ABSTRACT
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.
Subject(s)
Clinical Trials as Topic/methods , Drug-Related Side Effects and Adverse Reactions/diagnosis , Psychotropic Drugs/adverse effects , Adverse Drug Reaction Reporting Systems/standards , Biogenic Monoamines/metabolism , Clinical Trials as Topic/statistics & numerical data , Humans , Iatrogenic Disease , Medication Adherence/statistics & numerical data , Risk Assessment , Severity of Illness IndexABSTRACT
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.
Subject(s)
Chemoprevention , Psychotropic Drugs/pharmacology , Psychotropic Drugs/therapeutic use , Randomized Controlled Trials as Topic/methods , Chemoprevention/economics , Chemoprevention/methods , Cost-Benefit Analysis , Double-Blind Method , Humans , Meta-Analysis as Topic , Psychotropic Drugs/economics , Randomized Controlled Trials as Topic/economics , Remission Induction , Treatment OutcomeABSTRACT
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.
Subject(s)
Antipsychotic Agents/administration & dosage , Clinical Trials as Topic/methods , Schizophrenia/drug therapy , Antipsychotic Agents/economics , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/economics , Drug Design , Drug Discovery , Humans , Injections, Intramuscular , Treatment OutcomeABSTRACT
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.
Subject(s)
Clinical Trials as Topic/methods , Models, Theoretical , Psychiatry/methods , Animals , Clinical Trials as Topic/standards , Disease Progression , Drug Discovery/methods , Drug Evaluation, Preclinical/methods , Humans , Mental Disorders/drug therapy , Mental Disorders/pathology , Placebo Effect , Psychiatry/standards , Research Design/standardsABSTRACT
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).
Subject(s)
Clinical Trials as Topic/methods , Mental Disorders/drug therapy , Placebo Effect , Antidepressive Agents/therapeutic use , Clinical Trials as Topic/standards , Depressive Disorder, Major/drug therapy , Ecosystem , Humans , Placebos , Research Design/standardsABSTRACT
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.
Subject(s)
Electroconvulsive Therapy , Evidence-Based Medicine , Seizures/therapy , Animals , Electroconvulsive Therapy/adverse effects , Electroconvulsive Therapy/history , Electroconvulsive Therapy/methods , Electroencephalography , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Seizures/diagnosis , Seizures/historyABSTRACT
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.
Subject(s)
Biomarkers, Pharmacological/analysis , Clinical Trials as Topic/methods , Monitoring, Physiologic/methods , Neurosciences/methods , Psychiatry/methods , Antidepressive Agents/pharmacokinetics , Antidepressive Agents/therapeutic use , Antipsychotic Agents/pharmacokinetics , Antipsychotic Agents/therapeutic use , Humans , Mental Disorders/diagnosis , Mental Disorders/therapy , Psychotropic Drugs/pharmacokinetics , Psychotropic Drugs/therapeutic useABSTRACT
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.
Subject(s)
Bipolar Disorder/therapy , Clinical Trials as Topic/methods , Psychotherapy/methods , Comparative Effectiveness Research , Humans , Pragmatic Clinical Trials as Topic/methods , Randomized Controlled Trials as Topic/methods , Research Design , Treatment OutcomeABSTRACT
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.
Subject(s)
Patient Selection , Psychiatry/methods , Psychometrics/methods , Randomized Controlled Trials as Topic/methods , Humans , Mental Disorders/diagnosis , Mental Disorders/therapy , Mental Health Services/organization & administration , Mental Health Services/standards , Practice Guidelines as Topic , Psychiatry/standards , Psychometrics/standards , Qualitative Research , Randomized Controlled Trials as Topic/standardsABSTRACT
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.
Subject(s)
Data Interpretation, Statistical , Physicians , Randomized Controlled Trials as Topic/statistics & numerical data , Bias , Humans , Internal-External Control , Physician's Role , Randomized Controlled Trials as Topic/standards , Reproducibility of ResultsABSTRACT
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.
