Cognitive Remediation in Bipolar (CRiB2): study protocol for a randomised controlled trial assessing efficacy and mechanisms of cognitive remediation therapy compared to treatment as usual.

BACKGROUND: A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects. METHODS: CRiB2 is a two-arm, assessor-blind, multi-site, randomised controlled trial (RCT) comparing CR to treatment-as-usual (TAU). Participants are people with a diagnosis of BD, aged between 18 and 65, with no neurological or current substance use disorder, and currently euthymic. 250 participants will be recruited through primary, secondary, tertiary care, and the community. Participants will be block-randomised (1:1 ratio, stratified by site) to continue with their usual care (TAU) or receive a 12-week course of therapy and usual care (CR + TAU). The intervention comprises one-on-one CR sessions with a therapist supplemented with independent cognitive training for 30-40 h in total. Outcomes will be assessed at 13- and 25-weeks post-randomisation. Efficacy will be examined by intention-to-treat analyses estimating between-group differences in primary (i.e., psychosocial functioning at week 25 measured with the Functional Assessment Short Test) and secondary outcomes (i.e., measures of cognition, mood, patient-defined goals, and quality of life). Global cognition, metacognitive skills, affect fluctuation, and salivary cortisol levels will be evaluated as putative mechanisms of CR through mediation models. DISCUSSION: This study will provide a robust evaluation of efficacy of CR in people with BD and examine the putative mechanisms by which this therapy works. The findings will contribute to determining the clinical utility of CR and potential mechanisms of action. TRIAL REGISTRATION: Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry: https://www.isrctn.com/ISRCTN10362331 . Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting.

Psychedelics for treatment resistant depression: are they game changers?

INTRODUCTION: A new era of treatment for adults with treatment-resistant depression (TRD), which involves psychedelic substances, is dawning. Emerging evidence indicates that psychedelics can exert antidepressant effects through multiple neurobiological and psychological mechanisms. However, it remains to be seen if these new treatments will revolutionize the treatment of TRD. AREAS COVERED: The present review focuses on the efficacy of serotoninergic psychedelics psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and mescaline (3,4,5-trimethoxyphenethylamine), as well as 3,4-methylenedioxymethamphetamine (MDMA), for TRD. A systematic search was conducted for psilocybin in TRD as emerging trials had not yet been subject to review. A narrative review summarized findings on other psychedelics. EXPERT OPINION: Psychedelic therapy has created a paradigm shift in the treatment of TRD, as it can maximize therapeutic benefits and minimize potential risks. Psilocybin holds promise as a potential game-changer in the treatment of TRD, with initial evidence suggesting a rapid antidepressant effect sustained for some responders for at least 3 months. Nevertheless, further adequately powered, double-blind, comparator-controlled trials are required to explore and clarify the mechanisms of action and long-term effects of psychedelics in TRD. Psychedelics also hold promise for other psychiatric conditions, such as bipolar depression and post-traumatic stress disorder.

Does cognitive improvement translate into functional changes? Exploring the transfer mechanisms of cognitive remediation therapy for euthymic people with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is associated with cognitive and functional difficulties, persistent beyond mood episodes. Cognitive remediation (CR) is a psychological therapy targeting cognitive and functioning difficulties. Recent evidence suggests that CR may enhance long-term functioning but transfer mechanisms on functional outcomes have not been explored. We aim to investigate whether and how cognitive gains after CR transfer to functional improvement. METHODS: We considered data from a randomized controlled trial comparing CR (n = 40) to treatment-as-usual (TAU; n = 40) in euthymic people with BD. Treatment outcomes included individual cognitive domains and global cognition, psychosocial functioning, and goal attainment. Regression-based mediation and moderation modelling were used to assess whether and how post-treatment cognitive changes translate into functional improvement at follow-up, three months after treatment end. RESULTS: Cognitive gains after CR transferred to functional changes three months later: improvement in post-treatment global cognition partially mediated the effect of CR on psychosocial functioning (standardized indirect effect: -0.23, 95% CI -0.51 to -0.04). Goal attainment was not significantly mediated by changes in cognition, but post-treatment cognitive performance moderated the effect of CR on the GAS at follow-up (interaction effect: 0.78, 95% CI 0.08-1.55). CONCLUSIONS: Our findings suggest that cognitive improvements contribute to functional improvement but transfer mechanisms differ between psychosocial functioning and idiosyncratic recovery goals. Cognition accounted for only a proportion of the total CR effect on functional outcomes. Future studies should consider other variables, such as metacognition, that may drive the transfer of CR effects to functional outcomes.

