What predicts response to sertraline for people with depression in primary care? a secondary data analysis of moderators in the PANDA trial.

PURPOSE: Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment. METHODS: The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated. RESULTS: Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables. CONCLUSION: Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms.

Eye-movement desensitisation and reprocessing therapy (EMDR) to prevent transition to psychosis in people with an at-risk mental state (ARMS): mixed method feasibility study.

BACKGROUND: Trauma plays an important role in the development of psychosis, but no studies have investigated whether a trauma-focused therapy could prevent psychosis. AIMS: This study aimed to establish whether it would be feasible to conduct a multicentre randomised controlled trial (RCT) to prevent psychosis in people with an at-risk mental state (ARMS), using eye-movement desensitisation and reprocessing therapy (EMDR). METHOD: This started as a mixed-method randomised study comparing EMDR to treatment as usual but, as a result of low participant recruitment, was changed to a single-arm feasibility study. The proposed primary outcome for an RCT was transition to psychosis at 12-month follow-up. Data on secondary outcomes were also collected. Qualitative interviews were conducted with patients and therapists. RESULTS: Fourteen participants were recruited from the Early Intervention teams. Most people who expressed an interest in taking part attended an assessment to determine eligibility. All those eligible consented to take part. A total of 64% (7 of 11) of participants who were offered EMDR were followed up at 12 months. Of the 11 participants offered EMDR, one (11%, 95% CI: 0.2%, 48%) transitioned to psychosis. Nine patients and three therapists were interviewed. Participants who completed therapy (n = 4; mean 10.5 sessions) found EMDR helpful, but those who discontinued (n = 6; mean 5.2 sessions) said it had not benefitted them overall. Therapists said EMDR could be effective, although not for all patients. CONCLUSIONS: Future studies recruiting people with an ARMS to an RCT may need to extend recruitment beyond Early Intervention teams. Although some individuals found EMDR helpful, reasons for discontinuing need to be addressed in future studies.

Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. METHODS: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1-2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. DISCUSSION: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. TRIAL REGISTRATION: ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

Clinical factors associated with relapse in depression in a sample of UK primary care patients who have been on long-term antidepressant treatment.

BACKGROUND: This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long-term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression. METHODS: An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months. RESULTS: Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23-2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01-2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01-1.09) and HR 1.06 (95% CI 1.01-1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78-0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81-1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse. CONCLUSIONS: The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse.

Provision of online eye movement and desensitisation therapy (EMDR) for people with post-traumatic stress disorder (PTSD): a multi-method service evaluation.

Background: The evidence for the effectiveness of online EMDR for PTSD is scarce.Objective: This service evaluation aimed to assess how online EMDR compared to in-person EMDR, in terms of its potential effectiveness and acceptability to therapists and patients.Method: The evaluation was carried out in the Cardiff and Vale University Health Board Traumatic Stress Service. We compared the outcome of therapy (PTSD scores at end of treatment), number of sessions, drop-out rate, and adverse events using linear/logistic regression in those receiving online EMDR over a 12-month period with those who had received in-person therapy in the year previous to that. Interviews with therapists and clients who had provided or undertaken online EMDR explored their views and experiences of treatment. Interviews were analysed thematically.Results: 33 people received in-person EMDR (15.3 sessions, SD = 1.4), and 45 received online EMDR (12.4 sessions, SD = 0.9). 24 individuals completed therapy in-person, and 32 online. There was no evidence of a difference in therapy completion, drop-out rates or adverse events between the two delivery modes. There was weak evidence that those who completed EMDR online and had available data (N = 29), had slightly lower PTSD scores at the end of therapy compared to those who received in-person EMDR (N = 24) (17.1 (SD = 3.2) versus 24.5 (SD = 3.0), mean difference = 7.8, 95% CI -0.3, 15.9, p = .06). However, groups were not randomised and only those who completed treatment were analysed, so estimates may be biased. 11 patients and five therapists were interviewed. Overall, both therapists and clients viewed online EMDR as safe and effective. Benefits mentioned by clients included feeling more in control and not having to travel. Clients' concerns related to lack of privacy and 'transition time/space' between therapy and their daily lives.Conclusion: Results suggest that online EMDR is an acceptable, safe and effective alternative to in-person EMDR for PTSD in this service.

