Early onset of response with selective serotonin reuptake inhibitors in obsessive-compulsive disorder: a meta-analysis.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are recommended as the first-line pharmacologic treatment for obsessive-compulsive disorder (OCD). SSRI response is thought to be delayed in OCD, even more so than in major depression. We conducted a meta-analysis to examine the trajectory of treatment response to SSRIs and how this trajectory is modulated by dosage. DATA SOURCES: PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched on May 22, 2013, for randomized, placebo-controlled SSRI trials in OCD with the search terms "serotonin uptake inhibitors" [MeSH] OR "serotonin uptake inhibitors" [Pharmacologic Action] AND "obsessive-compulsive disorder" [MeSH]. There were no language limitations on the search. STUDY SELECTION: Randomized, placebo-controlled trials that examined the efficacy of SSRIs in the treatment of adults with OCD and utilized the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as an outcome were selected. DATA EXTRACTION: We extracted weekly symptom data from randomized, placebo-controlled trials of SSRIs for the treatment of adults with OCD in order to characterize the trajectory of pharmacologic response. Our primary outcome was weighted mean difference on the Y-BOCS of SSRI treatment compared to placebo. We used the PROC MIXED procedure in SAS to examine 6 possible models of SSRI response. Interaction terms were utilized to examine the effect of dose, individual agent, and year of publication on SSRI response. RESULTS: The meta-analysis included 17 trials of SSRIs including 3,276 subjects. A statistically significant benefit of SSRIs compared to placebo was seen within 2 weeks after the start of treatment (weighted mean difference = -0.91 [95% CI, -0.54 to -1.28], P < .001). A logarithmic response curve, indicating decreasing symptom improvement over time, provided the best fit for the trajectory of OCD symptom improvement. A significantly greater response was associated with using higher doses of SSRIs (P < .0001). CONCLUSIONS: These results suggest that the greatest incremental treatment gains in OCD are seen early on in SSRI treatment. This is consistent with a previous meta-analysis examining time course of SSRI action in major depressive disorder and contrasts with the widely held belief that SSRI response in OCD is delayed.

Systematic Review of Pharmacological and Behavioral Treatments for Skin Picking Disorder.

Skin picking disorder (SPD) is a newly recognized psychiatric disorder in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A systematic review was conducted to assess the efficacy of pharmacological and behavioral interventions for SPD. Electronic databases were searched for randomized controlled trials (RCTs) or uncontrolled trials involving at least 10 subjects that examined the efficacy of pharmacological and behavioral interventions for SPD. We examined the improvement associated with interventions compared with inactive control conditions in RCTs and improvement over time in uncontrolled trials and within the treatment arms of RCTs. We stratified studies on the basis of intervention type. Meta-analysis included 11 studies. All interventions (including inactive control conditions) demonstrated significant improvement over the course of short-term clinical trials in SPD. Only behavioral treatments demonstrated significant benefits compared with inactive control conditions. There was no evidence from RCTs that pharmacotherapy with selective serotonin reuptake inhibitors or lamotrigine were more effective at treating SPD than placebo. Our meta-analysis suggests that subjects with SPD show significant improvement during short-term trials, regardless of the efficacy of the underlying intervention. This finding suggests that uncontrolled trials are of particularly limited utility for assessing efficacy of treatments in SPD. Future research should concentrate on developing larger placebo-controlled RCTs to examine efficacy of novel pharmacological agents. In addition, research should focus on improving accessibility of behavioral treatments with demonstrated efficacy for SPD.

Obstetric and neonatal outcomes after antipsychotic medication exposure in pregnancy.

