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BACKGROUND: Trichotillomania (TTM; hair‐pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair‐pulling. Here we update a previous Cochrane Review on the effects of medication for TTM. OBJECTIVES: To assess the effects of medication for trichotillomania (TTM) in adults, children and adolescents compared with placebo or other medication. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, eleven other bibliographic databases, trial registries and grey literature sources (to 26 November 2020). We checked reference lists and contacted subject experts. SELECTION CRITERIA: We selected randomised controlled trials of medication versus placebo or other medication for TTM in adults, children and adolescents. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Twelve studies were included. We identified 10 studies in adults (286 participants) with a mean sample size of 29 participants per trial; one study in children and adolescents (39 participants); and, one study in adults and adolescents (22 participants: 18 adults and 4 adolescents). All studies were single‐centre, outpatient trials. Eleven studies compared medication and placebo (334 participants); one study compared two medications (13 participants). Studies were 5 to 13 weeks duration. We undertook meta‐analysis only for opioid antagonists as other comparisons contained a single study, or reported insufficient data. Antioxidants versus placebo in adults There was little to no difference in treatment response between antioxidant (35.7%) and placebo groups (28.6%) after six weeks, based on a single trial of silymarin (risk ratio (RR) 2.25, 95% confidence interval (CI) 0.84 to 5.99; 36 participants; low‐certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (18 participants; low‐certainty evidence). Antioxidants versus placebo in adolescents There was little to no difference in treatment response between antioxidant (50%) and placebo groups (25%) after six weeks, based on a single trial of silymarin (RR 2.00, 95% CI 0.28 to 14.20; 8 participants; low‐certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (8 participants; low‐certainty evidence). Antipsychotics versus placebo in adults There may be greater treatment response in the antipsychotic group (85%) compared to the placebo group (17%) after 12 weeks, based on a single trial of olanzapine (RR 5.08, 95% CI 1.4 to 18.37; 25 participants; low‐certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (25 participants; low‐certainty evidence). Cell signal transducers versus placebo in adults There was little to no difference in treatment response between cell signal transducer (42.1%) and placebo groups (31.6%) after 10 weeks, based on a single trial of inositol (RR 1.33, 95% CI 0.57 to 3.11; 38 participants; low‐certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (38 participants; low‐certainty evidence). Glutamate modulators versus placebo in adults There is probably greater treatment response in the glutamate modulator group (56%) compared to the placebo group (16%) after 12 weeks, based on a single trial of N‐acetylcysteine (RR 3.5, 95% CI 1.34 to 9.17; 50 participants; moderate‐certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (50 participants; low‐certainty evidence). Glutamate modulators versus placebo in children and adolescents There was little to no difference in treatment response between the glutamate modulator (25%) and placebo groups (21.1%) in children and adolescents, based on a single trial of N‐acetylcysteine (RR 1.19, 95% CI 0.37 to 3.77; 39 participants; low‐certainty evidence). There was little to no difference in dropouts due to adverse events between glutamate modulator (5%) and placebo (0%) groups, based on a single trial (RR 2.86, 95% CI 0.12 to 66.11; 39 participants; low‐certainty evidence). Opioid antagonists versus placebo in adults There may be little to no difference in treatment response between opioid antagonist (37.5%) and placebo groups (25%) after six to eight weeks, based on two studies of naltrexone, but the evidence is very uncertain (RR 2.14, 95% CI 0.25 to 18.17; 2 studies, 68 participants; very low‐certainty evidence). No data were available regarding dropouts due to adverse events. Selective serotonin reuptake inhibitors (SSRIs) versus placebo in adults There were no data available for treatment response to SSRIs. There was little to no difference in dropouts due to adverse events in the SSRI group (5.1%) compared to the placebo group (0%) after 6 to 12 weeks, based on two trials of fluoxetine (RR 3.00, 95% CI 0.33 to 27.62; 2 studies, 78 participants; low‐certainty evidence). Tricyclic antidepressants (TCAs) with predominantly serotonin reuptake inhibitor (SRI) actions versus placebo in adults There may be greater treatment response in the TCAs with predominantly SRI actions group (40%) compared to the placebo group (0%) after nine weeks, but the evidence is very uncertain, based on a single trial of clomipramine (RR 5.73, 95% CI 0.36 to 90.83; 16 participants; very low‐certainty evidence). There may be increased dropouts due to adverse events in the TCAs with predominantly SRI actions group (30%) compared to the placebo group (0%), but the evidence is very uncertain (RR 4.45, 95% CI 0.27 to 73.81; 16 participants; very low‐certainty evidence). TCAs with predominantly SRI actions versus other TCAs in adults There may be greater treatment response in the TCAs with predominantly SRI actions group compared to the other TCAs group after five weeks, based on a single trial comparing clomipramine to desipramine (mean difference (MD) ‐4.00, 95% CI ‐6.13 to ‐1.87; 26 participants; low‐certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (26 participants; low‐certainty evidence). AUTHORS' CONCLUSIONS: There was insufficient evidence from meta‐analysis to confirm or refute the efficacy of any agent or class of medication for the treatment of TTM in adults, children or adolescents. Preliminary evidence suggests there may be beneficial treatment effects for N‐acetylcysteine, clomipramine and olanzapine in adults based on four trials, albeit with relatively small sample sizes.