This service evaluation assessed how online Eye Movement Desensitisation and Reprocessing (EMDR) compared to in-person EMDR in people with PTSD.Individuals receiving online EMDR had lower PTSD scores at the end of therapy, but the evidence for this was weak and as this was not a randomised trial we do not know whether this was due to the mode of therapy or other characteristics of clients receiving online therapy.Clients and therapists generally viewed online EMDR as being safe and effective, and supported the availability of online EMDR for PTSD.

A comparative study of the anthropometric status of adults and children in urban and rural communities of the North West Region of Cameroon.

BACKGROUND: Cameroon, like many other developing countries, is experiencing a double burden of malnutrition. With increasing urbanization, communities are exposed to high calorie diets and sedentary lifestyles, which contribute to overnutrition. However, the nutritional status of the communities may vary with geographic location. The aim of the current study was to investigate the prevalence of underweight, overweight and abdominal obesity among adults as well as overweight, underweight, stunting and wasting among children in selected urban and rural communities of the North West Region (NWR) of Cameroon. The study also compared these parameters between selected urban and rural areas. METHODS: Cross-sectional study design was used to investigate the anthropometric status of adults (18-65 years) and children (1-5 years) from two rural (Mankon and Mendakwe) and two urban (Mankon and Nkwen) communities in the NWR of Cameroon. The study included 156 adults and 156 children per study site from different households. A multistage sampling technique was used to select the participants and study sites Anthropometric measurements were taken using standardised methods for selected indices: weight, height, waist circumference and mid-upper arm circumference (MUAC). Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 25 and a p-value of < 0.05 was considered statistically significant. RESULTS: Adults from Nkwen (urban) were either overweight (n = 74; 47.4%) or obese (n = 44; 28.2%) with 43.6% (n = 68) from urban Mankon obese, whilst adults from rural Mankon were normal weight (49.4%; n = 77), 2.6% (n = 4) from Mendakwe (rural) were underweight and 64.1% (n = 100) were normal weight. Children in the rural areas were severely underweight (n = 45; 14.4%), while children in the urban areas were either normal (n = 158; 50.6) or overweight (n = 43; 13.8%). More females in the urban sites (n = 39; 53.4% in Nkwen and n = 43; 69.4% in urban Mankon) had a large waist circumference (WC) compared to those in the rural sites (n = 17; 22.1% in Mendakwe and n = 24; 38.1% in rural Mankon). Males in the urban areas had large WC compared to those in the rural sites (n = 19; 24.4% in Nkwen; n = 23; 24.7% in urban Mankon; n = 15; 16.1% in rural Mankon and n = 2; 2.6% in Mendakwe). Mid-upper arm circumference (MUAC) values indicated that most children in both urban (n = 147; 94.2% in Nkwen; n = 152; 97.4% in urban Mankon) and rural areas (n = 142; 91.0% in rural Mankon; n = 154; 98.7% in Mendakwe) were not acutely malnourished. CONCLUSIONS: This study found a higher prevalence of overweight and obesity among adults and children in the urban areas of Nkwen and Mankon, compared to rural Mankon and Mendakwe. Thus, there is a need to investigate and address the causes of the high prevalence of overweight and obesity in these urban areas.

Integrated therapist and online CBT for depression in primary care (INTERACT): study protocol for a multi-centre randomised controlled trial.

