Drug use is common among individuals with schizophrenia. The rate of comorbid substance use disorder in persons with schizophrenia ranges widely between 10 and 70%, with variations largely attributed to methodological differences such as study population and variability in definitions of substance use (1). Data from the US Epidemiological Catchment Area Study showed that 47.0% of individuals with a lifetime diagnosis of schizophrenia or schizophreniform disorder met the criteria for any substance use (abuse and dependence), 27.5% met the criteria for any drug (other than alcohol) disorder, and 33.7% met criteria for an alcohol disorder (2). The odds of having these comorbid conditions were three to six times higher among those with schizophrenia as compared to the general population. A case-control study similarly reported higher number of patients with schizophrenia who had problem use of drugs and alcohol as compared to matched controls from the general population (3). More recently, a meta-analysis established a lifetime rate of cannabis use disorder at 27.1% among clinical samples of patients with schizophrenia (4). Drug use contributes to increased risk of psychosis (5) and while for some individuals such substance-induced psychosis could be a transient state, the clinical conditions could persist, mimicking the positive and negative symptoms observed in schizophrenia (6). The transition from substance-induced psychosis to primary psychotic disorder has been reported in the literature (7, 8).

Problematic use of drugs as discussed in this article generally refers to the use of drugs that resulted in physical, psychological, social and legal problems [for definitions, see Refs. (9) and (10)]. It has been linked with poorer course and outcomes for patients with schizophrenia. Drug abuse was a significant predictor of self-harm and suicide among those with schizophrenia (11, 12), and individuals with a dual diagnosis of substance use disorder and schizophrenia reported higher positive and negative symptoms, and were more likely to be medication non-compliant and depressed compared to those with a single diagnosis of schizophrenia (13). A longitudinal study among patients with recent onset of psychosis found that those with persistent use of cannabis had more positive symptoms and a continuous illness (i.e., no remission longer than 6 months) at follow-up (14). Furthermore, substance abuse in patients with schizophrenia was associated with increased rates of hospitalizations, incarceration and use of emergency services, as well as higher treatment expenditure (15, 16).

There is some evidence in the literature showing the effectiveness of treating drug-related problems among patients with a dual diagnosis of schizophrenia and substance use disorder (17–19). This included improvements in psychiatric outcomes in areas of global functioning, positive symptoms and quality of life, and in substance-related outcomes in terms of relapse and days abstinent. However, some studies have reported limited evidence on the effectiveness of psychosocial interventions (20, 21), and the absence of high-quality randomized controlled trials precluded definitive conclusions (22). Nonetheless, given the negative outcomes of substance use disorder in patients with schizophrenia and the potential improvement in outcomes with interventions, it remains important to identify the extent of problematic drug use in this population.

Singapore is a multi-ethnic city-state located in Southeast Asia with a resident population of 4.04 million (23). While the lifetime prevalence of schizophrenia and psychotic disorder in Singapore was established at 2.3% in the general population (24), little is known about the prevalence of problematic drug use among those with the condition. In the general population, the total number of individuals arrested for illicit drug use was 3,014 in 2020, a 15% drop from the previous year, and Methamphetamine remained the most commonly used drug (25). To date, only one study has been conducted in Singapore among patients with schizophrenia to examine substance abuse [alcohol and other substances; (26)], and two studies have examined hazardous alcohol use among patients with first episode psychosis, and among a mixed sample of outpatients with schizophrenia and depressive disorders (27, 28). Given the paucity of research particularly on drug use, this study was thus conducted with the aim to (i) establish the prevalence of problematic drug use in a clinical sample of patients with schizophrenia and related psychoses, (ii) identify sociodemographic correlates of problematic drug use, and (iii) explore associations between problematic drug use and smoking status, symptoms severity as well as quality of life.

The present study aimed to establish the prevalence of problematic drug use among patients with schizophrenia and related psychoses. It was found that 5.8% of patients surveyed in this study reported misusing drugs in the past 1 year, and 10.6% had problems with drug use and/or alcohol use. Notwithstanding the differences in study methodologies, our finding suggests that problematic drug use is less common among patients with schizophrenia in Singapore as compared to other countries (3, 4).

