Trastornos adaptativos y su manejo desde atención primaria / Adaptive disorders and their management in primary care

Introducción: El trastorno de adaptación describe una respuesta emocional y conductual desproporcionada a uno o más estresores psicosociales identificables. Existen múltiples situaciones capaces de generarnos una situación de estrés agudo. Sin embargo, uno de los requisitos necesarios para poder hablar de trastorno adaptativo es que ese o esos factores estresantes supongan un deterioro en el funcionamiento normal del individuo. Objetivos: El objetivo principal de este trabajo es analizar, mediante una revisión bibliográfica, el diagnóstico y abordaje de los trastornos adaptativos dentro del ámbito de Atención Primaria. El objetivo secundario es destacar la importancia de la detección y el tratamiento precoces, así como de la gestión multidisciplinar y la promoción de la salud mental. Resultados: Los principales factores de riesgo de los trastornos adaptativos son el desempleo, los bajos ingresos,el escaso apoyo social, las enfermedades físicas y la salud mental. La prevalencia es mayor en jóvenes,especialmente entre las mujeres, y existe un riesgo aumentado de suicidio en el subtipo de estado de ánimo depresivo. El Cuestionario Internacional de Trastornos Adaptativos es actualmente la principal herramienta diagnóstica, por establecer sus criterios diagnósticos en base a la definición teórica establecida por la CIE-11. El manejo de estos trastornos se realiza principalmente mediante terapia cognitivo-conductual. Conclusiones: Los trastornos de adaptación surgen como respuestas anormales ante ciertas situaciones estresantes. El papel de los médicos de Atención Primaria en el abordaje de este trastorno es primordial, siendo necesaria su detección y manejo precoz para disminuir los niveles de ansiedad disfuncionales que presentan los pacientes.(AU)

Introduction: Adjustment disorder describes a disproportionate emotional and behavioral response to one or more identifiable psychosocial stressors. There are multiple situations capable of generating an acute stressful situation. However, one of the requirements to be able to speak of an adaptive disorder is that the stressor(s) in question should lead to an impairment of the individual's normal functioning.Objectives: The main objective of this work is to analyze , through a literature review, the diagnosis and approach to the diagnosis and management of adaptive disorders in the Primary Care setting. The secondary objective is toemphasize the importance of early detection and treatment, as well as multidisciplinary management and mentalhealth promotion. Results: The main risk factors for adjustment disorders are unemployment, low income, low social support, physical illness, and personal history of mental health. The International Questionnaire of Adaptive Disorders is currently the principal diagnostic tool, as it establishes its diagnostic criteria based on the theoretical definition established by the ICD-11. The management of these disorders is mainly through cognitive behavioural therapy.Conclusions: Adjustment disorders arise as abnormal responses to certain stressful situations. The role of primary care physicians in dealing with this disorder is essential, and early detection and management are necessary to reduce the levels of dysfunctional anxiety that patients present.(AU)

Effect of a Dietary Supplement Combining Bioactive Peptides and Magnesium on Adjustment Disorder with Anxiety: A Clinical Trial in General Practice.

Anxiety is a high frequency disorder in the general population. It is usually treated with benzodiazepines, which cause side effects and a dependence that could make withdrawal difficult. Alternative treatments are therefore needed to reduce the use of anxiolytics, particularly for adjustment disorder with anxiety. An observational, multicentre, prospective, longitudinal study has been conducted by general practitioners and one gynaecologist to evaluate the efficacy of a dietary supplement on adjustment disorder with anxiety (Stress 2 study). Patients diagnosed as anxious with a score of ≥20 on the Hamilton Anxiety Rating Scale (Ham-A, first visit on Day 0 (V0)) were offered a 28-day treatment with a dietary supplement formulated with bioactive peptides from a fish protein hydrolysate (Gabolysat®), magnesium and vitamin B6. At the second visit (V1), the Ham-A Rating Scale, the Patient Global Impression scale (PGI) and the Clinical Global Impressions scale (CGI) were administered. A 50% reduction in the Ham-A score, was achieved for 41.9% of the patients. The mean Ham-A score decreased by 12.1 ± 5.7 points (p < 0.001) between V0 (25.6 ± 3.8) and V1 (13.6 ± 6.0). Furthermore, according to the CGI scale, the anxiety of 75.3% of patients improved significantly and very significantly, with limited side effects and a negligible rebound effect. In conclusion, adjustment disorder with anxiety seems to be effectively managed by an alternative and safer solution than benzodiazepines.

