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OBJECTIVE: Remitted bipolar disorder (BD) patients frequently present with chronic mood instability and emotional hyper-reactivity, associated with poor psychosocial functioning and low-grade inflammation. We investigated emotional hyper-reactivity as a dimension for characterization of remitted BD patients, and clinical and biological factors for identifying those with and without emotional hyper-reactivity. METHOD: A total of 635 adult remitted BD patients, evaluated in the French Network of Bipolar Expert Centers from 2010-2015, were assessed for emotional reactivity using the Multidimensional Assessment of Thymic States. Machine learning algorithms were used on clinical and biological variables to enhance characterization of patients. RESULTS: After adjustment, patients with emotional hyper-reactivity (n = 306) had significantly higher levels of systolic and diastolic blood pressure (P < 1.0 × 10-8 ), high-sensitivity C-reactive protein (P < 1.0 × 10-8 ), fasting glucose (P < 2.23 × 10-6 ), glycated hemoglobin (P = 0.0008) and suicide attempts (P = 1.4 × 10-8 ). Using models of combined clinical and biological factors for distinguishing BD patients with and without emotional hyper-reactivity, the strongest predictors were: systolic and diastolic blood pressure, fasting glucose, C-reactive protein and number of suicide attempts. This predictive model identified patients with emotional hyper-reactivity with 84.9% accuracy. CONCLUSION: The assessment of emotional hyper-reactivity in remitted BD patients is clinically relevant, particularly for identifying those at higher risk of cardiometabolic dysfunction, chronic inflammation, and suicide.
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Síntomas Afectivos , Trastorno Bipolar , Enfermedades Cardiovasculares , Trastornos del Metabolismo de la Glucosa , Aprendizaje Automático , Intento de Suicidio/estadística & datos numéricos , Adulto , Síntomas Afectivos/sangre , Síntomas Afectivos/epidemiología , Síntomas Afectivos/etiología , Síntomas Afectivos/fisiopatología , Trastorno Bipolar/sangre , Trastorno Bipolar/complicaciones , Trastorno Bipolar/epidemiología , Trastorno Bipolar/fisiopatología , Glucemia , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Femenino , Francia/epidemiología , Trastornos del Metabolismo de la Glucosa/sangre , Trastornos del Metabolismo de la Glucosa/epidemiología , Hemoglobina Glucada , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , RiesgoRESUMEN
Aripiprazole may be viewed as the prototype of third-generation antipsychotics. This concept is based on the notion of D2 partial agonism, whereas all molecules of first-and second generation were D2 antagonists. After reviewing the basic pharmacological notions linked to such concepts, the mechanisms of action of these molecules are addressed, with a particular focus on functional selectivity and biased ligand. One of the essential pharmacological properties of D2 agonists, and particularity aripiprazole, is their ability to not induce D2 supersensitivity as well as to reverse this supersensitivity when it has been induced by D2 antagonists. In clinical practice, this impacts the choice of treatment in first episode psychosis as well as in refractory schizophrenia. Animal research shows that D2 supersensitivity could contribute to worsen addictive trends. The pharmacokinetic incidence of D2 supersensitivity tends to favour the long-acting forms of partial agonists. The notion of partial agonism could finally lead to design fourth-generation antipsychotics, on the basis on research focusing on functional selectivity.
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Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Aripiprazol/farmacología , Aripiprazol/uso terapéutico , Agonistas de Dopamina/farmacología , Agonistas de Dopamina/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Animales , HumanosRESUMEN
Despite the lack of progress in the curative treatment of mental illness, especially schizophrenia, the accumulation of neuroscience data over the past decade suggests the re-conceptualization of schizophrenia. With the advent of new biomarkers and cognitive tools, new neuroscience technologies such as functional dynamic connectivity and the identification of subtle clinical features; it is now possible to detect early stages at risk or prodromes of a first psychotic episode. Current concepts reconceptualizes schizophrenia as a neurodevelopmental disorder at early onset, with polygenic risk and only symptomatic treatment for positive symptoms at this time. The use of such technologies in the future suggests new diagnostic and therapeutic options. Next steps include new pharmacological perspectives and potential contributions of new technologies such as quantitative system pharmacology brain computational modeling approach.