In general, the use of illicit drugs is lower in Singapore than most other countries, and this largely reflects Singapore's zero tolerance approach to drugs (43) and the success of anti-drug movement in the country. The Central Narcotics Bureau is the primary drug enforcement agency in Singapore and has four main strategies in place to keep the nation drug-free: preventive drug education, rigorous enforcement, treatment and rehabilitation, and aftercare and continued rehabilitation. These efforts are supported by other agencies including the Singapore Anti-Narcotics Association and the Yellow Ribbon Singapore. In the recent years, a rehabilitative and integrative approach toward individuals with drug related offenses has been embraced, and through community-based programs where efforts in early reintegration of these individuals into the community are made (44). Nonetheless, some challenges may remain in drug control and treatment strategies such as a need to focus on familial interventions and more research in the area of drug addiction (45, 46).

Results from the study revealed a considerable number of patients with schizophrenia who may be at risk of significant problematic drug use. Though not meeting the threshold in this study to be classified as having significant problematic drug use, 4.6% of those surveyed had a low degree of problematic drug use (i.e., DAST-10 score: 1–2). It remains that this group should be closely monitored for their drug use and brief counseling may be recommended for them (47). Given that several reasons have been identified for illicit drug use among individuals with psychotic disorders, including social reasons and as coping mechanism for symptoms and side-effects of medications (48, 49), future studies can aim to explore drug use motivations within this at-risk group to effectively intervene at an early stage. Furthermore, understanding the frequency and types of drugs used would be essential. In the local context, the study by Verma et al. (26) found that benzodiazepine was one of the frequently abused substances among patients with schizophrenia and the authors called for caution when prescribing these medications.

Consistent with studies in the literature which identified gender as a significant correlate of substance use (50–53), the current study found that more males than females had problematic drug use, and also problematic drug and/or alcohol use. Data from national statistics have shown that there were consistently more males than females who used illicit drugs in Singapore (54). Such a gender disparity could reflect differences in opportunity to use drug rather than vulnerability; males were found to have greater opportunities to use drug, but when once presented with the opportunity, females were as likely as males to initiate drug use (55). While the severity of substance use between both genders might be similar (56), females might be more susceptible to the negative effects of drugs use (57, 58) and also more likely to relapse following abstinence (59). Additionally, males and females with serious mental illness were found to differ in drug use behavior including ways to drugs access and reasons for drug use. Women were more likely to have drugs given to them by a significant other, and to report using drugs to test their ability to control drug use (60). In terms of hazardous alcohol use, several biological risk factors (e.g., genetic risks and gender differences in physiological effects of alcohol) and psychosocial risk factors (e.g., relating to social norms and general roles) have been proposed to account for the gender differences (61). These findings collectively suggest that effective treatment plans targeting problematic drug and alcohol use among patients with schizophrenia and related psychoses would need to consider such gender differences.

In line with studies that established the link between smoking and drug and alcohol use in patients with schizophrenia (62, 63) and also in the general population (64, 65), this study found that smoking behavior in patients with schizophrenia is significantly associated with problematic drug use. Smokers with nicotine dependence were five times more likely to have problematic drug use as compared to non-smokers, and four times more likely to have problematic drug use and/or alcohol use. These findings provided additional evidence of the close association between substance misuse and schizophrenia. Many hypotheses have been proposed to explain for this phenomenon, including common underlying genetic factors that predispose individuals to substance use behavior and schizophrenia, and also the self-medication hypothesis which suggests that patients use substance to cope with their psychiatric symptoms and the side-effects of medications (66). There also exist evidence for the gateway hypothesis which posits that smoking serves as a gateway substance to illicit drug use (67, 68). Given the high co-occurrence of problematic drug use and alcohol use along with nicotine dependence, it is recommended that routine assessments of nicotine use be conducted among patients with schizophrenia and related psychoses to closely evaluate for potential problems with drug use and alcohol use.