Evaluating the mechanisms of social cognition intervention in schizophrenia: A proof-of-concept trial.

BACKGROUND: Social cognition interventions have shown promise for improving social functioning in people with schizophrenia. However, it is unclear how changes in social cognition affect social functioning. This study evaluates the impact of a social cognition intervention (GRASP - GRoup trAining for Social skills in Psychosis) on social cognition and social functioning outcomes and explores how two mechanisms, affect and physiological arousal, may drive changes. METHOD: A two-arm single blind (assessor) randomized pilot trial comparing GRASP plus treatment-as-usual (TAU) with TAU alone in people with a diagnosis of schizophrenia. Participants were assessed with measures of social cognition, social functioning, and symptoms. All participants undertook a week-long mobile health assessment (experience sampling method) measuring social behavior and affect and used a wearable device recording autonomic activity. Assessments were performed at baseline and at week 10. RESULTS: Forty-eight participants were randomly allocated to the treatment or control condition. Individuals randomized to GRASP did not show improvements on experience sampled social behavior and social cognition measures compared to controls. However, participants in the GRASP group enjoyed social contact more and had lower levels of negative affect and higher levels of positive affect compared to controls. There was no evidence of autonomic changes (i.e., electrodermal activity) associated with social behavior resulting from the therapy. CONCLUSION: Social cognition interventions may be helpful in improving the quality of social contacts in people with schizophrenia by decreasing negative affect. Increase in social behavior may require longer periods to be evident. Future studies should consider how social cognition interventions may alter qualitative aspects associated with social behavior.

Cognitive remediation for people with bipolar disorder: The contribution of session attendance and therapy components to cognitive and functional outcomes.

BACKGROUND: Cognitive remediation (CR) can reduce cognitive and functional difficulties in people with bipolar disorder (BD). To date, there is limited evidence on the contribution of session attendance and therapy components to treatment outcomes. This study explores whether attendance and core CR components contribute to treatment outcomes. METHODS: This is a secondary analysis using data from a randomized controlled trial comparing CR plus treatment-as-usual (TAU; n = 40) to TAU only (n = 40) in euthymic people with BD. Session attendance was measured by number of sessions and by achieving therapy completion, pre-defined as attending ≥20 sessions. We used instrumental variable analysis to examine the effect of attendance on treatment outcomes. We then considered the association between core therapy components (i.e., massed practice, errorless learning, strategy use, therapist contact) and post-treatment outcome changes using correlation. RESULTS: The CR group improved significantly in measure of global cognition, psychosocial functioning, and goal attainment. Therapy recipients attended 27.1 sessions on average, with 32 (80%) completing the minimum number of 20 sessions. Attending more sessions and achieving therapy completion were associated with improved treatment outcomes, but this relationship was not significant within the subgroup of CR completers. Improvement in psychosocial functioning was associated with therapist contact and goal attainment with selecting useful strategies during therapy. CONCLUSIONS: Our findings highlight the relevance of session attendance, specifically the importance of achieving a minimum threshold of CR sessions, for outcome improvement. Strategy use and therapist contact might facilitate improvements in psychosocial functioning and personal recovery goals.

Towards personalizing cognitive remediation therapy: Examining moderators of response for euthymic people with bipolar disorder.

