Coexisting severe mental illness (psychosis) and substance misuse: assessment and management in healthcare settings

This guideline covers assessing and managing people aged 14 years and over with coexisting severe mental illness (psychosis) and substance misuse. It aims to help healthcare professionals guide people with psychosis with coexisting substance misuse to stabilise, reduce or stop their substance misuse, to improve treatment adherence and outcomes, and to enhance their lives.

# Introduction
This guideline covers the assessment and management of adults and young people (aged 14 years and older) who have a clinical diagnosis of psychosis with coexisting substance misuse.
The term psychosis is used to describe a group of severe mental health disorders characterised by the presence of delusions and hallucinations that disrupt a person's perception, thoughts, emotions and behaviour. The main forms of psychosis are schizophrenia (including schizoaffective disorder, schizophreniform disorder and delusional disorder), bipolar disorder or other affective psychosis.
Substance misuse is a broad term encompassing, in this guideline, the harmful use of any psychotropic substance, including alcohol and either legal or illicit drugs. Such use is usually, but not always, regarded as a problem if there is evidence of dependence, characterised by psychological reinforcement of repeated substance-taking behaviour and, in some cases, a withdrawal syndrome. However, substance misuse can be harmful without dependence, especially among people with a coexisting psychosis.
Approximately 40% of people with psychosis misuse substances at some point in their lifetime, at least double the rate seen in the general population. In addition, people with coexisting substance misuse have a higher risk of relapse and hospitalisation, and have higher levels of unmet needs compared with other inpatients with psychosis who do not misuse substances.
Substance misuse among individuals with psychiatric disorders is associated with significantly poorer outcomes than for individuals with a single disorder. These outcomes include worsening psychiatric symptoms, poorer physical health, increased use of institutional services, poor medication adherence, homelessness, increased risk of HIV infection, greater dropout from services and higher overall treatment costs. Social outcomes are also significantly worse, including greater homelessness and rooflessness, a higher impact on families and carers, and increased contact with the criminal justice system.
Rooflessness here refers to living rough or on the streets, whereas homelessness encompasses people who are living in shelters.
People with psychosis commonly take various non-prescribed substances as a way of coping with their symptoms, and in a third of people with psychosis, this amounts to harmful or dependent use. The outcome for people with psychosis and coexisting substance misuse is worse than for people without coexisting substance misuse, partly because the substances used may exacerbate the psychosis and partly because substances often interfere with pharmacological or psychological treatment. This guideline aims to help healthcare professionals guide people with psychosis and coexisting substance misuse to stabilise, reduce or stop their substance misuse, to improve treatment adherence and outcomes, and to enhance their lives.
As well as primary and secondary services, this guideline also applies to services that are delivered by the third sector and commissioned by the NHS.# Recommendations
People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.
Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.

# Definitions of depression and severity
Depression refers to a wide range of mental health problems characterised by the absence of a positive affect (a loss of interest and enjoyment in ordinary things and experiences), low mood and a range of associated emotional, cognitive, physical and behavioural symptoms. For more detail, see the International Classification of Diseases-11 (ICD-11) or the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for depression.
Depression severity exists along a continuum and is essentially composed of 3 elements:
symptoms (which may vary in frequency and intensity)
duration of the disorder
the impact on personal and social functioning.
Severity of depression is therefore a consequence of the contribution of all of these elements.
Traditionally, depression severity has been grouped under 4 categories (subthreshold, mild, moderate and severe) but in the development of this guideline the committee wanted to develop a way of representing the severity of depression which best represents the available evidence on the classification and would help the uptake of the recommendations in routine clinical practice. This guideline has therefore defined new episodes of depression as less severe or more severe depression.
Less severe depression encompasses subthreshold and mild depression, and more severe depression encompasses moderate and severe depression. Thresholds on validated scales were used in this guideline as an indicator of severity. For example, a score 16 on the PHQ-9 scale was used, with scores less than 16 defined as less severe depression, and scores of 16 or more defined as more severe depression.
The following guidance is based on the best available evidence. The full guideline gives details of the methods and the evidence used to develop the guidance.

