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Background: Exercise offers improvement to physical and mental health symptoms as well and cognitive function in patients with psychosis. However, patients with psychosis are often less ready to benefit from exercise intervention because of the difficulties in motivation. This study aimed to examine the effectiveness of adjunctive motivational coaching on exercise intervention in women with psychosis in Hong Kong. Methods: From a community mental health programme for women, patients with a diagnosis of psychotic disorder (within 5 years of first onset) were randomly allocated to receive 12 30-minute sessions of motivational coaching or psychoeducation in a group format. Both groups additionally received exercise intervention sessions consisting of yoga, stretching and high-intensity interval training. Primary outcome was the total physical activity level measured by the International Physical Activity Questionnaire. Results: Fifty-seven patients (mean [SD] age, 34.47 [12.44] years) were randomised into motivational coaching ( n = 30) or psychoeducation ( n = 27) treatment groups. The motivational coaching group had a significantly higher total physical activity level (4601.67 [686.59] vs 2524.82 [723.73] metabolic equivalent task-min/week, r2 = 0.473, p = 0.04) after the intervention and at 6 months post-intervention. Moderate and light physical activity levels were significantly higher in the motivational coaching group after intervention and at 6 months, respectively. Additionally, symptoms of bizarre behaviour were improved in the motivational coaching group at 6 months. Younger, unemployed, unmarried and those with longer durations of untreated psychosis generally showed larger improvements in the motivational coaching group. Conclusion: Motivational coaching may augment the effects of exercise interventions, as reflected by higher physical activity participation. Motivational coaching augmentation has the potential to further improve exercise intervention outcomes.

Objectives: Effective treatment of depression is a key target for suicide prevention strategies. However, only around one-third of young people with suicide risk respond to evidence-based treatments. Understanding the trajectory of suicidal ideation, as a marker of suicide risk, over the course of evidence-based treatment for depression might provide insight into more targeted and effective treatments. Methods: This is a secondary analysis of data from the multicentre Youth Depression Alleviation–Combined Treatment trial. A total of 153 young people aged 15–25 years diagnosed with major depressive disorder were randomly assigned in this double-blind, placebo-controlled trial to either cognitive behavioural therapy plus fluoxetine or cognitive behavioural therapy plus placebo. Participants were assessed for depression and suicidal ideation at baseline and at weeks 4, 8 and 12. Results: Using group-based trajectory modelling, we identified two distinct depression trajectories. The first (Improving; 54.9%; n = 83) comprised those who experienced a consistent decline in depression symptoms. The second (Persisting; 45.1%; n = 70) comprised those who, despite treatment, still had clinically significant levels of depression by the end of treatment. For suicidal ideation, we identified four distinct trajectories: Non-clinical (15.5%; n = 20), Low Improving (47.1%; n = 75), High Improving (24.8%; n = 38) and High Persisting (12.7%; n = 20). Treatment allocation was not significantly associated with trajectory membership for either depression or suicidal ideation. Conclusion: Understanding the course of depression and suicidal ideation during treatment has important implications for managing suicide risk. The findings suggest that there is an identifiable group of young people for whom enhanced psychological and/or pharmacological intervention might be required to ensure a better treatment response. Specific interventions for those with suicidal ideation may also be prudent from the outset. Clinical trial registration: The Youth Depression Alleviation–Combined Treatment trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612001281886).

Background: Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. Methods: Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery–Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery–Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. Results: A total of 112 participants were included in the pooled data (Dean et al., n = 71; Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms – differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen’s D (95% confidence interval): 0.71 [0.29, 1.14], p Conclusion: The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. Trial registrations: NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012.

Objective: Alcohol use disorder and social anxiety disorder are interconnected disorders that commonly co-occur. We report the first trial to assess whether integrated treatment for social anxiety and alcohol use disorder comorbidity improves outcomes relative to standard alcohol-focussed treatment. Method: Participants were recruited to a randomised controlled trial, and randomly allocated to one of two treatments, Integrated ( n = 61) or Control (alcohol-focussed; n = 56). Assessment and treatment session were conducted at two sites in Sydney, Australia. Inclusion criteria were as follows: (1) clinical diagnosis of social anxiety disorder and (2) Diagnosis or sub-clinical symptoms of alcohol use disorder. Diagnoses were determined according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.). All participants ( n = 117) received 10 sessions of cognitive behavioural treatment and motivational enhancement. The Integrated treatment simultaneously targeted social anxiety disorder, alcohol use disorder and the connections between these disorders. The Control treatment focussed on alcohol use disorder only. Outcomes were assessed at 6-month follow-up, with interim assessments at post-treatment and 3 months. Primary outcomes were social anxiety disorder severity (composite Social Phobia Scale and Social Interaction Anxiety Scale), alcohol use disorder severity (standard drinks per day and Severity of Alcohol Dependence Questionnaire) and quality of life (Short-Form Health survey) was assessed to capture the combined impairment of social anxiety and alcohol use disorder comorbidity. Results: At 6-month follow-up, both conditions showed significant reductions in social anxiety and alcohol use disorder symptoms, and improved quality of life. There was no evidence of between-condition differences for alcohol outcomes, with mean consumption reduced by 5.0 (0.8) and 5.8 (1.0) drinks per day following Alcohol and Integrated treatments, respectively. Integrated treatment achieved greater improvements in social anxiety symptoms (mean difference = −14.9, 95% confidence interval = [−28.1, −1.6], d = 0.60) and quality of life (mean difference = 7.6, 95% confidence interval = [1.2, 14.0], d = 0.80) relative to alcohol-focused treatment. Conclusion: These results suggest that integrated social anxiety and alcohol use disorder treatment enhances quality of life and social anxiety disorder symptom improvement, but not alcohol outcomes, compared to treatment focussed on alcohol use disorder alone.