BACKGROUND: Recent evidence suggests that cognitive remediation (CR) may reduce cognitive and functional difficulties in people with bipolar disorder (BD). However, there is a limited understanding of whether, and which, pre-treatment factors influence who will benefit from CR and this information could help to develop optimal therapy delivery. We aim to identify and examine baseline factors moderating post-treatment improvement. METHODS: This is a secondary analysis of data from a randomized controlled trial comparing CR (n = 40) to treatment-as-usual (TAU; n = 40) in euthymic people with BD. Elastic net regression was used to identify patient characteristics and baseline measures associated with post-treatment improvement in cognition, psychosocial functioning, and goal attainment. We then tested the moderating effect of retained variables on each outcome using multivariable linear regression. RESULTS: Despite lower baseline cognitive performance being associated with greater post-treatment changes in cognition and psychosocial functioning, there was no evidence of treatment response moderation. CR effect on goal attainment was larger for participants with better baseline cognitive performance, but this moderating effect did not reach significance (p = 0.09). Those with more severe baseline subjective cognitive complaints (p = 0.03) and more previously completed psychological therapies (p = 0.02) had also larger gains in goal attainment. CONCLUSIONS: Treatment benefits in cognition and psychosocial functioning might not be affected by pre-treatment factors and patient characteristics. However, baseline cognition and perceived deficits may influence the effect of CR on achieving recovery goals. Therapy adaptations may be required to exert greater benefits for less responsive patients.

Predictors of psychosocial functioning in euthymic patients with bipolar disorder: A model selection approach.

BACKGROUND: Functional impairment is a major target in the treatment of bipolar disorder (BD), but the magnitude and type of functional difficulties differ across patients. Findings on predictors of overall functioning and specific functional areas are inconsistent. We aimed to characterize functional difficulties and identify factors associated with global functioning and individual domains in euthymic patients. METHODS: The Functional Assessment Short Test (FAST) was used to assess overall psychosocial functioning and specific functional domains in 80 euthymic participants with BD. Participants also completed a clinical interview and a cognitive assessment. Model selection with elastic net regression was performed to identify predictors of global functioning. We then examined the association of these predictors with individual functional domains using correlation. RESULTS: FAST scores indicated moderate or severe impairment for 54% of the sample, with occupational functioning showing the highest impairment rate. Elastic net regression selected a model with three variables (higher residual depressive symptoms, lower executive functioning, more perceived cognitive deficits) as predictors of overall functioning. No significant associations were found between these predictors. Depressive symptoms were associated with interpersonal relationships and leisure time, executive skills with occupational functioning, and perceived deficits with cognitive functioning. CONCLUSIONS: Residual depressive symptoms were the strongest predictor of overall functioning which highlights the importance of assessing and targeting subthreshold symptoms for recovery. Executive difficulties were associated with functioning, particularly occupational skills, independently of depressive symptoms. Interventions targeting these difficulties, such as cognitive and functional remediation, may be key treatment options towards facilitating functional recovery.

Cognitive impairment in euthymic patients with bipolar disorder: Prevalence estimation and model selection for predictors of cognitive performance.

Objectives Although cognitive dysfunction is a prominent feature of bipolar disorder (BD), previous research presents limitations in estimating the proportion of euthymic patients experiencing clinically relevant deficits and identifying predictors of cognitive difficulties. We explored the relevance of recommended definitions of clinically significant cognitive impairment for functional outcomes, estimated its prevalence, and identified patient characteristics associated with cognition. Methods We assessed cognitive performance across four domains in 80 euthymic participants with BD. Participants were categorized based on two criteria for clinically significant cognitive impairment and we assessed the ability of these criteria to differentiate participant performance on established functional outcomes. Variable selection with elastic net regression was used to identify sociodemographic and clinical factors associated with cognitive performance. Selected variables were examined as predictors of clinically significant cognitive impairment with logistic regression. Results According to the selected criterion, 34% presented with clinically significant cognitive impairment. Poorer current cognitive performance was associated with older age, lower estimated premorbid IQ, more currently prescribed psychotropic medications, fewer previous psychological therapies, and current use of antipsychotics. A model with premorbid IQ, psychotropic medications and previous psychological therapies as predictors of cognitive impairment correctly classified 75% of the participants. Conclusions This is one of the first studies to use a model selection approach to identify factors associated with cognitive difficulties in BD. Our findings offer the initial steps towards a predictive model for cognitive impairment. This could improve treatment decisions and prioritization for euthymic patients with BD, particularly the implementation of cognitive interventions.

The Maudsley 3-item Visual Analogue Scale (M3VAS): Validation of a scale measuring core symptoms of depression.