# Principles of care

## Working with adults and young people with psychosis and coexisting substance misuse
When working with adults and young people with known or suspected psychosis and coexisting substance misuse, take time to engage the person from the start, and build a respectful, trusting, non-judgemental relationship in an atmosphere of hope and optimism. Be direct in your communications, use a flexible and motivational approach, and take into account that:
stigma and discrimination are associated with both psychosis and substance misuse
some people will try to conceal either one or both of their conditions
many people with psychosis and coexisting substance misuse fear being detained or imprisoned, being given psychiatric medication forcibly or having their children taken into care, and some fear that they may be 'mad'.
When working with adults and young people with known or suspected psychosis and coexisting substance misuse:
ensure that discussions take place in settings in which confidentiality, privacy and dignity can be maintained
avoid clinical language without adequate explanation
provide independent interpreters (who are not related to the person) if needed
aim to preserve continuity of care and minimise changes of key workers in order to foster a therapeutic relationship.

## Race and culture
Healthcare professionals working with adults and young people with psychosis and coexisting substance misuse should ensure that they are competent to engage, assess, and negotiate with service users from diverse cultural and ethnic backgrounds and their families, carers or significant others.'Significant other' refers not just to a partner but also to friends and any person the service user considers to be important to them.
Work with local black and minority ethnic organisations and groups to help support and engage adults and young people with psychosis and coexisting substance misuse. Offer organisations and groups information and training about how to recognise psychosis with coexisting substance misuse and access treatment and care locally.

## Providing information
Offer written and verbal information to adults and young people appropriate to their level of understanding about the nature and treatment of both their psychosis and substance misuse. Written information should:
include the information for the public (available in English and Welsh), which contains a list of organisations that can provide more information
be available in the appropriate language or, for those who cannot use written text, in an alternative format (audio or video).
All healthcare professionals in primary, secondary or specialist substance misuse services working with adults and young people with psychosis should offer information and advice about the risks associated with substance misuse and the negative impact that it can have on the experience and management of psychosis.

## Working with and supporting families, carers and significant others
Encourage families, carers or significant others to be involved in the treatment of adults and young people with psychosis and coexisting substance misuse to help support treatment and care and promote recovery.
When families, carers or significant others live or are in close contact with the person with psychosis and coexisting substance misuse, offer family intervention as recommended in NICE guideline on psychosis and schizophrenia in adults.
When families, carers or significant others are involved in supporting the person with psychosis and coexisting substance misuse, discuss with them any concerns about the impact of these conditions on them and on other family members.
Offer families, carers or significant others a carer's assessment of their caring, physical, social, and mental health needs. Where needs are identified, develop a care plan for the family member or carer.
Offer written and verbal information to families, carers or significant others appropriate to their level of understanding about the nature and treatment of psychosis and substance misuse, including how they can help to support the person. Written information should be available in the appropriate language or, for those who cannot use written text, in an accessible format (audio or video).
Offer information to families, carers or significant others about local family or carer support groups and voluntary organisations, including those for psychosis and for substance misuse, and help families, carers or significant others to access these.
Negotiate confidentiality and sharing of information between the person with psychosis and coexisting substance misuse and their family, carer or a significant other.'Significant other' refers not just to a partner but also to friends and any person the service user considers to be important to them.
Ensure the needs of young carers or dependent adults of the person with psychosis and coexisting substance misuse are assessed. Initiate safeguarding procedures where appropriate (see recommendations 1.1.16 to 1.1.20 on safeguarding issues).

## Support for healthcare professionals
Working with people with psychosis and coexisting substance misuse can be challenging and healthcare professionals should seek effective support  for example, through professional supervision or staff support groups.

