Jonathan Ipser

Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis

BACKGROUND Pharmacological treatment is widely used for post-traumatic stress disorder (PTSD) despite questions over its efficacy. AIMS To determine the efficacy of all types of pharmacotherapy, as monotherapy, in reducing symptoms of PTSD, and to assess acceptability. METHOD A systematic review and meta-analysis of randomised controlled trials was undertaken; 51 studies were included. RESULTS Selective serotonin reuptake inhibitors were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.23, 95% CI -0.33 to -0.12). For individual pharmacological agents compared with placebo in two or more trials, we found small statistically significant evidence of efficacy for fluoxetine, paroxetine and venlafaxine. CONCLUSIONS Some drugs have a small positive impact on PTSD symptoms and are acceptable. Fluoxetine, paroxetine and venlafaxine may be considered as potential treatments for the disorder. For most drugs there is inadequate evidence regarding efficacy for PTSD, pointing to the need for more research in this area.

Evidence-based pharmacotherapy of post-traumatic stress disorder (PTSD)

Post-traumatic stress disorder (PTSD) is a prevalent and disabling disorder. Recognition of neurobiological abnormalities associated with this condition suggests the potential efficacy of medication in its treatment. Nevertheless, questions regarding the efficacy of medications remain, despite general endorsement by clinical practice guidelines of selective serotonin reuptake inhibitors (SSRIs) as first-line agents in treating PTSD. This paper reviews evidence from randomized controlled trials (RCTs) for the efficacy of acute and long-term pharmacotherapy for PTSD, including the treatment of refractory PTSD. In addition, we conducted a systematic meta-analysis to compare the efficacy of different medications in treating PTSD. The effects of methodological study features (including year of publication, duration, number of centres) and sample characteristics (proportion of combat veterans, gender composition) were also tested. The largest body of evidence for short- and long-term efficacy of medication currently exists for SSRIs, with promising initial findings for the selective noradrenergic reuptake inhibitor venlafaxine and the atypical antipsychotic risperidone. Treatment effect was predicted by number of centres and recency of the study, with little evidence that sample characteristics predicted response. Evidence for the effectiveness of benzodiazepines is lacking, despite their continued use in clinical practice. Finally, the α1 antagonist prazosin and the atypical antipsychotics show some efficacy in treatment-resistant PTSD. Adequately powered trials that are designed in accordance with best-practice guidelines are required to provide conclusive evidence of clinically relevant differences in efficacy between agents in treating PTSD, and to help estimate clinical and methodological predictors of treatment response.

Functional magnetic resonance imaging during emotion recognition in social anxiety disorder: an activation likelihood meta-analysis.

Background: Social anxiety disorder (SAD) is characterized by abnormal fear and anxiety in social situations. Functional magnetic resonance imaging (fMRI) is a brain imaging technique that can be used to demonstrate neural activation to emotionally salient stimuli. However, no attempt has yet been made to statistically collate fMRI studies of brain activation, using the activation likelihood-estimate (ALE) technique, in response to emotion recognition tasks in individuals with SAD. Methods: A systematic search of fMRI studies of neural responses to socially emotive cues in SAD was undertaken. ALE meta-analysis, a voxel-based meta-analytic technique, was used to estimate the most significant activations during emotional recognition. Results: Seven studies were eligible for inclusion in the meta-analysis, constituting a total of 91 subjects with SAD, and 93 healthy controls. The most significant areas of activation during emotional vs. neutral stimuli in individuals with SAD compared to controls were: bilateral amygdala, left medial temporal lobe encompassing the entorhinal cortex, left medial aspect of the inferior temporal lobe encompassing perirhinal cortex and parahippocampus, right anterior cingulate, right globus pallidus, and distal tip of right postcentral gyrus. Conclusion: The results are consistent with neuroanatomic models of the role of the amygdala in fear conditioning, and the importance of the limbic circuitry in mediating anxiety symptoms.

Systematic review of pharmacotherapy of disruptive behavior disorders in children and adolescents

RationalePharmacotherapy is frequently considered in the treatment of disruptive behavior disorders (DBDs) in children and adolescents. There are, however, no systematic reviews of this literature.ObjectivesThe aim of this work is to determine whether medication is effective in treating pediatric disruptive behavior disorders and related problems of impulse control, as well as to examine differences in the treatment response and tolerability of different medication classes and agents.Materials and methodsRandomized controlled trials of the pharmacotherapy of DBDs in children and adolescents were reviewed, and a meta-analysis of 14 trials (823 participants) was conducted.ResultsThere is some evidence of the effectiveness of medication in treating DBDs, with positive outcomes for lithium and risperidone in particular. Pharmacotherapy also demonstrated some efficacy in reducing symptoms of aggression. Medication was relatively well-tolerated, as indicated by equivalent dropout rates in medication and comparison groups.ConclusionsThere are relatively few controlled trials of the pharmacotherapy of disruptive behavior disorders or other impulse control disorders, despite the importance of research in this area. Given the potential adverse effects of agents such as lithium and risperidone, a careful risk–benefit analysis is needed for each patient.

