs) and other antidepressants; it seemed more doubtful for tricyclic and monoamine oxidase inhibitors (MAOIs). Contrary to the literature, we found an association between hyponatremia and exposure to agomelatine (ROR=4.1, 95% CI [2.2 to 7.7]), mianserine (ROR=2.7, 95% CI [2.0 to 3.7]) and tianeptine (ROR=6.1, 95% CI [4.7 to 7.9]). CONCLUSION: This study suggests to stay alert to electrolyte disorders when using all antidepressants, not only serotonin reuptake inhibitors.

[Switching and stopping antidepressants]. / Recommandations pour switcher et arrêter les antidépresseurs.

Major depressive disorder (MDD) is a common, typically recurrent, sometimes chronic and very disabling disorder, with a lifetime prevalence of 20%. Moreover, antidepressant treatments may be partially effective. Studies have found that up to 60% of patients with MDD do not fully respond to the first antidepressant prescribed. Thus, switching antidepressants is a common strategy for antidepressant non-responders. When switching between antidepressants, an appropriate switching strategy should be used, depending on the characteristics of the first and the second antidepressant and patient's background. Patients should be informed that antidepressants can cause discontinuation symptoms if stopped abruptly after prolonged used. Relapse and exacerbation of depression can also occur during a switch. Thus, all antidepressant switches must be carried out cautiously and under close observation. This article summarizes the recommendations for an optimal antidepressant switch.

[What place for placebo in clinical trials conducted on psychiatric patients?] / Quelle place pour le placebo dans les essais cliniques en psychiatrie ?

Placebo effect remains a crucial issue in current clinical trials. Most clinical trials rely on the hypothesis of equivalent placebo response rates in both placebo and specific drug arms ("additive model"). But contrary to this dominant and rarely questioned hypothesis, several aspects may influence placebo response. A few recent meta-analyses and reviews have shown evidence for several clinical and methodological factors, which are able to modulate placebo response. In psychiatry research, placebo response has been mainly explored through antidepressant trials. In early clinical trials, drug-placebo differences were initially significant and robust. However, more recent clinical trials have not yielded similar results, and rather show narrowed antidepressant-placebo differences. Several factors may be involved in this absence of comparability: intrinsic properties of new antidepressants, changes in clinical criteria and classifications, symptomatic remission rather than global remission criteria, industrial and institutional constraints. Moreover, results from antidepressant trials (laboratory conditions) remain hardly fully transposable to clinical routine (ecological conditions).

[Gap junctions: A new therapeutic target in major depressive disorder?]. / Les jonctions gap: une nouvelle cible thérapeutique pour le traitement des troubles dépressifs majeurs?

Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder.

[Use of antidepressants in the treatment of negative symptoms of schizophrenia]. / Utilisation des antidépresseurs dans le traitement des symptômes négatifs de la schizophrénie.

Negative symptoms account for a clinical dimension of schizophrenia. They are partly the cause of functional disability of this disease. Clinical experience shows that antipsychotics have little or no effect on these symptoms. The aim of this review is to gather existing data on the treatment of negative symptoms with antidepressants. The combination of antipsychotics with antidepressants is a therapeutic strategy commonly used for the treatment of these symptoms. The pro-dopaminergic effects of antidepressants explain their effectiveness on negative symptoms. There are many comparative, randomized, controlled studies evaluating the efficacy of antidepressant associated with antipsychotic for the treatment of negative symptoms. Furthermore three meta-analyses have been conducted. The overall results suggest that the use of antidepressants may contribute to clinical improvement of negative symptoms in schizophrenia. The limitations of these studies are the small number of patients included and the definition and assessment of negative symptoms. The existing scales are not sufficiently discriminating. Further research using new measurement tools should help refine these results.

[Treatment-resistant anxiety disorders: A literature review of drug therapy strategies]. / Troubles anxieux résistants : revue des stratégies de traitements médicamenteux.