Objective Neurocognitive dysfunction has been associated with post‐traumatic stress disorder (PTSD) and major depressive disorder (MDD). However, although PTSD is often comorbid with MDD, there is little neurocognitive work to date on individuals who suffer from both PTSD and MDD. Here, we compared neurocognitive domains in individuals with PTSD, MDD, and comorbid PTSD and MDD with those of healthy controls. Methods Participants comprised of mothers enrolled in the Drakenstein Child Health Study, a study exploring child health determinants in the Drakenstein district, Western Cape. N = 175 mothers (between 18 and 50 years) were recruited and divided into 4 groups: PTSD, MDD, PTSD with MDD, and healthy controls. Participants were assessed using the computerized NIH Toolbox, and paper and pencil neurocognitive tests. Domains assessed included executive function, memory, attention, learning, and processing speed. Results Distinct patterns of neurocognitive dysfunction were observed in this sample. PTSD was associated with more intrusion errors and MDD was associated with delayed recall impairment, relative to healthy controls. PTSD with comorbid MDD was associated with processing speed impairments, relative to healthy controls, and monodiagnostic groups. No group differences were observed on measures of attention and executive function. Conclusion Distinct patterns of neurocognitive dysfunction were associated with diagnoses of MDD and PTSD. Greater anticipated dysfunction and impairment in comorbid PTSD and MDD was not observed, however. Further work is needed to replicate and extend these findings., Neurocognitive dysfunction of PTSD, depression, and PTSD with comorbid depression was examined in a group of low–middle‐income women. We found that PTSD, MDD, and PTSD with comorbid MDD presented with dysfunction in different cognitive domains.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: 1) To determine the overall efficacy and tolerability of TMS in the treatment of PTSD. 2) To identify clinical and methodological factors that increase response to treatment with TMS.

Chronic methamphetamine use is associated with executive functioning deficits that suggest dysfunctional cognitive control networks (CCNs) in the brain. Likewise, abnormal connectivity between intrinsic CCNs and default mode networks (DMNs) has also been associated with poor cognitive function in clinical populations. Accordingly, we tested the extent to which methamphetamine use predicts abnormal connectivity between these networks, and whether, as predicted, these abnormalities are compounded in patients with a history of methamphetamine-associated psychosis (MAP). Resting-state fMRI data were acquired from 46 methamphetamine-dependent patients [19 with MAP, 27 without (MD)], as well as 26 healthy controls (CTRL). Multivariate network modelling and whole-brain voxel-wise connectivity analyses were conducted to identify group differences in intrinsic connectivity across four cognitive control and three DMN networks identified using an independent components analysis approach (meta-ICA). The relationship of network connectivity and psychotic symptom severity, as well as antipsychotic treatment and methamphetamine use variables, was also investigated. Robust evidence of hyper-connectivity was observed between the right frontoparietal and anterior DMN networks in MAP patients, and 'normalized' with increased duration of treatment with antipsychotics. Attenuation of anticorrelated anterior DMN-dorsal attention network activity was also restricted to this group. Elevated coupling detected in MD participants between anterior and posterior DMN networks became less apparent with increasing duration of abstinence from methamphetamine. In summary, we observed both alterations of RSN connectivity between DMN networks with chronic methamphetamine exposure, as well as DMN-CCN coupling abnormalities consistent with possible MAP-specific frontoparietal deficits in the biasing of task-appropriate network activity.

