Relationship between obsessive compulsive symptomatology and severity of psychotic symptoms in schizophrenia: Meta-analysis and meta-regression analysis.

BACKGROUND: Schizophrenia patients often show obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) and their presence has been associated with poorer prognosis. However, the impact of OCS/OCD on psychotic severity remains unclear. The aim of this study is twofold: 1) to investigate the effect of OCS/OCD on the severity of positive, negative, and global psychotic symptoms of schizophrenia patients and 2) to analyze the effect of patient and study-related covariates on moderating this relationship. METHODS: A systematic review and meta-analysis (SRMA) of studies comparing the severity of psychotic symptoms among schizophrenia patients with and without OCS/OCD was performed. Standardized mean difference (SMD) was calculated for positive, negative, and global psychotic symptoms. The difference of SMD (Diff SMD) was calculated to analyze the effect of covariates on study outcomes using meta-regression. RESULTS: Sixty-seven studies involving 7740 patients were included. Patients with schizophrenia and OCS/OCD showed a slightly higher severity of positive (SMD = 0.17, p value = 0.0089) and global psychotic symptoms (SMD = 0.24, p value = 0.0104) than patients without OCS/OCD but no differences in negative symptoms were found between groups (SMD = 0.11, p value = 0.0367). Only one covariate "proportion of patients without antipsychotics (AP)" was found to modify the effect on psychotic severity (Diff SMD = -0.008, p value = 0.002). CONCLUSIONS: Comorbid OCS/OCD in schizophrenia has, at most, a minor impact on psychotic severity. Variability in this effect was considerable and was poorly explained by the covariates analyzed.

Discontinuation of pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder: meta-analysis of 63 studies enrolling 11,788 patients.

BACKGROUND: The risk-benefit balance of pharmacological treatment for children and adolescents with ADHD and the factors that moderate this relationship are unclear. METHODS: A systematic review and meta-analysis of randomised, placebo-controlled clinical trials (RPCCTs) investigating the efficacy of pharmacological treatment in children or adolescents with ADHD was carried out. Meta-analysis of treatment discontinuation, clinician-, parent- and teacher-rated efficacy and adverse events was performed. The effect of covariates was studied. RESULTS: Sixty-three studies were included. Ten drugs were investigated, with atomoxetine and methylphenidate the most frequently studied. RPCCTs had mostly a short duration (7.9 weeks). All-cause treatment discontinuation was lower with pharmacological treatment than placebo (OR = 0.68). Pharmacological treatment was more efficacious than placebo independently of the rater (clinician, standardised mean difference (SMD) 0.74; parent, SMD = 0.63; or teacher, SMD = 0.75). Evidence of publication bias was found for clinician-rated efficacy, especially in industry-sponsored RPCCT. Psychostimulants showed a higher efficacy and were associated with a better outcome on treatment discontinuation than non-stimulant drugs. Efficacy was smaller in RPCCTs for which a psychiatric comorbid disorder was an inclusion criterion, was larger in studies with a commercial sponsorship and showed a negative association with treatment length. CONCLUSIONS: In the short term, pharmacological treatment provides moderate-high symptom relief, is safe and shows lower treatment discontinuation than placebo, suggesting a suitable risk-benefit balance, particularly with psychostimulants. The efficacy is lower in patients with a comorbid psychiatric disorder and should be assessed periodically, as it appears to reduce over time. Publication bias of clinician-rated efficacy in studies with a commercial sponsor is suggested.

Clinical guideline for the treatment of dual pathology in the adult population.

Editorial del vol 28-1.

Efficacy, safety and variability in pharmacotherapy for adults with attention deficit hyperactivity disorder: a meta-analysis and meta-regression in over 9000 patients.