OBJECTIVE: Antipsychotic medications are used by increasing numbers of women of reproductive age. The safety of these medications during pregnancy has not been well described. We undertook a systematic review and meta-analysis of the adverse obstetric and neonatal outcomes associated with exposure to antipsychotics during pregnancy. DATA SOURCES: PubMed, Reprotox, and ClinicalTrials.gov were searched to identify potential studies for inclusion. METHODS OF STUDY SELECTION: Case-control or cohort studies estimating adverse birth outcomes associated with antipsychotic exposure during pregnancy were included. Pooled odds ratios (ORs) were used for dichotomous outcomes and weighted mean differences were used for neonatal birth weight and gestational age. Thirteen cohort studies, including 6,289 antipsychotic-exposed and 1,618,039 unexposed pregnancies, were included. TABULATION, INTEGRATION, AND RESULTS: Antipsychotic exposure was associated with an increased risk of major malformations (absolute risk difference [ARD] 0.03, 95% confidence interval [CI] 0.00-0.05, P=.04, Z=2.06), heart defects (ARD 0.01, 95% CI 0.00-0.01, P<.001, Z=3.44), preterm delivery (ARD 0.05, 95% CI 0.03-0.08, P<.001, Z=4.10), small-for-gestational-age births (ARD 0.05, 95% CI 0.02-0.09, P=.006, Z=2.74), elective termination (ARD 0.09, 95% CI 0.05-0.13, P<.001, Z=4.69), and decreased birth weight (weighted mean difference -57.89 g, 95% CI -103.69 to -12.10 g, P=.01). There was no significant difference in the risk of major malformations (test for subgroup differences: χ²=0.07, degrees of freedom=1, P=.79) between typical (OR 1.55, 95% CI 1.21-1.99, P=.006) and atypical (OR 1.39, 95% CI 0.66-2.93, P=.38) antipsychotic medications. Antipsychotic exposure was not associated with risk of large-for-gestational-age births, stillbirth, and spontaneous abortion. Although antipsychotic exposure during pregnancy was associated with increased risk of adverse obstetric and neonatal outcomes, this association does not necessarily imply causation. This analysis was limited by the small number of included studies and limited adjustment in studies for possible confounders. CONCLUSION: Women requiring antipsychotic treatment during pregnancy appear at higher risk of adverse birth outcomes, regardless of causation, and may benefit from close monitoring and minimization of other potential risk factors during pregnancy.

Meta-analysis: parental interventions for preschool ADHD.

OBJECTIVE: Although psychostimulants are commonly utilized to treat preschoolers with ADHD, side effects and parental preferences limit their use in younger children. The current meta-analysis examines the efficacy of parent interventions for the treatment of ADHD in preschoolers. METHOD: We searched PubMed and the Cochrane Library for randomized, controlled trials comparing behavioral interventions for preschool children with ADHD. Our primary outcome measure was mean improvement in an ADHD rating scale compared with control conditions. RESULTS: Eight trials were included in the final analysis, totaling 399 participants. There was a significant benefit of parental behavioral interventions compared with control conditions (standardized mean difference [SMD] = 0.61, 95% confidence interval = [0.40, 0.83], z = 5.6, p < .001). CONCLUSION: The present meta-analysis provides preliminary evidence that parental interventions are an efficacious treatment for preschool ADHD. Future research is needed to compare the relative efficacy of parental interventions for ADHD with medication management and to determine if the combination of parental training and medication management is more effective than either condition alone.

A meta-analysis of computerized cognitive-behavioral therapy for the treatment of DSM-5 anxiety disorders.

OBJECTIVE: Access to qualified cognitive-behavioral therapy (CBT) remains a major barrier to improving clinical outcomes in anxiety disorders. The current meta-analysis examined the efficacy of computerized CBT (cCBT) for anxiety disorders and the durability of treatment gains during follow-up. DATA SOURCES: We searched PubMed and references from included trials and previous meta-analyses in the area. STUDY SELECTION: We included randomized controlled trials assessing the efficacy of cCBT for non-OCD and non-PTSD anxiety disorders. DATA EXTRACTION: Forty trials involving 2,648 participants were included in this meta-analysis. We used a fixed-effect model to examine standardized mean difference in posttreatment anxiety levels. cCBT was compared to wait-list, in-person CBT, and Internet control. We also examined moderators of cCBT treatment gains over follow-up. RESULTS: Meta-analysis indicated that cCBT was significantly more effective than wait-list control in the treatment of anxiety disorders (standardized mean difference [SMD] = 0.92 [95% CI, 0.83 to 1.02], k = 31, z = 18.8, P < .001). Moderator analyses also found that cCBT targeting specific anxiety disorders had greater efficacy than that targeting mixed anxiety symptoms. The efficacy of cCBT was equivalent to in-person CBT in studies that compared them head-to-head, for both children and adults (SMD = 0.05 [95% CI, -0.09 to 0.19], k = 15, z = 0.7, P = .46). Longitudinal studies indicate that individuals undergoing cCBT tended to continue to improve after completion of treatment, with longer follow-up periods associated with greater symptom reduction. CONCLUSIONS: cCBT represents an efficacious intervention for the treatment of anxiety disorders and may circumvent barriers to accessing traditional CBT treatments. Further research is needed to examine the effectiveness of cCBT in real-world settings, for individuals with clinical comorbidities, and in comparison with more ecologically valid comparison conditions.