The call for relevance : South African psychology ten years into democracy

A number of scholars during the 1980s and early 1990s questioned the relevance of psychology in South Africa. In this paper we characterise the nature of what became known as the ‘relevance debate’, and then investigate whether South African psychology has become more relevant during the nations first ten years of democracy. Themes which are identified with respect to this issue include the apparent increasing representation of marginalised groups within South African psychology, the conscious responsiveness of psychologists to post-apartheid policy imperatives and issues, their alignment with international theoretical trends, and finally, an increasing recognition of the political nature of South African psychology. The authors conclude that a more productive approach within future debates regarding relevance in psychology would be to examine the nature of knowledge production within the discipline.

Pharmacotherapy for social anxiety disorder: a systematic review

Social anxiety disorder (SAD) is a prevalent, disabling disorder. We aimed to assess the effects of pharmacotherapy for SAD and to determine whether particular classes of medication are more effective and/or better tolerated than others. A systematic review and meta-analysis was conducted of all published and unpublished placebo-controlled randomized controlled trials (RCTs) undertaken between 1966 and 2007. A rigorous search, which included searching the Cochrane CCDANTR, MEDLINE and PsycINFO electronic databases, yielded a total of 51 RCTs (9914 participants) considered eligible for inclusion in the review. On average, over half of trial participants responded to medication, as assessed with the improvement item of the Clinical Global Impressions scale (55.2%), with approximately four participants having to be treated for an average of 12 weeks before an additional person responded to medication, relative to placebo (number needed to benefit = 4.19). There was substantial variation across medication classes in the number of dropouts due to adverse events, with an average number needed to harm of 14.4. Maintenance and relapse prevention studies confirm the value of longer-term medication in treatment responders. Medication was also effective in reducing SAD symptoms, comorbid depressive symptoms and associated disability. However, evidence for the efficacy of β-blockers in treating performance anxiety was lacking. Taken together, trials of selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors provide the largest evidence base for agents that are both effective and well tolerated. This review is an updated version of a Cochrane Review in The Cochrane Library, Issue 4, 2004. Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review.

Meta-analysis of functional brain imaging in specific phobia

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.

Opioids: from physical pain to the pain of social isolation.

The opioid systems play an important role in mediating both physical pain and negative affects (eg, the pain of social isolation). From an evolutionary perspective, it is not surprising that the neurocircuitry and neurochemistry of physical pain would overlap with that involved in complex social emotions. Exposure to trauma as well as a range of gene variants in the opioid system may be associated with alterations in opioid systems function, with changes in reward processing, and with vulnerability to substance abuse. A role for interventions with opioid agents in depression and anxiety disorders has been suggested.

1H-MRS in autism spectrum disorders: a systematic meta-analysis

We conducted a systematic review and meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies comparing autism spectrum disorder (ASD) patients with healthy controls, with the aim of profiling ASD-associated changes in the metabolites N-acetyl-aspartate (NAA) and Creatine (Cr). Meta-regression models of NAA and Cr levels were employed, using data from 20 eligible studies (N = 852), to investigate age-dependent differences in both global brain and region-specific metabolite levels, while controlling for measurement method (Cr-ratio versus absolute concentrations). Decreased NAA concentrations that were specific to children were found for whole-brain grey and white matter. In addition, a significant decrease in NAA was evident across age categories in the parietal cortex, the cerebellum, and the anterior cingulate cortex. Higher levels of Cr were observed for ASD adults than children in global grey matter, with specific increases for adults in the temporal lobe and decreased Cr in the occipital lobe in children. No differences were found for either NAA or Cr in the frontal lobes. These data provide some evidence that ASD is characterized by age-dependent fluctuations in metabolite levels across the whole brain and at the level of specific regions thought to underlie ASD-associated behavioural and affective deficits. Differences in Cr as a function of age and brain region suggests caution in the interpretation of Cr-based ratio measures of metabolites. Despite efforts to control for sources of heterogeneity, considerable variability in metabolite levels was observed in frontal and temporal regions, warranting further investigation.

Augmentation of Cognitive Behavioral Therapy with Pharmacotherapy

There has long been interest in combining pharmacotherapy with psychotherapy, including cognitive behavioral therapy (CBT). More recently, basic research on fear extinction has led to interest in augmentation of CBT with the N-methyl Daspartate (NMDA) glutamate receptor partial agonist D-cycloserine (DCS) for anxiety disorders. In this article, the literature on clinical trials that have combined pharmacotherapy and CBT is briefly reviewed, focusing particularly on the anxiety disorders. The literature on CBT and DCS is then systematically reviewed. A series of randomized placebo-controlled trials on panic disorder, obsessive-compulsive disorder, social anxiety disorder, and specific phobia suggest that low dose DCS before therapy sessions may be more effective compared with CBT alone in certain anxiety disorders. The strong translational foundation of this work is compelling, and the positive preliminary data gathered so far encourage further work. Issues for future research include delineating optimal dosing, and demonstrating effectiveness in real-world settings.