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Antipsicóticos , Intervención Médica Temprana/métodos , Farmacología Clínica/métodos , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Antipsicóticos/clasificación , Antipsicóticos/uso terapéutico , Encéfalo , Niño , Preescolar , Continuidad de la Atención al Paciente , Diagnóstico Precoz , Femenino , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Embarazo , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiología , Esquizofrenia/patología , Psicología del Esquizofrénico , Integración de Sistemas , Adulto JovenRESUMEN
OBJECTIVE: To identify risk factors for suicide attempts (SA) in individuals commencing treatment for a manic or mixed episode. METHOD: A total of 3390 manic or mixed cases with bipolar disorder (BD) type I recruited from 14 European countries were included in a prospective, 2-year observational study. Poisson regression models were used to identify individual and treatment factors associated with new SA events. Two multivariate models were built, stratified for the presence or absence of prior SA. RESULTS: A total of 302 SA were recorded prospectively; the peak incidence was 0-12 weeks after commencing treatment. In cases with a prior history of SA, risk of SA repetition was associated with younger age of first manic episode (P = 0.03), rapid cycling (P < 0.001), history of alcohol and/or substance use disorder (P < 0.001), number of psychotropic drugs prescribed (P < 0.001) and initiation of an anticonvulsant at study entry (P < 0.001). In cases with no previous SA, the first SA event was associated with rapid cycling (P = 0.02), lifetime history of alcohol use disorder (P = 0.02) and initiation of an anticonvulsant at study entry (P = 0.002). CONCLUSION: The introduction of anticonvulsants for a recent-onset manic or mixed episode may be associated with an increased risk of SA. Further BD studies must determine whether this link is causal.
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Anticonvulsivantes/efectos adversos , Trastorno Bipolar/tratamiento farmacológico , Intento de Suicidio/estadística & datos numéricos , Adulto , Anticonvulsivantes/uso terapéutico , Trastorno Bipolar/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución de Poisson , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the prevalence and clinical profile of males and females who develop antidepressant treatment-emergent mania (ATEM). METHOD: From an original sample of 754 patients with BD, we identified ATEM+ cases (n = 75) and ATEM- controls (n = 135) that met stringent criteria. We specifically examined the combinations of clinical factors that best classified males and females as ATEM+ cases. RESULTS: Seventy-five individuals were classified as ATEM+; 87% of ATEM events occurred during antidepressant monotherapy. Regression analyses demonstrated that the presence of an alcohol and/or substance use disorder [Odds Ratio (OR) 6.37], a history of one or more suicide attempts (OR 4.19) and higher number of depressive episodes per year of illness (OR 1.71) correctly classified 73% of males. In contrast, 84% of females were correctly classified on the basis of a positive history of thyroid disorder (OR 3.23), a positive family history of BD I (OR 2.68) and depressive onset polarity (OR 2.01). CONCLUSION: Using stringent definitions of ATEM status to reduce the probability of inclusion of false-positive cases and false-negative controls, we identified for the first time that the risk profiles for the development of an ATEM differ significantly according to gender.