Although specific phobia is a prevalent anxiety disorder, evidence regarding its underlying functional neuroanatomy is inconsistent. A meta-analysis was undertaken to identify brain regions that were consistently responsive to phobic stimuli, and to characterize changes in brain activation following cognitive behavioral therapy (CBT). We searched the PubMed, SCOPUS and PsycINFO databases to identify positron emission tomography and functional magnetic resonance imaging studies comparing brain activation in specific phobia patients and healthy controls. Two raters independently extracted study data from all the eligible studies, and pooled coordinates from these studies using activation likelihood estimation, a quantitative meta-analytic technique. Resulting statistical parametric maps were compared between patients and healthy controls, in response to phobic versus fear-evoking stimuli, and before and after therapy. Thirteen studies were included, comprising 327 participants. Regions that were consistently activated in response to phobic stimuli included the left insula, amygdala, and globus pallidus. Compared to healthy controls, phobic subjects had increased activation in response to phobic stimuli in the left amygdala/globus pallidus, left insula, right thalamus (pulvinar), and cerebellum. Following exposure-based therapy widespread deactivation was observed in the right frontal cortex, limbic cortex, basal ganglia and cerebellum, with increased activation detected in the thalamus. Exposure to phobia-specific stimuli elicits brain activation that is consistent with current understandings of the neuroanatomy of fear conditioning and extinction. There is evidence that the effects of CBT in specific phobia may be mediated through the same underlying neurocircuitry.

Background Anxiety disorders are a potentially disabling group of disorders which are prevalent in childhood and adolescence. The recognition of the early onset of anxiety disorders, and their successful treatment with medication in adults, has led to the growing interest in using medication for paediatric anxiety disorders. Objectives To assess the efficacy and tolerability of medication for treating paediatric anxiety disorders. Search strategy We searched the Cochrane Depression, Anxiety & Neurosis Group specialised register (CCDANCTR-Studies), MEDLINE (via PubMed 1966 to August 2008), EMBASE (1966 to August 2008), and PsycINFO (1972 to August 2008). Various electronic registers were searched for unpublished studies. Reference lists of retrieved articles were searched for additional studies. Selection criteria All randomised controlled trials (RCTs) of pharmacotherapy in childhood/adolescent anxiety disorders. Data collection and analysis Two raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class, and by medication agent for the selective serotonin reuptake inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a random effects model, heterogeneity was assessed, and subgroup/sensitivity analyses were undertaken. Main results 22 short-term (

Background Post-traumatic stress disorder (PTSD) is a debilitating disorder which, after a sufficient delay, may be diagnosed amongst individuals who respond with intense fear, helplessness or horror to traumatic events. There is some evidence that the use of pharmacological interventions immediately after exposure to trauma may reduce the risk of developing of PTSD. Objectives To assess the effects of pharmacological interventions for the prevention of PTSD in adults following exposure to a traumatic event. Search methods We searched the Cochrane Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) (to 14 February 2014). This register contains relevant reports of randomised controlled trials from the following bibliographic databases: CENTRAL (all years); EMBASE (1974 to date); MEDLINE (1950 to date) and PsycINFO (1967 to date). We identified unpublished trials by searching the National Institute of Health (NIH) Reporter, the metaRegister of Controlled Trials database (mRCT) and the WHO International Clinical Trials Registry Platform (to December 2013). We scanned the reference lists of articles for additional studies. We placed no constraints on language and setting. Selection criteria We restricted studies to randomised controlled trials (RCTs) of pharmacological interventions compared with placebo for the prevention of PTSD in adults. Data collection and analysis Two authors (TA and JI) independently assessed trials for eligibility and inclusion based on the review selection criteria. We independently extracted sample, methodological, outcome and 'Risk of bias' data, as well as the number of side effects, from each trial and entered these into a customised data extraction form. We contacted investigators for missing information. We calculated summary statistics for continuous and dichotomous variables (if provided). We did not undertake subgroup analyses due to the small number of included studies. Main results We included nine short-term RCTs (duration 12 weeks or less) in the analysis (345 participants; age range 18 to 76 years). Participants were exposed to a variety of traumas, ranging from assault, traffic accidents and work accidents to cardiac surgery and septic shock. Seven studies were conducted at single centres. The seven RCTs included four hydrocortisone studies, three propranolol studies (of which one study had a third arm investigating gabapentin), and single trials of escitalopram and temazepam. Outcome assessment measures included the Clinician-Administered PTSD Scale (CAPS), the 36-Item Short-Form Health Survey (SF-36) and the Center for Epidemiological Studies – Depression Scale (CES-D). In four trials with 165 participants there was moderate quality evidence for the efficacy of hydrocortisone in preventing the onset of PTSD (risk ratio (RR) 0.17; 95% confidence interval (CI) 0.05 to 0.56; P value = 0.004), indicating that between seven and 13 patients would need to be treated with this agent in order to prevent the onset of PTSD in one patient. There was low quality evidence for preventing the onset of PTSD in three trials with 118 participants treated with propranolol (RR 0.62; 95% CI 0.24 to 1.59; P value = 0.32). Drop-outs due to treatment-emergent side effects, where reported, were low for all of the agents tested. Three of the four RCTs of hydrocortisone reported that medication was more effective than placebo in reducing PTSD symptoms after a median of 4.5 months after the event. None of the single trials of escitalopram, temazepam and gabapentin demonstrated evidence that medication was superior to placebo in preventing the onset of PTSD. Seven of the included RCTs were at a high risk of bias. Differential drop-outs between groups undermined the results of three studies, while one study failed to describe how the allocation of medication was concealed. Other forms of bias that might have influenced study results included possible confounding through group differences in concurrent medication and termination of the study based on treatment response. Authors' conclusions There is moderate quality evidence for the efficacy of hydrocortisone for the prevention of PTSD development in adults. We found no evidence to support the efficacy of propranolol, escitalopram, temazepam and gabapentin in preventing PTSD onset. The findings, however, are based on a few small studies with multiple limitations. Further research is necessary in order to determine the efficacy of pharmacotherapy in preventing PTSD and to identify potential moderators of treatment effect.