Objective: Currently, pharmaceutical treatment options for autism spectrum disorder are limited. Brain glutaminergic dysregulation is observed in autism spectrum disorder. N-acetylcysteine, which can be converted to glutathione and subsequently release glutamate into the extracellular space, and thus reduce glutamatergic neurotransmission at synapses, is considered a potential drug for autism spectrum disorder treatment. Here, we analyzed the treatment effects of N-acetylcysteine on autism spectrum disorder in randomized controlled trials. Study design: Updated systematic review and meta-analysis. Data sources: By systematically searching the PubMed, Embase and Cochrane Library, we obtained five randomized controlled trials. Study selection: Meta-analyses were performed to examine the improvement in autistic behaviors as measured by the Aberrant Behavior Checklist, Social Responsiveness Scale and Repetitive Behavior Scale–Revised, using mean difference with a 95% confidence interval and a random-effects model. Data Synthesis: After 8–12 weeks of N-acetylcysteine supplementation, the pooled result of four trials revealed an improvement in Aberrant Behavior Checklist total score (mean difference = 1.31, 95% confidence interval = [0.42, 2.20]). When one trial was excluded, the sensitivity test result was stronger (mean difference = 1.88, 95% confidence interval = [0.92, 2.83]). The pooled results of three trials revealed significant improvements in hyperactivity (mean difference = 4.80, 95% confidence interval = [1.20, 8.40]) and irritability (mean difference = 4.07, 95% confidence interval = [1.13, 7.04]). Regarding Social Responsiveness Scale, the pooled result of two trials showed significant improvement in social awareness after 8–12 weeks of N-acetylcysteine supplementation (mean difference = 1.34, 95% confidence interval = [0.09, 2.59]). No differences were observed in the pooled results of two trials using Repetitive Behavior Scale, either in the total or the subscales. Conclusion: We concluded that N-acetylcysteine is safe and tolerable, reduces hyperactivity and irritability and enhances social awareness in children with autism spectrum disorder. However, further evidence should be sought before a general recommendation.

Objective: Clinical practice guidelines recommend that community mental health services provide preventive care for clients’ chronic disease risk behaviours; however, such care is often not routinely provided. This study aimed to assess the effectiveness of offering clients an additional consultation with a specialist clinician embedded within a community mental health service, in increasing client-reported receipt of, and satisfaction with, preventive care. Method: A randomised controlled trial was undertaken in one Australian community mental health service. Participants ( N = 811) were randomised to receive usual care (preventive care in routine consultations; n = 405) or usual care plus the offer of an additional consultation with a specialist preventive care clinician ( n = 406). Blinded interviewers assessed at baseline and 1-month follow-up the client-reported receipt of preventive care (assessment, advice and referral) for four key risk behaviours individually (smoking, poor nutrition, alcohol overconsumption and physical inactivity) and all applicable risks combined, acceptance of referrals and satisfaction with preventive care received. Results: Analyses indicated significantly greater increases in 12 of the 18 preventive care delivery outcomes in the intervention compared to the usual care condition from baseline to follow-up, including assessment for all risks combined (risk ratio = 4.00; 95% confidence interval = [1.57, 10.22]), advice for all applicable risks combined (risk ratio = 2.40; 95% confidence interval = [1.89, 6.47]) and offer of referral to applicable telephone services combined (risk ratio = 20.13; 95% confidence interval = [2.56, 158.04]). For each component of care, there was a significant intervention effect for at least one of the individual risk behaviours. Participants reported high levels of satisfaction with preventive care received, ranging from 77% (assessment) to 87% (referral), with no significant differences between conditions. Conclusion: The intervention had a significant effect on the provision of the majority of recommended elements of preventive care. Further research is needed to maximise its impact, including identifying strategies to increase client uptake.

Background:Up to one in five women meet diagnostic criteria for an anxiety disorder during the perinatal period (i.e. pregnancy and up to 1 year postpartum). While psychotropic medications are effective, they are associated with risks for mothers and babies. There is a growing demand for evidence-based non-pharmacological treatments for perinatal anxiety.Objective:To evaluate the effectiveness of a cognitive behavioral group therapy protocol for perinatal anxiety.Methods:In total, 96 women were randomized to cognitive behavioral group therapy or waitlist at a clinic specializing in women’s mental health. Participants were 22–41 years of age, pregnant or up to 6 months postpartum and had an anxiety disorder with or without comorbid depression.Results:Compared to waitlist, participants in cognitive behavioral group therapy reported significantly greater reductions in the primary outcome of anxiety (State-Trait Inventory of Cognitive and Somatic Anxiety, η2p = .19; Hamilton Anxiety Rating Scale, η2p = .16), as well as in secondary outcomes including worry (Penn State Worry Questionnaire, η2p = .29), perceived stress (Perceived Stress Scale, η2p = .33) and depressive symptoms (Edinburgh Postnatal Depression Scale, η2p = .27; Montgomery–Åsberg Depression Rating Scale, η2p = .11). Maternal status (pregnant, postpartum) and medication use were unrelated to treatment outcomes. All gains were maintained, or continued to improve, at 3-month follow-up.Conclusion:Cognitive behavioral group therapy was effective in improving anxiety and related symptoms among women with anxiety disorders in the perinatal period.