Subject(s)
Clinical Trials as Topic , Mental Disorders/therapy , Psychiatry/methods , Psychiatry/trends , Brain/pathology , Clinical Trials as Topic/methods , Clinical Trials as Topic/organization & administration , Clinical Trials as Topic/standards , Computer Simulation , Humans , Mental Disorders/epidemiology , Pharmacoepidemiology , Pharmacogenomic Testing/methods , Pharmacogenomic Testing/trends , Research Design/standards , User-Computer InterfaceABSTRACT
Recent investigations performing exploratory and confirmatory factor analysis have suggested that negative symptoms are multidimensional, including evidence for at least two distinct negative symptom subdomains: diminished expression and amotivation. Guidance for selection of instruments for measurement of negative symptoms is rapidly evolving. As there are continuing advances in the description of negative symptoms, new instruments are under development, and new data on the performance of instruments emerge from clinical trials. The Scale for Assessment of Negative Symptoms (SANS), the Positive and Negative Syndrome Scale (PANSS), and the Negative Symptom Assessment-16 (NSA-16) are considered to be reliable and valid measures for negative symptom trials but differ with respect to their domain coverage, use of informants, integration of global scores, administration time and comprehensiveness of their structured interviews. In response to the 2005 NIMH - MATRICS consensus statement, work groups are field testing and refining two new measures, the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS). Both address the five currently recognized domains of negative symptoms, differentiate appetitive from consummatory aspects of anhedonia and address desire for social relationships. Thus far, both have exhibited promising psychometric properties.
Subject(s)
Psychometrics , Schizophrenia/diagnosis , Schizophrenic Psychology , Humans , Psychiatric Status Rating Scales , Schizophrenia/therapyABSTRACT
For a long time, treatment of schizophrenia has been essentially focussed on positive symptoms managing. Yet, even if these symptoms are the most noticeable, negative symptoms are more enduring, resistant to pharmacological treatment and associated with a worse prognosis. In the two last decades, attention has shift towards cognitive deficit, as this deficit is most robustly associated to functional outcome. But it appears that the modest improvement in cognition, obtained in schizophrenia through pharmacological treatment or, more purposely, by cognitive enhancement therapy, has only lead to limited amelioration of functional outcome. Authors have claimed that pure cognitive processes, such as those evaluated and trained in lots of these programs, may be too distant from real-life conditions, as the latter are largely based on social interactions. Consequently, the field of social cognition, at the interface of cognition and emotion, has emerged. In a first part of this article we examined the links, in schizophrenia, between negative symptoms, cognition and emotions from a therapeutic standpoint. Nonetheless, investigation of emotion in schizophrenia may also hold relevant premises for understanding the physiopathology of this disorder. In a second part, we propose to illustrate this research by relying on the heuristic value of an elementary marker of social cognition, facial affect recognition. Facial affect recognition has been repeatedly reported to be impaired in schizophrenia and some authors have argued that this deficit could constitute an endophenotype of the illness. We here examined how facial affect processing has been used to explore broader emotion dysfunction in schizophrenia, through behavioural and imaging studies. In particular, fMRI paradigms using facial affect have shown particular patterns of amygdala engagement in schizophrenia, suggesting an intact potential to elicit the limbic system which may however not be advantageous. Finally, we analysed facial affect processing on a cognitive-perceptual level, and the aptitude in schizophrenia to manipulate featural and configural information in faces.
Subject(s)
Cognition , Emotions , Schizophrenic Psychology , Humans , Schizophrenia/therapyABSTRACT
A number of neuroanatomical and neurofonctional abnormalities have been evidenced by cerebral imaging studies in patients suffering from schizophrenia. Nevertheless, those specifically associated with the negative symptoms of this disease are still insufficiently known. This work is a review of selected studies that have assessed the brain correlates of negative symptoms in schizophrenia. Approaches using structural imaging have highlighted reduction of gray matter density or cortical thickness associated with negative symptoms, which is rather sparsely distributed within the frontal and temporal regions, localized nevertheless more particularly in the frontal medial and orbitofrontal areas, as well as the amygdalo-hippocampic complex. These deficits are concurrent with a loss of integrity of the principal paths of white matter tracts between frontal and limbic regions. On the other hand, neurofonctional abnormalities associated with negative symptoms involve especially the frontal areas and limbic striatum. A disturbed functioning within the fronto-striatal loops, related to a striatal dopaminergic deficit, may represent a potential explanatory hypothesis of the negative symptoms of schizophrenia, as suggested by studies using Positron Emission Tomography on this topic or neuroimaging studies on the effects of antipsychotics. A better identification of the cerebral abnormalities associated with the negative dimension of schizophrenia, with regard to the lateralization of these abnormalities or to their changes during the course of the disease, could offer new therapeutic modalities for the treatment of this dimension which, until now, remains few responsive to conventional pharmacological treatments.