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Ipser JC, Stein DJ, Hawkridge S, Hoppe L. Pharmacotherapy for anxiety disorders in children and adolescents. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD005170. DOI: 10.1002/14651858.CD005170.pub2. Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2010 John Wiley & Sons, Ltd.

Anxiety disorders are a potentially disabling group of disorders which are prevalent in childhood and adolescence. The recognition of the early onset of anxiety disorders, and their successful treatment with medication in adults, has led to the growing interest in using medication for paediatric anxiety disorders.To assess the efficacy and tolerability of medication for treating paediatric anxiety disorders.We searched the Cochrane Depression, AnxietyNeurosis Group specialised register (CCDANCTR-Studies), MEDLINE (via PubMed 1966 to August 2008), EMBASE (1966 to August 2008), and PsycINFO (1972 to August 2008). Various electronic registers were searched for unpublished studies. Reference lists of retrieved articles were searched for additional studies.All randomised controlled trials (RCTs) of pharmacotherapy in childhood/adolescent anxiety disorders.Two raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class, and by medication agent for the selective serotonin reuptake inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a random effects model, heterogeneity was assessed, and subgroup/sensitivity analyses were undertaken.22 short-term (= 16 weeks) RCTs were included in the analysis (2519 participants). The majority of the trials assessed the efficacy of the SSRIs (N = 15).Medication and placebo response occurred in 58.1% and 31.5% of patients, respectively (Number of studies (N) = 14, Number needed to treat (NNT) = 4). Medication was more effective than placebo in reducing overall symptom severity in OCD in a post-hoc comparison (N = 7, Weighted Mean Difference (WMD) = -4.45, 95%CI = -5.94, -2.97, n = 765). Medication was less well tolerated than placebo overall, though the absolute proportion of participants who withdrew due to drug-related adverse events was low (4.9%).Medication treatments can be effective in paediatric anxiety disorders, acting to reduce core symptoms, and should be considered as part of the treatment of these disorders. The greatest number of trials showing efficacy to date have assessed the SSRIs in treating paediatric OCD.There is no clear evidence to show that any particular class of medication is more effective or better tolerated than any other. As quantitative data was only available for the SSRIs and venlafaxine the routine use of benzodiazepines cannot be recommended, especially given concerns of dependency and treatment -related emergent adverse events associated with this class of drugs.Future RCTs could help identify potential clinical moderators of treatment efficacy. Studies of the long-term efficacy of medication treatment, optimal dosage, as well as direct comparisons of pharmacotherapy and psychotherapy are also warranted.