AIMS: Low mood and anhedonia are the core symptoms of major depressive disorder (MDD). However, there is no established visual analogue scale that measures pervasiveness of both symptoms. We aimed to validate the Maudsley 3-item Visual Analogue Scale (M3VAS) as a measure of core depressive symptoms and suicidality. METHODS: This is a cross-sectional secondary analysis combining data from two randomised controlled trials covering a broad range of depression severity from euthymia to severe depression. We validated the M3VAS by testing: 1) latent construct domains using factor analysis; 2) internal consistency using Cronbach's alpha; and 3) convergent validity by correlating M3VAS scores against scores on the Quick Inventory of Depressive Symptomatology-16 item (QIDS-SR-16), which is validated for use in clinical trials. RESULTS: Of 180 patients in the combined cohort, 177 (98.3%) provided complete data on the M3VAS and QIDS-SR-16. The mean (SD) age was 41.6 (13.0) years and 59.3% were female. Using factor analysis, one eigenvalue above 1 was produced (2.39) that explained 79.6% of the variance, indicating a one-factor model. Cronbach's alpha was 0.87, demonstrating good internal consistency. Total M3VAS scores correlated strongly (r = 0.72, p<0.001) with QIDS-SR-16 scores, indicating good convergent validity. LIMITATIONS: This was a cross-sectional study and was not validated against a clinician-rated assessment for depression. CONCLUSION: The M3VAS is a simple, valid instrument for the assessment of core depressive symptoms and suicidality across the depression spectrum. Future studies should test the longitudinal validity of the M3VAS in detecting changes in core depressive symptoms and suicidality over time.

Inflammatory biomarkers and cognitive functioning in individuals with euthymic bipolar disorder: exploratory study.

BACKGROUND: Neurobiological research frequently implicates inflammatory and neurogenic components with core aspects of bipolar disorder. Even in periods of symptom remission (euthymia), individuals with bipolar disorder experience cognitive impairments, which are increasingly being proposed as an outcome for interventions; identifying biomarkers associated with cognitive impairment in people with bipolar disorder could advance progress in this therapeutic field through identifying biological treatment targets. AIMS: We aimed to identify proteomic biomarker correlates of cognitive impairment in individuals with euthymic bipolar disorder. METHOD: Forty-four adults with a bipolar disorder diagnosis in euthymia underwent a battery of cognitive assessments and provided blood for biomarkers. We examined a comprehensive panel of inflammatory and trophic proteins as putative cross-sectional predictors of cognition, conceptualised according to recommended definitions of clinically significant cognitive impairment (binary construct) and global cognitive performance (continuous measure). RESULTS: A total of 48% of the sample met the criteria for cognitive impairment. Adjusting for potentially important covariates, regression analyses identified lower levels of three proteins as significantly and independently associated with cognitive deficits, according to both binary and continuous definitions (interleukin-7, vascular endothelial growth factor C and placental growth factor), and one positively correlated with (continuous) global cognitive performance (basic fibroblast growth factor). CONCLUSIONS: This study identifies four candidate markers of cognitive impairment in bipolar disorder, none of which have been previously compared with cognitive function in participants with bipolar disorder. Pending replication in larger samples and support from longitudinal studies, these markers could have implications for treating cognitive dysfunction in this patient population.

Cognitive remediation therapy for patients with bipolar disorder: A randomised proof-of-concept trial.