Objective: To examine the effects of 18 months of intensive stabilisation with medication management and Interpersonal and Social Rhythm Therapy or Non-specific Supportive Clinical Management on cognitive function in young people with bipolar disorder. Determinants of change in cognitive function over the 18 months of the trial were also examined. Method: Patients aged 15–36 years with Bipolar I Disorder, Bipolar II Disorder and Bipolar Not Otherwise Specified were recruited. From a battery of cognitive tests, change scores for pre-defined domains of cognitive function were created based on performance at baseline and follow-up. Change was compared between the two therapy groups. Regression analysis was used to determine the impact of a range of clinical variables on change in cognitive performance between baseline and follow-up. Results: One hundred participants were randomised to Interpersonal and Social Rhythm Therapy ( n = 49) or Non-specific Supportive Clinical Management ( n = 51). Seventy-eight patients underwent cognitive testing at baseline and 18 months. Across both groups, there were significant improvements in a Global Cognitive Composite score, Executive Function and Psychomotor Speed domains from baseline to 18 months. Lower scores at baseline on all domains were associated with greater improvement over 18 months. Overall, there was no difference between therapies in change in cognitive function, either in a global composite score or change in domains. Conclusion: While there was no difference between therapy groups, intensive stabilisation with psychological therapy was associated with improved cognitive function, particularly in those patients with poorer cognitive function at baseline. However, this was not compared with treatment as usual so cannot be attributed necessarily to the therapies.

Objective: This study examined the secondary mental health outcomes of two contrasting alcohol prevention approaches, whereby one intervention targets common underlying personality risk for alcohol use and mental health problems ( Preventure) and the other targets alcohol- and drug-related behaviours and cognitions ( Climate Schools). Methods: A 2 × 2 cluster randomised controlled factorial design trial was conducted in 26 Australian schools randomised to the following 4 conditions: Climate Schools ( n = 6), Preventure ( n = 7), combined Climate Schools and Preventure (CAP; n = 6) or treatment as usual (TAU; n = 7). Participants completed questionnaires at baseline, 6, 12, 24 and 36 months post-baseline including the Brief Symptom Inventory anxiety and depression scales and hyperactivity and conduct scales of the Strengths and Difficulties Questionnaire. Analyses focused on students who were at high-risk based on personality traits ( n = 947; Mage = 13.3). The effectiveness of each approach in reducing symptoms of internalising and externalising problems was assessed using multi-level mixed effects analysis. Results: Main effects for each intervention relative to not receiving that intervention revealed significant main effects of Preventure in reducing anxiety symptoms ( d = −0.27, 95% confidence interval [CI] = [−0.53, −0.01], p Conclusion: This study is the first to report the effectiveness of personality-targeted alcohol prevention in reducing internalising and externalising symptoms relative to an active control, providing evidence in favour of its specificity in preventing concurrent substance use and mental health problems among high-risk youth.

Objective: Internet-delivered cognitive behavioural therapy for insomnia is efficacious for insomnia, and post hoc analyses suggest mood improvements. We undertook the first clinical trial evaluating the efficacy of Internet-delivered cognitive behavioural therapy for insomnia on depressive symptoms as an adjunct to guideline-based treatment of depressive disorders. Methods: Older men undergoing psychiatrist-coordinated treatment for major depressive disorder or dysthymia and who had significant insomnia symptoms were randomised to either adjunctive Internet-delivered cognitive behavioural therapy for insomnia (Sleep Healthy Using The Internet) or online sleep psychoeducation. The primary outcome was change in depressive symptoms (Centre for Epidemiological Studies Depression scale) from baseline to week 12 (post intervention). Secondary outcomes were insomnia and anxiety symptoms. Results: In all, 87 men were randomised (Internet-delivered cognitive behavioural therapy for insomnia = 45; psychoeducation = 42). The mean observed Centre for Epidemiological Studies Depression scale changes by week 12 were 8.2 (standard deviation = 11.5) and 3.9 (standard deviation = 12.8) for Internet-delivered cognitive behavioural therapy for insomnia and psychoeducation, respectively. The adjunctive effect size of 0.35 in favour of Sleep Healthy Using The Internet programme was not statistically significant (group × time difference in the Mixed effect Model Repeat Measurement analysis difference 4.3; 95% confidence interval = [−1.2, 9.8]; p = 0.15). There was a statistically significant effect on insomnia symptoms (group × time p = 0.02, difference 2.7; 95% confidence interval = [0.2, 5.3]; effect size = 0.62). There were no differences in insomnia or depression at 6 months or differential effects on anxiety at any time point. There were no reported adverse trial-related events in the intervention arm. Conclusion: Adjunctive Internet-delivered cognitive behavioural therapy for insomnia for older men being treated for depression can improve insomnia in the short term, without apparent harm. The short-term depressive symptom effect size in this pilot trial was comparable to other adjunctive interventions and may warrant a larger, definitive trial.

Objective: Borderline personality disorder affects up to 2% of the population and is associated with poor functioning, low quality of life and increased mortality. Psychotherapy is the treatment of choice, but it is unclear whether specialized psychotherapies (dialectical behavior therapy, mentalization-based treatment, transference-focused therapy and schema therapy) are more effective than non-specialized approaches (e.g. protocolized psychological treatment, general psychiatric management). The aim of this systematic review is to investigate the effectiveness of these psychotherapies. Methods: PubMed, PsycINFO, CINAHL, EMBASE and CENTRAL were searched from inception to November 2017. Included randomized controlled trials were assessed on risk of bias and outcomes were meta-analyzed. Confidence in the results was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. The review has been reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: A total of 20 studies with 1375 participants were included. Specialized psychotherapies, when compared to treatment as usual or community treatment by experts, were associated with a medium effect based on moderate quality evidence on overall borderline personality disorder severity (standardized mean difference = –0.59 [95% confidence interval: –0.90, –0.28]), and dialectical behavior therapy, when compared to treatment as usual, with a small to medium effect on self-injury (standardized mean difference = –0.40 [95% confidence interval: –0.66, –0.13]). Other effect estimates were often inconclusive, mostly due to imprecision. Conclusion: There is moderate quality evidence that specialized psychotherapies are effective in reducing overall borderline personality disorder severity. However, further research should identify which patient groups profit most of the specialized therapies.