This study found that patients with greater symptoms severity were more likely to have problematic drug use and/or alcohol use. A study by Spencer et al. (69) similarly demonstrated symptoms severity as a significant predictor of cannabis or alcohol use among individuals with psychotic disorder, and this was mediated by their motives for using substances; worse symptoms resulted in stronger motives which in turn lead to stronger psychological dependence on substances. It may also be plausible that the problematic use of drug and alcohol contributed to greater symptoms severity. A study among older adults with schizophrenia found that higher levels of alcohol consumption was associated with higher levels of general psychopathology, and among them individuals with comorbid alcohol abuse had more severe negative symptoms and general psychopathology (70). Similarly, in a longitudinal study among persons with psychotic disorder, a reduction in the quantity of alcohol consumed predicted reduction in depressive symptoms, though not with anxiety nor psychotic symptoms (71). However, contradictory findings have been reported in the literature where some patients experienced symptom reduction (decreased anxiety and depression) following alcohol and cannabis use (72), which may in part be due to differences in the types of substance examined and study methodologies.

A significant negative association was observed between physical health domain of quality of life and problematic drug use and/or alcohol use. It may be plausible that patients who perceived poor health from the physical side effects of anti-psychotic medications used illicit drugs or alcohol to relieve such negative experiences (49, 73). It is equally plausible that poor health could be directly attributed to the consequences of misusing drugs (74). Prior studies have similarly reported poorer quality of life among patients with schizophrenia who were current substance users (75) and among those with current stimulant drug use (76). However, contrary to these findings, the study by Herman (77) found that inpatients with comorbid schizophrenia and substance abuse disorder reported better quality of life than those non-substance abusing inpatients. The author attributed this disparity to group differences in terms of lower levels of psychopathology and better executive functioning in the former group. Future studies may look into exploring these clinical variables in understanding the associations of problematic drug use in patients with schizophrenia and related psychoses.

There are a few limitations of this study to be considered when interpreting the results. Firstly, participant's self-reported data was used and thus the extent of problematic drug use could be underestimated due to social desirability bias. However, measures were taken to reduce such bias whereby participants were reassured regarding data confidentiality and were given the privacy to complete the questionnaire on their own. Next, the data collection period overlapped with the COVID-19 pandemic and the demand and supply of illicit drugs could have been affected due to movement restrictions across country borders. This might have influenced the availability and thus frequency of drug use among the study participants. The cross-sectional design of the study limits the ability to draw conclusions on the causal effects of associations examined. Lastly, as participants recruited in this study were outpatients, findings may not be generalizable to inpatient setting where clinical profile of patients differs (e.g., severity of psychotic symptoms, higher comorbidity with substance use) and is likely to influence the prevalence and associations established in this study.

Despite its limitations, this study in many ways contributed to extant literature on problematic drug use among patients with schizophrenia and related psychoses. Most studies have explored substance misuse in psychiatric population and relatively few have focused solely on non-alcohol misuse. Having a clearer differentiation and studying a distinct category of substance misuse allows researchers and healthcare professionals to disentangle correlates and effects of different substances. This study has examined both problematic drug use, and also problematic drug and/or alcohol use among patients with schizophrenia and related psychoses. Given the paucity of related research conducted in Singapore, results from this study can provide valuable insights into drug misuse in the local context and inform healthcare professionals when developing care plans tailored to patients' needs.

Data may be available upon reasonable request and subjected to approval by the institutional review board (IRB). This is a requirement mandated for this research study by our IRB and funders. Requests to access the dataset should be directed to the senior author, Mythily Subramaniam, mythily@imh.com.sg.

The studies involving human participants were reviewed and approved by National Healthcare Group Domain Specific Review Board. The patients/participants provided their written informed consent to participate in this study.

AJ, YM, SV, and MS were involved in the design and conception of the study. SC, AJ, JL, SS, ES, and LC were involved in participant recruitment and data collection. SC undertook the data analysis with assistance from JL. SC drafted the manuscript with supervision from AJ and MS. All authors contributed to the article and approved the submitted version.

The study was funded through the Singapore Ministry of Health's National Medical Research Council under the Centre Grant Programme (Grant No: NMRC/CG/M002/2017_IMH).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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