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Antidepresivos/efectos adversos , Trastorno Bipolar/psicología , Adolescente , Adulto , Antidepresivos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Caracteres Sexuales , Adulto JovenRESUMEN
OBJECTIVE: To evaluate aggressiveness during a major depressive episode (MDE) and its relationship with bipolar disorder (BD) in a post hoc analysis of the BRIDGE-II-MIX study. METHOD: A total of 2811 individuals were enrolled in this multicenter cross-sectional study. MDE patients with (MDE-A, n = 399) and without aggressiveness (MDE-N, n = 2412) were compared through chi-square test or Student's t-test. A stepwise backward logistic regression model was performed. RESULTS: MDE-A group was more frequently associated with BD (P < 0.001), while aggressiveness was negatively correlated with unipolar depression (P < 0.001). At the logistic regression, aggressiveness was associated with the age at first depressive episode (P < 0.001); the severity of mania (P = 0.03); the diagnosis of BD (P = 0.001); comorbid borderline personality disorder (BPD) (P < 0.001) but not substance abuse (P = 0.63); no current psychiatric treatment (P < 0.001); psychotic symptoms (P = 0.007); the marked social/occupational impairment (P = 0.002). The variable most significantly associated with aggressiveness was the presence of DSM-5 mixed features (P < 0.001, OR = 3.815). After the exclusion of BPD, the variable of lifetime suicide attempts became significant (P = 0.013, OR = 1.405). CONCLUSION: Aggressiveness seems to be significantly associated with bipolar spectrum disorders, independently from BPD and substance abuse. Aggressiveness should be considered as a diagnostic criterion for the mixed features specifier and a target of tailored treatment strategy.
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Agresión/fisiología , Trastorno Bipolar/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Adulto , Trastorno Bipolar/epidemiología , Trastorno de Personalidad Limítrofe/epidemiología , Trastorno de Personalidad Limítrofe/fisiopatología , Comorbilidad , Estudios Transversales , Trastorno Depresivo Mayor/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The aim of our study was to investigate, in bipolar patients, whether affect lability was associated with suicidal ideation incidence during 2-year follow-up, and which subtype of affect lability was associated with suicidal ideation. METHOD: A total of 319 euthymic or mildly depressed bipolar outpatients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups according to the occurrence of suicidal ideation during a 2-year follow-up. Affect lability was assessed by the French version of the Affect Lability Scale. RESULTS: Bipolar patients with high affect lability were more likely to report suicidal ideation during follow-up, even after adjustment for age, study level, rapid cycling, current depression level, anxiety disorder, and lifetime history SA (OR = 2.47; 95% CI [1.15-5.30], P = 0.01). The risk of suicidal ideation increased with the level of affect lability. More specifically, the propensity to switch from neutral to elation affect, from anxious to depressive affect (or inversely), and from neutral to anger affect predicted suicidal ideation. CONCLUSION: Reducing affective lability could become a new therapeutic target of suicidal prevention in bipolar disorder.
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Trastorno Bipolar/psicología , Intento de Suicidio/estadística & datos numéricos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Ideación Suicida , Intento de Suicidio/psicologíaRESUMEN
OBJECTIVE: The study focused on the relationship between mixed depression and borderline personality disorder (BPD). METHOD: The sample comprised 2811 patients with a major depressive episode (MDE). Clinical characteristics were compared in patients with (BPD+) and without (BPD-) comorbid BPD and in BPD+ with (MXS+) and without (MXS-) mixed features according to DSM-5 criteria. RESULTS: A total of 187 patients (6.7%) met the criteria for BPD. A DSM-IV-TR diagnosis of bipolar disorder (BD) was significantly more frequent in patients with BPD+ than in patients with BPD. Patients with BPD+ were significantly younger and reported lower age at onset than BPD-. Patients with BPD+ also showed more hypomania/mania in first-degree relatives in comparison with patients with BPD-, as well as more psychiatric comorbidity, mixed features, atypical features, suicide attempts, prior mood episodes and antidepressant-induced hypo/manic switches. Mixed features according to DSM-5 criteria were observed in 52 (27.8%) BPD+. In comparison with MXS-, MXS+ were significantly younger at age of onset and at prior mood episode and had experienced more mood episodes and hypo/manic switches with antidepressant treatments. CONCLUSION: Major depressive episode patients with comorbid BPD reported a high prevalence of mixed features and BD. The presence of DSM-5 mixed features in MDE patients with BPD may be associated with complex course and reduced treatment response.