Objective: Functional remission represents an intermediate functional milestone toward recovery. Differential relationships of negative symptom sub-domains with functional remission in first-episode psychosis are understudied. We aimed to examine rate and predictors of functional remission in people with first-episode psychosis in the context of a 3-year follow-up of a randomized controlled trial comparing 1-year extension of early intervention (i.e. 3-year early intervention) with step-down psychiatric care (i.e. 2-year early intervention). Method: A total of 160 participants were recruited upon completion of a 2-year specialized early intervention program for first-episode psychosis in Hong Kong and underwent a 1-year randomized controlled trial comparing 1-year extended early intervention with step-down care. Participants were followed up and reassessed 3 years after inclusion to the trial (i.e. 3-year follow-up). Functional remission was operationalized as simultaneous fulfillment of attaining adequate functioning (measured by Social and Occupational Functioning Scale and Role Functioning Scale) at 3-year follow-up and sustained employment in the last 6 months of 3-year study period. Negative symptom measure was delineated into amotivation (i.e. motivational impairment) and diminished expression (i.e. reduced affect and speech output). Data analysis was based on 143 participants who completed follow-up functional assessments. Results: A total of 31 (21.7%) participants achieved functional remission status at 3-year follow-up. Multivariate regression analysis showed that lower levels of amotivation ( p = 0.010) and better functioning at study intake ( p = 0.004) independently predicted functional remission (Final model: Nagelkerke R2 = 0.40, χ2 = 42.9, p Conclusion: Only approximately one-fifths of early psychosis patients were found to achieve functional remission. Functional impairment remains an unmet treatment need in the early stage of psychotic illness. Our results further suggest that amotivation may represent a critical therapeutic target for functional remission attainment in early psychosis.

Objective: Few studies have examined differential predictors of response to psychotherapy for depression. Greater understanding about the factors associated with therapeutic response may better enable therapists to optimise response by targeting therapy for the individual. The aim of the current exploratory study was to examine patient characteristics associated with response to cognitive behaviour therapy and schema therapy for depression. Methods: Participants were 100 outpatients in a clinical trial randomised to either cognitive behaviour therapy or schema therapy. Potential predictors of response examined included demographic, clinical, functioning, cognitive, personality and neuropsychological variables. Results: Individuals with chronic depression and increased levels of pre-treatment negative automatic thoughts had a poorer response to both cognitive behaviour therapy and schema therapy. A treatment type interaction was found for verbal learning and memory. Lower levels of verbal learning and memory impairment markedly impacted on response to schema therapy. This was not the case for cognitive behaviour therapy, which was more impacted if verbal learning and memory was in the moderate range. Conclusion: Study findings are consistent with the Capitalisation Model suggesting that therapy that focuses on the person’s strengths is more likely to contribute to a better outcome. Limitations were that participants were outpatients in a randomised controlled trial and may not be representative of other depressed samples. Examination of a variety of potential predictors was exploratory and requires replication.

Background: Internet-delivered cognitive behaviour therapy may increase access by young adults to evidence-based treatments for anxiety and depression. Objective: The aim of this study was to compare the efficacy of an Internet-delivered cognitive behaviour therapy intervention designed for adults aged 18–24 years, when delivered in clinician-guided versus self-guided formats. Design: The intervention, the Mood Mechanic Course, is a transdiagnostic treatment that simultaneously targets symptoms of anxiety and depression using cognitive and behavioural skills. The brief intervention comprised four lessons, delivered over 5 weeks. Following a brief telephone interview, young adults ( n = 191) with symptoms of anxiety and depression were randomly allocated to either (1) clinician-guided treatment ( n = 96) or (2) self-guided treatment ( n = 95). Results: At post treatment, large reductions (average improvement; clinician guided vs self-guided) were observed in symptoms of anxiety (44% vs 35%) and depression (40% vs 31%) in both groups. Significant improvements were also observed in general psychological distress (33% vs 29%), satisfaction with life (18% vs 15%) and disability (36% vs 29%). No marked or consistent differences in clinical outcomes emerged between conditions at post-treatment, at 3-month or 12-month follow-up. Satisfaction was high with both treatment formats, but slightly higher for clinician-guided treatment. Conclusion: These results indicate the potential of carefully developed Internet-delivered cognitive behaviour therapy interventions for young adults with anxiety and depression provided in either self or therapist-guided format. Further large-scale research is required to determine the short- and long-term advantages and disadvantages of different models of support.

It is unclear whether blockade of the angiotensin system has effects on mental health. Our objective was to determine the impact of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers on mental health domain of quality of life.Meta-analysis of published literature.PubMed and clinicaltrials.gov databases. The last search was conducted in January 2017.Randomized controlled trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker were selected. Study participants were adults without any major physical symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the Cochrane Collaboration.Eleven studies were included in the analysis. When compared with placebo or other antihypertensive medications, AT1R blockers and angiotensin converting enzyme inhibitors were associated with improved overall quality of life (standard mean difference = 0.11, 95% confidence interval = [0.08, 0.14], p0.0001), positive wellbeing (standard mean difference = 0.11, 95% confidence interval = [0.05, 0.17], p0.0001), mental (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval = [0.01, 0.16], p0.0001) domains of QoL. No significant difference was found for the depression domain (standard mean difference = 0.05, 95% confidence interval = [0.02, 0.12], p = 0.15).Use of angiotensin blockers and inhibitors for the treatment of hypertension in otherwise healthy adults is associated with improved mental health domains of quality of life. Mental health quality of life was a secondary outcome in the included studies. Research specifically designed to analyse the usefulness of drugs that block the angiotensin system is necessary to properly evaluate this novel psychiatric target.

