Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients.

OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. METHODS: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. CONCLUSION: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN) guidelines for the management of patients with partially responsive depression and treatment-resistant depression: Update 2024.

INTRODUCTION: The purpose of this update is to add newly approved nomenclatures and treatments as well as treatments yet to be approved in major depressive disorder, thus expanding the discussions on the integration of resistance factors into the clinical approach. METHODS: Unlike the first consensus guidelines based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) developed an update of these guidelines for the management of partially responsive depression (PRD) and treatment-resistant depression (TRD). The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for PRD and TRD. RESULTS: The recommendations addressed three areas judged as essential for updating the previous 2019 AFPBN guidelines for the management of patients with TRD: (1) the identification of risk factors associated with TRD, (2) the therapeutic management of patients with PRD and TRD, and (3) the indications, the modalities of use and the monitoring of recent glutamate receptor modulating agents (esketamine and ketamine). CONCLUSION: These consensus-based guidelines make it possible to build bridges between the available empirical literature and clinical practice, with a highlight on the 'real world' of the clinical practice, supported by a pragmatic approach centred on the experience of specialised prescribers in TRD.

Rural-urban variation in incidence of psychosis in France: a prospective epidemiologic study in two contrasted catchment areas.

BACKGROUND: The aim of our study is to provide data on the incidence of psychotic disorders in France and compare the incidence rates in populations with different levels of urbanization. METHODS: We prospectively included the incident cases of psychotic disorders from two catchment areas with contrasted levels of urbanization. In the more rural area, we also calculated incidence rates in three different groups of population defined by the size of towns in which they live (small, medium and large towns). RESULTS: The annual incidence of psychosis was greater in the urban area (36.02/100000 person-year at risk) than in the rural area (17.2/100000 person-year at risk).Non-affective psychoses were the majority of cases and their incidence was greater in males and younger subjects. The affective psychoses were slightly more frequent in women and showed less variation with age. In the rural centre, greater levels of urbanicity were associated with an increase in the incidence of all psychoses (affective and non-affective). CONCLUSIONS: Our study confirms previous observations of increased incidence rates for non-affective psychoses in the more urbanized areas and suggests that a similar pattern might be present for affective psychoses.

What is the evidence for the use of second-generation antipsychotic long-acting injectables as maintenance treatment in bipolar disorder?

BACKGROUND: In recent years, the use of second-generation antipsychotics long-acting injectable in the maintenance treatment of bipolar disorder has sparked interest in improving adherence and reducing the risk of relapse. AIMS: This report aims to review the available evidence concerning the use of second-generation antipsychotics depot in bipolar disorder and specify the typology of patients that could be eligible for this formulation. METHODS: A systematic review of the literature was conducted using Pubmed and EMBASE. RESULTS: Data available for the clinician assessing the interests of second-generation antipsychotics depot in long-term treatment of bipolar disorder are limited to risperidone. It seems particularly relevant for bipolar patients with poor adherence or early in the course of illness and can be used as monotherapy with manic polarity. It should always be considered for use in combination with at least one other mood stabilizer in patients with depressive polarity. As for other medications, the benefit/risk ratio for a long-acting should be evaluated individually. CONCLUSIONS: If using a depot formulation could be considered for all patients in order to approach a perfect compliance, patients with certain clinical profiles could be an argument for prioritizing the use of long-acting injectable as maintenance treatment. Additional studies are needed with other second-generation antipsychotics depot in bipolar patients to generalize their use in the maintenance treatment of bipolar disorder but the future golden standard of studies with long-acting formulations remains to be defined.

Prospective Acceptability of Digital Therapy for Major Depressive Disorder in France: Multicentric Real-Life Study.

