Clinical experience has shown considerable potential benefits from long-term continuous medication for chronic or relapsing forms of schizophrenia. These benefits have not always been realised.

To review the research literature in order to understand the problems of long-term medication and use of antipsychotic oral medication and long-acting injections (LAIs), and to place these in an historical context.

Review of literature.

Research showed that the potential success of LAI therapy depends on the quality of the follow-up service.

Following the advent of second-generation oral antipsychotics confidence in the use of LAIs has eroded and that mistakes made in LAI use during the past century may be repeated.

Differences in the ICD–10 and DSM–IV definitions for the same disorder impede international communication and research efforts. The forthcoming parallel development of DSM–V and ICD–11 offers an opportunity to harmonise the two classifications.

This paper aims to facilitate the harmonisation process by identifying diagnostic differences between the two systems.

DSM–IV–TR criteria sets and the ICD–10 Diagnostic Criteria for Research were compared and categorised into those with identical definitions, those with conceptually based differences and those in which differences are not conceptually based and appear to be unintentional.

Of the 176 criteria sets in both systems, only one, transient tic disorder, is identical. Twenty-one per cent had conceptually based differences and 78% had non-conceptually based differences.

Harmonisation of criteria sets, especially those with non-conceptually based differences, should be prioritised in the DSM–V and ICD–11 development process. Prior experience with the DSM–IV and ICD–10 harmonisation effort suggests that for the process to be successful steps should be taken as early as possible.

Depot antipsychotics are widely used in clinical practice. Long-acting formulations of second-generation antipsychotics are now being developed and introduced.

To review the pharmacology, pharmacokinetics and adverse effect profiles of currently available antipsychotic long-acting injections (LAIs).

The psychopharmacological properties of first- and second-generation antipsychotic LAIs are reviewed using data available up to October 2008.

First-generation antipsychotic (FGA) LAIs are associated with a high rate of acute and chronic movement disorders. Risperidone LAI is better tolerated in this respect, but is associated with hyperprolactinaemia and weight gain. Olanzapine LAI causes weight gain and other metabolic effects but appears not to be associated with an important incidence of movement disorders.

Dosing of LAIs is complicated by delayed release of drug, changes in plasma levels without change in dose, and by the lack of data establishing clear dose requirements. All LAIs offer the prospect of assured adherence (although patients may still default on treatment) but their use is complicated by adverse effects, complex pharmacokinetics and confusion over dose–response relationships.

Cognitive functioning in affective psychosis and schizoaffective disorder is much less studied compared with schizophrenia.

To quantitatively undertake a meta-analysis of the available data that directly compares cognitive functioning across schizophrenia, schizoaffective disorder and affective psychosis.

Following a thorough literature review, 31 studies that compared the performances of people with schizophrenia (1979 participants) with that of those with affective psychosis or schizoaffective disorder (1314 participants) were included. To determine the effect of demographic and clinical confounders, meta-regression and subgroup analyses were conducted.

In 6 of 12 cognitive domains, people with schizophrenia performed worse than people with schizoaffective disorder or affective psychosis. However, the between-group differences were small and the distribution of effect sizes showed substantial heterogeneity. The between-group differences were driven by a higher percentage of males, more severe negative symptoms and younger age at onset of illness in the schizophrenia samples.

Neuropsychological data do not provide evidence for categorical differences between schizophrenia and other groups. However, a subgroup of individuals with schizophrenia who have more severe negative symptoms may be cognitively more impaired than those with affective psychosis/schizoaffective disorder.

The neuropharmacological actions of antidepressants are well characterised but our understanding of how these changes translate into improved mood are still emerging.

To investigate whether actions of antidepressant drugs on emotional processing are a mediating factor in the effects of these drugs in depression.

We examined key published findings that explored the effects of antidepressants on behavioural and functional magnetic resonance imaging (fMRI) measures of emotional processing.

Negative emotional bias has been reliably associated with depression. Converging results suggest that antidepressants modulate emotional processing and increase positive emotional processing much earlier than effects on mood. These changes in emotional processing are associated with neural modulation in limbic and prefrontal circuitry.

Antidepressants may work in a manner consistent with cognitive theories of depression. Antidepressants do not act as direct mood enhancers but rather change the relative balance of positive to negative emotional processing, providing a platform for subsequent cognitive and psychological reconsolidation.