Anxiety disorders are widespread psychiatric conditions with significant social and professional disability, poor quality of life, an increased risk of suicide, and frequent attendance of medical services. Serotonin reuptake inhibitors (SRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) have demonstrated a rather robust efficacy for the treatment of most of anxiety disorders. Nevertheless a substantial number of patients are resistant or still suffer from residual symptoms despite this first line treatment. The objective of our paper is to review relevant studies for the pharmacologic management of anxiety disorders resistant to the first line treatment. For this purpose, we conducted a pubmed/medline search for double-blind placebo-controlled trials of treatment-resistant anxiety disorders. An adequate trial for a SRI in the treatment of obsessive-compulsive disorder (OCD) should continue for at least 12 weeks. Special considerations of the comorbidities and symptom profile could help in the choice of an appropriate pharmacotherapy. Several trials have highlighted the efficacy of antipsychotics as an add-on to SRI in treatment-resistant OCD such as haloperidol more so when comorbid with a tic disorder, or risperidone that can reduce OCD as well as depressive symptoms. Aripiprazole has been shown efficacious in two placebo-controlled double-blind trials, while the efficacy of quetiapine and olanzapine remains controversial. Other trials showed some efficacy of anticonvulsants (lamotrigine, topiramate), pindolol, memantin and N-acetylcystein as an adjunctive treatment to SRI for resistant OCD. Few trials have investigated selective serotonin reuptake inhibitors (SSRI) or SNRI resistant generalized anxiety disorder showing a failure of adjunctive therapy with olanzapine, quetiapine, ziprasidone and risperidone. These studies were underpowered and very limited in number. Adjunctive risperidone for resistant post-traumatic stress disorder (PTSD) showed benefit in some but not all trials. Olanzapine was beneficial for the reduction of the CAPS score in addition to the improvement of sleep disturbances. Furthermore, prazosin was efficacious by reducing PTSD symptoms, sleep disturbances, nightmares, and psychological distress. One double-blind placebo-controlled study was conducted to investigate treatment-resistant social phobia showing no benefit of pindolol add-on paroxetine. Our results demonstrate that the pharmacological management of treatment-resistant anxiety disorders is not sufficiently investigated in double-blind placebo-controlled trials, despite a growing evidence in favor of antipsychotics and some other pharmacological agents in resistant OCD and, to a lesser extent, PTSD. Hence, there is a crucial need for larger double-blind placebo-controlled trials for resistant anxiety disorders. Finally, being out of the scope of our review, we omitted studies of non-pharmacologic therapies.

[Treatment of depressive mixed states]. / Le traitement des dépressions mixtes.

Mixed states are a frequent mood state characterized by the mixture of manic and depressive symptoms. Their clinical description has been studied for centuries but has known a renewal of interest recently. Several authors intend to redefine its diagnostic criteria to develop an appropriate therapeutic strategy. Current recommendations suggest to treat mixed depression as a mixed state whatever the dominant polarity is, and therefore according to the rules of therapeutic management of the manic state. Mood stabilizers and antipsychotic medications are indicated and have proven their effectiveness. Lithium, which was considered controversial, now appears to have some therapeutic value, especially in the prevention of suicidal behavior. The depressive component of mixed states, even pronounced, should not be an argument for a prescription of antidepressants, at the risk of aggravating clinical components such as irritability and impulsivity and increasing the danger of suicide attempt. Furthermore, electroconvulsivetherapy represents a real alternative ; psychotherapies have their place in relapse prevention and psychoeducation, but not during acute phases. Finally, an accurate assessment and appropriate management of suicide risk should be a constant concern for the clinicians.

[Sexual side effects of pharmacological treatments]. / La iatrogénie médicamenteuse en médecine sexuelle.

