Trauma plays an important role in the development of psychosis, but no studies have investigated whether a trauma-focused therapy could prevent psychosis.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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].

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.

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.

This study aimed to investigate the association between antidepressant use and adverse events.

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.

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).

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.

This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.

We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.

Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.

When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.

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).

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.

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%).

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.

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.

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).

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.

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. National Institute for Health Research.

Depression is expensive to treat, but providing ineffective treatment is more expensive. Such is the case for many patients who do not respond to antidepressant medication.

To assess the cost-effectiveness of cognitive–behavioural therapy (CBT) plus usual care for primary care patients with treatment-resistant depression compared with usual care alone.

Economic evaluation at 12 months alongside a randomised controlled trial. Cost-effectiveness assessed using a cost-consequences framework comparing cost to the health and social care provider, patients and society, with a range of outcomes. Cost-utility analysis comparing health and social care costs with quality-adjusted life-years (QALYs).

The mean cost of CBT per participant was £910. The difference in QALY gain between the groups was 0.057, equivalent to 21 days a year of good health. The incremental cost-effectiveness ratio was £14 911 (representing a 74% probability of the intervention being cost-effective at the National Institute of Health and Care Excellence threshold of £20 000 per QALY). Loss of earnings and productivity costs were substantial but there was no evidence of a difference between intervention and control groups.

The addition of CBT to usual care is cost-effective in patients who have not responded to antidepressants. Primary care physicians should therefore be encouraged to refer such individuals for CBT.

Antidepressant prescribing is widespread. Nonetheless, response to antidepressants is variable. If it was possible to predict response to medication and thus tailor treatment accordingly, this would not only improve patient outcomes but may also have economic benefits.

To test the hypothesis that individuals with more severe depression would benefit more from noradrenaline reuptake inhibitors (NARIs) than selective serotonin reuptake inhibitors (SSRIs) compared with individuals with less severe depression.

Individuals recruited from UK primary care who met ICD-10 criteria for a depressive episode and scored 15 or more on the Beck Depression Inventory (BDI) were randomised to either an SSRI (citalopram 20mg daily) or a NARI (reboxetine 4mg twice daily). Randomisation was by means of a remote automated telephone system. The main outcome was depressive symptoms measured by the BDI total score 6 weeks after randomisation. (Trial registration: ISRCTN31345163.)

In total, 601 participants were randomised (citalopram: n = 298, reboxetine: n = 303). Ninety-one per cent were followed up at 6 weeks (citalopram: n = 274, reboxetine: n = 272). There was little evidence to support an interaction between treatment and severity of depression (interaction term: 0.02, 95% CI −0.59 to 0.62, P = 0.96). Adjustment for potential confounders (age, gender, employment status, history of depression, number of life events and social support) did not affect the findings (interaction term: 0.06, 95% CI −0.54 to 0.66, P = 0.85).

Treatment with NARIs does not confer any advantage over SSRI treatment for outcome in those with more severe depressive illness presenting in primary care.

Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs).

To test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants.

In an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163).

Altogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score at 6 weeks was 0.50 (95% CI −2.04 to 3.03, P = 0.70), which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype.

It is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression.

In a representative sample of the UK population we found that common mental disorders (as a group and in ICD–10 diagnostic categories) and subthreshold psychiatric symptoms at baseline were both independently associated with new-onset functional disability and significant days lost from work at 18-month follow-up. Subthreshold symptoms contributed to almost half the aggregate burden of functional disability and over 32 million days lost from work in the year preceding the study. Leaving these symptoms unaccounted for in surveys may lead to gross underestimation of disability related to psychiatric morbidity.

Therapist-delivered online cognitive–behavioural therapy (CBT) has been found to be effective for depression in primary care.

To determine the cost-effectiveness of online CBT compared with usual care.

Economic evaluation at 8 months alongside a randomised controlled trial. Cost to the National Health Service (NHS), personal costs, and the value of lost productivity, each compared with outcomes based on the Beck Depression Inventory and quality-adjusted life-years (QALYs). Incremental analysis indicated the NHS cost per QALY gain.

Online CBT was more expensive than usual care, although the outcomes for the CBT group were better. Cost per QALY gain based on complete case data was £17 173, and £10 083 when missing data were imputed.

Online CBT delivered by a therapist in real time is likely to be cost-effective compared with usual care if society is willing to pay at least £20 000 per QALY; it could be a useful alternative to face-to-face CBT.

Scarce longitudinal data exist on the occurrence of psychotic symptoms in the general population.

To estimate the incidence of, and risk factors for, self-reported psychotic symptoms in Great Britain.

Data from the 18-month follow-up of a national survey were used. Incident cases were those who endorsed one or more items on the Psychosis Screening Questionnaire at follow-up, but not at baseline. The association between factors recorded at baseline and incident self-reported symptoms was examined.

At follow-up, 4.4% of the general population reported incident psychotic symptoms. Six factors were independently associated with incident symptoms: living in a rural area; having a small primary support group; more adverse life events; smoking tobacco; neurotic symptoms; and engaging in a harmful pattern of drinking.

A small but not insignificant percentage of the population of Great Britain reported incident psychotic symptoms over 18 months. The risk factors for psychotic symptoms showed some similarities with risk factors for schizophrenia, but there were also some striking differences. The relationship between such risk factors and the factors that perpetuate psychotic symptoms remains to be ascertained.