BACKGROUND: Cognitive behavioural therapy (CBT) is an effective treatment for depression. Self-directed online CBT interventions have made CBT more accessible at a lower cost. However, adherence is often poor and, in the absence of therapist support, effects are modest and short-term. Delivering CBT online using instant messaging is clinically and cost-effective; however, most existing platforms are limited to instant messaging sessions, without the support of between-session "homework" activities. The INTERACT intervention integrates online CBT materials and 'high-intensity' therapist-led CBT, delivered remotely in real-time. The INTERACT trial will evaluate this novel integration in terms of clinical and cost-effectiveness, and acceptability to therapists and clients. METHODS: Pragmatic, two parallel-group multi-centre individually randomised controlled trial, with 434 patients recruited from primary care practices in Bristol, London and York. Participants with depression will be identified via General Practitioner record searches and direct referrals. INCLUSION CRITERIA: aged ≥ 18 years; score ≥ 14 on Beck Depression Inventory (BDI-II); meeting International Classification of Diseases (ICD-10) criteria for depression. EXCLUSION CRITERIA: alcohol or substance dependency in the past year; bipolar disorder; schizophrenia; psychosis; dementia; currently under psychiatric care for depression (including those referred but not yet seen); cannot complete questionnaires unaided or requires an interpreter; currently receiving CBT/other psychotherapy; received high-intensity CBT in the past four years; participating in another intervention trial; unwilling/unable to receive CBT via computer/laptop/smartphone. Eligible participants will be randomised to integrated CBT or usual care. Integrated CBT utilises the standard Beckian intervention for depression and comprises nine live therapist-led sessions, with (up to) a further three if clinically appropriate. The first session is 60-90 min via videocall, with subsequent 50-min sessions delivered online, using instant messaging. Participants allocated integrated CBT can access integrated online CBT resources (worksheets/information sheets/videos) within and between sessions. Outcome assessments at 3-, 6-, 9- and 12-month post-randomisation. The primary outcome is the Beck Depression Inventory (BDI-II) score at 6 months (as a continuous variable). A nested qualitative study and health economic evaluation will be conducted. DISCUSSION: If clinically and cost-effective, this model of integrated CBT could be introduced into existing psychological services, increasing access to, and equity of, CBT provision. TRIAL REGISTRATION: ISRCTN, ISRCTN13112900. Registered on 11/11/2020. Currently recruiting participants. Trial registration data are presented in Table 1.

The identification and management of people with an at-risk mental state (ARMS) for psychosis in primary and secondary care services: A qualitative interview study.

AIMS: Early intervention in people with an at-risk mental state (ARMS) for psychosis can prevent the onset of psychosis. Clinical guidelines recommend that ARMS are referred to triage services, and then to Early Intervention (EI) teams in secondary care for assessment and treatment. However, little is known about how ARMS patients are identified and managed in UK primary and secondary care. This study explored patients' and clinicians' views of ARMS patients' care pathways. METHODS: Eleven patients, 20 GPs, 11 clinicians from the triaging Primary Care Liaison Services (PCLS) and 10 EI clinicians were interviewed. Data were analysed thematically. RESULTS: Most patients said their symptoms started in adolescence with depression and anxiety. Before being referred to EI teams, most patients were referred by their GP to well-being services for talking therapies, which they had not found helpful. Some GPs said secondary care's high acceptance thresholds and scarce treatment availability made them reluctant to refer to EI teams. Triage in PCLS was influenced by patients' risk of self-harm, and formulation of psychotic symptoms; only those without clear evidence of other pathology and not at high risk of self-harm were referred to EI teams, the others being referred to Recovery/Crisis services. Although patients referred to EI teams were offered an assessment, only some EI teams were commissioned to treat ARMS. CONCLUSIONS: Individuals meeting ARMS criteria might not receive early intervention due to high treatment thresholds and limited treatment availability in secondary care, suggesting clinical guidelines are not being met for this patient group.

Neuropsychological markers of antidepressant action: a secondary analysis of the ANTLER randomised controlled trial.

BACKGROUND: Antidepressants have been proposed to act via their influence on emotional processing. We investigated the effect of discontinuing maintenance antidepressant treatment on positive and negative self-referential recall and the association between self-referential recall and risk of relapse. METHODS: The ANTLER trial was a large (N = 478) pragmatic double-blind trial investigating the clinical effectiveness of long-term antidepressant treatment for preventing relapse in primary care patients. Participants were randomised to continue their maintenance antidepressants or discontinue via a taper to placebo. We analysed memory for positive and negative personality descriptors, assessed at baseline, 12- and 52-week follow-up. RESULTS: The recall task was completed by 437 participants. There was no evidence of an effect of discontinuation on self-referential recall at 12 [positive recall ratio 1.00, 95% CI (0.90-1.11), p = 0.93; negative recall ratio 1.00 (0.87-1.14), p = 0.87] or 52 weeks [positive recall ratio 1.03 (0.91-1.17), p = 0.62; negative recall ratio 1.00 (0.86-1.15), p = 0.96; ratios larger than one indicate higher recall in the discontinuation group], and no evidence of an association between recall at baseline or 12 weeks and later relapse [baseline, positive hazard ratio (HR) 1.02 (0.93-1.12), p = 0.74; negative HR 1.01 (0.90-1.13), p = 0.87; 12 weeks, positive HR 0.99 (0.89-1.09), p = 0.81; negative HR 0.98 (0.84-1.14), p = 0.78; ratios larger than one indicate a higher frequency of relapse in those with higher recall]. CONCLUSIONS: We found no evidence that discontinuing long-term antidepressants altered self-referential recall or that self-referential recall was associated with risk of relapse. These findings suggest that self-referential recall is not a neuropsychological marker of antidepressant action.