INTRODUCTION: Sexual side effects of pharmacologiocal agents are not well known. METHODS: Medical literature was reviewed and combined with expert opinion of the authors. RESULTS: Confirmation of a drug iatrogenesis is made by intrinsic imputability based on the clinical history and extrinsic imputability based on published references. First ranking in the list of drugs responsible for adverse sexual effects in both sexes are the selective reuptake inhibitors (SSRI). They can cause erectile dysfunction and ejaculatory disorders, and in both sexes orgasmic and arousal disorders. Among the drugs whose mechanism is primordial are the neuroleptics firstly, among antalgics tramadol and strong opioid agonists are also potentially deleterious to different degrees on sexual function. Among antihypertensive drugs only thiazide diuretics increase the risk of erectile dysfunction. Among alpha blockers tamusolin and silodosin are frequently responsible for anejaculation. On a less serious level, 5α-reductase inhibitors are associated with sexual disorders in men treated for lower urinary tract symptoms (LUTS) linked to symptomatic benign prostatic hypertrophy. LH-RH antagonists and anti-androgens suppress desire in men, tamoxifen reduces this in women and can also cause dyspareunia and vaginal dryness. The drugs responsible for iatrogenic priapism are also described. A correlation between the pathology treated and the responsibility of the drug for sexual dysfunction can coexist. This is the case for depression, psychosis, hypertension, chronic pain and LUTS; sexual dysfunction is part of the clinical picture. CONCLUSION: Sexual side effects of pharmacological treatments are not unusual and must be systematically surveyed in men and women complaining about sexual dysfunction.

Factors Associated With Initiation of Antidepressant Medication in Adults With Type 1 and Type 2 Diabetes: A Primary Care Retrospective Cohort Study in Ontario, Canada.

OBJECTIVES: Depression in patients with diabetes mellitus is common and associated with poorer outcomes. This study aims to identify demographic, socioeconomic and medical factors associated with the initiation of antidepressant medication after a diagnosis of diabetes in adult patients without a previous prescription for antidepressants. We also examined frequency of primary care visits in the year after antidepressant initiation compared with the year before treatment began. METHODS: This was a retrospective cohort study using routinely collected electronic medical record data spanning January 2011 to December 2019 from the University of Toronto Practice-based Research Network (UTOPIAN) Data Safe Haven. Our primary outcome was a first prescription for an antidepressant in patients with diabetes. We used a mixed-effects logistic regression model to identify sociodemographic and medical factors associated with this event. RESULTS: Among 22,750 patients with diabetes mellitus, 3,055 patients (13.4%) began taking an antidepressant medication. Increased odds of antidepressant initiation were observed in younger patients (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.39 to 2.26), females (OR, 1.60; 95% CI, 1.46 to 1.7), those receiving insulin treatment (OR, 1.59; 95% CI, 1.43 to 1.78) and cases of polypharmacy (OR, 3.67; 95% CI, 3.29 to 4.11). There was an increase in the mean number of primary care visits from 4.6 to 5.9 per year after antidepressant initiation. CONCLUSIONS: In patients with diabetes, age, sex and medical characteristics were associated with the initiation of antidepressants. These patients accessed primary care more frequently. Screening and prevention of depression, particularly in these subgroups, could reduce its personal and systemic burdens.

Association Between Antidepressant Use and Adherence to Anti-hyperglycemic Medications in Adults With Type 2 Diabetes and Depression: A Retrospective Cohort Study.

OBJECTIVES: Depression is a known risk factor for poor medication adherence, but it is unclear whether depression treatment affects adherence rates. In this study, we examined the association between pharmacologic treatment of a new depressive episode and subsequent adherence to oral anti-hyperglycemic medications. METHODS: In this retrospective cohort study we used administrative health data to follow adult new metformin users in Alberta, Canada, between 2008 and 2018. Depressive episodes starting ≥1 year after metformin initiation were identified and individuals starting antidepressant treatment within the first 90 days were compared with those who did not. The proportion of days covered (PDC) with oral anti-hyperglycemic medications in the subsequent year (days 91 to 455) was used to estimate adherence. The association between antidepressant treatment and poor adherence (PDC<0.8) was examined using multivariate logistic regression models. RESULTS: A new depressive episode occurred in 6,201 people, with a mean age of 56.0 (standard deviation [SD], 15.4) years. Of this cohort, 3,303 (53.2%) were women. Mean PDC was 0.55 (SD, 0.41); 924 (57.0%) of 1,621 people who started antidepressant treatment and 2,709 (59.2%) of 4,580 controls had poor adherence (p=0.13). After adjusting for baseline comorbidities and other characteristics, antidepressant treatment was associated with a lower likelihood of poor adherence (adjusted odds ratio, 0.85; 95% confidence interval, 0.75 to 0.96; p=0.007). CONCLUSIONS: Although overall adherence to anti-hyperglycemic medications was low after onset of a depressive episode, antidepressant treatment was associated with a lower likelihood of poor adherence.