OBJECTIVES: Cognitive remediation therapy (CRT) may benefit people with bipolar disorder type I and II for whom cognitive impairment is a major contributor to disability. Extensive research has demonstrated CRT to improve cognition and psychosocial functioning in people with different diagnoses, but randomised trials of evidenced therapy programmes are lacking for bipolar disorders. The Cognitive Remediation in Bipolar (CRiB) study aimed to determine whether an established CRT programme is feasible and acceptable for people with bipolar disorders. METHODS: This proof-of-concept, single-blind randomised trial recruited participants aged 18-65 with bipolar disorder, not currently experiencing an episode. They were 1:1 block randomised to treatment-as-usual (TAU) with or without individual CRT for 12 weeks. The partly computerised CRT programme ("CIRCuiTS") was therapist-led and is evidence-based from trials in those with psychotic illnesses. Data were collected and analysed by investigators blinded to group allocation. The main outcomes (week 13 and 25) examined participant retention, intervention feasibility and putative effects of CRT on cognitive and psychosocial functioning via intention-to-treat analyses. TRIAL REGISTRATION: ISRCTN ID32290525. RESULTS: Sixty participants were recruited (02/2016-06/2018) and randomised to CRT (n = 29) or TAU (n = 31). Trial withdrawals were equivalent (CRT n = 2/29; TAU n = 5/31). CRT satisfaction indicated high acceptability. Intention-to-treat analyses (N = 60) demonstrated greater improvements for CRT- than TAU-randomised participants: at both week 13 and 25, CIRCuiTS participants showed larger improvements in the following domains (week 25 effect sizes reported here): IQ (SES = 0.71, 95% CI [0.29,1.13]), working memory (SES = 0.70, 95% CI [0.31,1.10]), executive function (SES = 0.93, 95% CI [0.33,1.54]), psychosocial functioning (SES = 0.49, 95% CI [0.18,0.80]) and goal attainment (SES = 2.02, 95% CI [0.89,3.14]). No serious adverse events were reported. CONCLUSIONS: CRT is feasible for individuals with bipolar disorders and may enhance cognition and functioning. The reported effect sizes from this proof-of-concept trial encourage further investigation in a definitive trial.

Role of cognitive reserve in cognitive variability in euthymic individuals with bipolar disorder: cross-sectional cluster analysis.

BACKGROUND: People with bipolar disorder have moderate cognitive difficulties that tend to be more pronounced during mood episodes but persist after clinical remission and affect recovery. Recent evidence suggests heterogeneity in these difficulties, but the factors underlying cognitive heterogeneity are unclear. AIMS: To examine whether distinct cognitive profiles can be identified in a sample of euthymic individuals with bipolar disorder and examine potential differences between subgroups. METHOD: Cognitive performance was assessed across four domains (i.e. processing speed, verbal learning/memory, working memory, executive functioning) in 80 participants. We conducted a hierarchical cluster analysis and a discriminant function analysis to identify cognitive profiles and considered differences in cognitive reserve, estimated cognitive decline from premorbid cognitive functioning, and clinical characteristics among subgroups. RESULTS: Four discrete cognitive profiles were identified: cognitively intact (n = 25; 31.3%); selective deficits in verbal learning and memory (n = 15; 18.8%); intermediate deficits across all cognitive domains (n = 30; 37.5%); and severe deficits across all domains (n = 10; 12.5%). Cognitive decline after illness onset was greater for the intermediate and severe subgroups. Cognitive reserve scores were increasingly lower for subgroups with greater impairments. A smaller proportion of cognitively intact participants were using antipsychotic medications compared with all other subgroups. CONCLUSIONS: Our findings suggest that individuals with cognitively impaired profiles demonstrate more cognitive decline after illness onset. Cognitive reserve may be one of the factors underlying cognitive variability across people with bipolar disorder. Patients in the intermediate and severe subgroups may be in greater need of interventions targeting cognitive difficulties.

Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis.

Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD. The NMA compared the intervention effectiveness of depressive symptoms for TRD augmentation. Of 36 included trials, 27 were suitable for inclusion in NMA, and no psychological trials could be included in the absence of a common comparator. Antipsychotics (13 trials), mood stabilizers (three trials), NMDA-targeting medications (five trials), and other mechanisms (3 trials) were compared against placebo. NMDA treatments were markedly superior to placebo (ES = 0.91, 95% CI 0.67 to 1.16) and head-to-head NMA suggested that NMDA therapies had the highest chance of being an effective treatment option compared to other pharmacological classes. This study provides the most comprehensive evidence of augmenters' effectiveness for TRD, and our GRADE recommendations can be used to guide guidelines to optimize treatment choices. Although conclusions are limited by paucity of, and heterogeneity between, trials as well as inconsistent reports of treatment safety. This work supports the use of NMDA-targeting medications such as ketamine.

Cognitive enhancement interventions for people with bipolar disorder: A systematic review of methodological quality, treatment approaches, and outcomes.