## Safeguarding issues
If people with psychosis and coexisting substance misuse are parents or carers of children or young people, ensure that the child's or young person's needs are assessed according to local safeguarding procedures. See also, safeguarding children on the Gov.uk website.
If children or young people being cared for by people with psychosis and coexisting substance misuse are referred to CAMHS under local safeguarding procedures:
use a multi-agency approach, including social care and education, to ensure that various perspectives on the child's life are considered
consider using the Common Assessment Framework (CAF); advice on this can be sought from the local named lead for safeguarding.
If serious concerns are identified, health or social care professionals working with the child or young person (see recommendation 1.1.17) should develop a child protection plan.
When working with people with psychosis and coexisting substance misuse who are responsible for vulnerable adults, ensure that the home situation is risk assessed and that safeguarding procedures are in place for the vulnerable adult. Advice on safeguarding vulnerable adults can be sought from the local named lead for safeguarding.
Consider adults with psychosis and coexisting substance misuse for assessment according to local safeguarding procedures for vulnerable adults if there are concerns regarding exploitation or self-care, or if they have been in contact with the criminal justice system.

## Consent, capacity and treatment decisions
Before undertaking any investigations for substance misuse, and before each treatment decision is taken:
provide service users with full information appropriate to their needs about psychosis and substance misuse and the management of both conditions, to ensure informed consent
understand and apply the principles underpinning the Mental Capacity Act (2005), and be aware that mental capacity is decision-specific (that is, if there is doubt about mental capacity, assessment of mental capacity should be made in relation to each decision)
be able to assess mental capacity using the test set out in the Mental Capacity Act (2005).These principles should apply whether or not people are being detained or treated under the Mental Health Act (1983; amended 1995 and 2007).

## Advance decisions and statements
Develop advance decisions and advance statements in collaboration with adults with psychosis and coexisting substance misuse, especially if their condition is severe and they have been treated under the Mental Health Act (1983; amended 1995 and 2007). Record the decisions and statements and include copies in the care plan in primary and secondary care. Give copies to the person, their care coordinator, and their family, carer or a significant other if the person agrees.'Significant other' refers not just to a partner but also to friends and any person the service user considers to be important to them.
Take advance decisions and advance statements into account in accordance with the Mental Capacity Act (2005). Although advance decisions and advance statements can be overridden using the Mental Health Act (1983; amended 1995 and 2007), try to honour them wherever possible.

## Working with the voluntary sector
Healthcare professionals in primary care and secondary care mental health services, and in specialist substance misuse services, should work collaboratively with voluntary sector organisations that provide help and support for adults and young people with psychosis and coexisting substance misuse. Ensure that advocates from such organisations are included in the care planning and care programming process wherever this is possible and agreed by the person with psychosis and coexisting substance misuse.
Healthcare professionals in primary care and secondary care mental health services, and in specialist substance misuse services, should work collaboratively with voluntary sector organisations providing services for adults and young people with psychosis and coexisting substance misuse to develop agreed protocols for routine and crisis care.

# Recognition of psychosis with coexisting substance misuse
Healthcare professionals in all settings, including primary care, secondary care mental health services, CAMHS and accident and emergency departments, and those in prisons and criminal justice mental health liaison schemes, should routinely ask adults and young people with known or suspected psychosis about their use of alcohol and/or prescribed and non-prescribed (including illicit) drugs. If the person has used substances ask them about all of the following:
particular substance(s) used
quantity, frequency and pattern of use
route of administration
duration of current level of use.In addition, conduct an assessment of dependency (see NICE guidelines on drug misuse in over 16s: opioid detoxification and alcohol-use disorders: diagnosis, assessment and management of harmful drinking (high-risk drinking) and alcohol dependence) and also seek corroborative evidence from families, carers or significant others, where this is possible and permission is given.
Healthcare professionals in all settings, including primary care, secondary care mental health services, CAMHS and accident and emergency departments, and those in prisons and criminal justice mental health liaison schemes, should routinely assess adults and young people with known or suspected substance misuse for possible psychosis. Seek corroborative evidence from families, carers or significant others, where this is possible and permission is given.'Significant other' refers not just to a partner but also to friends and any person the service user considers to be important to them.

# Primary care

## Referral from primary care
Refer all adults and young people with psychosis or suspected psychosis, including those who are suspected of coexisting substance misuse, to either secondary care mental health services or CAMHS for assessment and further management.
Refer all adults and young people with substance misuse or suspected substance misuse who are suspected of having coexisting psychosis to secondary care mental health services or CAMHS for assessment and further management.