Several magnetic resonance imaging (MRI) studies have identified structural abnormalities in association with bipolar disorder. The literature is, however, heterogeneous and there is remaining uncertainty about which brain areas are pivotal to the pathogenesis of the condition.

To identify, appraise and summarise volumetric MRI studies of brain regions comparing bipolar disorder with an unrelated control group and individuals with schizophrenia.

A systematic review and random-effects meta-analysis was carried out to identify key areas of structural abnormality in bipolar disorder and whether the pattern of affected areas separated bipolar disorder from schizophrenia. Significant heterogeneity was explored using meta-regression.

Participants with bipolar disorder are characterised by whole brain and prefrontal lobe volume reductions, and also by increases in the volume of the globus pallidus and lateral ventricles. In comparison with schizophrenia, bipolar disorder is associated with smaller lateral ventricular volume and enlarged amygdala volume. Heterogeneity was widespread and could be partly explained by clinical variables and year of publication, but generally not by differences in image acquisition.

There appear to be robust changes in brain volume in bipolar disorder compared with healthy volunteers, although most changes do not seem to be diagnostically specific. Age and duration of illness appear to be key issues in determining the magnitude of observed effect sizes.

Reducing use of hospital wards and improving their quality are central aims of mental health service policy. However, no comprehensive synthesis is available of evidence on residential alternatives to standard acute psychiatric wards.

To assess the effectiveness and cost-effectiveness of and satisfaction with residential alternatives to standard acute in-patient mental health services.

A systematic search identified controlled studies comparing residential alternatives with standard in-patient services. Studies were described and assessed for methodological quality. Results from higher quality studies are presented and discussed.

Twenty-seven relevant studies were identified. Nine studies of moderate quality provide no contraindication to identified alternative service models and limited preliminary evidence that community-based alternatives may be cheaper and individuals more satisfied than in standard acute wards.

More research is needed to establish the effectiveness of service models and target populations for residential alternatives to standard acute wards. Community-based residential crisis services may provide a feasible and acceptable alternative to hospital admission for some people with acute mental illness.

The relationship between cognition and age at onset of schizophrenia is largely unknown.

To compare cognitive deficits in individuals with youth-onset and late-onset schizophrenia with those in adults with first-episode schizophrenia.

Twenty-nine databases (including EMBASE, MEDLINE and PsycINFO) were searched from 1980 to 2008. Selected publications had to include healthy controls and analyse separately individuals diagnosed with schizophrenia or a related disorder and individuals with first-episode, youth-onset or late-onset schizophrenia. Descriptive and cognitive data were extracted and the latter aggregated into 22 cognitive measures. Cohen's effect size raw and weighted means of cognitive deficits were generated and compared in the three groups.

Individuals with youth-onset and first-episode schizophrenia demonstrate large deficits (mean effect size ⩾0.8) on almost all cognitive measures. Individuals with youth-onset schizophrenia demonstrate larger deficits than those with first-episode schizophrenia on arithmetic, executive function, IQ, psychomotor speed of processing and verbal memory. In contrast, those with late-onset schizophrenia demonstrate minimal deficits on arithmetic, digit symbol coding and vocabulary, but larger ones on attention, fluency, global cognition, IQ and visuospatial construction.

Individuals with youth-onset schizophrenia have severe cognitive deficits, whereas those with late-onset schizophrenia have some relatively preserved cognitive functions. This finding supports the view that severity of the disease process is associated with different ages at onset. In addition, the cognitive pattern of people with late-onset schizophrenia suggests that their deficits are specific rather than solely as a result of ageing and related factors.

Antipsychotic long-acting injections (LAIs) are often used in an attempt to improve medication adherence in people with schizophrenia.

To compare first-generation antipsychotic long-acting injections (FGA–LAIs) with first- and second-generation oral antipsychotics in terms of clinical outcome.

Systematic literature review.

A meta-analysis of randomised controlled trials (RCTs) showed no difference in relapse or tolerability between oral antipsychotics and FGA–LAIs but global improvement was twice as likely with FGA–LAIs. Four prospective observational studies were identified; two studies reported lower discontinuation rates for FGA–LAIs compared with oral medication and two found that outcome was either no different or better with oral antipsychotics. Mirror-image studies consistently showed reduced in-patient days and admissions following a switch from oral antipsychotics to FGA–LAIs.