BACKGROUND: Major depressive disorder is one of the leading causes of disability worldwide. Although most international guidelines recommend psychological and psychosocial interventions as first-line treatment for mild to moderate depression, access remains limited in France due to the limited availability of trained clinicians, high costs for patients in the context of nonreimbursement, and the fear of stigmatization. Therefore, online blended psychological treatment such as Deprexis could improve access to care for people with depression. It has several advantages, such as easy accessibility and scalability, and it is supported by evidence. OBJECTIVE: This study aims to evaluate the real-life acceptability of Deprexis for people with depression in France outside of a reimbursement pathway. METHODS: Deprexis Acceptability Study Measure in Real Life (DARE) was designed as a multicenter cross-sectional study in which Deprexis was offered to any patient meeting the inclusion criteria during the fixed inclusion period (June 2022-March 2023). Inclusion criteria were (1) depression, (2) age between 18 and 65 years, (3) sufficient French language skills, and (4) access to the internet with a device to connect to the Deprexis platform. Exclusion criteria were previous or current diagnoses of bipolar disorder, psychotic symptoms, and suicidal thoughts during the current episode. The primary objective was to measure the prospective acceptability of Deprexis, a new digital therapy. Secondary objectives were to examine differences in acceptability according to patient and clinician characteristics and to identify reasons for refusal. All investigators received video-based training on Deprexis before enrollment to ensure that they all had the same level of information and understanding of the program. RESULTS: A total of 245 patients were eligible (n=159, 64.9% were women and n=138, 56.3% were single). The mean age was 40.7 (SD 14.1) years. A total of 78% (n=191) of the patients had moderate to severe depression (according to the Patient Health Questionnaire-9 [PHQ-9]). More than half of the population had another psychiatric comorbidity (excluding bipolar disorder, psychotic disorders, and suicidal ideation). A total of 33.9% (n=83) of patients accepted the idea of using Deprexis; the main reason for refusal was financial at 83.3% (n=135). Multivariate logistic regression identified factors that might favor the acceptability of Deprexis. Among these, being a couple, being treated with an antidepressant, or having a low severity level favored the acceptance of Deprexis. CONCLUSIONS: DARE is the first French study aiming at evaluating the prospective acceptability of digital therapy in the treatment of depression. The main reason for the refusal of Deprexis was financial. DARE will allow better identification of factors influencing acceptability in a natural setting. This study highlights the importance of investigating factors that may be associated with the acceptability of digital interventions, such as marital status, medication use, and severity of depression.

Clinicians' attitudes toward the use of long-acting injectable antipsychotics.

Depot formulations are not widely used in everyday practice. This study aimed to assess psychiatrists' attitudes toward the use of long-acting injectable (LAI) antipsychotics in schizophrenia. We interviewed 113 French psychiatrists about the factors that influenced their prescription of LAI antipsychotics. Multidimensional and cluster analyses were used to detect correlations. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk for extrapyramidal symptoms; and for second-generation LAI, it is the unavailability of the equivalent oral formulation. Four factors incite the psychiatrists to prescribe LAI. Two different clusters of patients can also be identified. Most factors influencing the clinicians' attitudes toward the use of LAI antipsychotics are shared in many countries. Conversely, some attitudes related to organizational aspects, particularly the relevance of health care costs, may vary from one country to another.

[Mixed states]. / États mixtes.

The issue of mixed states has an important place in the debate on psychiatric nosography since the end of 19th century. The current definition of mixed states according to the DSM- IV, as a thymic episode of bipolar disorder type I, is probably somewhat too restrictive in clinical practice. Due to the clinical heterogeneity of bipolar disorder, the mixed states will define within a dimensional approach, likely in the next DSM- V. As the evolution, the prognosis or the therapeutic strategies differ from what is applied in other thymic episodes, this transition from "mixed state" to manic or depressive episodes "with mixed features" may be relevant in practice.

Repetitive Transcranial Magnetic Stimulation (rTMS) as a Promising Treatment for Craving in Stimulant Drugs and Behavioral Addiction: A Meta-Analysis.

