Recommendations for research

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline.

1 Determining prevalence, risk and protective factors, and course of illness

What are the prevalence, risk and protective factors, and course of illness for different combinations of psychosis and coexisting substance misuse (for example, schizophrenia and cannabis misuse or bipolar disorder and alcohol misuse)?

Why this is important

Studies vary in terms of the definitions and diagnosis of psychosis and substance misuse, and how they are conducted. This makes it difficult to draw conclusions about prevalence and patterns in patient groups differentiated by diagnosis, ethnicity and other demographics. Additionally, most studies are cross-sectional, so little is known about how both conditions change over time. Moreover, there is little guidance about which levels and patterns of substance misuse in which patient groups are associated with the worst clinical and social outcomes. Such information is necessary to target resources at groups most at risk of very poor outcomes.

This question should be answered using a longitudinal study design with a representative sample large enough to establish the prevalence, pattern, and epidemiology of different combinations of psychosis and coexisting substance misuse, associated social determinants, treatment and outcome. The study should also collect information that could inform the development of new interventions or the modification of existing interventions to improve prognosis.

2 Predicting the onset of substance misuse in young people with psychosis

What risk factors predict the onset of substance misuse in young people with psychosis?

Why this is important

People with psychosis and coexisting substance misuse are more likely to be non-adherent to prescribed medication, and have poor engagement with treatment programmes, increased risk of suicide, more and longer inpatient stays, increased risk of violence and time spent in the criminal justice system, and poorer overall prognosis. Because the onset of psychosis at a younger age is also an indicator of poor prognosis, people with a combination of younger age of onset and coexisting substance misuse may have a particularly poor prognosis. A clearer understanding of the risk and protective factors for substance misuse in young people with psychosis, and the interrelationship of the two conditions over time, may facilitate the development of treatment approaches for the coexisting conditions in this group. This may then improve the longer term outcome for a group of people who tend to have a poor prognosis.

This question should be answered using a prospective cohort study design.

3 Psychosocial interventions versus standard care

Are psychosocial interventions clinically and cost effective when compared with standard care for people with psychosis and coexisting substance misuse?

Why this is important

Psychosocial interventions are recommended for the treatment of substance misuse, with contingency management showing particular promise. However, they have not been adequately tested in people who also have psychosis.

This question should be answered using a randomised controlled trial that examines short- and medium-term outcomes over at least 18 months. Studies should focus on people whose misuse of substances is most often encountered in clinical practice and has the greatest impact on mental health (such as cannabis and polysubstance misuse) and on those interventions – such as contingency management, cognitive therapy and relapse prevention – that show most promise in people with substance misuse without psychosis. Those providing the intervention should be trained and supervised to ensure that the results are robust and generalisable. Outcomes should reflect both observer and service user-rated assessments of improvement (including mental health and social functioning) and the intervention's acceptability. Studies need to be large enough to determine the intervention's costs and cost effectiveness.

4 Environmental interventions versus standard care

Are environmental interventions clinically and cost effective when compared with standard care for people with psychosis and coexisting substance misuse?

Why this is important

Social and other environmental factors can play a role in triggering and maintaining substance misuse in people with psychosis, and in reducing the likelihood of progress and recovery. Evidence suggests that when the primary focus of management involves improving the environment, both conditions may improve.

This question should be answered using a randomised controlled trial that examines short- and medium-term outcomes over at least 12 months. Studies should focus on people with psychosis whose misuse of substances is most often encountered in clinical practice and has the greatest impact on mental health (such as cannabis and polysubstance misuse), and on interventions that take a collaborative approach to identifying and modifying social and environmental factors that may trigger substance misuse. Those providing the intervention should be trained and supervised to ensure that the results are robust and generalisable. Outcomes should reflect both observer and service user-rated assessments of improvement (including mental health and social functioning) and the intervention's acceptability. Studies need to be large enough to determine the intervention's costs and cost effectiveness.

5 Clozapine versus other pharmacological interventions

Is clozapine clinically and cost effective when compared with other pharmacological interventions for people with psychosis and coexisting substance misuse?

Why this is important

The NICE guideline on psychosis and schizophrenia states that clozapine should be offered to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs. However, there is insufficient evidence to guide healthcare professionals about the use of clozapine in people with psychosis and coexisting substance misuse. Expert opinion often advocates clozapine as having a particular role in this population, but the evidence to support such statements is lacking. Clozapine is expensive and has a wide range of side effects, some of which may be life-threatening if not monitored correctly.

This question should be answered using a randomised controlled trial in which participants are stratified for the presenting problem. It should report short- and longer-term outcomes (including substance misuse, acceptability of the intervention, and cost effectiveness) of at least 12 months' duration.

  • National Institute for Health and Care Excellence (NICE)