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OBJECTIVE: It is suggested that age at onset (AAO) of bipolar I disorder (BP-I) is decreasing. We tested for a birth-cohort effect on AAO using admixture analysis. METHOD: A clinical sample of 3896 BP-I cases was analysed using two approaches: (i) in a subsample with untruncated AAO × birth year distribution (n = 1865), we compared the best-fitting model for the observed AAO in patients born ≤1960 and >1960, (ii) to control for potential confounders, two separate subsamples born ≤1960 and >1960 were matched for age at interview (n = 250), and a further admixture analysis was undertaken. RESULTS: The two approaches indicated that the proportion of cases in the early AAO category was significantly greater in cases born >1960; manic onsets were also more frequent in the early onset BP-I cases born >1960. CONCLUSION: The decrease in AAO of BP-I in recent birth-cohorts appears to be associated with an increase in the proportion of cases in the early onset subgroup; not with a decrease in the mean AAO in each putative subgroup. This could indicate temporal changes in exposure to risk factors for mania.
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Trastorno Bipolar/epidemiología , Adulto , Edad de Inicio , Trastorno Bipolar/diagnóstico , Efecto de Cohortes , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
Adverse effects of psychotropic medications must be systematically assessed during a clinical trial. This systematic and mandatory evaluation, for the patient safety first, will also allow to establish for the tested molecule, an efficiency/tolerance ratio which could be compared to preexisting medications, and guide the clinician prescriptions. These side effects are closely related to the pharmacological profile of the tested molecule, in particular its monoamine binding profile. Antipsychotics are taken as an example, with a focus on classical clinical side effects related to each monoamine transmission blocking.
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Ensayos Clínicos como Asunto/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Psicotrópicos/efectos adversos , Sistemas de Registro de Reacción Adversa a Medicamentos/normas , Monoaminas Biogénicas/metabolismo , Ensayos Clínicos como Asunto/estadística & datos numéricos , Humanos , Enfermedad Iatrogénica , Cumplimiento de la Medicación/estadística & datos numéricos , Medición de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
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.
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Quimioprevención , Psicotrópicos/farmacología , Psicotrópicos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Quimioprevención/economía , Quimioprevención/métodos , Análisis Costo-Beneficio , Método Doble Ciego , Humanos , Metaanálisis como Asunto , Psicotrópicos/economía , Ensayos Clínicos Controlados Aleatorios como Asunto/economía , Inducción de Remisión , Resultado del TratamientoRESUMEN
After reminding the various phases of the development of molecules, this article will state the stages of commercialisation of treatments, underlining the FDA (Food and Drug Administration) and the EMA (European Medicine Agency) requirements. Like all the other treatments available in Europe and in the United States, the long acting injectable antipsychotics (LAI) have to prove their efficacy compared to placebo and their non-inferiority compared to a treatment of reference, usually the same molecule in the oral form. These criteria of efficacy have evolved over time. If initially classical criteria of symptomatic intensity (score on scale PANSS) were considered, criteria more adequate from a clinical perspective, such as relapse, but also related to functioning, quality of life and, more recently, costs-effectiveness have appeared. This evolution is probably due to several factors: vision on mental illness, progress in patient's rights and aspirations, but also the pregnant place of health costs recently taken in the evaluation of treatments. These modifications are also based on the indications of L.A.I., i.e. stabilized patients for whom the challenge is rehabilitation care more than the control of symptoms.
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Antipsicóticos/administración & dosificación , Ensayos Clínicos como Asunto/métodos , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/economía , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/economía , Diseño de Fármacos , Descubrimiento de Drogas , Humanos , Inyecciones Intramusculares , Resultado del TratamientoRESUMEN
Drug development of new compounds implies to define the dosage as well as the conditions of their use (indication, treatment duration, drug interactions, warnings ). This information requires the identification of the time course response. The decisions made during the clinical phases are now based on mathematical models. These models are continuously described and improved during all phases of the drug development using data collected in healthy volunteers and patients. Their objectives are to describe the most precisely, the link between the compound characteristics (pharmacology), the patient demographics and the effects. Further, the natural history of the disease, the placebo effect and the probability of dropping out will be integrated into the model to optimize the evaluation of the compound. These technical improvements are not only statistical, in the sense that they allow a better understanding of the advantages and pitfalls of the new drug. This article presents these methods used in psychiatry and which will become the new standard of drug evaluation.