Antidepressant use and risk of adverse outcomes: population-based cohort study.

BACKGROUND: Antidepressants are one of the most widely prescribed drugs in the global north. However, little is known about the health consequences of long-term treatment. AIMS: This study aimed to investigate the association between antidepressant use and adverse events. METHOD: The study cohort consisted of UK Biobank participants whose data was linked to primary care records (N = 222 121). We assessed the association between antidepressant use by drug class (selective serotonin reuptake inhibitors (SSRIs) and 'other') and four morbidity (diabetes, hypertension, coronary heart disease (CHD), cerebrovascular disease (CV)) and two mortality (cardiovascular disease (CVD) and all-cause) outcomes, using Cox's proportional hazards model at 5- and 10-year follow-up. RESULTS: SSRI treatment was associated with decreased risk of diabetes at 5 years (hazard ratio 0.64, 95% CI 0.49-0.83) and 10 years (hazard ratio 0.68, 95% CI 0.53-0.87), and hypertension at 10 years (hazard ratio 0.77, 95% CI 0.66-0.89). At 10-year follow-up, SSRI treatment was associated with increased risks of CV (hazard ratio 1.34, 95% CI 1.02-1.77), CVD mortality (hazard ratio 1.87, 95% CI 1.38-2.53) and all-cause mortality (hazard ratio 1.73, 95% CI 1.48-2.03), and 'other' class treatment was associated with increased risk of CHD (hazard ratio 1.99, 95% CI 1.31-3.01), CVD (hazard ratio 1.86, 95% CI 1.10-3.15) and all-cause mortality (hazard ratio 2.20, 95% CI 1.71-2.84). CONCLUSIONS: Our findings indicate an association between long-term antidepressant usage and elevated risks of CHD, CVD mortality and all-cause mortality. Further research is needed to assess whether the observed associations are causal, and elucidate the underlying mechanisms.

Rise in prescribing for anxiety in UK primary care between 2003 and 2018: a population-based cohort study using Clinical Practice Research Datalink.

BACKGROUND: Little is known about trends in prescribing of anxiolytics (antidepressants, benzodiazepines, beta-blockers, anticonvulsants, and antipsychotics) for treatment of anxiety. Several changes may have affected prescribing in recent years, including changes in clinical guidance. AIM: To examine trends in prescribing for anxiety in UK primary care between 2003 and 2018. DESIGN AND SETTING: A population-based cohort study using Clinical Practice Research Datalink (CPRD) data. METHOD: Analysis of data from adults (n = 2 569 153) registered at CPRD practices between 2003 and 2018. Prevalence and incidence rates were calculated for prescriptions of any anxiolytic and also for each drug class. Treatment duration was also examined. RESULTS: Between 2003 and 2018, prevalence of any anxiolytic prescription increased from 24.9/1000 person-years-at-risk (PYAR) to 43.6/1000 PYAR, driven by increases in those starting treatment, rather than more long-term use. Between 2003 and 2006, incidence of any anxiolytic prescription decreased from 12.8/1000 PYAR to 10.0/1000 PYAR; after which incidence rose to 13.1/1000 PYAR in 2018. Similar trends were seen for antidepressant prescriptions. Incident beta-blocker prescribing increased over the 16 years, whereas incident benzodiazepine prescriptions decreased. Long-term prescribing of benzodiazepines declined, yet 44% of prescriptions in 2017 were longer than the recommended 4 weeks. Incident prescriptions in each drug class have risen substantially in young adults in recent years. CONCLUSION: Recent increases in incident prescribing, especially in young adults, may reflect better detection of anxiety, increasing acceptability of medication, or an earlier unmet need. However, some prescribing is not based on robust evidence of effectiveness, may contradict guidelines, and there is limited evidence on the overall impact associated with taking antidepressants long term. As such, there may be unintended harm.