[Diagnosis and treatment of adjusment disorder in primary care]. / Diagnóstico y tratamiento del trastorno de adaptación en Atención Primaria.

Adjustment disorder (AD) corresponds to the combination of affective, cognitive and behavioral symptoms that appear after a stressful event. It is a frequent reason for consultation in primary care and is one of the most common diagnoses in suicide attempts attended in the emergency department. Its essential feature is that the symptoms must appear in direct relation to an event perceived as stressful, so it tends to be transitory if the event ceases or the patient adapts. The mainstay of treatment are psychosocial interventions, aimed at modifying the event or its consequences, supporting adaptation and optimizing resources to cope with the event. However, prescription of psychotropic drugs is favored in practice, when its use should be limited to symptomatic relief. This highlights the need to properly identify and treat it. This article presents the strategies for diagnosis and treatment of AD in primary care.

Therapeutic Interventions for Adjustment Disorder: A Systematic Review.

BACKGROUND: Adjustment disorder requires therapeutic intervention because of its complications, which include a significant risk of suicide, but evidence-based therapeutic guidelines are not available. AREAS OF UNCERTAINTY: The main problem is related to answer to the following question: What is the optimal therapeutic approach to adjustment disorder? In this respect we review all randomized controlled trials that aimed to investigate therapeutic interventions for adjustment disorder in adult populations. DATA SOURCES: Comprehensive search of the electronic database PubMed (January 1980-June 2019). The review included clinical trials that aimed to investigate a psychological or pharmacological treatment for adjustment disorder in adult population and reported outcome data for therapeutic interventions. RESULTS: The search identified 23 studies that fulfilled the inclusion criteria for this review. Pharmacotherapy interventions were the focus of 11 studies that used various medications and dosages including viloxazine, lormetazepam, S-adenosylmethionine, pivagabine, trazodone, clorazepate, etifoxine, lorazepam, diazepam, afobazole, and plant extracts (Kava-kava, Euphytose, and Ginkgo biloba) on a total number of 1020 patients. Psychotherapy interventions were identified in 12 studies that used mirror therapy, short-term dynamic psychotherapy, yoga meditation, body-mind-spirit technique, mindfulness, bibliotherapy (self-help manual), humor training, and cognitive behavioral therapy. CONCLUSIONS: Psychotherapy seems indicated for mildly symptomatic adjustment disorder. Given the fact that adjustment disorder with severe symptoms is associated with a high risk of suicidal ideation and suicide attempts, clinicians must consider the potential benefit of using psychotropic agents such as benzodiazepines, antidepressants, or etifoxine.

Alcohol Consumption or Excessive Use of Psychotropic Medication Prior to Suicidal Self-injury in Patients with Adjustment Disorder, Depression, and Schizophrenia: A Cross-sectional Study.