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Ensayos Clínicos como Asunto/métodos , Modelos Teóricos , Psiquiatría/métodos , Animales , Ensayos Clínicos como Asunto/normas , Progresión de la Enfermedad , Descubrimiento de Drogas/métodos , Evaluación Preclínica de Medicamentos/métodos , Humanos , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/patología , Efecto Placebo , Psiquiatría/normas , Proyectos de Investigación/normasRESUMEN
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).
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Ensayos Clínicos como Asunto/métodos , Trastornos Mentales/tratamiento farmacológico , Efecto Placebo , Antidepresivos/uso terapéutico , Ensayos Clínicos como Asunto/normas , Trastorno Depresivo Mayor/tratamiento farmacológico , Ecosistema , Humanos , Placebos , Proyectos de Investigación/normasRESUMEN
OBJECTIVES: The first objective of this article is to summarize the history of electroconvulsive therapy (ECT) in psychiatry in order to highlight the transition from clinical level of evidence based on phenomenological descriptions to controlled trial establishing causal relationship. The second objective is to apply the criteria of causation for ECT, to focus on the dose-effect relationship criteria, and thus to analyze the conditions of application of these criteria for ECT. METHODS: A literature review exploring the use of electricity, ECT and electroencephalography (EEG) in psychiatry was conducted. The publications were identified from the Pubmed and GoogleScholar electronic databases. The scientific literature search of international articles was performed in July 2016. RESULTS: In 1784, a Royal commission established in France by King Louis XVI tested Mesmer's claims concerning animal magnetism. By doing that, the commission, including such prominent scientists as the chemist Anton Lavoisier and the scientist and researcher on electricity and therapeutics Benjamin Franklin, played a central role in establishing the criteria needed to assess the level of evidence of electrical therapeutics in psychiatry. Surprisingly, it is possible to identify the classical Bradford Hill criteria of causation in the report of the commission, except the dose-effect relationship criteria. Since then, it has been conducted blinded randomized controlled trials that confirmed the effectiveness of ECT against ECT placebos for the treatment of psychiatric disorders. At present, the dose-effect relationship criteria can be analyzed through an EEG quality assessment of ECT-induced seizures. CONCLUSIONS: EEG quality assessment includes several indices: TSLOW (time to onset of seizure activity ≤5Hz, seconds), peak mid-ictal amplitude (mm), regularity (intensity or morphology of the seizure (0-6)), stereotypy (global seizure patterning, 0-3) and post-ictal suppression (0-3). A manual rating sheet is needed to score theses indices. Such manual rating with example of EEG segments recording is proposed in this article. Additional studies are needed to validate this manual, to better establish the dose-response relationship for the ECT, and thus strengthen the position of the EEG as a central element for clinical good practice for ECT.
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Terapia Electroconvulsiva , Medicina Basada en la Evidencia , Convulsiones/terapia , Animales , Terapia Electroconvulsiva/efectos adversos , Terapia Electroconvulsiva/historia , Terapia Electroconvulsiva/métodos , Electroencefalografía , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Convulsiones/diagnóstico , Convulsiones/historiaRESUMEN
As in the usual care of patients, paraclinical investigations have today only a very modest role in clinical trials in psychiatry, mainly to complete the pre-therapeutical assessments prior to inclusion of subjects or to monitor treatment tolerance. Yet, the accumulation of data in neurosciences suggests the next emergence of biomarkers, whose interest is that they are closely associated to the biological disturbances underlying psychiatric illnesses, and that they are accessible by means of technological tools such as imaging devices. These tools allow to explore the effects on brain of psychotropic medications, such as antidepressants, antipsychotics, or mood stabilizers, in relation to their therapeutic action. The obtained results allow to consider the use of such biomarkers in clinical trials in addition to more conventional approaches. In particular, they could be used as targets to measure brain response to treatment in association with clinical response, to predict a therapeutic response from the neurofunctional characteristics of patients, or to establish the safety profile of drugs on the nervous system. The use of such biomarkers in clinical trials would help to better define the explored populations and their characteristics, as well as the variables to assess, and to better measure the impact of the treatments and their potential harmful effects on the nervous system.