RATIONALE: The factors underlying the variability in the results of randomized, placebo-controlled clinical trials (RPCCT) assessing pharmacological interventions for adults with attention deficit hyperactivity disorder (ADHD) are not fully understood. METHODS: A systematic review and meta-analysis of RPCCT comparing pharmacological treatment and placebo in adults with ADHD was carried out. The study outcomes were all-cause treatment discontinuation, efficacy on ADHD symptoms, and safety. Patient-, intervention-, and study design-related covariates were collected. Meta-regression methods were applied. RESULTS: Forty-four studies involving 9952 patients were included. All-cause treatment discontinuation was slightly higher with pharmacological treatment than with placebo (odds ratio (OR) = 1.18; 95 % confidence interval (CI) 1.02, 1.36; p = 0.003). A better outcome on all-cause treatment discontinuation was observed in studies that provided concomitant psychotherapy when compared to those that did not (rate of OR (ROR) = 0.68, p = 0.048). Pharmacological treatment was efficacious for reducing ADHD symptoms (standardized mean difference (SMD) = 0.45; 95 % CI 0.37, 0.52; p < 0.00001), with stronger intervention effects found in studies investigating stimulant drugs (difference of SMD (Diff SMD) = 0.18, p = 0.017), in shorter studies (Diff SMD = -0.01, p = 0.044), and when clinician-rated scales were used (Diff SMD = 0.44, p < 0.0001). Pharmacological treatment was associated with more frequent adverse events (AEs) (OR = 2.29; 95 % CI 1.97, 2.66; p = 0.006). Studies with a lead-in phase and with a higher proportion of patients previously treated with stimulants were associated with a better safety outcome (ROR = 0.59, p = 0.017; ROR = 0.98, p = 0.036, respectively). CONCLUSION: Pharmacological treatment provides mild symptom improvement but is associated with frequent AEs and higher treatment discontinuation than placebo, particularly when no concomitant psychotherapy is administered. Stimulants appear more efficacious than non-stimulant drugs and the former should be preferred over the latter. The efficacy of pharmacological treatment should be monitored over time because it may decrease progressively.

Toxicodermias por telaprevir en el tratamiento de la infección crónica por el genotipo 1 del virus de la hepatitis C. Estudio prospectivo / Drug eruptions induced by telaprevir in patients with chronic hepatitis C virus genotype 1 infection: a prospective study

INTRODUCCIÓN: Telaprevir es un fármaco que administrado junto a interferón y ribavirina incrementa de forma significativa la respuesta al tratamiento de la infección por el virus de la hepatitis C. Sin embargo, su empleo incrementa también la probabilidad de desarrollar efectos adversos, en muchos casos cutáneos que pueden condicionar el mantenimiento del tratamiento. OBJETIVO: Conocer la incidencia, características clínicas y evolutivas y respuesta al tratamiento de las toxicodermias por telaprevir en el contexto del tratamiento de la infección por el virus de la hepatitis C. MATERIAL Y MÉTODOS: Estudio prospectivo observacional realizado entre mayo de 2012 y julio de 2013 en el que se incluyeron aquellos pacientes que iniciaron tratamiento con telaprevir durante ese periodo. En aquellos en los que se detectaron toxicodermia se recogieron los datos demográficos de los pacientes, las características clínicas de las lesiones y la evolución tras la aplicación de las recomendaciones de las guías clínicas. RESULTADOS: De un total de 43 pacientes que recibieron tratamiento triple un 46% presentó toxicodermia atribuible a telaprevir. En el 90% de los casos esta fue leve o moderada (grados 1 o 2) y consistió en un exantema constituido por pápulas y placas eritematoedematosas y descamativas. En alrededor de un tercio de los pacientes se comprobó la progresión de la toxicodermia, principalmente en extensión, durante el curso del tratamiento. En 2 casos (4,6%) las lesiones cutáneas condicionaron la suspensión del fármaco. Un 79% de los tratados (34 pacientes) alcanzó una respuesta viral sostenida tras el tratamiento. CONCLUSIONES: Las toxicodermias asociadas a telaprevir son frecuentes en el curso del tratamiento y a menudo progresivas. Sin embargo, solo de forma excepcional condicionan su suspensión