The use of alcohol or drug(s) prior to self-injury is a possible inducing factor for suicidal self-injuries among patients with adjustment disorder. We analyzed the cases of 175 individuals who were admitted to the intensive care unit (ICU) of Tokyo Medical and Dental University Medical Hospital for suicidal self-injury to determine whether alcohol consumption or an excessive use of prescribed psychotropic medications prior to self-injury is more common in patients with adjustment disorder. During a 7-year period (July 2006 to June 2013) following their deliberate self-injuries, 971 patients were admitted to the ICU. Our study sample (n=175) was restricted to patients with adjustment disorder (n=48), major depressive disorder (n=90), or schizophrenia (n=37). The outcome variable was alcohol consumption or excessive use of medications prior to suicidal self-injury. A logistic regression analysis revealed that the patients with adjustment disorder more commonly showed alcohol consumption or excessive medication use prior to their suicidal self-injury compared to those with schizophrenia (odds ratio: 8.10; 95%CI: 2.97-24.60). To inhibit suicidal self-injury among patients with adjustment disorder, it is important to continue efforts to provide psychoeducation about alcohol use and to instruct the patients to take their prescribed medication(s) only as directed by their physician.

Association of Early Treatment With Chronicity and Hazard of Hospitalization After New Adjustment Disorder.

OBJECTIVE: This study aimed to examine the effect of early treatment with psychotherapy or psychoactive medications on later hospitalizations for patients with a new diagnosis of adjustment disorder. METHODS: Commercial claims data from Truven Health MarketScan were used. Patient-level propensity score matching was performed, and the authors fit an inverse probability of treatment weighting to a Cox proportional hazard model. RESULTS: Early receipt of psychoactive medication instead of psychotherapy was associated with an increased hazard of later psychiatric hospitalization (hazard ratio [HR]=2.61, 95% confidence interval [CI]=2.07-3.28) and overall hospitalization (HR=1.12, 95% CI=1.04-1.21). Specifically, benzodiazepines were associated with increased hazard of later psychiatric hospitalization (HR=1.59, 95% CI=1.02-2.51), which did not differ from medications overall. In contrast, early receipt of psychotherapy was associated with a small decrease in the hazard of later psychiatric hospitalization (HR=0.85, 95 % CI=0.73-0.99) but had no effect on overall hospitalizations. CONCLUSIONS: Early medication treatment for adjustment disorder was associated with greater overall and psychiatric hospitalization compared with no early medication treatment. This study suggests that an observed provider preference to use medications to treat patients who have comorbid physical illness may have deleterious long-term effects.

Pharmacotherapy of psychiatric inpatients with adjustment disorder: current status and changes between 2000 and 2016.

Adjustment disorder is a temporary change in behaviour or emotion as a reaction to a stress factor. Therapy consists of psychotherapy, and pharmacotherapy can be advised. However, data on the real-life pharmacological treatment are sparse. Prescription data for 4.235 psychiatric inpatients diagnosed with adjustment disorder in the time period 2000-2016 were analysed. The data were obtained from the Drug Safety Programme in Psychiatry (AMSP). Data were collected on two reference days per year; prescription patterns and changes over time were analysed. Of all patients, 81.2% received some type of psychotropic drug. Mostly antidepressants (59.8%), antipsychotics (35.5%), and tranquilisers (22.6%) were prescribed. Prescription rates for antidepressants decreased slightly over the years, while rates for antipsychotics increased, especially for atypical antipsychotics. It is important to note that the diagnosis "adjustment disorder" is most likely a working diagnosis that is used for patients in immediate need of psychiatric aid. Overall, pharmacotherapy for inpatients with this diagnosis is mostly symptom-oriented and focuses on depressive moods, agitation and anxiety. Therapy regimes changed over time and show an increased use of atypical antipsychotics with sedative properties. However, for most of the medication, there are neither evidence-based studies nor guidelines, and drugs might be contraindicated in some cases.

Acute transient psychotic disorder precipitated by Brexit vote.

A man in his 40s was brought to the accident and emergency department in an acute psychotic state, 3 weeks after the European Union referendum results in the UK were declared. His mental health had deteriorated rapidly following the announcement of the results, with significant concerns about Brexit. He presented as agitated, confused and thought disordered. He had auditory hallucinations, and paranoid, referential, misidentification and bizarre delusions. He recovered completely within 2 weeks after a brief admission and treatment with olanzapine. He had experienced a similar episode of much less severity 13 years previously after major work related stress which resolved completely within a few days. He was experiencing stress related to work and family prior to the current episode which could potentially have been a contributory factor. Political events can act as major psychological stressors and have a significant impact on the mental health of people, especially those with a predisposition to develop mental illness.

