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A letter to the editor is presented in response to an article in the December 1992 issue about the use of the atypical antipsychotic clozapine after an episode of neuroleptic malignant syndrome.

Background: Depression is highly prevalent in people living with HIV (PLWH) but remains under treated in Sub-Saharan Africa. In this context, we conducted the first study of Group Interpersonal Therapy (IPT) to treat depression in PLWH in Senegal. We assessed the perceptions and experiences of patients and group facilitators, as well as barriers to implementation., Methods: This study was conducted at the Fann National University Hospital Center in Dakar, the urban capital of Senegal. Qualitative data were collected during the implementation phase (February to June 2020 and then from January to February 2021), with a 6-month pause due to the COVID-19 pandemic. Twenty-five patients and three group facilitators were individually interviewed by a socio-anthropologist. Qualitative data were analyzed thematically., Results: Group IPT was perceived as successful and beneficial by patients and facilitators. Patients reported positive experiences with group IPT and sustained outcomes. Beyond improving depressive symptoms, patients reported improvements in their social and professional lives, and the development of skills to prevent relapse. Group facilitators noted the benefits of therapy for their patients and for their professional skills, reporting greater clinical competence and improved supportive skills. Challenges to intervention implementation included confidentiality and patient privacy concerns, healthcare accessibility issues, and time demands., Conclusion: In this first qualitative study of group IPT for depression in PLWH in Senegal, participants described both positive experiences with the intervention and challenges to its implementation. Future studies, conducted in suburban and rural communities outside of Dakar, would further inform the implementation of IPT in Senegal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bernard, Mané, Ziadeh, Tine, Diaw, Benzekri, Ndiaye, Samba, Font, Bottai, Jacquesy, Verdeli, Ngom, Dabis, Seydi and de Rekeneire.)

Depression is highly prevalent in people living with HIV (PLWH) and has negative consequences for daily life and care. We evaluated for the first time the acceptability, feasibility and benefits of group interpersonal therapy (IPT), combined with a task-shifting approach, to treat depression in PLWH in Senegal. PLWH with depression received group IPT following the World Health Organization protocol. Acceptability and feasibility criteria were defined from the literature data. The PHQ-9, the WHODAS, and the 12-item-stigma scale were used, pre- and post-treatment, including a 3-month follow-up, to assess depressive symptom severity, functioning and stigma, respectively. General linear mixed models were used to describe changes in outcomes over time. Of 69 participants, 60 completed group IPT. Refusal to enroll and dropout rates were 6.6 and 12.7%, respectively. Ninety-seven percent of participants attended at least seven out of eight sessions. Patients and facilitators endorsed group IPT, with willingness to recommend it. Depressive symptoms and disability improved drastically and sustainably. We showed that group IPT is well accepted and feasible in Senegal as treatment for depression in PLWH. Combined with a task-shifting approach, it can narrow the gap in mental health treatment. Implementation may be enhanced by refining patient identification procedures and increasing treatment accessibility., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2023.)

Proving the efficacy of a psychotropic drug is a medical, scientific and ethical need. Psychotropic drug development is now a highly complex process, which takes several years and which is very expensive. It involves multiple steps of preclinical and clinical pharmacological refinement and testing. Methodology of studies to prove curative or preventive effect of psychotropic drugs is well codified. Preclinical studies include pharmacokinetic data, toxicology and performance in various animal models of pathology. Clinical phases are centered on randomized controlled double blind trials for demonstrating efficacy and safety/tolerability. This methodology follows strict criteria to avoid bias and to prove internal and external validity of the results. All the results from randomized controlled trials or RCTs lead to different levels of evidence of Evidence-Based Medicine (EBM): gold standard is RCTs while the lowest reference is clinical case or expert opinion. However, it is possible to level criticism at these data issued from RCTs. The main matter is that studies do not reflect the healthcare reality in daily life. For these reasons, a real debate between evaluation of efficacy and effectiveness is acute. Effectiveness refers to the overall effects of psychotropic drugs in naturalistic conditions. Furthermore, analysis of costs and financial benefits are more and more important from social and economic points of view. Official agencies and health insurances look after them very carefully. This article deals with these issues and provides examples using data from the international literature. These examples are drawn from RCTs, naturalistic studies, meta-analysis, pharmaco-economic studies and concern neuroleptics, antipsychotics, antidepressants, and mood-stabilizers., (© L’Encéphale, Paris, 2016.)