Socioeconomic Indicators of Treatment Prognosis for Adults With Depression: A Systematic Review and Individual Patient Data Meta-analysis.

Importance: Socioeconomic factors are associated with the prevalence of depression, but their associations with prognosis are unknown. Understanding this association would aid in the clinical management of depression. Objective: To determine whether employment status, financial strain, housing status, and educational attainment inform prognosis for adults treated for depression in primary care, independent of treatment and after accounting for clinical prognostic factors. Data Sources: The Embase, International Pharmaceutical Abstracts, MEDLINE, PsycINFO, and Cochrane (CENTRAL) databases were searched from database inception to October 8, 2021. Study Selection: Inclusion criteria were as follows: randomized clinical trials that used the Revised Clinical Interview Schedule (CIS-R; the most common comprehensive screening and diagnostic measure of depressive and anxiety symptoms in primary care randomized clinical trials), measured socioeconomic factors at baseline, and sampled patients with unipolar depression who sought treatment for depression from general physicians/practitioners or who scored 12 or more points on the CIS-R. Exclusion criteria included patients with depression secondary to a personality or psychotic disorder or neurologic condition, studies of bipolar or psychotic depression, studies that included children or adolescents, and feasibility studies. Studies were independently assessed against inclusion and exclusion criteria by 2 reviewers. Data Extraction and Synthesis: Data were extracted and cleaned by data managers for each included study, further cleaned by multiple reviewers, and cross-checked by study chief investigators. Risk of bias and quality were assessed using the Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools, respectively. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses-Individual Participant Data (PRISMA-IPD) reporting guidelines. Main Outcomes and Measures: Depressive symptoms at 3 to 4 months after baseline. Results: This systematic review and individual patient data meta-analysis identified 9 eligible studies that provided individual patient data for 4864 patients (mean [SD] age, 42.5 (14.0) years; 3279 women [67.4%]). The 2-stage random-effects meta-analysis end point depressive symptom scale scores were 28% (95% CI, 20%-36%) higher for unemployed patients than for employed patients and 18% (95% CI, 6%-30%) lower for patients who were homeowners than for patients living with family or friends, in hostels, or homeless, which were equivalent to 4.2 points (95% CI, 3.6-6.2 points) and 2.9 points (95% CI, 1.1-4.9 points) on the Beck Depression Inventory II, respectively. Financial strain and educational attainment were associated with prognosis independent of treatment, but unlike employment and housing status, there was little evidence of associations after adjusting for clinical prognostic factors. Conclusions and Relevance: Results of this systematic review and meta-analysis revealed that unemployment was associated with a poor prognosis whereas home ownership was associated with improved prognosis. These differences were clinically important and independent of the type of treatment received. Interventions that address employment or housing difficulties could improve outcomes for patients with depression.

Sensitivity to missing not at random dropout in clinical trials: Use and interpretation of the trimmed means estimator.

Outcome values in randomized controlled trials (RCTs) may be missing not at random (MNAR), if patients with extreme outcome values are more likely to drop out (eg, due to perceived ineffectiveness of treatment, or adverse effects). In such scenarios, estimates from complete case analysis (CCA) and multiple imputation (MI) will be biased. We investigate the use of the trimmed means (TM) estimator for the case of univariable missingness in one continuous outcome. The TM estimator operates by setting missing values to the most extreme value, and then "trimming" away equal fractions of both groups, estimating the treatment effect using the remaining data. The TM estimator relies on two assumptions, which we term the "strong MNAR" and "location shift" assumptions. We derive formulae for the TM estimator bias resulting from the violation of these assumptions for normally distributed outcomes. We propose an adjusted TM estimator, which relaxes the location shift assumption and detail how our bias formulae can be used to establish the direction of bias of CCA and TM estimates, to inform sensitivity analyses. The TM approach is illustrated in a sensitivity analysis of the CoBalT RCT of cognitive behavioral therapy (CBT) in 469 individuals with 46 months follow-up. Results were consistent with a beneficial CBT treatment effect, with MI estimates closer to the null and TM estimates further from the null than the CCA estimate. We propose using the TM estimator as a sensitivity analysis for data where extreme outcome value dropout is plausible.

How much change is enough? Evidence from a longitudinal study on depression in UK primary care.

