Previous studies have shown the high prevalence and risk of substance use among individuals with psychotic disorders [2, 4, 16]. However, most previous studies on alcohol use in patients with schizophrenia had small sample size, a cross-sectional design, or a short observation period. To the best of our knowledge, this is the first nationwide population study on the effect of alcohol use on clinical outcomes of schizophrenia. The HIRA claim database was used to select the incident cohort of schizophrenia, from which the comorbid AUD group was selected as the case group. With matched controls, between- and within-group analyses were conducted to compare the rates of psychiatric admissions and ER visits and MPR. There were significantly higher rates of psychiatric admissions and ER visits and lower MPR in the comorbid AUD group compared to the control group before and after the diagnosis AUD. The decrease in the rates of psychiatric admissions and ER visits after the diagnosis of AUD was significantly greater in the comorbid AUD group compared to the control group. After the diagnosis of AUD, MPR decreased in the control group but increased in the comorbid AUD group.
The prevalence of AUD among patients with schizophrenia was lower in this study compared to previous studies although the study population was sufficiently large. Several previous studies showed that individuals with psychotic disorders had a higher prevalence of alcohol abuse compared to the general population [2, 16]. A meta-analysis of 60 studies [6] worldwide showed a median prevalence of current AUD in schizophrenia of 9%. Another meta-analysis reported a lifetime prevalence of AUD in schizophrenia of 24.3% [1]. The discrepancy from previous studies may be attributed to the use of claim data from clinical practice in this study. Considering that clinicians focus on chief complaints, which are mainly auditory hallucinations or delusions, of patients with a psychotic disorder, comorbid psychiatric diagnoses, such as AUD and substance use disorder, could be disregarded in clinical practice because of the very low prevalence of illegal drug abuse and dependence in South Korea [17]. Moreover, since the incident cohort of our study was composed of first episode schizophrenia patients, a mean observation period of 5.1 years in this study might not be sufficiently long to determine the lifetime prevalence of AUD among patients with schizophrenia.
The onset age and sex ratio differed between the comorbid AUD (n = 1,598) and the patients with only schizophrenia (n = 62,844). The mean onset age of schizophrenia was significantly higher in the comorbid AUD group (44.3 ± 12.2 years) than in the patients with only schizophrenia (40.8 ± 12.7 years). The mean observation period was longer in the comorbid AUD group (5.1 ± 2.5 years) than in the patients with only schizophrenia (4.0 ± 2.8 years), consistent with previous studies. This might imply the distinct characteristic of the schizophrenia with comorbid AUD. Similar findings were also found in previous studies. An Indian comparative study showed that patients with schizophrenia with comorbid AUD were older at the onset of schizophrenia compared to the controls [18]. A Swedish study reported a late onset age of schizophrenia and longer illness duration in patients with a history of substance abuse although without statistical significance [19]. The late onset age of schizophrenia and shorter duration of illness were found in a survey conducted in 1994 in South Westminster, including 271 patients with schizophrenia with lifetime prevalence of alcohol abuse of 22.1% [20]. The larger proportion of men in the comorbid AUD group in this study was consistent with results of some previous studies on AUD in schizophrenia [4, 18, 19, 21].
Regarding antipsychotics use, to date, there has been no well-designed comparative study between patients with schizophrenia with and without comorbid AUD. In our study, there was a shorter mean total duration of antipsychotics treatment and higher mean number of prescribed antipsychotics in the comorbid AUD group compared to the control group. The number of treatment discontinuations was also higher in the current study. These results suggest that antipsychotic treatment of patients with schizophrenia with comorbid AUD would be complicated and challenging. Patients with schizophrenia with comorbid AUD could show lower drug compliance or need more antipsychotics to control psychiatric symptoms despite drug compliance.
A prospective community study reported the association of alcohol use in schizophrenia with a higher rate of rehospitalization. Drake et al. examined the pattern of alcohol use among 115 patients with schizophrenia. According to that study, alcohol use was associated with medication noncompliance, increased symptomatology, and a higher rate of rehospitalization. Even minimal alcohol use predicted rehospitalization [14], consistent with our study. In our study, all outcome variables were worse in the comorbid AUD group compared to the control group, regardless of the time point. The results indicated that in patients with schizophrenia with comorbid AUD, poorer treatment compliance and clinical outcomes before the diagnosis of AUD improved after the diagnosis of AUD. The improvement after the diagnosis of AUD might be attributable to clinicians reconsidering other factors influencing clinical outcomes, such as family education, a psychiatric history, and engagement in psychiatric care in the community when making the comorbid diagnosis of AUD. Clinical outcomes in the comorbid AUD group were worse even before the diagnosis of AUD probably because schizophrenia with comorbid AUD is a distinct subtype of schizophrenia; however, further research is required to achieve confirmative evidence.
To our knowledge, this was the first nationwide population-based study on the effect of comorbidity of AUD on clinical outcomes of schizophrenia. Unlike previous studies, which had mostly been performed in the 1990s, our study had a large sample size and utilized various types of variables as the marker of clinical outcomes. This could be strengths of our study. In addition to between-group comparisons, we performed within-group comparisons to observe the time-varying patterns of dependent variables. This comparative design was not found in previous studies on AUD or schizophrenia.
This study had a few limitations. First, it was based on the claim data from clinical practice, not created for research purposes, introducing a possibility of disregarding comorbid psychiatric diagnoses. Thus, the prevalence of AUD among patients with schizophrenia was lower in this study than in previous studies. This may limit the generalizability of our results. Second, patients with comorbid AUD in this study might not represent the entire population of interest. The comorbid AUD group could comprise severe cases of AUD, considering the high prevalence of alcohol-related disorders in South Korea [22, 23], suggesting that mild alcohol abuse could be disregarded in clinical practice.