To correctly interpret the results of a randomised controlled trial (RCT), practitioners have to spot bias and other potential problems present in the trial. Internal as well as external validity of the trial are linked to the presence of such bias. The internal validity is ensured by a clear definition of the objectives of the trial. The number of patients to be included in the trial is calculated on the basis of the main objective of the trial and more precisely on the basis of the primary endpoint selected to assess the efficacy of treatment. This is the best way to ensure that the statistical significance of the result may have a clinical relevance. Internal validity depends also on the process of patients selection, the methods used to ensure comparability of groups and treatments, the criteria employed to assess efficacy, and the methods for the analysis of data. External validity refers to subjects that have been excluded from the trial, limitations of RCTs, as well as the coherence and clinical relevance of the trial. Internal validity has to be fueled by external validity., (© L’Encéphale, Paris, 2016.)

An inventory on the two critical dimensions that structure the Randomized Controlled Trial in Psychiatry, namely the definition of inclusion criteria for eligible patients for testing and the choice of psychometric methods of pathology assessment and its evolution during the experiment, considers the importance of increasingly numerous and precise international recommendations. Taking into account the formal constraints of industrial, questioning the cultural differences of the methodological approach of the tests, meeting the requirements of feasibility and ever increasing security, frequent cumbersome procedure often contrasts with the modest nature of the results. A better definition to include patients in randomized trials is desirable and it asks to return to the clinic studying the expectations of patients and their response to the therapeutic situation. Excessive standardization otherwise required for ensuring the objective nature of the assessment hampers the collection of original and varied clinical features of importance in the further definitions of indications. On the way to a resumption of the single case study, we can expect from qualitative methods applied to small groups of subjects, optimization principles of patient selection for the upcoming randomized trial and greater chance to address the relevant details of clinical response to the therapeutic situation. This is what has led to the discovery of psychotropic drugs and which is involved in the various modalities of the qualitative approach. For example, and beyond the exploration of clinical drug effects, the study of the experience of psychiatric inpatient care in the Healing Garden, conducted on a small group and on the basis of the narrative analysis of their experience, notes several operating thematic dimensions: a reduction in the perception of symptoms of the disease, the impression of regaining a foothold into reality, the interest of a differently perceived doctor-patient relationship, the advantage of renewed power to act and the recognition of the importance of support from others, patients recovering somehow « vitality » of touch with reality. This suggests the possibility to establish an appropriate rating scale for such a specific therapeutic situation and to provide a more accurate and efficient recruitment for a comparative objective demonstration. Moreover, this construction of meaning reinforces the therapeutic benefit of treatment in Healing Garden and offers new dimensions for research., (© L’Encéphale, Paris, 2016.)