BACKGROUND: The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists. METHODS: A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a 'global rating of change' scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R). RESULTS: For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) -26.7 to -14.9) on the PHQ-9; 23% (95% CI -27.8 to -18.0) on the BDI-II and 26.8% (95% CI -33.5 to -20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were -1.7, -3.5 and -1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement. CONCLUSIONS: An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit. FUNDING: Funding. National Institute for Health Research.

PTSD as a mediator of the relationship between trauma and psychotic experiences.

BACKGROUND: Traumatic experiences are associated with a higher risk of psychotic illnesses, but little is known about potentially modifiable mechanisms underlying this relationship. This study aims to examine whether post-traumatic stress disorder (PTSD) symptoms mediate the relationship between trauma and psychotic experiences (PEs). METHODS: We used data from the Avon Longitudinal Study of Parents and Children to examine whether: PTSD symptoms mediate the relationships between (a) childhood trauma and adolescent PEs (study of adolescent PEs; n = 2952), and (b) childhood/adolescent trauma and PEs in early adulthood (study of adult PEs; n = 2492). We examined associations between variables using logistic regression, and mediation using the parametric g-computation formula. RESULTS: Exposure to trauma was associated with increased odds of PEs (adolescent PEs: ORadjusted 1.48, 95% CI 1.23-1.78; adult PEs: ORadjusted 1.57, 95% CI 1.25-1.98) and PTSD symptoms (adolescent PTSD: ORadjusted 1.59, 95% CI 1.31-1.93; adult PTSD: ORadjusted 1.50, 95% CI 1.36-1.65). The association between PTSD symptoms and PE was stronger in adolescence (ORadjusted 4.63, 95% CI 2.34-9.17) than in adulthood (ORadjusted 1.62, 95% CI 0.80-3.25). There was some evidence that PTSD symptoms mediated the relationship between childhood trauma and adolescent PEs (proportion mediated 14%), though evidence of mediation was weaker for adult PEs (proportion mediated 8%). CONCLUSIONS: These findings are consistent with the hypothesis that PTSD symptoms partly mediate the association between trauma exposure and PEs. Targeting PTSD symptoms might help prevent the onset of psychotic outcomes.

Trends in the recording of anxiety in UK primary care: a multi-method approach.

PURPOSE: Anxiety disorders are common. Between 1998 and 2008, in the UK, GP recording of anxiety symptoms increased, but the recording of anxiety disorders decreased. We do not know whether such trends have continued. This study examined recent trends in the recording of anxiety and explored factors that may influence GPs' coding of anxiety. METHODS: We used data from adults (n = 2,569,153) registered with UK general practices (n = 176) that contributed to the Clinical Practice Research Datalink between 2003 and 2018. Incidence rates and 95% confidence intervals were calculated for recorded anxiety symptoms and diagnoses and were stratified by age and gender. Joinpoint regression was used to estimate the years trends changed. In addition, in-depth interviews were conducted with 15 GPs to explore their views and management of anxiety. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: The incidence of anxiety symptoms rose from 6.2/1000 person-years at risk (PYAR) in 2003 to 14.7/1000 PYAR in 2018. Between 2003 and 2008, the incidence of anxiety diagnoses fell from 13.2 to 10.1/1000 PYAR; markedly increasing between 2013 and 2018 to 15.3/1000 PYAR. GPs mentioned that they preferred using symptom codes to diagnostic codes to avoid assigning potentially stigmatising or unhelpful labels, and commented on a rise in anxiety in recent years, especially in young adults. CONCLUSION: Recent increases in the recording of both anxiety diagnoses and symptoms may reflect increased presentation to primary care, especially in young adults. There is a clear need to understand the reasons for this, and this knowledge may be critical in the prevention and treatment of anxiety.

Cost-Utility Analysis of Discontinuing Antidepressants in England Primary Care Patients Compared with Long-Term Maintenance: The ANTLER Study.