The use of traditional psychostimulants (methylphenidate and dexamphetamine) and stimulant-like drugs (modafinil and armodafinil) for the treatment of depression is a growing concern given the lack of research evidence supporting their effectiveness. The current article describes the role of stimulants in treating depression – specifically their risks and benefits and their potential use alongside antidepressants. Clinically, the rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived, and this suggests that they likely operate via different mechanisms to conventional antidepressants. More importantly, there is little evidence from randomised controlled trials supporting their efficacy in treating depression, although modafinil has been shown to be effective in reducing prominent depressive symptoms, such as fatigue. Research is urgently required to clarify psychostimulants’ mechanisms of action and to evaluate their long-term benefits and risks in the treatment of major and bipolar depression. Ultimately, specificity of action needs to be determined to inform the sophisticated clinical use of psychostimulants in the management of depression. Until then they should only be prescribed if absolutely necessary, and even then their prescription should be facilitatory and time limited unless it is for investigational purposes.

Objectives: Both antidepressant medications and psychological therapy are common treatments for depression in postpartum women. Antidepressant treatment may have a number of practical disadvantages, including a preference by women to avoid medication while breastfeeding. Consequently, more information about the relative benefits of the two modalities in the perinatal period is helpful. In the treatment of depressive disorders there is some evidence that combination therapies (pharmacological plus psychological treatment) may be more efficacious than either form of mono-therapy in isolation. However, in the treatment of postnatal depression, such evidence is limited. Method: Forty five postpartum women with a DSM-IV diagnosis of depression were randomised to receive either: 1) cognitive behavioural therapy (CBT); 2) sertraline, or 3) a combination of both treatment modalities. Psychometric measures were collected weekly for 12 weeks, with a follow-up at 24 weeks. Results: Symptoms of depression and anxiety were reduced to a significant degree following all three treatments. CBT mono-therapy was found to be superior to both sertraline mono-therapy and combination therapy after 12 weeks. The CBT mono-therapy group appeared to display the most rapid initial gains after treatment commencement. Conclusions: In this sample, a specialised CBT program for postnatal depression was found to be superior as a mono-therapy compared to sertraline, a commonly prescribed SSRI antidepressant. This is in contrast to previous studies which have found no detectable difference in the efficacies of drug and psychological treatment for postnatal depression. Unlike some previous work, this study allowed a statistically independent evaluation of CBT mono-therapy for postnatal depression compared to both antidepressant and combination therapy. In line with previous studies in postpartum women, there was no detectable advantage of combining pharmacological and psychological treatments in the short term.

Objective: To assess, from a health sector perspective, the incremental cost-effectiveness of three treatment recommendations in the most recent Australian Clinical Practice Guidelines for posttraumatic stress disorder (PTSD). The interventions assessed are trauma-focused cognitive behavioural therapy (TF-CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of PTSD in adults and TF-CBT in children, compared to current practice in Australia. Method: Economic modelling, using existing databases and published information, was used to assess cost-effectiveness. A cost-utility framework using both quality-adjusted life-years (QALYs) gained and disability-adjusted life-years (DALYs) averted was used. Costs were tracked for the duration of the respective interventions and applied to the estimated 12 months prevalent cases of PTSD in the Australian population of 2012. Simulation modelling was used to provide 95% uncertainty around the incremental cost-effectiveness ratios. Consideration was also given to factors not considered in the quantitative analysis but could determine the likely uptake of the proposed intervention guidelines. Results: TF-CBT is highly cost-effective compared to current practice at $19,000/QALY, $16,000/DALY in adults and $8900/QALY, $8000/DALY in children. In adults, 100% of uncertainty iterations fell beneath the $50,000/QALY or DALY value-for-money threshold. Using SSRIs in people already on medications is cost-effective at $200/QALY, but has considerable uncertainty around the costs and benefits. While there is a 13% chance of health loss there is a 27% chance of the intervention dominating current practice by both saving dollars and improving health in adults. Conclusion: The three Guideline recommended interventions evaluated in this study are likely to have a positive impact on the economic efficiency of the treatment of PTSD if adopted in full. While there are gaps in the evidence base, policy-makers can have considerable confidence that the recommendations assessed in the current study are likely to improve the efficiency of the mental health care sector.

Objective: Agomelatine is a new antidepressant with unique melatonin receptor type 1A (MTNR1A) and 1B ( MTNR1B) agonism and serotonergic receptor 5-hydroxytryptamine receptor 2C (5-HT-2C) antagonism. Several studies of patients with major depressive disorder (MDD) have confirmed the superior efficacy and safety of agomelatine in comparison with established treatments, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs). This meta-analysis comprehensively shows the efficacy, acceptability, and safety of agomelatine in comparison with SSRIs and SNRIs used as antidepressants in MDD. Method: Comprehensive electronic database searches were performed to identify reports of head-to-head randomized controlled trials that have compared agomelatine with SSRIs or SNRIs in terms of efficacy/effectiveness in treating MDD. Response and remission rates at both acute (6–12 weeks) and follow-up (24 weeks) phases, Clinical Global Impression-Improvement Scale response and remission rates, changes in depression scale scores, improvements in subjective sleep, dropout rates, and side effect rates were extracted and analysed. Results: The meta-analysis included six head-to-head trials involving 1871 patients. In the acute phase, agomelatine had higher response rates (relative risk (RR) 1.08, 95% confidence interval (CI) 1.02–1.15) compared to SSRIs and SNRIs. In the remission analysis, only acute remission rates (RR 1.12, 95% CI 1.01–1.24) significantly differed. The action of agomelatine was superior on the Leeds Sleep Evaluation Questionnaire-Quality of Sleep score (mean difference 4.05, 95% CI 0.61–7.49). Discontinuation due to inefficacy did not differ between agomelatine and SSRIs/SNRIs (RR 0.74, 95% CI 0.42–1.28). Compared to SSRIs and SNRIs, however, agomelatine revealed a lower rate of discontinuation due to side effects (RR 0.38, 95% CI 0.25–0.57). Conclusions: Agomelatine has significantly higher efficacy and potential acceptability compared to SSRIs and SNRIs when treating MDD. However, the difference in efficacy is not considered clinically relevant. Because of its unique chronobiotic effects, agomelatine may be useful for the management of some MDD patients with circadian disturbance.