Background: Telephone-administered psychotherapies (T-P) provided as an adjunct to antidepressant medication may improve response rates in major depressive disorder (MDD). The goal of this study was to compare telephone-administered social rhythm therapy (T-SRT) and telephone-administered intensive clinical management (T-ICM) as adjuncts to antidepressant medication for MDD. A secondary goal was to compare T-P with Treatment as Usual (TAU) as adjunctive treatment to medication for MDD., Methods: 221 adult out-patients with MDD, currently depressed, were randomly assigned to 8 sessions of weekly T-SRT (n=110) or T-ICM (n=111), administered as an adjunct to agomelatine. Both psychotherapies were administered entirely by telephone, by trained psychologists who were blind to other aspects of treatment. The 221 patients were a posteriori matched with 221 depressed outpatients receiving TAU (controls). The primary outcome measure was the percentage of responders at 8 weeks post-treatment., Results: No significant differences were found between T-SRT and T-ICM. But T-P was associated with higher response rates (65.4% vs 54.8%, p=0.02) and a trend toward higher remission rates (33.2% vs 25.1%; p=0.06) compared to TAU., Limitations: Short term study., Conclusions: This study is the first assessing the short-term effects of an add-on, brief, telephone-administered psychotherapy in depressed patients treated with antidepressant medication. Eight sessions of weekly telephone-delivered psychotherapy as an adjunct to antidepressant medication resulted in improved response rates relative to medication alone., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Theoretical Background: Interpersonal therapy (IPT) is a brief, structured psychotherapy initially intended to treat adult depression that was developed in the 1970s and manualized in 1984 by G. Klerman and his team. Two main theories served as a basis for its design: Bowlby's attachment theory and communication theory. Klerman theorized that tensions and problems in interpersonal relationships (i.e. disputes) cause psychological distress in vulnerable individuals that may lead to a major depressive episode. Clinical and epidemiological studies have shown that an insecure attachment style is strongly associated with lifetime depression. Severe depressive episodes have been correlated with avoidant attachment in women., Therapy Structure and Techniques: IPT is based on the hypothesis that recent or ongoing disturbances in interpersonal relationships either trigger or follow the onset of mood disorder. In practice, IPT assists patients in analysing their interpersonal relationship modes, correlating their relational states with their mood and in learning to use better communication. Resolving difficulties in interpersonal relationships through the use of better communication skills promotes the improvement of depressive symptoms. Klerman identified four interpersonal areas that seem to be highly correlated with depressive episodes: grief (a close and important personal relation who has died), interpersonal disputes (conflicts with significant people such as a spouse or another close family member), role transition (significant life changes such as retirement, parenthood or chronic and invalidating illness) and interpersonal deficits (patients who have limited social contacts and few interpersonal relations). Classically, IPT is planned around 12-16 weekly sessions. During the initial sessions, the therapist will explore all existing interpersonal relations and any significant dysfunctions, both recent and ongoing. Following this interview, the area the patient considers as driving the current depressive episode will be designated as the focus of therapy. Evaluation of depressive symptoms by a quantitative measure (i.e. Visual Analogue Scale) and qualitative measures (activity, pleasure, quality of life) reoccurs at each session. During the intermediate sessions, therapy uses current situations and events in the designated area that particularly affect the patient's mood. Coping, communication and decision-making skills are gradually improved through a number of techniques. These include non-directive and directive exploration, clarification, encouragement of affect, and communication analysis. The therapeutic relationship is empathetic and encouraging of all progress the patient makes. The final phases close the therapy and help the patient to plan future actions and improvements., Clinical Trials of Ipt and Developments: Several controlled clinical trials in adult populations have demonstrated the efficacy of IPT in treating Major Depressive Disorder (initial and recurrent episodes). It has been recommended as an appropriate treatment option in several guidelines. It can be provided in individual, couple or group formats. There remains an ongoing discussion of the efficacy of monthly maintenance sessions in recurrent depression. Since its conception, clinical trials have explored its use in specific populations such as adolescents and the elderly. IPT has also been the object of trial in other disorders such as post-partum depression, bipolar disorder, social phobia and eating disorders., Conclusion: This article reviews the basic principles and objectives of this therapeutic model. Theoretical concepts and results from research are also discussed. The approach is briefly described and the various therapeutic phases are discussed. Clinical trials have shown that IPT is effective in treating major depressive disorder in a wide variety of populations. Further trials are necessary to determine its efficacy in other psychiatric disorders., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Kindling and behavioural sensitization were probably the first among the animal models of affective disorders, to suggest that genes-environment interactions were likely to be involved in the pathophysiology of these disorders. Cross-sensitization among stressors, drugs of abuse and illness episodes was deemed to be supported by the induction of a series of transcription factors, such as the proto-oncogene c-fos that subsequently alter gene expression by binding at DNA sites and inducing mRNAs for substances that may exert effects over long time periods. This was an anticipation of epigenetics which is currently defined as a functional modification to the DNA that does not involve an alteration of sequence. Epigenetic modifications are most commonly regulated by DNA methylation and histone acetylation which are usually associated with the silencing and activation of gene transcription, respectively. In animal models, it was shown that parents can actively remodel epigenetic marks, and thus affect patterns of gene expression in the offspring, whereas environmental adversity decreases parental investment in the offspring and thus alters phenotypic development. In line with this, some laboratories have sought to identify changes in gene expression in post mortem brain samples of humans with affective disorders. Finally, gene-environment interactions have been directly studied, both in animals and humans, by testing how a functional polymorphism in candidate genes would moderate the influence of stressful life events on behavioural expression. Interesting results have been found and