Real-World Direct Health Care Costs Associated with Psychotropic Polypharmacy Among Adults with Common Cancer Types in the United States.

BACKGROUND: Psychotropic polypharmacy is not uncommon among cancer patients and may contribute to the increased direct health care cost burden in this population. OBJECTIVE: To estimate average direct health care costs in the year following cancer diagnosis among cancer patients receiving psychotropic polypharmacy compared with those without psychotropic polypharmacy, using a multivariable analysis framework. METHODS: A retrospective cross-sectional study was conducted among patients aged 18 years and older diagnosed with the most commonly occurring cancers (breast, prostate, lung, and colorectal) in the United States during 2011-2012 using the deidentified Optum Clinformatics Data Mart commercial claims database. Psychotropic polypharmacy was defined as concurrent use of 2 or more psychotropic medications for at least 90 days. Direct health care costs in the year following cancer diagnosis were estimated as total medical payments made by the health plans and were derived from claims files. A generalized linear regression model with log-link function and gamma distribution was used to model average direct health care costs, controlling for baseline patient demographic and clinical covariates. RESULTS: Average annual direct health care costs for cancer patients with psychotropic polypharmacy ($53,497; SD $72,590) were higher than those without psychotropic polypharmacy ($38,255; SD $59,844), with an unadjusted average cost difference of $15,242 (P < 0.0001). In the adjusted regression model, the average difference in costs shrunk to $5,888 but remained notable. When examined by type of cancer, average direct health care costs for all cancer patients with psychotropic polypharmacy were significantly higher than those for patients without psychotropic polypharmacy, except for colorectal cancer patients. CONCLUSIONS: Overall health care costs were higher among cancer patients with psychotropic polypharmacy compared with those without psychotropic polypharmacy. Our findings support the need for future research to better understand the benefits and risks of psychotropic polypharmacy, given its potential to cause adverse health outcomes and avoidable health care utilization and costs for this vulnerable patient population. DISCLOSURES: This study was funded by the American Association of Colleges of Pharmacy (AACP) New Investigator Award mechanism, which was received by Vyas. Aroke was partially supported by the AACP grant for conducting data analysis of the study. Kogut is partially supported by Institutional Development Award Number U54GM115677 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds Advance Clinical and Translational Research (Advance-CTR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health and the AACP. The authors report no conflicts of interest. An abstract of this study was presented as a poster at the American Association of Colleges of Pharmacy Annual Meeting on July 22, 2018, in Boston, MA.

Anxiolytics targeting GABAA receptors: Insights on etifoxine.

OBJECTIVES: Anxiety and adjustment disorders are among the most prevalent mental health conditions. This review focuses on γ-aminobutyric acid receptor type A (GABAAR)-mediated anxiolysis, describing the action of both endogenous and exogenous modulators of GABAAR. Future directions and innovative strategies to alleviate anxiety symptoms are discussed, with a particular emphasis on etifoxine. METHODS: We used available data from the recent literature to update the mode of action of anxiolytics. We focussed our search on anxiolytics acting at GABAARs, as well as on the pharmacological properties of formerly and currently prescribed anxiolytics. RESULTS: Considering the adverse effects of current treatments aimed at increasing inhibitory controls, optimisation of existing pharmacotherapies is of crucial importance. Among the alternative compounds targeting the GABAergic system, translocator protein (TSPO) ligands, such as etifoxine (EFX), which promote endogenous neurosteroidogenesis, are emerging as promising candidates for anxiety relief. In several papers comparing the efficacy of benzodiazepines and EFX, EFX showed interesting properties with limited side effects. Indeed, neurosteroids are potent GABAAR modulators with highly underrated anxiolytic properties. CONCLUSIONS: Novel therapeutic strategies have been emerging following the recognition of neurosteroids as potent anxiolytics. Featured at the top of the list for well-tolerated anxiety relief, TSPO ligands such as etifoxine appear promising.

