Ludovic Samalin

Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness

BackgroundLong-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice.MethodsBased on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee.ResultsLAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. Recommendations for medication management when switching oral antipsychotics to LAI antipsychotics are proposed. Recommendations are also given for the use of LAI in specific populations.ConclusionIn an evidence-based clinical approach, psychiatrists, through shared decision-making, should be systematically offering to most patients that require long-term antipsychotic treatment an LAI antipsychotic as a first-line treatment.

Clinical potential of lurasidone in the management of schizophrenia

Lurasidone is a new second-generation antipsychotic approved in October 2010 by the Food and Drug Administration for the treatment of schizophrenia. Like other second-generation antipsychotics, lurasidone is a powerful antagonist of D2 dopamine and 5HT2A serotonin receptors, but differs from the other second-generation antipsychotics in its action profile for certain receptors. Lurasidone is the second-generation antipsychotic with the greatest affinity for 5HT7 receptors and has a high affinity for 5HT1A serotonin receptors, compatible with favorable effects on cognitive function and an antidepressant action. By contrast, lurasidone has a low affinity for and α1 α2C-adrenergic and 5HT2C serotonin receptors, and no affinity for histaminergic H1 or muscarinic M1 receptors, suggesting a better tolerability profile than the other second-generation antipsychotics. Lurasidone has demonstrated its efficacy in several short-term trials in acute schizophrenia, promptly and significantly reducing total Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores compared with placebo. Several long-term studies are in progress to assess its efficacy in the maintenance treatment of schizophrenic patients. The efficacy of lurasidone with regard to cognitive functions and depressive symptoms seems good, but requires further work. Lurasidone differs from the other second-generation antipsychotics by having a good tolerability profile, in particular for cardiometabolic tolerability. However, it seems to have a significant although moderate link with the occurrence of akathisia, extrapyramidal symptoms, and hyperprolactinemia at the start of treatment. This tolerance profile greatly broadens the scope of second-generation antipsychotics and so supports the view of some authors that the term “second-generation antipsychotic” is now outdated. Other therapeutic perspectives of lurasidone are assessed here, in particular bipolar depression.

Dépistage et prise en charge du trouble bipolaire : Résultats

La premiere strategie therapeutique recommandee est soit l’initiation en monotherapie d’un antipsychotique de seconde generation (AP2G) soit l’association d’un AP2G avec le lithium (Li) ou un anticonvulsivant (AC). Si vous decidez l’utilisation d’une monotherapie par AP2G : un delai avant reevaluation de 3 semaines vous est conseille ; • en cas d’absence d’efficacite, on vous recommande de • verifier l’observance, d’optimiser la posologie, et enfin d’associer un second SH.

Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder

The aims of the present study were to confirm the impact of residual symptoms on overall functioning in a large sample of euthymic patients with bipolar disorder in real‐life conditions and to explore the relationship between residual symptoms and specific areas of functional impairment.

Recommandations Formalisées d’Experts de l’AFPBN : prescription des neuroleptiques et antipsychotiques d’action prolongée

BACKGROUND Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice. METHODS The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia. RESULTS LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors. CONCLUSION A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed.Resume Introduction En pratique clinique, l’utilisation des formes a action prolongee des neuroleptiques et des antipsychotiques de seconde generation, reste faible malgre leur interet dans les strategies de prevention de la rechute dans la schizophrenie ou dans le trouble bipolaire. L’Association Francaise de Psychiatrie Biologique et Neuropsychopharmacologie a elabore des Recommandations, dont l’objet est l’emploi de ces formes galeniques specifiques. Le but de ce travail est de faciliter l’utilisation des antipsychotiques d’action prolongee en pratique clinique. Methodes La methodologie employee est celle dite des « Recommandations Formalisees d’Experts », basee sur les donnees de la litterature et le consensus formalise d’un panel d’experts. Resultats Les antipsychotiques d’action prolongee sont recommandes chez les patients souffrant de schizophrenie, d’un trouble schizo-affectif, d’un trouble delirant ou d’un trouble bipolaire. Les formulations d’action prolongee des antipsychotiques de seconde generation sont preconisees comme traitement de maintenance des le premier episode d’une schizophrenie et en deuxieme ligne comme traitement de maintenance dans le trouble bipolaire. L’emploi des neuroleptiques a action prolongee n’est pas recommande dans la phase precoce du trouble schizophrenique et dans le trouble bipolaire. Pour le panel d’experts, les antipsychotiques a action prolongee ne doivent pas etre reserves aux patients non observant ou ayant des rechutes frequentes, mais doivent etre systematiquement proposes chez tous les patients necessitant un traitement antipsychotique au long cours. Des strategies d’utilisation specifiques lors d’une instauration d’une formulation a action prolongee ou lors d’un changement d’antipsychotique sont proposees. Des preconisations sont faites pour le traitement de certains groupes (femmes enceintes, sujets âges, sujets en situation de precarite ou en detention). Conclusion La place des antipsychotiques a action prolongee evolue vers une utilisation plus systematique et en premiere intention, pour les patients necessitant un traitement antipsychotique de maintenance dans une demarche de decision medicale partagee.

Methodological differences between pharmacological treatment guidelines for bipolar disorder: what to do for the clinicians?

