Recommendations for research

In 2013 the guideline committee made the following recommendations for research.

1 What are the long-term outcomes, both psychotic and non‑psychotic, for children and young people with attenuated or transient psychotic symptoms suggestive of a developing psychosis, and can the criteria for 'at risk states' be refined to better predict those who will and those who will not go on to develop psychosis?

The suggested programme of research would be in two phases. First, a systematic review and meta‑analysis of prospective observational studies/cohorts of children and young people identified at high or ultra‑high risk of developing psychosis would be undertaken. The review would identify risk and protective factors most strongly associated with the later development of psychotic and non‑psychotic outcomes. Second, the factors identified in the first phase would be used to identify a large cohort of children and young people with these factors and to evaluate the effectiveness of these refined criteria for predicting the later development of psychotic and non‑psychotic outcomes.

Why this is important

A major problem with trials of treatments for populations of children and young people deemed to be 'at risk' or 'at ultra‑high risk' of developing psychosis is identifying the precise symptoms and/or behaviours or (risk) factors that are most strongly associated with the development of psychosis; and conversely, which (protective) factors are likely to be associated with a lowered risk of later psychosis. At present, identified factors have a low predictive value, with only about 10–20% of children and young people who have been identified as at high risk going on to develop psychosis. If these risk and protective factors could be refined, it would be possible to better target children and young people who are most at risk, and reduce the numbers of those thought to be 'at risk' who do not go on to later develop psychosis.

2 What is the clinical and cost effectiveness of omega‑3 fatty acids in the treatment of children and young people considered to be at high risk of developing psychosis?

The suggested programme of research would need to test out, using an adequately powered, multicentre randomised controlled design, the likely benefits and costs of using omega‑3 fatty acids for children and young people at high risk of developing psychosis. The outcomes considered should include transition to psychosis, quality of life, symptomatic and functional improvements, treatment acceptability, side effects and self‑harm. There should be follow‑up at 3 years. The trial should also estimate the cost effectiveness of intervening.

Why this is important

A number of interventions have been trialled in an attempt to avert the development of psychosis, including drugs, psychological interventions and other interventions. A relatively recent, moderate‑sized randomised controlled trial of omega‑3 fatty acids has shown the best evidence of any intervention, to date, reducing the rates of transition from 'high risk' states to a sustained psychosis. However, this is a single trial, which is underpowered, undertaken in one centre and lacks any health economic analysis.

3 What is the clinical and cost effectiveness for family intervention combined with individual CBT in the treatment of children and young people considered to be at high risk of developing psychosis and their parents or carers?

The suggested programme of research would need to test out, using an adequately powered, multicentre, randomised controlled design, the likely benefits and costs of providing family intervention, combined with individual CBT, for children and young people at high risk of developing psychosis and their parents or carers. The outcomes considered should include transition to psychosis, quality of life, symptomatic and functional improvements, treatment acceptability and self‑harm. There should be follow‑up at 3 years. The trial should also estimate the cost effectiveness of intervening.

Why this is important

A number of interventions have been trialled in an attempt to avert the development of psychosis, including drugs, psychological interventions and other interventions. After the first episode of psychosis, family intervention as an adjunct to antipsychotic medication substantially and significantly reduces relapse rates. A single small trial combining CBT family treatment with individual CBT without antipsychotic treatment suggested an important reduction in transition rates to the first psychosis.

4 What is the clinical and cost effectiveness of psychological intervention alone, compared with antipsychotic medication and compared with psychological intervention and antipsychotic medication combined, in young people with first episode psychosis?

The programme of research would compare the clinical and cost effectiveness of psychological intervention alone, compared with antipsychotic medication, and compared with psychological intervention and antipsychotic medication combined, for young people in the early stages of psychosis using an adequately powered study with a randomised controlled design. The combination of psychological interventions most likely to have an impact is family intervention and individual CBT. The key outcomes should include symptoms, relapse rates, quality of life, treatment acceptability, experience of care, level of psychosocial functioning and the cost effectiveness of the interventions.

Why this is important

The personal and financial cost of psychosis and schizophrenia to the person, their family and friends, and to society is considerable. The personal cost is reflected in a suicide rate of nearly 15% among people with schizophrenia, a lifelong unemployment rate that varies between 50 and 75%, depending on geographical location, and reduced life expectancy. The additional cost to the healthcare system for one person with schizophrenia is estimated to reach over £50,000 per year, on average, throughout their life.

Currently, the mainstay of treatment is antipsychotic medication, but the potential adverse effects are such that there is considerable impetus to develop alternative treatment strategies to allow either lower doses or to remove the need for medication entirely. It has been recognised that psychological interventions as an adjunct to antipsychotic medication have an important part to play in the treatment of schizophrenia. NICE guideline CG82 identified family intervention and CBT as adjunct treatments and current evidence suggests that these interventions are cost saving. However, evidence for adjunctive family intervention and CBT is lacking in children and young people with psychosis. Furthermore, there has been one recent positive trial of CBT as a first‑line treatment, without antipsychotics, for young people in the early stages of psychosis.

5 What is the clinical effectiveness of clozapine for children and young people with schizophrenia with symptoms unresponsive to antipsychotic medication and psychological treatment combined?

The suggested programme of research would need to test out, using an adequately powered, randomised controlled design, the likely benefits of using clozapine, compared with another antipsychotic, for children and young people with symptoms of schizophrenia unresponsive to antipsychotic medication and psychological treatment combined. The outcomes considered should include quality of life, symptomatic and functional improvements, treatment acceptability, side effects and length of hospitalisation.

Why this is important

Currently, about 30% of people with schizophrenia have symptoms that do not respond adequately to treatment with an antipsychotic. Although precise figures are unavailable, especially for children and young people, smaller percentages of people do not respond when a second, alternative, antipsychotic and an adequate course of psychological treatment have been tried. For these people, clozapine, which has a different dopamine receptor subtype blocking profile from other antipsychotics, has become an important treatment option in adults. However, evidence is lacking (only one study) about the effectiveness of clozapine for 'treatment‑resistant schizophrenia' in children and young people.

6 What is the most effective management strategy for preventing the development of excessive weight gain and metabolic syndrome associated with the use of antipsychotic medication in children and young people?

The suggested programme of research would be in two parts: (1) a longitudinal cohort study (a national observational database of at least 12 months' duration) to determine the incidence and predictors of adverse physical effects of antipsychotic medication; (2) a randomised controlled trial of behavioural and/or medical approaches to reduce weight gain and the risk of metabolic syndrome associated with antipsychotic medication.

Why this is important

Rapid weight gain associated with antipsychotic medication and poor physical health (smoking, lack of exercise) leading to type 2 diabetes and metabolic syndrome are major sources of morbidity and premature mortality in young people with psychosis and schizophrenia. Most evidence of adverse effects comes from short‑term studies of antipsychotics (maximum 8–12 weeks). In contrast, very little is known about the longer term adverse effects of these drugs. Evidence is needed both on longer term adverse effects as well as on effective early intervention strategies that reduce these risk factors and improve physical health outcomes.

  • National Institute for Health and Care Excellence (NICE)