Pharmacotherapy of adjustment disorder: A review.

BACKGROUND: Adjustment disorder has been reconceptualized as a trauma- and stressor-related condition, and there is a growing understanding of the psychobiology of stress responses. Against this context it is timely to review of the pharmacotherapy of adjustment disorder. METHODS: A comprehensive electronic database (Pubmed) was searched for randomised controlled trials of the pharmacotherapy of adjustment disorder. Data from each trial were extracted and collated. RESULTS: To date there have been relatively few controlled trials in this area. Comparator trials provide limited support for a number of antidepressant agents, and a series of studies indicate that etifoxine is superior to buspirone and benzodiazepines for adjustment disorder with anxiety. CONCLUSIONS: The work done has been useful insofar as it provides clinicians with some insights into the advantages and disadvantages of a number of pharmacotherapy options. Additional rigorously designed trials are needed to further advance the field.

A Systematic Review of Psychological and Pharmacological Treatments for Adjustment Disorder in Adults.

Adjustment disorder is a common psychiatric disorder, yet knowledge of the efficacious treatments for adjustment disorder is limited. In this systematic review, we aimed to examine psychological and pharmacological interventions that target adjustment disorder in adults to determine which interventions have the best evidence for improving adjustment disorder symptoms. We performed database searches for literature published between January 1980 and September 2016 and identified studies that included both a sample majority of individuals diagnosed with adjustment disorder and findings on adjustment disorder symptom outcomes. There were 29 studies that met the inclusion criteria for qualitative synthesis; the majority of studies (59%) investigated psychological therapies rather than pharmacological treatments (35%). The range of psychological therapies tested was diverse, with the majority containing cognitive behavioral therapy (CBT) components (53%), followed by three studies that were psychodynamic-related, three studies that were behavioral therapy-based, and two studies that involved relaxation techniques. We rated individual studies using a modified National Health and Medical Research Council quality and bias checklist and then used the Grading of Recommendations Assessment, Development and Evaluation (GRADE; Grade Working Group, 2004) system to rate the overall quality of the evidence. Despite several randomized controlled trials, the quality of the evidence for positive effects of all psychological and pharmacological treatments on symptoms of adjustment disorder was ranked as low to very low. Future high-quality research in the treatment of adjustment disorder has the potential to make a significant difference to individuals who struggle to recover after stressful events.

Antidepressants for the treatment of depression in people with cancer.

BACKGROUND: Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have been shown to have a negative impact in terms of quality of life, compliance with anti-cancer treatment, suicide risk and likely even the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results. OBJECTIVES: To assess the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage). SEARCH METHODS: We searched the following electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 6), MEDLINE Ovid (1946 to June week 4 2017), Embase Ovid (1980 to 2017 week 27) and PsycINFO Ovid (1987 to July week 4 2017). We additionally handsearched the trial databases of the most relevant national, international and pharmaceutical company trial registers and drug-approving agencies for published, unpublished and ongoing controlled trials. SELECTION CRITERIA: We included RCTs comparing antidepressants versus placebo, or antidepressants versus other antidepressants, in adults (aged 18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis). DATA COLLECTION AND ANALYSIS: Two review authors independently checked eligibility and extracted data using a form specifically designed for the aims of this review. The two authors compared the data extracted and then entered data into Review Manager 5 using a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We retrieved a total of 10 studies (885 participants), seven of which contributed to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update we included one additional unpublished study. These new data contributed to the secondary analysis, while the results of the primary analysis remained unchanged.For acute-phase treatment response (6 to 12 weeks), we found no difference between antidepressants as a class and placebo on symptoms of depression measured both as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants; very low certainty evidence) and as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants; very low certainty evidence). No trials reported data on follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, showing no difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants; very low certainty evidence). No clear evidence of a beneficial effect of antidepressants versus either placebo or other antidepressants emerged from our analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low certainty evidence). In terms of dropouts due to any cause, we found no difference between antidepressants as a class compared with placebo (RR 0.85, 95% CI 0.52 to 1.38, seven RCTs, 479 participants; very low certainty evidence), and between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the certainty (quality) of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity. AUTHORS' CONCLUSIONS: Despite the impact of depression on people with cancer, the available studies were very few and of low quality. This review found very low certainty evidence for the effects of these drugs compared with placebo. On the basis of these results, clear implications for practice cannot be deduced. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent to prescribe may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. To better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.