replicated for unipolar depression, however date are scarce for bipolar disorder. Findings from these studies allow the building of more sophisticated models for unipolar and bipolar genetics., (Copyright © 2010 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Psychological therapies dedicated to bipolar patients have attracted major interest and many publications have been devoted to them in the last five years. The efficiency of Psychoeducation, Cognitive and behavioral therapy, Behavioral family therapy and Interpersonal and Social Rhythm Therapy, have specially been focused on. These approaches share a common background of psychoeducation and are closely linked with the transnosographical model from Zubin and Spring as well as basic behavioral and cognitive technical requirements. All these therapies focus on medication adherence, regular lifestyle, early recognition of relapse and early pharmacologic intervention. There are some differences between advantages from each approach, but the overall effect is positive in enhancing medication adherence and preventing manic relapses, and also in preventing depressive episodes and improving quality of life. These robust and corroborating results should probably be integrated in future guidelines for the management of bipolar disorders., (Copyright © 2010 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Management of bipolar disorder has undergone many revisions in recent years as new agents and treatments have been developed and studied with variable success. In conjunction with the advent of novel therapies and indications, there has been an increase in the understanding of the phenomenology and neurobiology of bipolar disorder that has made the classification and management of the illness necessarily more sophisticated. However, there remains a significant delay of 8 years in detecting and diagnosing bipolar disorder, and a further need to improve treatments. However, this paper has emphasized the need to be aware of recent advances and the emerging uses of new pharmacological treatments in the management of bipolar disorder. It has also highlighted the need for tailoring management to the individual. In particular, the successful treatment of bipolar disorder requires achieving prophylaxis and preventing relapse. In this regard, maintenance therapy is of paramount importance, and thus the tolerability of agents needs to be considered throughout treatment and should be factored into all management decisions. At the centre is the individual with bipolar disorder and the need to maintain a healthy therapeutic relationship. However, it is important to note that the evidence synthesized in this paper serves only as a guide to the management of bipolar disorder and that, in clinical practice, all treatment recommendations require contextual interpretation, the consideration of local factors and the consultation of additional resources., (Copyright © 2010 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Bipolar disorder is common, recurrent, often severe and debiliting disorder. All types of bipolar disorder have a common determinant: depressive episode. It is justify to propose a psychotherapy which shown efficacy in depression. Howewer, perturbations in circadian rhythms have been implicated in the genesis of each episode of the illness. Biological circadian dysregulation can be encouraged by alteration of time-givers (Zeitgebers) or occurrence of time-disturbers (Zeitstörers). Addition of social rhythm therapy to interpersonal psychotherapy leads to create a new psychotherapy adaptated to bipolar disorders: InterPersonal and Social Rhythm Therapy (IPSRT). IPSRT, in combinaison with medication, has demonstrated efficacy as a treatment for bipolar disorders. IPSRT combines psychoeducation, behavioral strategy to regularize daily routines and interpersonal psychotherapy which help patients cope better with the multiple psychosocial and relationship problems associated with this chronic disorder. The main issues of this psychotherapy are: to take the history of the patient's illness and review of medication, to help patient for "grief for the lost healthy self" translated in the french version in "acceptance of a long-term medical condition", to give the sick role, to examinate the current relationships and changes proximal to the emergence of mood symptoms in the four problem areas (unresolved grief, interpersonal disputes, role transitions, role déficits), to examinate and increase daily routines and social rhythms. French version of IPSRT called TIPARS (with few differences), a time-limited psychotherapy, in 24 sessions during approximatively 6 months, is conducted in three phases. In the initial phase, the therapist takes a thorough history of previous episodes and their interpersonal context and a review of previous medication, provides psychoeducation, evaluates social rhythms, introduces the Social Rhythm Metric, identifies the patient's main interpersonal problem area, and contractualizes the therapy. In the second phase, the therapist focuses work with patient toward regulating the patient's daily routines as well as resolving the interpersonal problem areas relevant to episodes (mainly interpersonal disputes and role transitions). In the third or terminaison phase, the therapist evaluates efficacy of the therapy, enhances the patient's independent functioning and develops strategies for relapse prevention. The further maintenance phase suggests differents strategies as maintenance therapy or focused intensive interventions on specific topics., (Copyright © 2010 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To quantify the factors associated with non-adherence to medication among stable patients suffering from schizophrenia in the context of universal access to care., Methods: This naturalistic, multicentric study was conducted in 15 French public hospitals in a region of south-eastern France during a 1 week period in 2008. All consecutive outpatients with stable schizophrenia were recruited. Adherence was assessed with the 10-item Drug Attitude Inventory (DAI). Measures included socio-demographic characteristics, clinical characteristics, insight using the Scale to assess Unawareness of Mental Disease (SUMD), and therapeutic alliance using the Patient Session Questionnaire (PSQ). Regression models were used to identify the risk factors associated with non-adherence., Results: The study included 291 patients, 30% of whom were considered to be non-adherent. Non-adherence increased with duration of untreated psychosis (DUP) (OR = 1.12, 95%CI = 1.03-1.22), lack of insight only for the dimension 'effect of medication' (OR = 3.23, 95%CI = 1.05-9.89), and a low level of therapeutic alliance (OR = 0.45, 95%CI = 0.32-0.64). Individuals prescribed atypical antipsychotic drugs were more likely to be adherent than those prescribed typical antipsychotics (OR = 0.37, 95%CI = 0.13-1.0)., Conclusions: DUP, prescription of typical antipsychotics, therapeutic alliance and insight were the most important features associated with non-adherence. This study also suggests that economic factors such as the service delivery system should not be neglected in public strategies aimed at addressing problems of non-adherence in non-universal coverage health systems.

