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Pharmacotherapy for co-occurring alcohol and drug disorders in schizophrenia and bipolar disorder: where is the evidence?

Both epidemiological and clinical studies consistently report high rates of substance use among individuals with schizophrenia and bipolar disorder (1,2). Up to 90% smoke cigarettes, while between 40 and 60% misuse other substances (2,3). Co-occurring substance use disorders (SUDs) (excluding tobacco smoking) appear to be more prevalent (up to 75%) among young people with first-episode psychosis (4), as well as those who are homeless or involved with the criminal justice system. The most frequently misused substances are cannabis, alcohol and psychostimulants, mirroring patterns of use evident within the general population, although misuse of more than one substance is relatively common (2,3). Co-occurring SUDs affect medication adherence and service engagement (2,3), and can precipitate mixed states and rapid cycling in bipolar disorder (5). SUDs substantially increase the burden on patients, their families and the health care system, and those with co-occurring disorders generally do poorly in standard treatment settings (2). Indeed, such patients have lower rates of remission and increased rates of relapse, hospitalisation, housing instability, blood-borne virus infection [e.g. human immunodeficiency virus (HIV)], suicide, violent behaviour, incarceration and early mortality (2,3). It is therefore not surprising that many clinicians feel overwhelmed or not sufficiently skilled to manage such patients (2). Despite such clear consequences, SUDs are frequently underdiagnosed or ignored within psychiatric treatment settings, with many clinicians considering that SUD treatment should be assessed and managed independently of the mental disorder. In younger populations, psychosis or mood instability in the context of co-occurring substance misuse can present a particularly difficult diagnostic challenge, especially if the substance use is longstanding (6). As such, it is not uncommon for these patients to be excluded from psychiatric services if their substance use is deemed to be the primary problem, although there is good evidence that individuals with substance-induced psychosis are a particularly high-risk group for later transition to psychotic disorders, and have high levels of psychological morbidity (6). Such stigma is also evident within the clinical treatment literature, with SUDs being a common exclusion criterion from the bulk of existing pharmaceutical industry trials. Thus, while we have good evidence for the efficacy of psychotropic medications in the treatment of schizophrenia and bipolar disorder uncomplicated by substance misuse, we have limited evidence for their utility in the treatment of patients with co-occurring SUDs. Whether they are as effective and whether recommended dosages are applicable to this population remain legitimate clinical questions. Despite such concerns, most clinicians prescribe similar pharmacotherapeutic regimes for patients with co-occurring SUD as those without substance use issues, with limited outcome-related research available to inform practice. What then is the current state of the literature in terms of the pharmacotherapy of co-occurring disorders? Despite the wealth of large randomised controlled trial data available for bipolar disorder and schizophrenia, most studies examining the pharmacotherapy of co-occurring disorders have been case studies, case series, open-label trials or retrospective surveys (3,7). While a few randomised prospective trials have been conducted, they have typically been small in size with limited long-term follow-up (7,8). They have also tended to examine the efficacy of existing psychotropic agents (i.e. antipsychotics or mood stabilisers) rather than the role of adjunctive pharmacotherapies that specifically target each disorder. Nonetheless, despite such limitations, there is a growing body of evidence that directly informs clinical treatment. In terms of schizophrenia, few studies with typical antipsychotics have been conducted. While there is no clear evidence that oral neuroleptics decrease substance misuse in patients with co-occurring SUDs, there are concerns that they may actually exacerbate use, particularly as extrapyramidal side-effects appear to be more commonly reported by patients with co-occurring disorders (3,7). A number of small open-label studies have reported positive outcomes for flupenthixol decanoate over 6–12 months (7); however, it is unclear how much this reflects adequate antipsychotic treatment, rather than specific characteristics of the agent itself. Few other studies of depot preparations have been conducted, although a recent open-label randomised trial reported better substance use and psychosis outcomes over 6 months for patients on long-acting injectable risperidone when compared with zuclopenthixol (9). Studies examining the effectiveness of oral atypical agents have generally been