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Biomarcadores Farmacológicos/análisis , Ensayos Clínicos como Asunto/métodos , Monitoreo Fisiológico/métodos , Neurociencias/métodos , Psiquiatría/métodos , Antidepresivos/farmacocinética , Antidepresivos/uso terapéutico , Antipsicóticos/farmacocinética , Antipsicóticos/uso terapéutico , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Psicotrópicos/farmacocinética , Psicotrópicos/uso terapéuticoRESUMEN
Extensive evidence demonstrates that psychotherapy can be an efficacious and effective health care service for a wide range of mental health and health conditions. Recently, an important distinction between efficacy research and effectiveness research has been made within research focused on the outcome of psychotherapy. Data from both efficacy and effectiveness studies are fundamental to a complete understanding of the potential impact of a psychotherapy and the way to carry successful psychotherapeutics interventions to routine clinical practice. Efficacy studies, using randomized controlled trials, maximize the internal validity of a study by the use of design features, such as random assignment to a psychotherapeutic intervention and control conditions, training of therapists to a specified level of competence in providing the treatment, and ensuring that all participants have the condition that the treatment was designed to address. The randomized controlled trials allowed to objectify the efficacy of the psychotherapies in multiple pathological contexts, as we will see with the example of bipolar disorders. On the other hand, effectiveness studies strive to maximize external validity (while maintaining an adequate level of internal validity) by locating the study within clinical service sites that provide ongoing health services, using clinicians who are routinely providing psychological services and patients who have been referred to the clinical settings. These studies do not allow understanding changes and psychotherapeutic processes in real practice. A solution might be found in using pragmatic case studies in a systematic manner to constitute ecologically valid samples and measure change and psychotherapeutic processes during clinically significant periods of time.
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Trastorno Bipolar/terapia , Ensayos Clínicos como Asunto/métodos , Psicoterapia/métodos , Investigación sobre la Eficacia Comparativa , Humanos , Ensayos Clínicos Pragmáticos como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Resultado del TratamientoRESUMEN
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 ¼ 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.
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Selección de Paciente , Psiquiatría/métodos , Psicometría/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Servicios de Salud Mental/organización & administración , Servicios de Salud Mental/normas , Guías de Práctica Clínica como Asunto , Psiquiatría/normas , Psicometría/normas , Investigación Cualitativa , Ensayos Clínicos Controlados Aleatorios como Asunto/normasRESUMEN
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.
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Interpretación Estadística de Datos , Médicos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Sesgo , Humanos , Control Interno-Externo , Rol del Médico , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Reproducibilidad de los ResultadosRESUMEN
Clinical trials in psychiatry allow to build the regulatory dossiers for market authorization but also to document the mechanism of action of new drugs, to build pharmacodynamics models, evaluate the treatment effects, propose prognosis, efficacy or tolerability biomarkers and altogether to assess the impact of drugs for patient, caregiver and society. However, clinical trials have shown some limitations. Number of recent dossiers failed to convince the regulators. The clinical and biological heterogeneity of psychiatric disorders, the pharmacokinetic and pharmacodynamics properties of the compounds, the lack of translatable biomarkers possibly explain these difficulties. Several breakthrough options are now available: quantitative system pharmacology analysis of drug effects variability, pharmacometry and pharmacoepidemiology, Big Data analysis, brain modelling. In addition to more classical approaches, these opportunities lead to a paradigm change for clinical trials in psychiatry.