BACKGROUND: Patients with bipolar disorder (BD) suffer from cognitive deficits across several domains. The association between cognitive performance and psychosocial functioning has led to the emergence of cognition as a treatment target. OBJECTIVE: This study reviews the existing literature on cognitive enhancement interventions for people with BD, focusing on different treatment approaches and methodological quality. METHODS: We conducted a systematic search following the PRISMA guidelines. Sample characteristics and main outcomes for each study and treatment characteristics for each approach were extracted. Study quality was assessed using the Clinical Trials Assessment Measure (CTAM) and Cochrane Collaboration's Risk of Bias tool by independent raters. RESULTS: Eleven articles reporting data from seven original studies were identified encompassing 471 participants. Two treatment approaches were identified, cognitive and functional remediation. For controlled studies, methodological quality was modest (average CTAM score = 60.3), while the overall risk of bias was considered moderate. Beneficial effects on cognitive or functional outcomes were reported in the majority of studies (91%), but these findings were isolated and not replicated across studies. Key methodological limitations included small sample sizes, poor description of randomization process, high attrition rates, and participant exclusion from the analysis. CONCLUSIONS: Findings are promising but preliminary. Quality studies were few and mostly underpowered. Heterogeneity in sample characteristics, outcome measures, and treatment approaches further limit the ability to generalize findings. Adequately powered trials are required to replicate initial findings, while moderators of treatment response and mechanisms of transfer need to be explored.

A systematic review of moderators of cognitive remediation response for people with schizophrenia.

BACKGROUND: There is evidence that cognitive remediation (CR) is moderately effective in improving cognitive and functional difficulties in people with schizophrenia. However, there is still a limited understanding of what influence different treatment responses. AIM: To identify moderators influencing CR response in people with schizophrenia. METHODS: This systematic review follows PRISMA guidelines. Searches were conducted up to January 2019 on PubMed and PsychInfo to identify randomized controlled trials of CR reporting analyses of moderators of treatment response. All papers were assessed for methodological quality and information on sample size, intervention and control condition, moderators, outcomes, effect of moderator on outcomes and demographic characteristics from each study was extracted and critically summarised. RESULTS: Thirty-six studies were included, considering 2737 participants. Study participants consisted on average of people in their late-thirties, mostly men, with over 10 years of illness. The review identified moderators that could be grouped into five categories: demographics, biological, cognitive and functional, psychological, and illness-related characteristics. The assessment of methodological quality showed that many studies had a high risk of bias. CONCLUSIONS: There was no high-quality replicated evidence which identifies reliable moderators of CR response. Many moderators were not replicated or presented in single, underpowered studies. Studies also investigated moderators independently despite their potential to overlap (e.g. age and education). Future research should concentrate on evaluating, with sound studies, the role moderators may play in affecting CR treatment response. This information can inform who will benefit most from the therapy and help to improve the benefits of CR.

Feasibility and acceptability of brief cognitive remediation targeting metacognition in acute inpatients with psychosis: a case series.

Cognitive remediation (CR) is an intensive intervention targeting cognitive impairment with the aim of improving functioning in people with psychotic disorders. Shorter forms of CR based on metacognition and targeting awareness of cognitive problems may be more appropriate for acute inpatient settings where time is limited. The objective of the study was to evaluate the feasibility and acceptability of a new brief course of CR targeting cognitive and metacognitive difficulties within an acute inpatient psychiatric setting. Thirteen male service users with psychosis received a three-week course of CR. Participants were assessed at baseline and post-treatment on cognitive measures, subjective cognitive complaints, functional impairment, and symptom severity. Feasibility was assessed based on engagement, attendance, and attrition. Acceptability was evaluated through treatment satisfaction. Eight participants completed therapy, with 81% session attendance. Therapy was considered acceptable, with the majority of participants considering it satisfactory. Potential benefit analysis showed a significant post-treatment improvement in global cognition and memory. Subjective cognitive complaints did not change over time. It was concluded that it is feasible to deliver brief CR in an acute inpatient setting. Context of delivery and engagement are challenges for optimal therapy implementation. CR protocol adaptations made to promote metacognitive competencies may compensate for lack of intensive practice.

Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis.

BACKGROUND: Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD. METHOD: Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions. RESULTS: Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25-1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23-1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81-1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.80-1.30) and psychological (ES = 1.43, 95% CI 0.50-2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66-0.91) and psychological control (ES = 0.94, 95% CI 0.36-1.52). CONCLUSIONS: Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.Declaration of interestIn the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.