## Physical healthcare
Monitor the physical health of adults and young people with psychosis and coexisting substance misuse, as described in the NICE guideline on psychosis and schizophrenia in adults. Pay particular attention to the impact of alcohol and drugs (prescribed and non-prescribed) on physical health. Monitoring should be conducted at least once a year or more frequently if the person has a significant physical illness or there is a risk of physical illness because of substance misuse.

# Secondary care mental health services

## Competence
Healthcare professionals working within secondary care mental health services should ensure they are competent in the recognition, treatment and care of adults and young people with psychosis and coexisting substance misuse.
Healthcare professionals working within secondary care mental health services with adults and young people with psychosis and coexisting substance misuse should consider having supervision, advice, consultation and/or training from specialists in substance misuse services. This is to aid in the development and implementation of treatment plans for substance misuse within CAMHS or adult community mental health services.

## Pathways into care
Do not exclude adults and young people with psychosis and coexisting substance misuse from age-appropriate mental healthcare because of their substance misuse.
Do not exclude adults and young people with psychosis and coexisting substance misuse from age-appropriate substance misuse services because of a diagnosis of psychosis.
For most adults with psychosis and coexisting substance misuse, treatment for both conditions should be provided by healthcare professionals in secondary care mental health services such as community-based mental health teams.

## Coordinating care
Consider seeking specialist advice and initiating joint working arrangements with specialist substance misuse services for adults and young people with psychosis being treated by community mental health teams, and known to be:
severely dependent on alcohol or
dependent on both alcohol and benzodiazepines or
dependent on opioids and/or cocaine or crack cocaine.Adult community mental health services or CAMHS should continue to provide care coordination and treatment for the psychosis within joint working arrangements.
Consider seeking specialist advice and initiate joint working arrangements with specialist substance misuse services if the person's substance misuse:
is difficult to control and/or
leads to significant impairment of functioning, family breakdown or significant social disruption such as homelessness.
If a person with psychosis and coexisting substance misuse requires planned detoxification from either drugs or alcohol, this should take place in an inpatient setting (see section 1.6).
Delivery of care and transfer between services for adults and young people with psychosis and coexisting substance misuse should include a care coordinator and use the Care Programme Approach.

## Assessment
Adults and young people with psychosis and coexisting substance misuse attending secondary care mental health services should be offered a comprehensive, multidisciplinary assessment, including assessment of all of the following:
personal history
mental, physical and sexual health
social, family and economic situation
accommodation, including history of homelessness and stability of current living arrangements
current and past substance misuse and its impact upon their life, health and response to treatment
criminal justice history and current status
personal strengths and weaknesses and readiness to change their substance use and other aspects of their lives. The assessment may need to take place over several meetings to gain a full understanding of the person and the range of problems they experience, and to promote engagement.
When assessing adults and young people with psychosis and coexisting substance misuse, seek corroborative evidence from families, carers or significant others where this is possible and permission is given. Summarise the findings, share this with the person and record it in their care plan.'Significant other' refers not just to a partner but also to friends and any person the service user considers to be important to them.
Review any changes in the person's use of substances. This should include changes in:
the way the use of substances affects the person over time
patterns of use
mental and physical state
circumstances and treatment. Share the summary with the person and record it in their care plan.
When assessing adults and young people with psychosis and coexisting substance misuse, be aware that low levels of substance use that would not usually be considered harmful or problematic in people without psychosis, can have a significant impact on the mental health of people with psychosis.
Regularly assess and monitor risk of harm to self and/or others and develop and implement a risk management plan to be reviewed when the service users' circumstances or levels of risk change. Specifically consider additional risks associated with substance misuse, including:
physical health risks (for example, withdrawal seizures, delirium tremens, blood-borne viruses, accidental overdose, and interactions with prescribed medication) and
the impact that substance use may have on other risks such as self-harm, suicide, self-neglect, violence, abuse of or by others, exploitation, accidental injury and offending behaviour.

