Adherence to treatment guidelines in clinical practice for using electroconvulsive therapy in major depressive episode.

BACKGROUND: ECT is the most effective treatment of major depressive episode (MDE) but remains a neglected treatment. The French Society for Biological Psychiatry and Neuropsychopharmacology aimed to determine whether prescribing practice of ECT followed guidelines recommendations. METHODS: This multicenter, retrospective study included adult patients with major depressive disorder (MDD) or bipolar disorder (BD), who have been treated with ECT for MDE. Duration of MDE and 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: Seven hundred and forty-five individuals were included. The mean duration of MDE before ECT was 10.1 months and the mean number of lines of treatment before ECT was 3.4. It was significantly longer for MDD single episode than recurrent MDD and BD. The presence of first-line indications for using ECT was significantly associated to shorter duration of MDE (9.1 vs 13.1 months, p<0.001) and lower number of lines of treatment before ECT (3.3 vs 4.1, p<0.001). LIMITATIONS: This is a retrospective study and not all facilities practicing ECT participated that could limit the extrapolation of the results. CONCLUSION: Compared to guidelines, ECT was not used as first-line strategy in clinical practice. The presence of first-line indications seemed to reduce the delay before ECT initiation. The improvements of knowledge and access of ECT are needed to decrease the gap between guidelines and clinical practice.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

[French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression]. / Prise en charge des troubles dépressifs résistants : recommandations françaises formalisées par des experts de l'AFPBN et de la fondation FondaMental.

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

Risk factors for treatment resistance in unipolar depression: a systematic review.

BACKGROUND: Treatment resistant depression is a complex disorder and an important source of morbidity and mortality. Identification of risk factors of resistance may be useful to improve early recognition as well as treatment selection and prediction of outcome in patients with depression. METHODS: The aim of this paper was to review the current status of knowledge regarding risk factors of treatment resistance in unipolar depression, in patients who failed to respond to at least two successive and adequate antidepressant treatments. RESULTS: Systematic literature search yielded 8 publications exploring clinical and biological factors. Specific psychiatric comorbidities, psychosocial factors, clinical characteristics of the depressive episode and biological markers emerge as possible risk factor for treatment resistant depression. LIMITATIONS: Due to the lack of objective definition and diagnostic criteria for treatment resistant depression, and the paucity of reports on risk factors, our review only summarized a small number of studies. CONCLUSION: Future investigations of risk factors should help to improve the understanding of the mechanisms underlying resistance in mood disorders and contribute to improve their therapeutic management.

[Aripiprazole long-acting for the maintenance treatment of schizophrenia.] / Aripiprazole injectable à libération prolongée dans le traitement de maintenance de la schizophrénie.

Antipsychotics are the cornerstone for the maintenance treatment of schizophrenia patients. Their long-acting formulations are helpful for preventing relapses through improvement of adherence to medication and a better pharmacokinetic coverage. However, their use is often reserved for refractory or non-observant clinical forms because of limitations among both clinicians and patients. The development of a new formulation of long-acting injectable aripiprazole administered every 4 weeks is a new option. Two randomized controlled trials vs. placebo and vs. oral aripiprazole respectively show a superiority and non-inferiority in terms of relapse prevention. Meanwhile, a mirror-image study demonstrates fewer hospitalizations. The safety profile is comparable to the oral formulation, particularly in terms of metabolic and neurological side-effects. As mentioned in various professional recommendations, long-acting injectable antipsychotics, so long-acting injectable aripiprazole, are one of the major strategies of the maintenance treatment for patients with schizophrenia.

[Efficacy of aripiprazole for the treatment of schizophrenia: what dose is required?]. / Efficacité de l'aripiprazole dans le traitement de la schizophrénie : quelle dose pour quel effet ?

OBJECTIVE: Problem of the choice of antipsychotic dose is a key issue in clinical practice. It determines the efficacy and safety of treatment. Aripiprazole is recommended at a dose of between 10 and 15 mg/day in the treatment of schizophrenia, with a dose range considered to be effective, between 10 and 30 mg/day. This wide therapeutic range prompted us to investigate the existence of a possible dose-effect relationship for aripiprazole in the treatment of schizophrenia. METHOD: We conducted a literature review from PubMed and EMBASE database, with the keywords: aripiprazole, schizophrenia. We limited it to studies published in English and French, with the main objective to assess the efficacy of aripiprazole in patients with schizophrenia. We selected only randomized clinical trials, double-blind, controlled against placebo or against an active comparator. Studies in which aripiprazole was studied added to another antipsychotic were not retained. RESULTS: Twenty-two randomized, double-blind, controlled studies were selected. Three studies assessed the efficacy of aripiprazole on agitation symptoms in patients with schizophrenia and for which a dose of aripiprazole between 1 and 15mg showed significant efficacy compared to placebo. Seven clinical trials focused on the effect of aripiprazole short term (less than 12weeks). For the primary endpoint (PANSS scores), aripiprazole was superior to placebo or equivalent to active comparators (risperidone, olanzapine or haloperidol). These short-term studies revealed a range of effective doses from 10 mg/day to 20 mg/day. Five studies, lasting between 16 and 52 weeks, with a primary endpoint being the time to discontinuation for any cause for two studies, the time before relapse in one study, and the improvement in PANSS scores for the two other studies. On these different endpoints, aripiprazole was effective at average doses between 15 and 28.1 mg/day. The safety of aripiprazole was particularly favourable in these trials. Finally, we listed seven post-hoc analyses. In support of these long-term analyses on different endpoints, aripiprazole showed significant efficacy at higher doses (20 and 30 mg/day) than those used in the agitation treatment. CONCLUSIONS: No study was designed to compare aripiprazole doses in schizophrenia. Nevertheless, efficacy on agitation and hostility components had been observed for doses of 10mg/day, or lower; whereas the antipsychotic effect in acute or maintenance phase appeared optimal for doses ranging from 10 to 25 mg/day. Only one study retained a minimum effective dose of 10mg/day on the PANSS scores. This literature review reveals an effective dose range between 10 and 25 mg/day for aripiprazole in schizophrenia. Less than 10 mg/day did not show significant efficacy on symptoms of schizophrenia, apart from a specific short-term effect on agitation, at very low doses (starting at 1mg). Optimization of treatment, at doses above 25 mg/day, cannot be the subject of evidence-based recommendations.