[Therapeutic drug monitoring of antidepressants: Why venlafaxine is the most monitored drug? A review of literature]. / Suivi thérapeutique pharmacologique des antidépresseurs : pourquoi la venlafaxine est le médicament le plus surveillé ? Une revue de la littérature.

Venlafaxine is the third most frequently prescribed antidepressant in France the last decade, with about 400,000 daily doses. Therapeutic drug monitoring (TDM) of this medication, by measuring the active moiety venlafaxine (V) and O-desmethylvenlafaxine (ODV), is recommended (level of recommendation 2). However, this antidepressant seems to be the one for which clinicians most often use TDM, much more frequently than escitalopram, which is more prescribed and for which TDM is also recommended. The main goal of this review is to provide an update on the TDM of venlafaxine: its therapeutic interval, its level of recommendation and the origin of its "success". From the literature does not enable to define a therapeutic interval for the active moiety V+ODV, that is to say a steady-state trough concentration allowing a clinical response without toxicity. Nevertheless, a target concentration from 100 to 400µg/L is certainly relevant for the majority of patients without any pharmacodynamic resistance ; though a greater concentration could result in an earlier response or could be required for a clinical response in a minority of patients. A patient with no clinical response despite a concentration greater than 1000µg/L should be proposed another antidepressant. Measurement of the ODV/V ratio is also a useful tool, values below 0.3 usually reflecting a slow metabolizer phenotype for cytochrome P-450 2D6, which is more at risk of adverse effects. Research for this phenotype probably explains many prescriptions for TDM.

[Changes in blood pressure after introduction of an antidepressant in a public institution of mental health]. / Évolution de la pression artérielle après introduction d'un antidépresseur en établissement public de santé mentale.

INTRODUCTION: Primary prescribing of antidepressants is common in general practice. The relationship between antidepressant introduction and blood pressure (BP) changes is not well established in the literature. The purpose of our study was to examine the short-term course of AHR with and without the introduction of an antidepressant into a public institution of mental health (EPSM). MATERIALS AND METHODS: An exposed/non-exposed single-centre analytical epidemiological study on a retrospective cohort, with a collection of data on stays between 2013 and 2015 at the EPSM in Armentières. The stays were divided into two groups: antidepressant treatment (introduced during the stay) and control (without antidepressant). BP measurements were taken over a 30-day period per stay. To assess the evolution of AHR across groups, we used a nested mixed linear regression model with multivariate adjustment. RESULTS: Out of 1241 stays analysed, 124 were in the treated group and 1117 in the control group. The average age was 44.6±14.7 years. The two groups were comparable on most of the variables analyzed. The change in systolic BP was associated with systolic BP values at baseline, history of hypertension, presence of an antihypertensive drug and BMI; the change in diastolic BP was associated with diastolic BP values at baseline, presence of an antihypertensive drug, BMI and history of bipolar disorder. We find no significant difference in the evolution of BP over time between the treated group and the control group over the 30 days of measurement per stay, after adjustment (evolution coefficient of +0.12mmHg systolic BP and -0.1mmHg diastolic BP, P=0.45 and 0.38 respectively). CONCLUSION: These results are reassuring on the early development of BP after the introduction of antidepressants. They should not overlook the frequent effects of depression and antidepressants on cardiovascular risk (decreased physical activity, dyslipidemia, weight gain, etc.).