## Biological/physical testing
Biological or physical tests for substance use (such as blood and urine tests or hair analysis) may be useful in the assessment, treatment and management of substance misuse for adults and young people with psychosis. However, this should be agreed with the person first as part of their care plan. Do not use biological or physical tests in routine screening for substance misuse in adults and young people with psychosis.

## Treatment
Before starting treatment for adults and young people with psychosis and coexisting substance misuse, review:
the diagnosis of psychosis and of the coexisting substance misuse, especially if either diagnosis has been made during a crisis or emergency presentation and
the effectiveness of previous and current treatments and their acceptability to the person; discontinue ineffective treatments.
When developing a care plan for an adult or young person with psychosis and coexisting substance misuse, take account of the complex and individual relationships between substance misuse, psychotic symptoms, emotional state, behaviour and the person's social context.
Ensure that adults and young people with psychosis and coexisting substance misuse are offered evidence-based treatments for both conditions (see recommendations 1.4.19 and 1.4.20).
For the treatment of psychosis, see NICE guideline on bipolar disorder or the guideline on NICE guideline on psychosis and schizophrenia in adults.
For the treatment of substance misuse, see:
NICE guidelines on alcohol-use disorders: diagnosis and clinical management of alcohol-related physical complications and alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence and/or
NICE guidelines on drug misuse in over 16s: psychosocial interventions and opioid detoxification.
When developing a treatment plan for a person with psychosis and coexisting substance misuse, tailor the plan and the sequencing of treatments to the person and take account of:
the relative severity of both the psychosis and the substance misuse at different times and
the person's social and treatment context and
the person's readiness for change.
Do not exclude adults and young people with psychosis and coexisting substance misuse from contingency management programmes because of their psychosis.
Use antipsychotics according to the guideline on NICE guidelines on psychosis and schizophrenia in adults or bipolar disorder because there is no evidence for any differential benefit for one antipsychotic over another for people with psychosis and coexisting substance misuse.
Use depot/long-acting injectable antipsychotics according to the NICE guideline on psychosis and schizophrenia in managing covert non-adherence with treatment for psychosis and not as a specific treatment for psychosis and coexisting substance misuse.
When prescribing medication for adults and young people with psychosis and coexisting substance misuse:
take into account the level and type of substance misuse, especially of alcohol, as this may alter the metabolism of prescribed medication, decrease its effectiveness and/or increase the risk of side effects
warn the person about potential interactions between substances of misuse and prescribed medication
discuss the problems and potential dangers of using non-prescribed substances and alcohol to counteract the effects or side effects of prescribed medication.

# Substance misuse services

## Competence
Healthcare professionals in substance misuse services should be competent to:
recognise the signs and symptoms of psychosis
undertake a mental health needs and risk assessment sufficient to know how and when to refer to secondary care mental health services.

## Assessment
Adults and young people with psychosis and coexisting substance misuse attending substance misuse services should be offered a comprehensive, multidisciplinary mental health assessment in addition to an assessment of their substance misuse.

## Joint working
Healthcare professionals in substance misuse services should be present at Care Programme Approach meetings for adults and young people with psychosis and coexisting substance misuse within their service who are also receiving treatment and support in other health services.
Specialist substance misuse services should provide advice, consultation, and training for healthcare professionals in adult mental health services and CAMHS regarding the assessment and treatment of substance misuse, and of substance misuse with coexisting psychosis.
Specialist substance misuse services should work closely with secondary care mental health services to develop local protocols derived from this guideline for adults and young people with psychosis and coexisting substance misuse. The agreed local protocols should set out responsibilities and processes for assessment, referral, treatment and shared care across the whole care pathway.

