Improvements are greatest in the earlier weeks of antipsychotic treatment of patients with non-resistant schizophrenia.

To address the early time-line for improvement with antipsychotics in treatment-resistant schizophrenia.

Randomised double-blind trials of antipsychotic medication in adult patients with treatment-resistant schizophrenia were investigated (last search June 2010). A series of meta-regression analyses were carried out to examine the effect of time on the average item scores in the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) at three or more distinct time points within the first 6 weeks of treatment.

Study duration varied from 4 weeks to 1 year and the definitions of treatment resistance as well as of treatment response were not necessarily consistent across 19 identified studies, resulting in highly variable rates of response (0–76%). The mean standardised baseline item score in the PANSS or BPRS was 3.4 (s.e. = 0.06) in the five studies included in the meta-regression analysis, with the average baseline Clinical Global Impression – Severity score being 5.2 (marked illness). For the pooled population treated with a range of antipsychotics (n = 1019), significant reductions in the mean item scores occurred during the first 4 weeks; improvements observed in later weeks were smaller and non-significant. In contrast, weekly improvement with clozapine was significant throughout (n = 356).

Our findings provide preliminary evidence that the majority of improvement with antipsychotics may occur relatively early. More consistent improvements with clozapine may be associated with a gradual titration. To further elucidate response patterns, future studies are needed to provide data over regular intervals during earlier stages of treatment.

The differential effects of so-called ‘first- and second-generation’ antipsychotic medications, when given in the first episode, on the long-term outcome of schizophrenia remain to be elucidated.

We compared the 9-year outcomes of individuals initially randomised to clozapine or chlorpromazine.

One-hundred and sixty individuals with treatment-naive, first-episode schizophrenia or schizophreniform disorder in a mental health centre in Beijing, China were randomised to clozapine or chlorpromazine treatment for up to 2 years, followed by up to an additional 7 years of naturalistic treatment. The primary outcome was remission status for individuals in each group.

Individuals in both groups spent essentially equal amounts of time in each clinical state over the follow-up time period (remission, 78%; intermediate, 8%; relapse, 14%). There were no significant differences on other measures of illness severity. The clozapine group was more likely than the chlorpromazine group to remain on the medication to which they were originally assigned (26% v. 10%, P = 0.01). There were no significant differences between the two groups on other secondary efficacy outcomes.

These findings support the comparability in effectiveness between antipsychotic medications but with slightly greater tolerability of clozapine in the treatment of first-episode psychosis.

Despite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability.

To compare indices of obesity, glucose, lipids and prolactin between antipsychotic-treated and antipsychotic-naive individuals with intellectual disability and also between participants with intellectual disability and controls from the general population.

Observational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls.

Antipsychotic treatment comprised: risperidone 48%, olanzapine 18%, thioxanthenes 10%, other 24%; monotherapy 95% of participants; mean treatment duration 8 years; median daily chlorpromazine equivalent dose 108mg (range 16–667). Metabolic indices were the same or more favourable in the intellectual disability group than the general population control group but overweight/obesity and type 2 diabetes were more prevalent in the women in the intellectual disability group than the control group. Metabolic indices were similar, statistically or clinically, between the antipsychotic-treated and the antipsychotic-naive groups but there was a non-significant trend towards a higher rate of type 2 diabetes in the antipsychotic group. A total of 100% and 70% of participants on amisulpride/sulpiride and risperidone respectively had hyperprolactinaemia, with secondary hypogonadism in 77% and 4% of affected women and men.

Antipsychotics, on average, did not increase metabolic risk, although the existence of a susceptible subgroup at risk of diabetes cannot be excluded. Some antipsychotics induced hyperprolactinaemic hypogonadism, requiring active management. However, our findings suggest that antipsychotics at the low doses routinely prescribed for people with intellectual disability are generally safe in relation to metabolic adverse effects, even if efficacy remains poorly defined.

In a baseline study among 7- and 8-year-old children with auditory vocal hallucinations, only limited functional impact was observed.

To assess 5-year course and predictors of auditory vocal hallucinations, as well as 5-year incidence and its risk factors.

A sample of 337 children, 12 and 13 years of age, were reassessed on auditory vocal hallucinations and associated symptoms after a mean follow-up period of 5.1 years.

The 5-year persistence and incidence rates were 24% and 9% respectively, with more new cases arising in urban areas. Both persistent and incident auditory vocal hallucinations were associated with problem behaviour in the clinical range of psychopathology as measured with the Child Behavior Checklist, particularly at follow-up, as well as with other psychotic symptoms, particularly at baseline. Persistence was predicted by baseline auditory vocal hallucinations severity, particularly in terms of external attribution of voices and hearing multiple voices, and was associated with worse primary school test scores and lower secondary school level.

First onset of auditory vocal hallucinations in middle childhood is not uncommon and is associated with psychopathological and behavioural comorbidity. Similarly, persistence of auditory vocal hallucinations in childhood is not uncommon and is associated with psychopathological, behavioural and cognitive alterations.

Although genetic epidemiological studies have confirmed increased rates of major depressive disorder among the relatives of people with bipolar affective disorder, no report has compared the clinical characteristics of depression between these two groups.

To compare clinical features of depressive episodes across participants with major depressive disorder and bipolar disorder from within bipolar disorder pedigrees, and assess the utility of a recently proposed probabilistic approach to distinguishing bipolar from unipolar depression. A secondary aim was to identify subgroups within the relatives with major depression potentially indicative of ‘genetic’ and ‘sporadic’ subgroups.