OBJECTIVE Numerous guidelines for bipolar disorder have been published. The aim of this article is to underline the main differences between consensus-based guidelines (CBG) and evidence-based guidelines (EBG) currently available for the management of bipolar disorder. METHODS A literature search for guidelines published since 2006 was performed. A qualitative analysis was then conducted to compare the methodologies and the guidelines contents. RESULTS Comparison between CBG and EBG found more similarities than differences. However, discordances were found in the first-line choice of treatment (monotherapy or combination, use of lamotrigine or lithium in bipolar depression), time to reassessment and duration of maintenance treatment, introduction as from the acute phase a regimen compatible with long-term use and pharmacotherapy during pregnancy. CONCLUSIONS The choice of policy, whatever the methodology used, is up to the authors and can, therefore, depend on their interpretation of the available scientific evidence. Combining both methodologies (CBG and EBG) enables us to meet the complete definition of evidence-based medicine.

Clinicians' Attitudes Toward the Use of Long-Acting Injectable Antipsychotics

Abstract 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.

Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder: an appraisal of phase III clinical trials of schizophrenia-targeted therapies as found in US and EU clinical trial registries

ABSTRACT Introduction: In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future. Areas covered: Recent (post 2013) phase III clinical trials of schizophrenia-targeted therapies were found in US and EU clinical trial registries. Two hundred fifty-three trials were identified, that included 16 investigational compounds. The antipsychotics brexpiprazole and cariprazine have been approved in the US, and although both are dopamine D2 receptor partial agonists, they differ markedly in their pharmacodynamic profiles. Encenicline and valbenazine are first-in-class candidates for treatment of cognitive impairment associated with schizophrenia (CIAS) and tardive dyskinesia, respectively. Eleven add-on compounds were previously approved for other therapeutic indications and are for the most part being studied at academic medical centers and smaller pharmaceutical companies for negative symptoms and CIAS or for specific populations (comorbidities, antipsychotic-induced obesity). Expert opinion: Promising new agents are emerging for schizophrenia and schizoaffective disorder. In addition to better-tolerated antipsychotics that treat positive symptoms, we could see the arrival of the first effective drug for negative symptoms and CIAS, which would strongly facilitate the ultimate goal of recovery in persons with schizophrenia.

Investigational drugs for anxiety in patients with schizophrenia

Introduction: Anxiety is a frequent symptom of schizophrenia, which is highly associated with an increased risk of relapse and suicide. The effect of antipsychotics on this clinical dimension is not specific and the common practice of prescribing benzodiazepines remains unsatisfactory. Areas covered: The authors review recent well-designed clinical trials for anxiety in patients with schizophrenia. The content includes information derived from trial databases, regulatory authorities and scientific literature. Expert opinion: Anxiety in schizophrenia has severe consequences and specific clinical features, which require a specific therapy, beyond benzodiazepines. In these past 2 years, two compounds (the anticonvulsant/anxiolytic pregabalin and the atypical antipsychotic quetiapine) were on Phase III/IV clinical trials for schizophrenia, with comorbid anxiety as a primary outcome measure. Potential for success is high, given their strong rationale and the clinical experience with both drugs. Anxiety (as a symptom) was a secondary outcome measure in trials for schizophrenia involving seven other compounds (lurasidone, amisulpride, bitopertin, oxytocin, famotidine, cannabidiol and the L-theanine and pregnenolone combination). Primary completion date is expected in the next 2 years. In spite of ancient positive results and a strong rationale, aripiprazole and related compounds were not in recent clinical trials. The authors believe that these compounds deserve more attention.

Dépistage et prise en charge du trouble bipolaire : Méthodologie

Dans le cadre de la creation de referentiels pouvant servir de base aux recommandations de pratiques professionnelles et/ou a une demarche d’amelioration de la qualite des soins, l’Association francaise de Psychiatrie Biologique et Neuropsychopharmacologique (AfPBN) au travers de sa section de psychopharmacologie, propose l’elaboration de Recommandations formalisees d’Experts (RfE) sur le depistage et la prise en charge du trouble bipolaire. Les RfE font partie des trois grands types de methodes participatives permettant d’aboutir a un « referentiel » les deux autres etant les Conferences de consensus (CC) et les Recommandations pour la pratique clinique (RPC). Cette demarche de constitution de Recommandations a l’origine s’est appliquee lorsque les donnees scientifiques etaient peu nombreuses, voire absentes, d’un niveau de preuve peu eleve ou conflictuel, ou lorsque les elements de reponse sont indirects ou traites seulement partiellement dans les differents travaux disponibles. Dans ce cas, le terme « accord professionnel fort » etait utilise sans reelle quantification du niveau ni du degre de convergence des avis. Or, les sujets concernes correspondent souvent a des domaines pour lesquels les pratiques s’averent peu ou mal codifiees, voire d’une grande variabilite. En raison meme de l’absence de donnees scientifiques indiscutables, une prise de position a un temps donne par un panel d’experts sur le depistage et la prise en charge du trouble bipolaire apparait donc necessaire. D’ou l’interet de mettre en place des Recommandations formalisees d’Experts elaborees dans une demarche methodologique definie, s’appuyant sur la pratique quotidienne, comprenant des « experts » de modalites d’exercice variees et reconnus pour leur expertise sur le trouble bipolaire. La demarche globale dans sa finalite s’organise en trois phases, la premiere concernant l’elaboration de la RfE, la deuxieme son applicabilite et la troisieme sa bonne diffusion.