Addiction is a mental disorder with limited available treatment options. The therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) on it, by targeting craving in particular, has been explored with heterogenous results. This meta-analysis uses updated evidence to assess overall rTMS efficacy on craving, differential effects between addiction types clustered into three groups (depressant (alcohol, cannabis, opiate), stimulant (nicotine, cocaine, methamphetamine), and behavioral addiction (gambling, eating disorder)), and stimulation settings. Studies on substance use, gambling, and eating disorders are included, with unrestricted stimulation settings, by searching the PubMed, Embase, PsycINFO, and Cochrane databases up to 30 April 2020. A total of 34 eligible studies (42 units of analysis) were identified. Because of highly significant heterogeneity in primary results, a sensitivity analysis was performed on a remaining sample of 26 studies (30 units of analysis). Analyses performed using random effects model revealed a small effect size favoring active rTMS over shamTMS stimulation in the reduction in craving. We found a significant difference between addiction types, with a persistent small effect only for stimulant and behavioral groups. In these groups we found no difference between the different combinations of target and frequency of stimulation, but a significant correlation between number of sessions and craving reduction. In conclusion, efficacy of rTMS on craving in stimulant and behavioral addiction was highlighted, but recommendations on optimal stimulation settings and its clinical application await further research.

[Disulfiram and addiction: reminders and new perspectives of use]. / Le disulfirame (Esperal(®)) dans le traitement des addictions : rappels et nouvelles perspectives d'utilisation.

Disulfiram is a relatively old molecule, which today remains marginal in the treatment of alcoholics diseases. Using this type of treatment is the subject of ethical debate. The prescription of this therapeutic requires clinical and biological rigorous evaluations before treatment. Its main action in treatment of alcoholism is related to the restraint of acetaldehyde dehydrogenase action causing the antabuse reaction. Prescription of disulfiram, supported by specialized programs of compartmental integrated care, brings significant benefit for alcoholic patients. Recently, following the discovery of its action on dopamine metabolism, disulfiram has been a renewed interest in the treatment of addictions to cocaine and pathological gambling. Although current data are insufficient to generalize its use in routine practice, they constitute a line of research interest for the future.

Pharmacotherapeutic approaches to treating depression during the perimenopause.

Introduction: Although postnatal depression is now well recognized, there is also a risk of depressive symptoms during perimenopause. The mechanisms underlying perimenopausal depression are still poorly understood; however, there are available treatment options. Areas covered: This review describes: the current pharmacotherapeutic approaches for perimenopausal depression, their strengths and weakness, and provides recommendations on how current treatment can be improved in the future. An electronic search identified specific guidelines for the treatment of perimenopausal depression released in 2018, as well as recent clinical studies on the subject. Expert opinion: The 2018 guidelines recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) as front-line medications for perimenopausal depression, but SSRIs and SNRIs are not always effective. The efficacy of estrogen in perimenopausal depression is well documented, but estrogen is not FDA-approved to treat mood disturbances in perimenopausal women. Clinical practice guidelines currently recommend to restrict hormone therapy to the symptomatic treatment of menopause (not for the prevention of chronic diseases). Research with new estrogenic compounds is under way to improve their benefit/risk ratio in perimenopausal depression.

Investigational drugs in recent clinical trials for treatment-resistant depression.

INTRODUCTION: The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and USA and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week. This observation was a turning point that opened the way for other, more selective glutamatergic modulators (intranasal esketamine, AVP-786, AVP-923, AV-101, and rapastinel). Of the remaining compounds, monoclonal antibodies open highly innovative therapeutic options, based on new pathophysiological approaches to depression. Expert commentary: Promising new agents are emerging for TRD treatment. Glutamatergic modulators likely represent a very promising alternative to monoaminergic antidepressant monotherapy. We could see the arrival of the first robust and rapid acting antidepressant drug in the near future, which would strongly facilitate the ultimate goal of recovery in persons with TRD.

[Other therapeutic strategies]. / Dépression résistante : les autres stratégies thérapeutiques.

Non-selective and irreversible MAOI have become as third or fourth-line strategy for the management of treatment-resistant depression. Non-selective and irreversible MAOI requires careful monitoring of drug interactions and dietary restrictions. Nutritional supplements such as omega-3 have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment. The glutamate antagonist ketamine has been found to produce beneficial effects in the management of treatment-resistant depression while administered alone. Dopamine and/or norepinephrine agonists, such as methylphenidate, modafinil or pramipexole, have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment.