The results are variable and inconclusive. Some evidence suggests that FGA–LAIs may improve outcome compared with oral antipsychotics. Methodological issues may partly explain the variable results. Selective recruitment in RCTs and lack of randomisation in observational studies are biases against LAIs, whereas regression to the mean in mirror-image studies favours LAIs. In terms of future research, a long-term pragmatic RCT of an FGA–LAI against an oral antipsychotic, in patients with problematic adherence, would be of value.

The aetiology of autism is unknown, although prenatal exposures have been the focus of epidemiological research for over 40 years.

To provide the first quantitative review and meta-analysis of the association between maternal pregnancy complications and pregnancy-related factors and risk of autism.

PubMed, Embase and PsycINFO databases were searched for epidemiological studies that examined the association between pregnancy-related factors and autism. Forty studies were eligible for inclusion in the meta-analysis. Summary effect estimates were calculated for factors examined in multiple studies.

Over 50 prenatal factors have been examined. The factors associated with autism risk in the meta-analysis were advanced parental age at birth, maternal prenatal medication use, bleeding, gestational diabetes, being first born v. third or later, and having a mother born abroad. The factors with the strongest evidence against a role in autism risk included previous fetal loss and maternal hypertension, proteinuria, pre-eclampsia and swelling.

There is insufficient evidence to implicate any one prenatal factor in autism aetiology, although there is some evidence to suggest that exposure to pregnancy complications may increase the risk.

People who use cannabis have an increased risk of psychosis an effect attributed to the active ingredient δ9-tetrahydrocannabinol (Δ9-THC). There has recently been concern over an increase in the concentration of Δ9-THC in the cannabis available in many countries.

To investigate whether people with a first episode of psychosis were particularly likely to use high-potency cannabis.

We collected information on cannabis use from 280 cases presenting with a first episode of psychosis to the South London & Maudsley National Health Service (NHS) Foundation Trust, and from 174 healthy controls recruited from the local population.

There was no significant difference between cases and controls in whether they had ever taken cannabis, or age at first use. However, those in the cases group were more likely to be current daily users (OR = 6.4) and to have smoked cannabis for more than 5 years (OR = 2.1). Among those who used cannabis, 78% of the cases group used high-potency cannabis (sinsemilla, ‘skunk’) compared with 37% of the control group (OR 6.8).

The finding that people with a first episode of psychosis had smoked higher-potency cannabis, for longer and with greater frequency, than a healthy control group is consistent with the hypothesis that Δ9-THC is the active ingredient increasing risk of psychosis. This has important public health implications, given the increased availability and use of high-potency cannabis.

Second-generation antipsychotics (SGAs) represent an advance in the long-term management of schizophrenia.

To review the available evidence concerning SGA long-acting injections (LAIs).

A systematic review of the literature was conducted using PubMed.

Risperidone long-acting injection was the first licensed SGA–LAI compound and is effective in the long-term management of schizophrenia, with a safety profile similar to that of oral risperidone. Olanzapine pamoate has recently been approved in Europe. In terms of efficacy, at injection intervals of up to 4 weeks it appears comparable to oral olanzapine, although the potential for ‘post-injection syndrome’ (delirium) calls for additional safety considerations. Paliperidone palmitate is currently under review with the licensing authorities. It also affords the potential advantage of monthly dosing.

More long-term comparisons of SGA–LAIs with oral SGAs as well as with first-generation antipsychotic LAIs are needed. These studies should include cost-effectiveness data.

Feedback of treatment outcome during the course of therapy (outcome management) is increasingly considered to be beneficial for improving the quality of mental healthcare.

To review the impact of feedback of outcome to practitioners and/or patients in specialist mental health services.

A systematic search and meta-analysis of controlled trials using outcome management in mental health services published in English or German language.

Twelve studies met inclusion criteria. Feeding back outcome showed a small, but significant (d = 0.10; 95% CI 0.01–0.19) positive short-term effect on the mental health of individuals that did not prevail in the long run. Subgroup analysis revealed no significant differences regarding feedback modalities. Outcome management did not contribute to a reduction of treatment duration.

Evidence on the effects of outcome management in mental healthcare is promising. More targeted research is needed in order to identify the effective ingredients of outcome feedback and to assess its cost-effectiveness.