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

7.6 Major clinical issues with psychosis and stimulant (including methampetamine) use

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• Psychostimulants can induce or precipitate psychotic states.
• Stimulant induced psychosis can often be indistinguishable from acute or chronic schizophrenia.
• Longer and heavier use of stimulants delays recovery and worsens the prognosis for stimulant induced psychosis.
• In an acute psychotic episode caused by a substance, treatment should involve efforts to encourage abstinence from stimulants which should result in the resolution of psychotic symptoms.
• Benzodiazepines (preferably oral but parenteral, if necessary) should be first-line agents in acute stimulant induced psychosis.
• Antipsychotics are useful second-line agents if benzodiazepines do not settle the agitation sufficiently.
• Limited ongoing antipsychotic use is justified if psychotic symptoms persist.

7.6.1 Effects of stimulants on psychotic disorders

Prevalence

• Stimulants are amongst the most commonly used substances in individuals with psychosis^{(1, 2, 265)}.
• Stimulants may be used to reduce the apathy and lack of energy associated with schizophrenia⁽³⁰⁸⁾.

Stimulant induced disorders

• Psychostimulants can induce or precipitate psychotic states^(32-38).
• Stimulants can induce brief positive and negative psychotic symptoms even in a healthy control group ⁽¹⁵⁾ and, irrespective of an individual's mental state, a large enough dose of stimulant can produce a brief psychotic disorder⁽³⁰⁾.
• Stimulant-induced psychotic states develop during the chronic stage of intoxication and clear within days to a week of ceasing use^{(2, 32, 309)}.
• However, repetitive use of stimulants may involve prolonged psychotic states that can last up to several months after cessation of use^{(33, 37)}.
• Stimulant-induced psychosis involves both positive and negative symptoms including paranoid hallucinatory (auditory and visual) states, bizarre ideas as well as volitional disturbances and can often be indistinguishable from acute or chronic schizophrenia^{(32, 37)}.
• After complete recovery, acute reappearance of paranoid states or relapse of psychosis can be induced by a single use of stimulant in people with a history of stimulant-induced psychosis, years after the initial psychosis has resolved^{(35, 37)}.
• Spontaneous reoccurrence of stimulant-induced paranoid hallucinatory states (flashbacks) can also occur in response to stress (as well as continued use) in subjects with history of stimulant induced psychosis^{(36, 37)}. This appears to be similar to how stress can induce a relapse in people with schizophrenia^{(34, 37)}.
• Longer and heavier use of stimulants delays recovery and worsens the prognosis for stimulant induced psychosis⁽³⁵⁾.
• The risk of stimulant-induced psychosis increases with increasing duration of stimulant use⁽³⁵⁾ and usually develops gradually with repeated episodes of stimulant use⁽³¹⁰⁾.
• Symptoms resembling both positive and negative symptoms of psychosis may continue after withdrawal and patients with persisting stimulant induced psychosis can develop long lasting residual symptoms resembling negative symptoms of schizophrenia⁽³¹⁰⁾.
• Acute stimulant-induced psychosis usually disappears shortly after the discontinuation of stimulant consumption and at the beginning of neuroleptic treatment⁽³⁵⁾.

Stimulant use in people with chronic psychosis

• People with an established psychotic disorder can experience an exacerbation of symptoms after acute exposure to psychostimulants, possibly due to an increase in monoamines^{(15, 30, 34)}.
• The presence of positive symptoms makes an individual more likely to experience a worsening of psychotic symptoms in response to a single administration of stimulant⁽³⁰⁾.
• There is debate as to whether compliance with antipsychotic medication will prevent relapse or worsening of symptoms if stimulants are used^{(30, 310)}.

7.6.2 Interactions between stimulants and therapeutic agents for psychotic disorders

• As stimulants act in an antagonistic manner, their combinations with antipsychotics that act as antagonists, particularly at dopamine receptors, are unlikely to result in more pronounced pharmacodynamic outcomes than if they were taken alone^x.
• Stimulant drugs are likely to exacerbate the side-effects of SSRI and SNRI antidepressants (and vice versa) used in the treatment of breakthrough depression in psychosis⁽²⁾ and may result in serotonin syndrome (Appendix 1)^{x(127, 179, 180)}. Patients should be warned of signs of serotonin syndrome and be monitored.
• MAO-Is (either irreversible or reversible) are contraindicated in people using amphetamines or MDMA. Deaths have been associated with concurrent use of moclobemide and MDMA^{xxx(181, 182)}.
• Fluoxetine, paroxetine and norfluoxetine can inhibit the metabolism of MDMA through inhibition of the CYPs involved in its metabolism and may therefore cause toxicity^x.

7.6.3 Management approaches to comorbid psychotic disorders and stimulant use

Assessment

• It is important to attempt to distinguish between people with an acute psychotic episode caused by substance use, a first episode of a psychotic disorder or an acute episode in someone with an established chronic psychotic disorder.

Treatment

Acute psychotic episode

• In an acute psychotic episode caused by a substance, treatment should involve efforts to encourage abstinence from stimulants⁽³⁰⁾ which should result in the resolution of psychotic symptoms.
• Benzodiazepines (preferably oral but parenteral if necessary) should be first-line agents in acute stimulant induced psychosis. Antipsychotics are useful second-line agents if benzodiazepines do not settle the agitation sufficiently.
• The use of benzodiazepines should be minimised for outpatient use as those with a history of substance use are at increased risk of benzodiazepine use^{(2, 196)}.
• Antipsychotics may be added if benzodiazepines are unsuccessful. However, for acute stimulant induced psychosis, their use is as an adjunctive tranquilliser.
• Limited ongoing use is justified if psychotic symptoms persist.

Longer term psychotic episode

• There are currently no pharmacotherapies for stimulant dependence⁽²⁾.
• As soon as the person has recovered, they should be regularly reviewed in order to reduce and cease antipsychotic medication.
• In those who have experienced more than one episode of psychosis, regular low dose use of antipsychotics may be necessary⁽³⁰⁾.
• There is some evidence that clozapine is effective in individuals with psychosis and comorbid stimulant use^{(2, 267)}.
• Olanzapine has also shown promising results when used by people with psychosis and stimulant-use disorders⁽²⁶⁷⁾. It has been shown to reduce stimulant use and both positive and negative psychotic symptoms related to stimulant use, and improve overall functioning*⁽³²⁾.
• Follow up of the psychotic episode is important to ensure that the patient has not developed an underlying functional psychotic disorder.

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