Objective: To compare the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder. Methods: In the present double-blind, randomized, placebo-controlled trial, 42 patients with a diagnosis of major depressive disorder based on DSM-IV criteria were randomly assigned into two groups to receive daily either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for 8 weeks. Depression severity was assessed at 2-week intervals using the 24-item Hamilton Depression Rating Scale (HDRS) as a primary outcome measure and the 21-item Beck Depression Inventory (BDI) as a secondary outcome measure. Serum 25(OH) vitamin D was measured at baseline and after intervention. Results: Forty patients completed the trial. A two-way repeated-measures analysis of variance showed that depression severity based on HDRS and BDI decreased significantly after intervention, with a significant difference between the two groups. The vitamin D + fluoxetine combination was significantly better than fluoxetine alone from the fourth week of treatment. Conclusions: In the present 8-week trial, the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms.

Objectives: Past controlled clinical trials centred on virtual reality exposure therapy (VRET) for agoraphobia mostly used multicomponent therapy with success. However, the present paper aimed to evaluate the independent effect of VRET for agoraphobia. Methods: A controlled study involving 18 agoraphobic participants assigned to two groups: VRET only and VRET with cognitive therapy. Nine specific virtual environments were developed using an affordable game level editor. Results: Questionnaires, behavioural tests and physiological measures indicated a positive effect of VRET. Correlations supported the predictive value of presence towards treatment outcome. The addition of cognitive therapy did not provide significant additional benefit. Conclusions: Overall, the isolated effects of VRET did not seem to be significantly less than the effects of VRET combined with cognitive therapy. Future research should explore the use of other components in addition to cognitive therapy and VRET for agoraphobia as well as its possible use in patients’ homes.

Objective: Early-intervention units have proliferated over the last decade, justified in terms of cost as well as treatment effect. Strong claims for extension of these programmes on economic grounds motivate a systematic review of economic evaluations of early-intervention programmes. Method: Searches were undertaken in the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and PsycINFO with keywords including ‘early intervention’, ‘ultra-high risk’, ‘prodrome’, ‘cost-effectiveness’, ‘psychosis’, ‘economic’, and ‘at-risk mental state’. Relevant journals, editorials, and the references of retrieved articles were hand-searched for appropriate research. Results: Eleven articles were included in the review. The more rigorous research (two randomized control trials and two quasi-experimental studies) suggested no difference in resource utilization or costs between early-intervention and treatment-as-usual groups. One small case-control study with evidence of significant bias concluded annual early-intervention costs were one-third of treatment-as-usual costs. Modelling studies projected reduced costs of early intervention but were based on assumptions since definitively revised. Cost-effectiveness analyses did not strongly support the cost-effectiveness of early intervention. No studies appropriately valued outpatient costs or addressed the feasibility of realizing reduced hospitalization in reduced costs. Conclusions: The published literature does not support the contention that early intervention for psychosis reduces costs or achieves cost-effectiveness. Past failed attempts to reduce health costs by reducing hospitalization, and increased outpatient costs in early-intervention programmes suggest such programmes may increase costs. Future economic evaluation of early-intervention programmes would need to correctly value outpatient costs and accommodate uncertainty regarding reduced hospitalization costs, perhaps by sensitivity analysis. The current research hints that cost differences may be greater early in treatment and in patients with more severe illness.

Objectives: To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) started with citalopram in first-episode young major depressive patients. Methods: In a 2-week double-blind study with a 2-week extended antidepressant phase, 60 first-episode young major depressive patients were randomly assigned to citalopram in combination with 2 weeks of either active or sham rTMS treatment. During the following 2 weeks, the patients continued only the citalopram treatment. The 17-item Hamilton depression rating scale (HAMD-17) and Montgomery–Asberg depression rating scale (MADRS) were used to assess the severity of depression. Moreover, the Wisconsin Card Sorting Test (WCST), Trail-Making Test (TMT), and Stroop Color–Word Test (SCWT) were used to assess executive function. Results: (1) There was a significantly greater number of early improvers (a reduction of HAMD-17 score ≥20% within the first 2 weeks) observed in the active rTMS group compared to the sham group (57% vs. 29%, χ2=4.667, p=0.031). (2) There was no significant difference observed in responder rates (46% vs. 36%, χ2=0.295, p=0.586) or in remission rates (39% vs. 29%, χ2=0.319, p=0.572) between the two groups at 4 weeks. (3) There was a significant difference seen in both HAMD-17 and MADRS scores between the two groups at 2 and 4 weeks. The active rTMS group showed a significantly faster score reduction compared to the sham group at 2 weeks (HAMD-17, t=13.444, p=0.001; MADRS, t=30.123, p=0.000), which was maintained at 4 weeks on both scales (HAMD-17, t=46.915, p=0.000; MADRS, t=39.996, p=0.000). (4) The patients did not deteriorate in executive performance, and even improved in categories on WCST and completed TMT faster in the active group. Conclusions: rTMS accelerated the rapidity of the antidepressant response in first-episode young depressive patients. Our results call for future rTMS studies with larger sample sizes, high intensity of stimuli, and longer duration to draw more definitive conclusions.

Objective: To compare the effectiveness of Internet cognitive behaviour therapy (CBT) with face-to-face CBT in social phobia. Methods: Randomized controlled trial of 75 patients with social phobia referred to an anxiety disorders clinic. A total of 37 patients participated, and post-treatment data was obtained from 25 Subjects (Ss). An intention to treat analysis was used. The same therapist (M.D.) treated both groups. Results: Both groups made significant progress on symptoms and disability measures. There were no significant differences in outcome between the Internet and face-to-face groups. The total amount of therapist time required was 18 min per patient for the Internet group and 240 min per patient for the face-to-face group. Conclusions: Both forms of treatment were equally effective and this is consistent with previous findings in depression and panic disorder. The difference in clinician time required was substantial. If Internet CBT was offered as ‘standard of care’ the staff time saved would permit a stepped care model in which in-depth therapy for the difficult to recover patients could be provided without an increase in staff.

