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Comorbidity of mental disorders and substance use: a brief guide for the primary care clinician

7.2 Comorbidity with Psychosis

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7.2.1 Schizophrenia

• There are few differences in acute symptoms between schizophrenia with substance use and substance-induced psychosis. Distinction is primarily made on the basis of resolution of symptoms after withdrawal from the substance⁽²⁾.
• Prodromal, or early non-specific symptoms of schizophrenia such as subtle personality changes, social withdrawal, reduced self-care and odd thinking, prior to the start of substance use and psychotic symptoms, may help make the distinction between a functional illness such as schizophrenia and substance-induced psychotic symptoms.
• Comorbid substance-use disorders are more common in people with psychosis than the general population^{(1, 2, 263)}.
• The number of injecting drug users is increasing in the general population. The rates of those with psychosis who are injecting drugs is increasing at a similar rate⁽²⁾.
• Problematic substance use has been associated with earlier onset of psychosis⁽²⁶³⁾.
• Even moderate use of substances can exacerbate psychotic symptoms which can make motivation for reduction of substance use difficult^{(1, 2, 263)}.
• Reasons for increased substance use in schizophrenia are dominated by self-medication hypotheses. The hypothesis is that people use substances in an effort to deal with their symptoms⁽¹⁵⁾.
  • Those with substance-use disorders and schizophrenia report fewer negative symptoms^{(1, 264, 265)}.
  • Self medication does explain some but not all of the reasons for comorbid substance use and schizophrenia⁽²⁶⁶⁾.
• Comorbid substance use and schizophrenia are associated with increased morbidity and poorer outcome^{(1, 2, 15, 263)} and, in the past, people with this combination have generally not responded as well to treatment as those without substance-use disorders⁽²⁶⁵⁾.
• Substance use is highly associated with treatment non-compliance^{(1, 15, 263)} and longer duration of untreated schizophrenia⁽²⁶⁵⁾.
• Decreases in substance use due to treatment retention is associated with reduced overall symptoms in people with psychosis⁽²⁶⁷⁾.

7.2.2 Bipolar disorder

• Large amounts of alcohol and other substance use frequently occur during the manic phase of bipolar illness.
• Manic symptoms are likely to be exacerbated by concurrent substance use, particularly stimulant and cannabis use.
• During the depressed phase of the illness period, there is also increased substance use with alcohol exacerbating depression, and the use of stimulants and cannabis having the risk of precipitating a manic swing or mixed symptoms.
• During periods of recovery, the person typically returns to limited use. Care is needed not to misdiagnose and attribute all problems to the substance intake.

7.2.3 General

• Comorbidity with other mental disorders is common amongst those with psychosis, in particular anxiety and depression^{(15, 251, 268)}.
• Coexisting personality disorder^{(251, 263)} can lead to poorer prognosis of substance use disorders in patients with schizophrenia^{(15, 263)}.
• Very little evidence is available to allow advice concerning safe levels of alcohol or substance use in patients with psychotic illnesses. The assumption can be made that any use during the active phase of illness will have a deleterious effect.
• Psychosis is associated with suicidal ideation and attempts which are exacerbated when comorbid substance use is involved^{(15, 251, 263, 268)}.

7.2.4 General management approaches to comorbidity

Assessment

• The person experiencing psychosis who is using substances presents diagnostic and management challenges for the clinician.
• It is important to differentiate between three different phenomena with regard to psychosis and substance use:
  • People can experience an acute psychotic episode in response to substance intoxication, withdrawal and use due to the effects of the substance.
  • Substances can precipitate a psychotic disorder in predisposed individuals which can persist in the absence of the psychoactive substance.
  • Some people have an underlying psychotic disorder that is exacerbated by concurrent use of substances, in particular cannabis and amphetamines.
• The use of substances can exacerbate symptoms in people with a chronic psychotic disorder, exacerbating the condition and interfering with rehabilitation.
• Non-response to medication for psychosis may be indicative of substance use. This should be investigated before attempting to change the antipsychotic medication^{(2, 262)}.
• Comorbid substance use in people with psychosis has the potential to affect cognitive ability⁽²⁶⁹⁾. This may impact on treatment approaches and prolong the time it takes to observe a positive response to treatment.

Treatment: Pharmacotherapy

• Most research has occurred in relation to schizophrenia and substance use, rather than bipolar disorder.
• There is little difference between schizophrenia and substance-induced psychosis in the treatment of acute symptoms. However, substance-induced psychosis does not normally require long-term maintenance with antipsychotic medication⁽²⁾.
• Despite a lack of controlled trials, it appears that people with comorbid substance use and schizophrenia fare better on newer atypical antipsychotics***^{(1, 2, 267, 270-274)}.
• Clozapine stands out as the most valuable treatment so far for comorbid substance use and schizophrenia***^{(1, 2, 267, 270, 272, 274, 275)}.
• Clozapine for schizophrenia appears to be as effective in people with substance use issues as it does in non-substance users**⁽²⁷⁶⁾. Additional substance use does not appear to interfere with the efficacy of clozapine for pyschosis⁽²⁷⁶⁾.
• As well as controlling psychotic symptoms, clozapine also shows evidence of reducing substance use in those with psychosis***^{(1, 2, 267, 270, 272, 274, 275)}.

Treatment: Psychotherapy

• The efficacy of CBT as a single treatment for psychosis is not affected by substance use***⁽²⁷⁷⁾.
• Integrated care for both disorders (including pharmacotherapy, motivational interviewing, CBT and caregiver interventions) significantly improves both psychotic positive symptoms and substance use***^{(1, 15, 267, 278)}.

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