Schizophrenic disorders are chronic disorders usually characterized by relapses alternating with periods of remission. A better understanding of the course of schizophrenic disorders is available with the models of psychotic vulnerability and the neurodevelopmental hypothesis. The relapses have numerous severe aspects, clinical, biological and conduct to a bad prognosis. A relapse prevention constitutes a major issue in regard of public health. A relapse prevention is possible with identification of relapse prodromal signs (or early signs of relapse). The relapse prodromal signs are often aspecific but remain stable in each patient. These relapse prodromal signs are similar to the initial prodromal signs, as well as in symptomatology than as their chronologic apparition. Specific psychoeducation strategy allows for each patient to learn its own stressful events and its own prodromal signs of relapse, as well as onset of each prodromal symptoms. A pilot study conducts to a psychoeducative program of relapse prevention centered on learning about prodromal symptoms and validation of a relapse prodromal signs questionnaire.

The principal alternatives to pharmacological treatment of major depressive disorder (besides electroconvulsive therapy) are different forms of psychotherapy, frequently used in combination with antidepressant drugs. The types of psychotherapy that have proven efficacy are mainly cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT). The efficacy of psychoanalytic therapy has not been proven in methodologically sound studies, despite its frequent use. Repetitive transcranial magnetic stimulation appears promising for some subtypes of depression. Vagal nerve stimulation is most often combined with antidepressant drugs for treatment-resistant depression. Light therapy, also called phototherapy, is frequently combined with sleep deprivation. It appears effective in some subtypes of depression. It is often prescribed together with antidepressants.

Clinical expectations in schizophrenia treatment have greatly increased since the introduction of new atypical antipsychotics, but the choice of therapeutic strategy has become more complex and reference guidelines are scarce. This paper summarizes the consensus of a broad range of professionals after long-term commercialization in France of an atypical antipsychotic, amisulpride. Participants were from psychiatric hospitals, private clinics, out-patients settings and research; all were experienced with the drug. Discussions focused on the practical use of amisulpride, as, in addition to the double-blind trials information, it may be useful for psychiatrists of other countries to intuitively understand the therapeutic properties of amisulpride. The topics selected include acute psychotic episodes, short- and long-term follow-up, feasibility of treating the initial phase, the elderly and switching treatments. The French experience emphasizes the central role of amisulpride as a first-line treatment of schizophrenia., (Copyright 2001 S. Karger AG, Basel.)

Based on the hypocatecholaminergic hypothesis in the depressive syndromes, this survey on 30 depressed patients compared to 21 control patients, attempts to state exactly the potential interactions between the noradrenergic system and the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid neuroendocrine axis. The biological indices used during this survey are: total plasmatic MHPG, the basic plasmatic cortisol, the thyroid hormones T3, T4, free T4, and the TSH. The results of this survey reveal a significative increase of the basic plasmatic cortisol among the depressed patients, including dysthymics, a decrease of the plasmatic MHPG during major depressions, and a significant fall of the total T3 among depressed men, as well as some correlations between the different axes, the interpretation of which remains "ticklish".

The authors report the results of an open trial which aims at specifying the clinical profile of responders to carbamazepine among a population of twenty patients aged from fifteen to seventy, suffering from endogenous, schizophrenic, affective psychoses and paranoid states according to the criteria of the ICD 9. The trial points out a proof of Kishimoto's criteria and a preferential acting of the molecule on schizo-affective psychoses and mixed affective states. The results are interpreted according to psychopathological concepts from the Vienna school that highlight the clinical profile of the responders.