Patients with bipolar disorder types 1 and 2 (n = 246) and patients with major depressive disorder from bipolar pedigrees (n = 120) were assessed using the Diagnostic Interview for Genetic Studies. Logistic regression was used to identify distinguishing clinical features and assess the utility of the probabilistic approach. Hierarchical cluster analysis was used to identify subgroups within the major depressive disorder sample.

Bipolar depression was characterised by significantly higher rates of psychomotor retardation, difficulty thinking, early morning awakening, morning worsening and psychotic features. Depending on the threshold employed, the probabilistic approach yielded a positive predictive value ranging from 74% to 82%. Two clusters within the major depressive disorder sample were found, one of which demonstrated features characteristic of bipolar depression, suggesting a possible ‘genetic’ subgroup.

A number of previously identified clinical differences between unipolar and bipolar depression were confirmed among participants from within bipolar disorder pedigrees. Preliminary validation of the probabilistic approach in differentiating between unipolar and bipolar depression is consistent with dimensional distinctions between the two disorders and offers clinical utility in identifying patients who may warrant further assessment for bipolarity. The major depressive disorder clusters potentially reflect genetic and sporadic subgroups which, if replicated independently, might enable an improved phenotypic definition of underlying bipolarity in genetic analyses.

Presentations to hospital with self-harm are common, associated with suicide and have an increased mortality, yet there is no accepted effective intervention.

To investigate whether problem-solving therapy would improve outcomes in adults presenting to hospital with self-harm, compared with usual care.

A Zelen randomised controlled trial was conducted in four district health boards in New Zealand. A second hospital presentation with self-harm at 1 year for all episodes, plus separate comparisons of first-time and repeat presentations at the index episode, were the a priori primary outcomes. The trial registration number was ACTRN12605000337673.

In an intention-to-treat analysis of all randomised patients (n = 1094) there was no significant difference at 12 months in the proportion of people who had presented again with self-harm when comparing all episodes (intervention 13.4%, usual care 14.1%; relative risk reduction RR = 0.05, 95% CI −0.28 to 0.30, P = 0.79) or where the index episode was the first episode (intervention 13.4%, usual care 9.4%, RR =–0.42, 95% CI −1.17 to 0.08, P = 0.37). Where the index episode was repeated self-harm, those who received therapy were less likely to present again with self-harm (intervention 13.5%, usual care 22.1%, RR = 0.39, 95% CI 0.07 to 0.60, number needed to treat 12, P = 0.03).

Problem-solving therapy is not recommended for everyone who presents to hospital with self-harm. Among adults with a history of self-harm it may be an effective intervention.

About 20% of major depressive episodes become chronic and medication-refractory and also appear to be less responsive to standard cognitive–behavioural therapy (CBT).

To test whether CBT developed from behavioural activation principles that explicitly and exclusively targets depressive rumination enhances treatment as usual (TAU) in reducing residual depression.

Forty-two consecutively recruited participants meeting criteria for medication-refractory residual depression were randomly allocated to TAU v. TAU plus up to 12 sessions of individual rumination-focused CBT. The trial has been registered (ISRCTN22782150).

Adding rumination-focused CBT to TAU significantly improved residual symptoms and remission rates. Treatment effects were mediated by change in rumination.

This is the first randomised controlled trial providing evidence of benefits of rumination-focused CBT in persistent depression. Although suggesting the internal validity of rumination-focused CBT for residual depression, the trial lacked an attentional control group so cannot test whether the effects were as a result of the specific content of rumination-focused CBT v. non-specific therapy effects.

Little is known about the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME); prospective studies suggest a role for premorbid mood disorder.

To examine childhood and early adult adversity, ill health and physical activity as premorbid risk markers for CFS/ME by 42 years, taking psychopathology into account.

Data were from the 1958 British birth cohort, a prospective study from birth to 42 years (n = 11 419). The outcomes were self-reported CFS/ME (n = 127) and operationally defined CFS-like illness (n = 241) at 42 years.

Adjusting for psychopathology, parental physical abuse (odds ratio (OR) = 2.10, 95% CI 1.16–3.81), childhood gastrointestinal symptoms (OR = 1.58, 95% CI 1.00–2.50) and parental reports of many colds (OR = 1.65, 95% CI 1.09–2.50) were independently associated with self-reported CFS/ME. Female gender and premorbid psychopathology were the only risk markers for CFS-like illness, independent of comorbid psychopathology.

This confirms the importance of premorbid psychopathology in the aetiological pathways of CFS/ME, and replicates retrospective findings that childhood adversity may play a role in a minority.

Mental disorders may increase the risk of physical violence among married couples.

To estimate associations between premarital mental disorders and marital violence in a cross-national sample of married couples.

A total of 1821 married couples (3642 individuals) from 11 countries were interviewed as part of the World Health Organization's World Mental Health Survey Initiative. Sixteen mental disorders with onset prior to marriage were examined as predictors of marital violence reported by either spouse.

Any physical violence was reported by one or both spouses in 20% of couples, and was associated with husbands' externalising disorders (OR = 1.7, 95% CI 1.2–2.3). Overall, the population attributable risk for marital violence related to premarital mental disorders was estimated to be 17.2%.

Husbands' externalising disorders had a modest but consistent association with marital violence across diverse countries. This finding has implications for the development of targeted interventions to reduce risk of marital violence.