Subject(s)
Brain/pathology , Neuroimaging , Schizophrenia/diagnosis , Schizophrenia/pathology , Schizophrenic Psychology , Brain/diagnostic imaging , Diagnostic Imaging , Humans , Positron-Emission Tomography , Schizophrenia/diagnostic imagingABSTRACT
Dual diagnosis of schizophrenia and substance-related disorders is common in psychiatric practice. Epidemiologic studies and report have established that the risk of a substance-related disorder was 4 to 5 times higher in a population of psychiatric patients than in the general population. However, little is known on the reason of this relationship and the treatments required. It's well known that a family history of psychosis is a risk factor of schizophrenia. Similarly a family history of substance use disorders increases the risk of using substances. Because the two disorders often occurred together, it could be hypothesized that a genetic risk factor is common. However, recent studies did not confirm this hypothesis and it seems that their genetic risks factor would be unrelated. Evidence now exists describing the different profiles of patients whether they used substance or not. Concerning negative symptoms clinical studies and meta-analyses have described fewer symptoms in schizophrenia patients with a substance use disorder. Among the different explanations that have been addressed, it seems that a lower capability of obtaining the substance could partly explain this relationship. Perhaps because patients with social withdrawal have more difficulties to find and spend the time required to obtain abused substances. At the opposite some products such as cocaine may relieve some symptoms especially anhedonia and alogia. However the link between substance-related disorders and negative symptoms is weak and decreases in more recent studies, probably because negative symptoms as well as addiction disorders are better characterized. Considering that treating psychiatric symptoms may not always lead to a decrease in the substance-related disorders but that patients who give up substances improve their psychotic symptoms, a therapeutic strategy should be planned for these dual disorders patients combining psychiatry and addiction interventions.
Subject(s)
Schizophrenia/complications , Schizophrenic Psychology , Substance-Related Disorders/complications , Substance-Related Disorders/psychology , Diagnosis, Dual (Psychiatry) , HumansABSTRACT
Treating negative symptoms of schizophrenia is a major issue and a challenge for the functional and social prognosis of the disease, to which they are closely linked. First- and second-generation antipsychotics allow a reduction of all negative symptoms. The hope of acting directly on primary negative symptoms with any antipsychotic is not supported by the literature. However, the effectiveness of first- and second-generation antipsychotics is demonstrated on secondary negative symptoms.
Subject(s)
Antipsychotic Agents/therapeutic use , Schizophrenia/drug therapy , Schizophrenic Psychology , HumansABSTRACT
Negative symptoms account for a clinical dimension of schizophrenia. They are partly the cause of functional disability of this disease. Clinical experience shows that antipsychotics have little or no effect on these symptoms. The aim of this review is to gather existing data on the treatment of negative symptoms with antidepressants. The combination of antipsychotics with antidepressants is a therapeutic strategy commonly used for the treatment of these symptoms. The pro-dopaminergic effects of antidepressants explain their effectiveness on negative symptoms. There are many comparative, randomized, controlled studies evaluating the efficacy of antidepressant associated with antipsychotic for the treatment of negative symptoms. Furthermore three meta-analyses have been conducted. The overall results suggest that the use of antidepressants may contribute to clinical improvement of negative symptoms in schizophrenia. The limitations of these studies are the small number of patients included and the definition and assessment of negative symptoms. The existing scales are not sufficiently discriminating. Further research using new measurement tools should help refine these results.
Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder/drug therapy , Depressive Disorder/etiology , Schizophrenia/complications , Schizophrenia/drug therapy , Schizophrenic Psychology , Antipsychotic Agents/therapeutic use , Dopamine Agents/therapeutic use , Drug Therapy, Combination , Humans , Randomized Controlled Trials as TopicABSTRACT
The management of negative symptoms appears to be a major challenge because of functional disability induced by these symptoms and their relative resistance to treatments currently on the market. The aim of this article is to review new approaches that may enable optimal management of these symptoms. First, we describe the methodological difficulties that hindered the development and evaluation of specific treatment, and objectives currently defined to enable the development of new pharmacological approaches. Then we present the monotherapy and adjuvant therapies that have been assessed, including first and second generation antipsychotics, psychostimulants, antidepressants, cholinergic and glutamatergic agents, the oxytocin, hormones and more invasive therapies such as transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT). Other molecules are under development and evaluation such alpha-7 nicotinic receptor agonists.
Subject(s)
Antipsychotic Agents/therapeutic use , Schizophrenia/drug therapy , Schizophrenia/therapy , Schizophrenic Psychology , Combined Modality Therapy , Electroconvulsive Therapy , Humans , Oxytocin/therapeutic use , Psychotropic Drugs/therapeutic use , Transcranial Magnetic StimulationABSTRACT
The aim of this review of the literature is to summarize the state of the knowledge concerning the relationship between negative symptoms in schizophrenia, electrophysiology and electrotherapy. The scientific literature search of international articles was performed during August and September 2015 using the PubMed electronic database. We used the following MeSH terms: "Negative symptoms", "Schizophrenia", "Electrophysiology", "Neurophysiology", "EEG power", "Alpha rhythm", "Transcranial magnetic stimulation", "Transcranial direct current stimulation", "Electroconvulsive therapy", "Neurofeedback", "Vagus Nerve Stimulation", "Deep Brain Stimulation", and "State dependent". Negative symptoms in schizophrenia are associated with altered activity in prefrontal cortex in functional neuroimaging studies. This is in line with electrophysiological measurements that found a change in EEG spectral power in the alpha frequency band over prefrontal brain regions. The notion of functional hypofrontality has led to hypotheses that electrotherapy applied to the prefrontal cortex may be an effective treatment of negative symptoms in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) were used to increase cortical activity in schizophrenia and achieve a clinical effect on negative symptoms. Three meta-analyses confirmed, with a moderate effect size, that rTMS is an effective treatment option for negative symptoms in schizophrenia. The two subsequently published prospective multicenter studies, however, found opposite results from each other. Two randomized controlled studies suggested that tDCS is an effective treatment option for negative symptoms. There is no study on the efficacy of neurofeedback, vagal nerve stimulation or deep brain stimulation on negative symptoms in schizophrenia. Additional studies are needed to confirm the efficacy of rTMS and tDCS on negative symptoms in schizophrenia. Influencing factors, related to clinical and stimulation parameters, of rTMS and tDCS on negative symptoms should be better investigated. Effects related to electrophysiological brain activity of the patient, especially in the alpha band, during the stimulation should also be better investigated. The action of electrotherapy may be state dependent, and a better understanding of electrophysiological effects of electrotherapy techniques could enable their optimization.
Subject(s)
Electric Stimulation Therapy , Electrophysiological Phenomena , Schizophrenia/physiopathology , Schizophrenia/therapy , Schizophrenic Psychology , Transcranial Direct Current Stimulation , Transcranial Magnetic Stimulation , HumansABSTRACT
During the past ten years, research on schizophrenia has witnessed a clear emphasis on studies based on negative symptoms. This interest can be explained in terms of diagnosis, specific treatment, functional prognosis and outcome issues. However, main current approaches consider negative symptoms from an operationalist view, which implies objective and atheoretical descriptions of clinical criteria, observed from a third person perspective. And the understanding of negative symptoms in schizophrenia, still a crucial issue of mental health, remains only partial. From a different perspective, psychopathology - and notably psychiatric phenomenology -, can provide a conceptual and clinical framework, taking into account subjective experience (first person perspective), based on a global understanding of the clinical situation lived by patients with schizophrenia. In the present review, we give a brief survey on the historical aspects of the description of negative symptoms. Then, we introduce the clinical contributions raised by clinical phenomenology. We principally develop Minkowski's notion of loss of vital contact, and Blankenburg's notion of loss of natural evidence. Then we highlight the current debates which are discussed and explored in contemporary psychopathology. In conclusion, we discuss the possible articulation between objective and subjective approaches, in order to better understand pauci-symptomatic forms of schizophrenia.