Meta-analysis: pharmacological treatment of pathological gambling.

BACKGROUND: This meta-analysis investigates the efficacy of pharmacological treatments for pathological gambling (PG). METHODS: We searched for randomized, placebo-controlled trials examining pharmacotherapy of pathological gamblers. A fixed-effects model was used to calculate the standardized mean difference (SMD) of the benefit of medication (stratified by class) compared to placebo. Secondary analyses examined the effects of publication bias, year of publication and adherence to intention-to-treat (ITT) principles on reported efficacy of interventions. RESULTS: Meta-analysis included 14 trials involving 1024 participants. Opiate antagonists demonstrated a small but significant benefit compared to placebo (SMD = 0.22 ± 0.10 (95% CI: 0.03-0.41), z = 2.3, p = 0.02). The reported efficacy of opiate antagonists was significantly associated with non-adherence to ITT principles in trials and earlier year of publication. Other medications had non-significant effect sizes compared to placebo but similar in magnitude to opiate antagonists. CONCLUSIONS: Current trial data provides limited support for the use of any pharmacological agent in the treatment of pathological gambling.

Meta-analysis: aerobic exercise for the treatment of anxiety disorders.

BACKGROUND: This meta-analysis investigates the efficacy of exercise as a treatment for DSM-IV diagnosed anxiety disorders. METHODS: We searched PubMED and PsycINFO for randomized, controlled trials comparing the anxiolytic effects of aerobic exercise to other treatment conditions for DSM-IV defined anxiety disorders. Seven trials were included in the final analysis, totaling 407 subjects. The control conditions included non-aerobic exercise, waitlist/placebo, cognitive-behavioral therapy, psychoeducation and meditation. A fixed-effects model was used to calculate the standardized mean difference of change in anxiety rating scale scores of aerobic exercise compared to control conditions. Subgroup analyses were performed to examine the effects of (1) comparison condition; (2) whether comparison condition controlled for time spent exercising and (3) diagnostic indication. RESULTS: Aerobic exercise demonstrated no significant effect for the treatment of anxiety disorders (SMD=0.02 (95%CI: -0.20-0.24), z = 0.2, p = 0.85). There was significant heterogeneity between trials (χ(2) test for heterogeneity = 22.7, df = 6, p = 0.001). The reported effect size of aerobic exercise was highly influenced by the type of control condition. Trials utilizing waitlist/placebo controls and trials that did not control for exercise time reported large effects of aerobic exercise while other trials report no effect of aerobic exercise. CONCLUSIONS: Current evidence does not support the use of aerobic exercise as an effective treatment for anxiety disorders as compared to the control conditions. This remains true when controlling for length of exercise sessions and type of anxiety disorder. Future studies evaluating the efficacy of aerobic exercise should employ larger sample sizes and utilize comparison interventions that control for exercise time.

The Effect of Calcium Chloride Added to the Irrigation Water on Quality and Shelf Life of Harvested Mushrooms.

A white hybrid (U-3) strain of cultivated mushrooms ( Agaricus bisporus ) was grown with 0 (control), 0.1 and 0.5% CaCl2 added to the irrigation water. Harvested mushrooms were stored in film-overwrapped packages at 13°C and evaluated after 0, 2, 4, and 7 or 8 d storage to determine treatment effects on quality and shelf life. At low concentration (0.1%), CaCl2 had no significant effect on production yield, quality, or postharvest shelf life, but at higher concentration (0.5%), CaCl2 decreased yield and increased quality and shelf life. At a concentration of 0.5%, yield was decreased by 16%, but solids content of harvested mushrooms was increased 16% and shelf life was increased by about 64%, mainly due to a decreased rate of postharvest bacterial growth and a concomitant reduction of surface browning.