[Switching and combining strategies of antidepressant medications]. / Dépression résistante : les stratégies de changement et d'association de médicaments antidépresseurs.

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.

[Potentiation strategies]. / Dépression résistante : les stratégies de potentialisation.

Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 µUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.

[How to define treatment-resistant depression?]. / Quelle définition pour la dépression résistante ?

The most largely used definition of the treatment-resistant depression relies on the failure of two successive trials of antidepressant treatment at an adequate dose and duration. The absence of response to previous antidepressant treatments should be assessed using specific and appropriate clinical instruments enabling a correct staging of the therapeutic resistance. A wide range of socio-demographic and clinical factors (i.e. psychiatric/somatic comorbidities) are classically associated with the therapeutic resistance. The aim of the treatment of major depression is to achieve a complete clinical remission. The presence of residual symptoms increases the risk for the subsequent occurrence of relapses and recurrences, hence facilitating the development of therapeutic resistance. The treatment-resistant depression has a deleterious impact on the social, familial or professional functioning, thereby leading to an impaired quality of life with serious socioeconomic consequences and costs.

Reducing Delusional Conviction through a Cognitive-Based Group Training Game: A Multicentre Randomized Controlled Trial.

OBJECTIVE: "Michael's game" (MG) is a card game targeting the ability to generate alternative hypotheses to explain a given experience. The main objective was to evaluate the effect of MG on delusional conviction as measured by the primary study outcome: the change in scores on the conviction subscale of the Peters delusions inventory (PDI-21). Other variables of interest were the change in scores on the distress and preoccupation subscales of the PDI-21, the brief psychiatric rating scale, the Beck cognitive insight scale, and belief flexibility assessed with the Maudsley assessment of delusions schedule (MADS). METHODS: We performed a parallel, assessor-blinded, randomized controlled superiority trial comparing treatment as usual plus participation in MG with treatment as usual plus being on a waiting list (TAU) in a sample of adult outpatients with psychotic disorders and persistent positive psychotic symptoms at inclusion. RESULTS: The 172 participants were randomized, with 86 included in each study arm. Assessments were performed at inclusion (T1: baseline), at 3 months (T2: post-treatment), and at 6 months after the second assessment (T3: follow-up). At T2, a positive treatment effect was observed on the primary outcome, the PDI-21 conviction subscale (p = 0.005). At T3, a sustained effect was observed for the conviction subscale (p = 0.002). Further effects were also observed at T3 on the PDI-21 distress (p = 0.002) and preoccupation subscales (p = 0.001), as well as on one of the MADS measures of belief flexibility ("anything against the belief") (p = 0.001). CONCLUSION: The study demonstrated some significant beneficial effect of MG.

Asenapine in bipolar I disorder: evidence and place in patient management.

Asenapine is a new second-generation antipsychotic approved in September 2010 by the European Medicines Agency for the treatment of bipolar disorder. It demonstrated significant efficacy compared with placebo in acute mania or mixed episodes as monotherapy or adjunctive therapy to mood stabilizers (lithium or valproate). Early improvement was noted at day 2 and was strongly associated with response and remission at week 3. Asenapine also appeared effective in treating acute mania in older patients with bipolar disorder. Post hoc analyses of asenapine showed efficacy in treating depressive symptoms during manic or mixed episodes compared with placebo. The efficacy of asenapine in patients with acute mania appeared to remain constant during maintenance treatment. Asenapine was reasonably well tolerated, especially with regard to metabolic effects. There were minimal signs of glucose elevation or lipid changes and the risk of weight gain appeared limited. The prolactin elevation was smaller than other antipsychotic comparators. Only oral hypoesthesia occurred as a new adverse event compared with other second-generation antipsychotics. Asenapine presents several advantages over other second-generation antipsychotics, such as sublingual formulation, early efficacy and good metabolic tolerability. This tolerability profile confirms the heterogeneity of the second-generation antipsychotic class and supports the view of some authors for the need to re-evaluate the boundaries of this group.