BACKGROUND: Depression is a common mental health condition with considerable negative impact on health and well-being. Although antidepressants are recommended as first-line treatment, there is limited evidence regarding the cost effectiveness of long-term maintenance antidepressants for preventing relapse. OBJECTIVES: Our objective was to calculate the mean incremental costs and quality-adjusted life-years (QALYs) over 12 months of discontinuing long-term antidepressant medication in well patients compared with maintenance, using patient-level trial data. METHODS: We conducted a cost-utility analysis of 478 participants from 150 UK general practices recruited to a randomised, double-blind trial (ANTLER). QALYs were calculated from EQ-5D-5L and 12-Item Short Form survey (SF-12) results, with primary analysis using the EQ-5D-5L value set for England. Resource use was collected from primary care patient electronic medical records and self-completed questionnaires capturing mental-health-related resource use. Costs were calculated by applying standard UK unit costs to resource use. Adjustments were made for baseline variables. RESULTS: Participants randomised to discontinuation had significantly worse utility scores at 3 months (- 0.032; 95% confidence interval [CI] - 0.053 to - 0.011) but no significant difference in QALYs (- 0.011; 95% CI - 0.026 to 0.003) or costs (£3.11; 95% CI - 41.28 to 47.50) at 12 months. The probability that discontinuation was cost effective compared with maintenance was 12.9% at a threshold of £20,000 per QALY gained. CONCLUSIONS: Discontinuation of antidepressants was unlikely to be cost effective compared with maintenance for currently well patients on long-term antidepressants. However, this analysis provides no information on the wider impact of antidepressants. Our findings provide information on the potential impact of discontinuing long-term maintenance antidepressants and facilitate improving guidance for shared patient-clinician decision making. TRIAL REGISTRATION: EudraCT number 2015-004210-26; ISRCTN number ISRCTN15969819.

Life events and treatment prognosis for depression: A systematic review and individual patient data meta-analysis.

OBJECTIVE: To investigate associations between major life events and prognosis independent of treatment type: (1) after adjusting for clinical prognostic factors and socio-demographics; (2) amongst patients with depressive episodes at least six-months long; and (3) patients with a first life-time depressive episode. METHODS: Six RCTs of adults seeking treatment for depression in primary care met eligibility criteria, individual patient data (IPD) were collated from all six (n = 2858). Participants were randomized to any treatment and completed the same baseline assessment of life events, demographics and clinical prognostic factors. Two-stage random effects meta-analyses were conducted. RESULTS: Reporting any major life events was associated with poorer prognosis regardless of treatment type. Controlling for baseline clinical factors, socio-demographics and social support resulted in minimal residual evidence of associations between life events and treatment prognosis. However, removing factors that might mediate the relationships between life events and outcomes reporting: arguments/disputes, problem debt, violent crime, losing one's job, and three or more life events were associated with considerably worse prognoses (percentage difference in 3-4 months depressive symptoms compared to no reported life events =30.3%(95%CI: 18.4-43.3)). CONCLUSIONS: Assessing for clinical prognostic factors, social support, and socio-demographics is likely to be more informative for prognosis than assessing self-reported recent major life events. However, clinicians might find it useful to ask about such events, and if they are still affecting the patient, consider interventions to tackle problems related to those events (e.g. employment support, mediation, or debt advice). Further investigations of the efficacy of such interventions will be important.

A Patient Stratification Approach to Identifying the Likelihood of Continued Chronic Depression and Relapse Following Treatment for Depression.

BACKGROUND: Subgrouping methods have the potential to support treatment decision making for patients with depression. Such approaches have not been used to study the continued course of depression or likelihood of relapse following treatment. METHOD: Data from individual participants of seven randomised controlled trials were analysed. Latent profile analysis was used to identify subgroups based on baseline characteristics. Associations between profiles and odds of both continued chronic depression and relapse up to one year post-treatment were explored. Differences in outcomes were investigated within profiles for those treated with antidepressants, psychological therapy, and usual care. RESULTS: Seven profiles were identified; profiles with higher symptom severity and long durations of both anxiety and depression at baseline were at higher risk of relapse and of chronic depression. Members of profile five (likely long durations of depression and anxiety, moderately-severe symptoms, and past antidepressant use) appeared to have better outcomes with psychological therapies: antidepressants vs. psychological therapies (OR (95% CI) for relapse = 2.92 (1.24-6.87), chronic course = 2.27 (1.27-4.06)) and usual care vs. psychological therapies (relapse = 2.51 (1.16-5.40), chronic course = 1.98 (1.16-3.37)). CONCLUSIONS: Profiles at greater risk of poor outcomes could benefit from more intensive treatment and frequent monitoring. Patients in profile five may benefit more from psychological therapies than other treatments.