# Inpatient mental health services

## Substance misuse
All inpatient mental health services should ensure that they have policies and procedures for promoting a therapeutic environment free from drugs and alcohol that have been developed together with service users and their families, carers or significant others. These should include: search procedures, visiting arrangements, planning and reviewing leave, drug and alcohol testing, disposal of legal and illicit substances, and other security measures. Soon after admission, provide all service users, and their families, carers or significant others, with information about the policies and procedures.'Significant other' refers not just to a partner but also to friends and any person the service user considers to be important to them.
When carrying out a comprehensive assessment for all adults and young people admitted to inpatient mental health services, ensure that they are assessed for current substance misuse and evidence of withdrawal symptoms at the point of admission.
Biological or physical tests for substance use should only be considered in inpatient services as part of the assessment and treatment planning for adults and young people with psychosis and coexisting substance misuse. Obtain consent for these tests and inform the person of the results as part of an agreed treatment plan. Where mental capacity is lacking, refer to the Mental Capacity Act (2005).
Ensure that planned detoxification from either drugs or alcohol is undertaken only:
with the involvement and advice of substance misuse services
in an inpatient setting, preferably in specialist detoxification units,  or designated detoxification beds within inpatient mental health services and
as part of an overall treatment plan. For the further management of opioid detoxification see the NICE guideline on drug misuse in over 16s: opioid detoxification. For the further management of assisted alcohol withdrawal see the NICE guideline on alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence.

## Discharge
Do not discharge adults and young people with psychosis and coexisting substance misuse from an inpatient mental health service solely because of their substance misuse.
When adults and young people with psychosis and coexisting substance misuse are discharged from an inpatient mental health service, ensure that they have:
an identified care coordinator and
a care plan that includes a consideration of needs associated with both their psychosis and their substance misuse and
been informed of the risks of overdose if they start reusing substances, especially opioids, that have been reduced or discontinued during the inpatient stay.

# Staffed accommodation

## Exclusion from services
Do not exclude people with psychosis and coexisting substance misuse from staffed accommodation (such as supported or residential care) solely because of their substance misuse
Do not exclude people with psychosis and coexisting substance misuse from staffed accommodation aimed at addressing substance misuse solely because of their diagnosis of psychosis.

## Aims of treatment
Ensure that people with psychosis and coexisting substance misuse who live in staffed accommodation receive treatment for both their psychosis and their substance misuse with the explicit aim of helping the person remain in stable accommodation.

# Specific issues for young people with psychosis and coexisting substance misuse

## Competence
Professionals in Tier 1 (primary care and educational settings) should be competent to recognise early signs of psychosis and substance misuse in young people.
Healthcare professionals in Tier 3 (community mental health teams) and Tier 4 (specialist inpatient and regional services) CAMHS, and in early intervention in psychosis services, should be competent in the management of psychosis and substance misuse in young people.

## Identification and referral
Professionals in Tier 1 (primary care and educational settings) should seek advice or consultation from Tier 2 CAMHS (primary care) when signs of psychosis are detected in young people. If healthcare professionals in Tier 2 CAMHS detect signs of psychosis in young people, a referral to Tier 3 CAMHS or early intervention in psychosis services for young people should be made according to local protocols.
Ask all young people seen in Tier 3 and Tier 4 CAMHS and in early intervention in psychosis services who have psychosis or suspected psychosis about substance misuse (see recommendation 1.2.1).
Children and young people who, after comprehensive assessment, are considered to be at high risk of harm to themselves or others, should be referred directly to Tier 4 CAMHS including inpatient services where necessary.

## Assessment and treatment
Healthcare professionals working with young people with psychosis and coexisting substance misuse should ensure they are familiar with the legal framework that applies to young people including the Mental Health Act (1983; amended 1995 and 2007), the Mental Capacity Act (2005), and the Children Act (2004).
For psychological, psychosocial, family and medical interventions for young people, follow the recommendations for adults in this guideline; they may need to be adapted according to the young person's circumstances and age. In addition, other agencies, including children's services, should be involved to ensure that the young person's educational, employment, family and housing needs are met.
When prescribing medication, take into account the young person's age and weight when determining the dose. If it is appropriate to prescribe unlicensed medication, explain to the young person and/or their parents or carers the reasons for doing this.
Those providing and commissioning services should ensure that:
age-appropriate mental health services are available for young people with psychosis and coexisting substance misuse and
transition arrangements to adult mental health services are in place where appropriate.# 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.

# 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.

# 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.

# 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.

# 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.

# 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.