Despite the high rates of AOD use among people with psychosis, most trials of pharmacotherapy for psychotic spectrum disorders have excluded people with AOD use disorders [779]. International clinical guidelines typically conclude that there is limited evidence to recommend the use of one antipsychotic over another among people with co-occurring AOD use disorders [778]; however, growing literature and corresponding reviews indicate that some antipsychotics show more promise than others. Most of the research to date has focused on those with a diagnosis of schizophrenia, but some studies have included people experiencing first-episode psychosis or diagnosed with other psychotic disorders (e.g., schizoaffective disorder, psychosis in the context of bipolar disorder, substance-induced psychosis).
Two main findings can be drawn from the research to date. Firstly, ‘atypical’ second generation antipsychotics appear to be more effective relative to ‘typical’ first generation antipsychotics (e.g., haloperidol), with reference to both psychiatric and AOD-related outcomes [967, 968]. It has been theorised that the increased AOD use found among those with psychotic disorders relates to dopamine dysfunction which is better addressed by the newer atypical antipsychotic agents than the older typical agents [969]. Atypical antipsychotics may also be preferred by clients as they are associated with fewer extrapyramidal side effects such as involuntary movements [778]. Furthermore, there has been some suggestion that typical antipsychotics may actually increase AOD use and craving [968]. Table 42 lists the names of some of the more common antipsychotics.
There is some evidence to suggest that clozapine [779, 942, 968, 970–972], paliperidone [973–976], and aripiprazole [967, 976–978] are most promising with respect to a variety of outcomes, including improvements in symptoms of psychosis and/or AOD use. AOD use has not been found to influence the efficacy of quetiapine, olanzapine, risperidone, or ziprasidone, for people with psychotic disorders [979]. Preliminary evidence suggests that ziprasidone shows similar efficacy relative to other antipsychotics, though may be more tolerable with fewer side effects [972].
The second main finding that can be drawn from studies to date is that the use of long-acting injectables (LAI), also referred to as depot medication, appear to produce better treatment outcomes among people with AOD use disorders relative to oral antipsychotics. Specifically, LAIs are associated with a lower rate of relapse to psychosis and longer time to relapse [980]. Paliperidone, aripiprazole and risperidone are specific medications where there is some evidence to suggest that the LAI form may be more effective (with respect to producing improvements in severity of psychosis and/or AOD use) relative to their corresponding oral preparation [973, 974, 976, 978, 981, 982]. People receiving monthly paliperidone LAI have also been shown to demonstrate greater treatment adherence, have lower rates of inpatient days, outpatient visits, long-term stays, and lower medical costs; relative to people receiving a range of other oral atypical antipsychotics [973–975]. While both paliperidone LAI and aripiprazole LAI have been linked with reductions in the severity of psychotic symptoms, aripiprazole has also been found to produce improvements in AOD cravings and quality of life [976].
There is also some evidence to suggest that some medications may be more effective than others depending on the type of AOD used. For example, olanzapine, risperidone and haloperidol may be particularly effective in improving symptoms of psychosis and reducing cannabis use among people with cannabis use disorder, while haloperidol and olanzapine have been recommended for those with cocaine use disorders [983]. For those with polydrug use disorder, atypical antipsychotics, in particular, olanzapine, may be more effective than typical antipsychotics [983]. It should be noted, however, that head-to-head comparison studies are rare and tend to be conducted over relatively short follow-up periods. A good approach to management is to tailor the choice of antipsychotic to the individual based on response, side-effect profile, and means of administration (oral versus LAI) .
Regarding amphetamine-induced psychosis specifically, findings have been mixed. A review of aripiprazole, haloperidol, quetiapine, olanzapine, and risperidone concluded that they were safe and effective in reducing both positive and negative symptoms of psychosis, but found no clear evidence for the superiority of one antipsychotic over another [984]. However, a subsequent review and metaanalysis of the efficacy of these drugs and paliperidone extended-release concluded that olanzapine and quetiapine are more efficacious than risperidone; and olanzapine, quetiapine, haloperidol, and paliperidone extended-release are more efficacious than aripiprazole, at reducing symptoms of amphetamine-induced psychosis [985].