INTRODUCTION: When co-administered with interferon and ribavirin, the prescription drug telaprevir significantly improves treatment response in patients with chronic hepatitis C virus (HCV) infection. Its use, however, also increases the likelihood of adverse effects that may lead to discontinuation of treatment. Cutaneous adverse effects are particularly common. OBJECTIVE: To determine the frequency and clinical characteristics of drug eruptions induced by telaprevir in patients receiving HCV treatment and to analyze the clinical course of lesions and response to treatment. MATERIAL AND METHODS: We performed a prospective observational study of all patients who started a treatment regimen that included telaprevir between May 2012 and July 2013. We recorded the demographic characteristics of the patients who developed telaprevir-induced eruptions, and analyzed the clinical characteristics of the lesions and their clinical course following the application of guideline-based treatment recommendations. RESULTS: Twenty (46%) of the 43 patients who received triple therapy with interferon, ribavirin, and telaprevir during the study period developed drug reactions attributable to telaprevir. The reaction was classified as mild or moderate (grades 1 or 2) in 90% of cases and consisted of an exanthem with erythematous-edematous scaling plaques and papules. The rash worsened, mainly by spreading, in about one-third of cases. The skin lesions led to discontinuation of treatment in 2 patients (4.6%). Sustained viral response was achieved in 34 patients (79%). CONCLUSIONS: Telaprevir-induced eruptions are common and often progress, but they rarely require patients to discontinue treatment

Drug eruptions induced by telaprevir in patients with chronic hepatitis C virus genotype 1 infection: a prospective study.

INTRODUCTION: When co-administered with interferon and ribavirin, the prescription drug telaprevir significantly improves treatment response in patients with chronic hepatitis C virus (HCV) infection. Its use, however, also increases the likelihood of adverse effects that may lead to discontinuation of treatment. Cutaneous adverse effects are particularly common. OBJECTIVE: To determine the frequency and clinical characteristics of drug eruptions induced by telaprevir in patients receiving HCV treatment and to analyze the clinical course of lesions and response to treatment. MATERIAL AND METHODS: We performed a prospective observational study of all patients who started a treatment regimen that included telaprevir between May 2012 and July 2013. We recorded the demographic characteristics of the patients who developed telaprevir-induced eruptions, and analyzed the clinical characteristics of the lesions and their clinical course following the application of guideline-based treatment recommendations. RESULTS: Twenty (46%) of the 43 patients who received triple therapy with interferon, ribavirin, and telaprevir during the study period developed drug reactions attributable to telaprevir. The reaction was classified as mild or moderate (grades 1 or 2) in 90% of cases and consisted of an exanthem with erythematous-edematous scaling plaques and papules. The rash worsened, mainly by spreading, in about one-third of cases. The skin lesions led to discontinuation of treatment in 2 patients (4.6%). Sustained viral response was achieved in 34 patients (79%). CONCLUSIONS: Telaprevir-induced eruptions are common and often progress, but they rarely require patients to discontinue treatment.

Pharmacological treatment of attention deficit hyperactivity disorder with co-morbid drug dependence.

BACKGROUND: Drug dependence is frequent in patients with attention deficit hyperactivity disorder (ADHD). Nevertheless, the efficacy and safety of pharmacological treatments in this population are unclear. METHODS: A systematic review with meta-analysis was performed. Randomised placebo-controlled clinical trials investigating the efficacy of pharmacological treatment in patients with co-occurring ADHD and substance use disorder (SUD) were included. ADHD symptom severity, drug abstinence and all-cause treatment discontinuation were the primary study endpoints. The effects of patient-, intervention- and study-related covariates over the primary outcomes were investigated by means of meta-regression. RESULTS: Thirteen studies were included, enrolling a total of 1,271 patients. A small to moderate reduction of ADHD symptoms was found. Meta-regression analysis identified the presence of a lead-in period as a covariate associated with reduced efficacy. Conversely, no beneficial effect was observed either on drug abstinence or treatment discontinuation. The efficacy on ADHD symptoms was smaller in studies with a lead-in period. A positive correlation between the efficacy for ADHD and that for SUD was found. CONCLUSIONS: The efficacy of pharmacological interventions for co-occurring ADHD and SUD has been little investigated. Mixed results were obtained: while pharmacological interventions improved ADHD symptoms, no beneficial effect on drug abstinence or on treatment discontinuation was noted. The strength of the recommendation of pharmacological treatment for co-occurring ADHD and SUD is therefore modest. The study was registered with the international prospective register of systematic reviews (PROSPERO): CRD 4212003414.