Intervenciones farmacológicas que mejoren la cognición y el funcionamiento adaptativo en el síndrome de Down: Progresos hasta la fecha / No disponible

Pese al creciente número de ensayos clínicos desarrollados para evaluar la cognición en el síndrome de Down, sus resultados para identificar intervenciones eficaces han sido muy limitados hasta la fecha. Las intervenciones en los modelos animales, con frecuencia muy favorables, no se han visto reflejadas en los ensayos clínicos. Esta revisión describe los resultados de los principales ensayos realizados. Ofrece consideraciones a los investigadores y describe estrategias a la industria farmacéutica para que se implique crecientemente en el descubrimiento de fármacos en el síndrome de Down

Although an increasing number of clinical trials have been developed for cognition in Down syndrome, there has been limited success to date in identifying effective interventions. This review describes the progression from pre-clinical studies with mouse models to human clinical trials research using pharmacological interventions to improve cognition and adaptive functioning in Down syndrome. We also provide considerations for investigators when conducting human clinical trials and describe strategies for the pharmaceutical industry to advance the field in drug discovery for Down syndrome

Deterioro cognitivo secundario a trastorno por uso de benzodiacepinas y su reversibilidad: a propósito de un caso / Cognitive impairment induced by benzodiazepine use disorder and its reversibility: a case report

No disponible

[Evaluation of the therapeutic efficacy and safety of the selective anxiolytic afobazole in generalized anxiety disorder and adjustment disorders: Results of a multicenter randomized comparative study of diazepam]. / Otsenka terapevticheskoi effektivnosti i bezopasnosti selektivnogo anksiolitika afobazola pri generalizovannom trevozhnom rasstroistve i rasstroistvakh adaptatsii: rezul'taty mnogotsentrovogo randomizirovannogo sravnitel'nogo s diazepamom issledovaniya.

AIM: to summarize the previously published results of a multicenter randomized clinical research phase III study trial of afobazole (INN: fabomotizole) versus diazepam in the treatment of patients with generalized anxiety disorder (GAD) and adjustment disorders (AD). SUBJECTS AND METHODS: Five investigating centers included 150 patients aged 18 to 60 years (60 patients with GAD and 90 with AD) a simple structure of anxiety disorders without concurrent mental, neurological or somatic disorders. Patients were randomized to take afobazole (30 mg/day; n=100) or diazepam (30 mg/day; n=50) for 30 days. Prior to drug administration, patients susceptible to placebo were excluded according to the results of its 7-day use. Withdrawal syndrome was evaluated within 10 days after completion of active therapy. The primary efficacy endpoint was the change of Hamilton Anxiety Rating Scale (HAMA) total score. The scores of the Clinical Global Impression (CGI) Scale and the Sheehan Scale as secondary efficacy endpoints  were analyzed. Drug safety was evaluated by assessment of adverse events. RESULTS: Afobazole and diazepam caused a significant reduction of HAMA total score. In the afobazole group, the reduction of anxiety  exceeded that in the diazepam group (the difference in the total score changes was 2.93 [0.67; 5.19]; p=0,01).The proportion of patients with reduction of disease severity was 72% in the afobazole group and 58% in the diazepam group. After therapy completion, the proportion of patients with no or mild disorder in the afobazole group was significantly higher than that in the diazepam group (69 and 44%, respectively; χ2=12.46; p=0,014). There was a trend toward a higher subjective patient-rated estimate of the afobazole effect using the Sheehan scale. There were a total of 15 and 199 adverse events in the afobazole and diazepam groups, respectively. No manifestations of afobazole withdrawal syndrome were found. Diazepam withdrawal syndrome was observed in 34 (68%) patients. CONCLUSION: Afobazole is an effective and safe drug to treat patients with GAD and AD and non-inferior than diazepam in the treatment of these disorders, however it is superior in terms of several variables, including the safety profile.