[The contributions of the evidence-based medicine or how to optimize the management of major depressive disorder]. / Les apports de « l'Evidence-Based Medicine ¼ (médecine basée sur les preuves) ou comment optimiser la prise en charge de l'épisode dépressif majeur.

In the early 1980s, Evidence-Based Medicine (EBM) has been developed in the Department of Clinical Epidemiology at McMaster Medical School in Canada to meet the ever-increasing need to integrate publications in clinical practice. In this approach, we cannot ever consider that the evidence will replace clinical experience. The quality of scientific data is prioritized taking into account the methodological characteristics of studies. It takes time to learn and practice the method, which is often difficult in daily practice. The concept of "management recommendations" covers multiple realities. It can rely on the results of clinical trials (randomized, controlled or not…), the trends from the meta-analysis that attempt to "simplify" the field of literature or the Clinical Practice Guidelines. Meta-analysis should be used with caution. They do not preclude the need to use the data "sources", but they help the comparability of results and synthesis work. However it should be aware that this is a work of interpretation. The controversy over the action of antidepressants compared to placebo in depression according to the severity of the episode shows that a result depends on the included studies, the statistical technique used, but also how the results are reported. The international literature produced many recommendations in the management of depression. It is useful to refer to it as the meta-analysis because they provide an overall view of the current state of knowledge. We can regret the lack of recent French recommendations that could articulate the specifics of the French practice and data from the literature. The use of guidelines in clinical practice remains low in all fields of medicine. However improving the consideration of the recommendations is an important issue because it is associated with improved patient care. It remains to develop a collective strategy to implement them. The Evidence-Based Medicine is a major change in the everyday clinical practice. It may be insufficiently known and understood, seems too complex, time-consuming and therefore inapplicable. We have to mobilize our efforts to improve our practices.

[Guidelines for the biological treatment of bipolar depression]. / Les recommandations professionnelles dans le traitement de la dépression bipolaire.

Numerous guidelines for the treatment of bipolar disorder have been published in the recent years. A review focusing on recent international and French guidelines the last 5 years on the management of bipolar depression was conducted. The comparison of guidelines showed differences in the choice of initial treatment: monotherapy (in first line: quetiapine and lamotrigine) or polypharmacotherapy (in first line: combination olanzapine/fluoxetine). All guidelines recommend in patients with inadequate response a therapeutic strategy in two steps. An initial clinical stage seeking the causes of poor therapeutic response and a second therapeutic stage trying to optimize the current treatment, to change treatment or to consider a co-therapy. In first line, the prophylactic drugs recommended are: lithium, valproate, quetiapine; olanzapine, risperidone (and long-acting formulation) and aripiprazole mainly for the prevention of manic episodes; lamotrigine limited to prevention of depressive episodes. The duration of treatment before patient reassessment and that of maintenance therapy are not consensual. The development of second-generation antipsychotics in bipolar depression is an interesting development for our therapeutic armamentarium and has been incorporated in recent guidelines.

Patient perspectives on use of long-acting antipsychotics in bipolar disorder: focus on risperidone injection.

In the last few years, oral second-generation antipsychotics have demonstrated mood-stabilizing properties and are now widely used in the treatment of bipolar disorder. Unfortunately, treatment of this chronic and complex illness is hampered with poor adherence on the part of patients. Long-acting injectable formulations of second-generation antipsychotics could combine the effect of oral second-generation antipsychotics in patients with bipolar disorder and the benefits of depot formulation with the assurance of steady medication delivery and thereby improve adherence. In this context, the efficacy and tolerance of risperidone long-acting injection (RLAI) for maintenance treatment in patients with bipolar disorder is assessed. The relevant studies found RLAI to be effective in preventive treatment of manic but not depressive recurrences in bipolar patients, with good tolerance. RLAI appeared to be particularly suitable for patients with known poor adherence to treatment or severe bipolar disorder (such as patients who relapse frequently). Lastly, if RLAI, unlike the first-generation antipsychotics, does not induce depressive symptoms, the different studies do not enable us to consider its use in monotherapy in the preventive treatment of patients with depressive polarity. Long-acting second-generation antipsychotics in bipolar patients are therefore associated with long-term benefits, but their use in clinical practice needs to be improved.