SummaryBackgroundTrial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients' organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments.MethodsIn our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094.FindingsWe recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p=0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p=0·0003), but did not differ for APT (0·7 [−0·9 to 2·3] points lower; p=0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p=0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p=0·0005), but did not differ for APT (3·4 [−1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p=0·0027; GET p=0·0059) and better physical function (CBT p=0·0002; GET p<0·0001). Subgroup analysis of 427 participants meeting international criteria for chronic fatigue syndrome and 329 participants meeting London criteria for myalgic encephalomyelitis yielded equivalent results. Serious adverse reactions were recorded in two (1%) of 159 participants in the APT group, three (2%) of 161 in the CBT group, two (1%) of 160 in the GET group, and two (1%) of 160 in the SMC-alone group.InterpretationCBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.FundingUK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.

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BackgroundSymptoms of attention-deficit hyperactivity disorder (ADHD) are known to persist into adulthood in the majority of cases.AimsTo determine the prevalence of methylphenidate, dexamfetamine and atomoxetine prescribing and treatment discontinuation in adolescents and young adults.MethodA descriptive cohort study using the UK General Practice Research Database included patients aged 15–21 years from 1999 to 2006 with a prescription for a study drug.ResultsPrevalence of prescribing averaged across all ages increased 6.23-fold over the study period. Overall, prevalence decreased with age: in 2006, prevalence in males dropped 95% from 12.77 per 1000 in 15-year-olds to 0.64 per 1000 in 21-year-olds. A longitudinal analysis of a cohort of 44 patients aged 15 years in 1999 demonstrated that no patient received treatment after the age of 21 years.ConclusionsThe prevalence of prescribing by general practitioners to patients with ADHD drops significantly from age 15 to age 21 years. The fall in prescribing is greater than the reported age-related decrease in symptoms, raising the possibility that treatment is prematurely discontinued in some young adults in whom symptoms persist.

Recent research has shown that worry is associated with distressing paranoia. Therefore, the aim was to target worry in a therapeutic intervention for individuals with delusions. It was predicted that a worry intervention would reduce levels of worry and paranoia distress. Twenty-four individuals with persistent persecutory delusions and high levels of worry were randomly assigned to receive a four session cognitive-behavioural worry intervention (W-CBT) or treatment as usual (TAU). The worry intervention was specifically designed not to target the content of delusions. In this open-label evaluation, assessments of worry and paranoia were conducted at baseline, at one month (end of treatment) and at two months. The worry intervention achieved a statistically significant reduction in worry which was maintained at two month follow up. A significant reduction in delusional distress was also reported. There was an indication that the worry intervention may also reduce the frequency of paranoid thoughts but this was not statistically significant. In the first trial specifically for persecutory delusions, a brief worry intervention was shown to have benefits. The results support a causal role for worry in paranoid experience.

Background England’s Time to Change programme to reduce mental health-related stigma and discrimination included a social marketing campaign using traditional and social media, and targeted middle-income groups aged 25–45 between 2009 and 2016. From 2017, the same age group on low to middle incomes were targeted, and the content focused on men’s mental health, by changing the advertising and adapting the ‘key messages’. This study investigates changes in stigma-related public knowledge, attitudes and desire for social distance in England since Time to Change began in 2008–19 and for 2017–19. Methods Using data from a face-to-face survey of a nationally representative quota sample of adults for England, we evaluated longitudinal trends in outcomes with regression analyses and made assumptions based on a simple random sample. The pre-existing survey used a measure of attitudes; measures of knowledge and desire for social distance were added in 2009. Results Reported in standard deviation units (95% CI), the improvement for knowledge for 2009–19 was 0.25 (0.19, 0.32); for attitudes, 2008–19, 0.32 (0.26, 0.39) and for desire for social distance, 2009–19 0.29 (0.23, 0.36). Significant interactions between year and both region and age suggest greater improvements in London, where stigma is higher, and narrowing of age differences. There were significant improvements between 2017 and 2019 in knowledge [0.09 (0.02, 0.16)] and attitudes [0.08 (0.02, 0.14)] but not social distance. Conclusion The positive changes support the effectiveness of Time to Change but cannot be definitively attributed to it. Inequalities in stigma by demographic characteristics present targets for research and intervention.

This article is written in response to the linked editorial by Dr Geraghty about the adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation (PACE) trial, which we led, implemented and published. The PACE trial compared four treatments for people diagnosed with chronic fatigue syndrome. All participants in the trial received specialist medical care. The trial found that adding cognitive behaviour therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. In this article, we suggest that Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial; these are corrected.

This study demonstrated no increase in the risk of sudden death associated with stimulants or atomoxetine. However, an increased risk of suicide was seen. Although we cannot exclude that the medications may contribute to the increased risk of suicide, there are other factors such as depression and antisocial behaviour that frequently co-exist with ADHD, which can also predispose to teenage suicide. Clinicians should identify patients at increased risk of cardiovascular events and identify those patients at increased risk of suicide, particularly males with co-morbid conditions, and monitor them appropriately.

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