Objective: To evaluate the demographic and clinical factors that predicted depression in adolescents at 6 months after treatment. Method: A total of 130 adolescents (aged 12 to 18 years) who had been clinically referred for treatment with a DSM-IV major depressive disorder, dysthymic disorder or minor depression were treated with either CBT, sertraline, their combination or supportive psychotherapy, in two randomized clinical trials using the same assessment instruments. Assessments in both studies were conducted at initial assessment, three months later at the conclusion of treatment, and at 6-month follow up. The data of these two trials were pooled. The primary outcome measures were the presence of a depressive disorder and the Reynolds Adolescent Depression Scale (RADS) score at 6-month follow up. Results: At baseline, only the Self Efficacy Questionnaire for Depressed Adolescents (SEQ-DA) predicted depression at 6-month follow up. Individual measures following 3 months of acute treatment that predicted depression at 6-month follow up were SEQ-DA, RADS, Revised Children's Manifest Anxiety Scale-total score, Global Assessment of Function, adolescent-rated Family Assessment Device General Functioning Subscale and adolescent-rated Visual Analogue Scores of mood states. Conclusion: Clinical variables as reported by the adolescent and identified by the clinician at baseline assessment and following 3 months of treatment predicted depression at 6-month follow up. No demographic variables were predictive of depression at 6-month follow up.

Objective: Risk of suicide attempt, suicidal ideation and deliberate self-harm is high among young people, yet limited evidence exists regarding effective interventions, particularly from randomized controlled trials. The aim of this study was to conduct a systematic review and meta-analysis of all randomized controlled trials testing interventions for adolescents and young adults who have presented to a clinical setting with any of these behaviours. Methods: The Cochrane Central Register of Controlled Trials, Medline, EMBASE and PsycINFO were searched for articles published from 1980 to June 2010. The following keywords formed the basis of the search strategy: ‘self-injurious behaviour’, ‘attempted suicide’, ‘suicide’, ‘suicidal behaviour’, ‘self-inflicted wounds’, ‘self-mutilation’, ‘self-harm’. We also hand searched conference abstracts from two major suicide prevention conferences and the reference lists of all retrieved articles and previous reviews. Results: There were 15 trials included in the review, with six ongoing trials also identified. In general, the reporting of the conduct of trials was poor, making it difficult to assess the risk of bias. The reporting of outcome data was inconsistent. No differences were found between treatment and control groups except in one study that found a difference between individual cognitive behavioural therapy and treatment as usual. Conclusion: The evidence regarding effective interventions for adolescents and young adults with suicide attempt, deliberate self-harm or suicidal ideation is extremely limited. Many more methodologically rigorous trials are required. However, in the meantime CBT shows some promise, but further investigation is required in order to determine its ability to reduce suicide risk among young people presenting to clinical services.

In the field of traumatic stress, chemoprophylaxis is a term that is often used but rarely well understood. There has been no shortage of debate on the issue, but few rigorous studies to ground the discussion. The purpose of the current paper is to explore the issues surrounding this contentious area. Databases including PubMed, PsychArticles and Web of Knowledge were searched using the key words ‘chemo or pharmaco’, ‘prevention or prophylaxis’, and ‘PTSD or post-traumatic stress’. Relevant journals and reference lists of the papers obtained through this search were scanned for additional references. Studies that investigated the use of pharmacotherapy to prevent the onset of post-traumatic stress disorder were considered for this paper. Studies that examined the treatment of established PTSD were excluded. A total of 15 empirical studies were included in the review (including five randomized controlled trials), and twice as many non-data-driven papers. Evidence for the prophylactic use of alcohol, morphine, propranolol, and hydrocortisone is presented, followed by a discussion of the many challenges of using pharmacological interventions in this context. While attention to this issue has increased in recent times, the dearth of empirical data has done little to further the field. Larger studies are indicated following small trials with medications such as propranolol and hydrocortisone. There remain a number of ethical and practical questions to be answered before the widespread use of chemoprophylaxis can be recommended.

Objective: The present study (Shyness 7) has two aims: Firstly, to replicate an earlier trial showing that a self-guided Internet treatment for social phobia is efficacious, and secondly, to examine whether the addition of self-guided motivational enhancement strategies improves completion rates and clinical outcomes. Method: Randomized controlled trial (RCT) of self-guided Internet-based cognitive behavioural treatment (iCBT), or iCBT plus self-guided motivational enhancement strategies (iCBT+MS), was conducted. An intention-to-treat and last observation carried forward model was used for data analyses. The participants consisted of 108 volunteers with social phobia. The iCBT intervention consisted of two online lessons about symptoms and treatment of anxiety disorders and six lessons about management of social phobia (the Shyness programme) with complex automated reminders. The motivational intervention was based on traditional techniques including understanding and exploring ambivalence about change using a cost–benefit analysis, developing and resolving discrepancy between values and symptoms, and enhancing self-efficacy for change. The main outcome measures were the Social Interaction Anxiety Scale and Social Phobia Scale. Results: More iCBT+MS group participants completed the eight lessons than iCBT group participants (75% versus 56%, respectively), but there were no between-group differences in outcome measures at post-treatment or at 3 month follow up. Large mean within-groups effect sizes (Cohen's d) for the two social phobia measures were found for both the iCBT and iCBT+ MS groups (1.1 and 0.95, respectively), which were sustained at 3 month follow up (1.06 and 1.07, respectively). Both iCBT and iCBT+MS group participants reported that the procedures were highly acceptable. Conclusions: Both self-guided versions of the Shyness programme were reliably efficacious, confirming that people with social phobia may significantly benefit from a highly structured self-guided intervention. The addition of motivational techniques increased completion rates but did not improve clinical outcomes or acceptability.