Effects of Direct-To-Consumer Advertising on Patient Prescription Requests and Physician Prescribing: A Systematic Review of Psychiatry-Relevant Studies.

OBJECTIVE: To systematically analyze the effects of direct-to-consumer advertising (DTCA) on patient requests for medication and physician prescribing across psychiatry-relevant studies. DATA SOURCES: MEDLINE, PsycINFO, Thomson Reuters' ISI Web of Knowledge, and Google Scholar were searched (1999-2014) using variations of the terms direct-to-consumer advertising and psychiatric. Reference lists and an online repository of DTCA manuscripts were also scrutinized. STUDY SELECTION: English-language studies collecting data at the point of service, focusing on or including psychiatric medication, and assessing the effects of DTCA on patient and/or physician behavior were included. Of 989 articles identified, 69 received full-text review. Four studies across 5 manuscripts met inclusion criteria. DATA EXTRACTION: Data were extracted on participants, study design, methodological quality, and results. Methodological quality of individual studies was assessed using adapted criteria from the Effective Public Health Practice Project. Confidence in conclusions across studies was determined using principles from the well-established GRADE system. FINDINGS: Due to lack of replication across strong randomized controlled trials (RCTs), no conclusions merited high confidence. With moderate confidence, we concluded that DTCA requests (1) are granted most of the time (1 RCT, 3 observational), (2) prompt higher prescribing volume (1 RCT, 1 observational), (3) promote greater adherence to minimally acceptable treatment guidelines for patients with depression (1 RCT), and (4) stimulate overprescribing among patients with an adjustment disorder (1 RCT). CONCLUSIONS: Findings suggest that DTCA requests are typically accommodated, promote higher prescribing volume, and have competing effects on treatment quality. More methodologically strong studies are needed to increase confidence in conclusions.

Optimizing Treatment of Complicated Grief: A Randomized Clinical Trial.