Objective: Atypical antipsychotics are increasingly drugs of first choice in schizophrenia. Amisulpride, a new atypical antipsychotic, is reported to be effective for both positive and negative symptoms of schizophrenia in Western countries but Indian experience is limited. The aim of the present study was therefore to conduct a trial of amisulpride versus olanzapine in Indian schizophrenia patients. Methods: Eighty adult patients of either sex were randomized to receive standard doses of the two drugs orally, in a single blind manner, for 12 weeks, with follow up at 4 and 8 weeks. Effectiveness was assessed by changes in scores on the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive Symptoms (SAPS), Scale for Assessment of Negative Symptoms (SANS), and physician-administered Clinical Global Impression (CGI) scale. Tolerability was assessed by treatment-emergent adverse drug reactions (ADRs). Results: Evaluable were 39 patients on amisulpride and 38 on olanzapine. The groups were comparable at baseline with respect to demographics, illness duration and rating scores. Final BPRS score was lower for olanzapine (33.2 ± 9.44) than for amisulpride (37.7 ± 9.67). SAPS and SANS scores and CGI rating improved individually in both arms but remained comparable between groups throughout the study period, but olanzapine reduced SAPS score to a greater extent. ADRs were encountered in 67.5% and 47.5% of patients (p = 0.113) on amisulpride and olanzapine, respectively. Tremor and insomnia were more frequent with amisulpride, while olanzapine caused more weight gain and sedation. No serious ADRs occurred. Conclusions: Amisulpride, although comparable to olanzapine on some measures, did not match the improvement seen with the latter drug in BPRS and SAPS scores. Despite differences in ADR profiles, overall tolerability was satisfactory for both drugs. In Indian patients, amisulpride should therefore be an alternative to olanzapine to a limited extent, such as when weight gain and sedation are undesirable.

Objective: The aim of the present study was to determine the efficacy of an Internet-based clinician-assisted computerized cognitive behavioural treatment (CaCCBT) programme for generalized anxiety disorder (the Worry programme). Methods: Forty-eight individuals meeting diagnostic criteria for generalized anxiety disorder (GAD) were randomly assigned to the Worry programme or to a waitlist control group. In the clinician-assisted Worry programme, participants complete six online lessons, weekly homework assignments, receive weekly email contact from a clinical psychologist, and contribute to a moderated online discussion forum with other participants. An intention-to-treat model was used for data analyses. The main outcome measures were Generalized Anxiety Disorder–7 Item Scale (GAD-7) and the Penn State Worry Questionnaire (PSWQ). Results: A total of 75% of treatment group participants completed all six lessons within the 9 week programme and post-treatment data were collected from 21/24 treatment group and 19/21 control group participants. Treatment group participants reported significantly reduced symptoms of worry as measured on the GAD-7 and PSWQ and reduced symptoms of depression as measured on the Patient Health Questionnaire–9 Item Scale (PHQ-9). Mean within- and between-groups effect sizes (Cohen's d) across the two measures of GAD were 1.3 and 1.1, respectively. Participants found the treatment programme acceptable and satisfactory. The clinician spent a total mean of 130 min per person over the programme. Conclusions: The Worry programme, the first randomized controlled trial of CaCCBT for GAD, resulted in clinically significant improvements. These results are consistent with literature indicating that Internet-based programmes, when combined with clinical guidance, can significantly reduce the symptoms of common mental disorders.

Objective: The relationship between motivation and recovery in anorexia nervosa has received increased attention in the research literature although few controlled investigations of increasing motivation in this population exist. Three questions were therefore examined in an inpatient anorexia nervosa population: (i) does baseline motivation predict change in eating pathology; (ii) does change in motivation predict change in eating pathology; and (iii) can we increase motivation to recover in this group? Method: Inpatients (n=47) in a specialist weight disorder unit with a mean age of 21.85 years (SD=5.37) were randomly allocated to receive four sessions of motivational interviewing with a novice therapist in addition to treatment as usual (n=22) or treatment as usual alone (n=25). Assessment of eating pathology and motivation to recover was conducted on three occasions: at admission (baseline), and at 2- and 6 week follow up. Eating pathology was assessed using the Eating Disorder Examination and self-reported motivation was assessed using the Anorexia Nervosa Stages of Change Questionnaire and six Likert scales. Results: Higher baseline motivation across five of the seven measures predicted significant decreases in eating pathology, and increased Anorexia Nervosa Stages of Change Questionnaire scores between baseline and 2 week follow up predicted significant improvement in eating pathology between baseline and 6 week follow up. Significantly more patients were lost to follow up from the treatment as usual compared to the motivational interviewing group. More patients in the motivational interviewing condition moved from low readiness to change at baseline to high readiness to change at 2 and 6 week follow up. Conclusions: Motivation is an important predictor of change in anorexia nervosa and preliminary evidence is provided that motivation can be improved in this population. Further investigations, however, of ways of improving motivation in this population need to be conducted, along with the impact of motivational changes on treatment outcome.

Objective: To compare therapeutic effects of eicosapentaenoic acid (EPA), fluoxetine and a combination of them in major depression. Method: Sixty outpatients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score ≥15 in the 17-item Hamilton Depression Rating Scale (HDRS) were randomly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine, or their combination for 8 weeks. Double dummy technique was used to double blind the study. Patients were assessed at 2 week intervals. Change in HDRS was the primary outcome measure. Results: Analysis of covariance for HDRS at week 8 across treatment groups was performed in 48 patients who completed at least 4 weeks of the study, with the last observation carried forward. Treatment, age of onset and baseline HDRS had a significant effect on HDRS at week 8. EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment. Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms. Response rates (≥50% decrease in baseline HDRS) were 50%, 56% and 81% in the fluoxetine, EPA and combination groups, respectively. Conclusions: In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder. EPA + fluoxetine combination was superior to either of them alone.