IMPORTANCE: To our knowledge, this is the first placebo-controlled randomized clinical trial to evaluate the efficacy of antidepressant pharmacotherapy, with and without complicated grief psychotherapy, in the treatment of complicated grief. OBJECTIVE: To confirm the efficacy of a targeted complicated grief treatment (CGT), determine whether citalopram (CIT) enhances CGT outcome, and examine CIT efficacy without CGT. DESIGN, SETTING, AND PARTICIPANTS: Included in the study were 395 bereaved adults who met criteria for CG recruited from March 2010 to September 2014 from academic medical centers in Boston, Massachusetts; New York, New York; Pittsburgh, Pennsylvania; and San Diego, California. Co-occurring substance abuse, psychosis, mania, and cognitive impairment were exclusionary. Study participants were randomized using site-specific permuted blocks stratified by major depression into groups prescribed CIT (n = 101), placebo (PLA; n = 99), CGT with CIT (n = 99), and CGT with PLA (n = 96). Independent evaluators conducted monthly assessments for 20 weeks. Response rates were compared under the intention-to-treat principle, including all randomized participants in a logistic regression with inverse probability weighting. INTERVENTIONS: All participants received protocolized pharmacotherapy optimized by flexible dosing, psychoeducation, grief monitoring, and encouragement to engage in activities. Half were also randomized to receive manualized CGT in 16 concurrent weekly sessions. MAIN OUTCOMES AND MEASURES: Complicated grief-anchored Clinical Global Impression scale measurments every 4 weeks. Response was measured as a rating of "much improved" or "very much improved." RESULTS: Of the 395 study participants, 308 (78.0%) were female and 325 (82.3%) were white. Participants' response to CGT with PLA vs PLA (82.5% vs 54.8%; relative risk [RR], 1.51; 95% CI, 1.16-1.95; P = .002; number needed to treat [NNT], 3.6) suggested the efficacy of CGT, and the addition of CIT did not significantly improve CGT outcome (CGT with CIT vs CGT with PLA: 83.7% vs 82.5%; RR, 1.01; 95% CI, 0.88-1.17; P = .84; NNT, 84). However, depressive symptoms decreased significantly more when CIT was added to treatment (CGT with CIT vs CGT with PLA: model-based adjusted mean [standard error] difference, -2.06 [1.00]; 95% CI, -4.02 to -0.11; P = .04). By contrast, adding CGT improved CIT outcome (CIT vs CGT with CIT: 69.3% vs 83.7%; RR, 1.21; 95% CI, 1.00-1.46; P = .05; NNT, 6.9). Last, participant response to CIT was not significantly different from PLA at week 12 (45.9% vs 37.9%; RR, 1.21; 95% CI, 0.82-1.81; P = .35; NNT, 12.4) or at week 20 (69.3% vs 54.8%; RR, 1.26; 95% CI, 0.95-1.68; P = .11; NNT, 6.9). Rates of suicidal ideation diminished to a substantially greater extent among participants receiving CGT than among those who did not. CONCLUSIONS AND RELEVANCE: Complicated grief treatment is the treatment of choice for CG, and the addition of CIT optimizes the treatment of co-occurring depressive symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01179568.

[Interest of computer-based cognitive behavioral stress management. Feasability of the Seren@ctif program]. / Intérêt d'un programme self help de gestion du stress sur support numérique. Étude de faisabilité du programme Seren@ctif.

INTRODUCTION: Cognitive-behavioural stress management programs have been studied in many countries. Many reports have shown beyond a doubt their efficacy to reduce perceived stress, anxiety symptoms and to improve quality of life of patients. Considering the very large number of people who could benefit from such programs but are unable to reach them, self-help programs have been offered. First presented as books (bibliotherapy), these programs then became enriched by computing and digital supports. Regrettably, many of the programs of stress management based on the Cognitive behavioural therapy (CBT) both in face-to-face and on digital support have been little evaluated in France. To our knowledge, the Seren@ctif program is the first French language self-help program of stress management proposed on digital support. AIM OF THE STUDY: We led a feasibility study of this program on 10 patients responding to the diagnosis of adjustment disorder with anxiety according to the DSM IV criteria. METHODS: The program includes 5 weekly sessions that the patient follows in our unit from a web site. He benefits from minimal contact with a medical member of staff before and after every session. Right from the first session an USB key is supplied to the patient containing videos, audio files, self-help book portfolio in the form of an e-guide, and log books with the exercises to be realized between each sessions of the 5 session program. The patient is encouraged to practice 20 minutes of exercises 5 or 6 days per week. The program's feasibility has been assessed in accordance with a standard satisfaction scale. Anxiety symptomatology has been quantified thanks to the Spielberger State-Trait Anxiety Inventory (STAI-Y-S). RESULTS: After the scheduled 5 weeks, good results were found in terms of acceptability and attractiveness. The average score to the satisfaction survey was at least equal to 4 out of 5 for each item. The mean score on the STAI-State decreased from 53,4 (SD: 8,29) to 44,2 (SD: 7,73) following the intervention. DISCUSSION: The Seren@ctif program may be useful within the framework of a psychoeducative approach. It could also be advised for people suffering from anxiety related to stress. Soon, the program will be tested on patients with usual care suffering from adjustment disorder with anxiety in order to precisely assess its benefits.