In this nested case-control study, we examined the association between antipsychotic discontinuation and suicide in schizophrenia patients, using data from the NHIS-NSC. Suicide risk in those who had discontinued antipsychotics for 30 days was greater relative to that observed in current users. In addition, schizophrenia patients who received medical aid were at greater suicide risk relative to other subjects, after controlling for covariates. Crude odds ratios in schizophrenia patients with moderate mental disability, sleep disorders, mood disorders, stress-related disorders, or substance abuse were higher relative to those observed in other subjects. Moreover, multiple psychiatric admissions, use of multiple types of antipsychotic medication, emergency department visits during the preceding year, and poor continuity of care related to psychiatric disorders predicted suicide in patients using antipsychotic medication.
Our findings are consistent with those of other studies examining the relationship between antipsychotic discontinuation and outcome measures, such as relapse, suicide attempts, and suicide-related mortality, in other populations. A Finnish observational high-risk cohort study involving hospitalized schizophrenia patients with a history of at least one suicide attempt showed that current use of any antipsychotic medication was associated with lower suicide-related mortality relative to that observed for previous use.12 A large cohort study conducted by Walker et al. suggested that suicide incidence in schizophrenia patients who had discontinued clozapine was higher relative to that of those who currently used antipsychotics.20 A study involving schizophrenia patients aged 15–45 years, who had been prescribed olanzapine or risperidone for at least 90 days suggested that those who did not have prescriptions for antipsychotics filled on time were more likely to commit suicide relative to those who had prescriptions filled promptly.21 A five-year observational study involving patients with first-episode psychosis indicated that ceasing antipsychotic medication increased first-relapse rate almost fivefold, and the cumulative rates second- and third-relapse rate, relative to those observed with continued treatment.14 These findings indicated that cessation of drug therapy increased the incidence of repeated relapse, which could increase suicide risk.
There could be an explanation for the finding that suicide risk increased in schizophrenia patients who discontinued antipsychotic medication. One possible explanation for our findings is that schizophrenia patients acknowledged their psychosis-related conditions following treatment during the acute phase of psychotic illness. They might have experienced simultaneous depressive symptoms, which could have increased the risk of suicide during the high-risk period. Another explanation could be that the results occurred because of schizophrenia patients’ characteristics or the severity of mental health disorders, such as depression, stress, and substance abuse, rather than a direct causal effect of antipsychotics; however, irrespective of the reason for the increased risk, these patients require particularly close monitoring during treatment and shortly after cessation of antipsychotic medication. Furthermore, poor patients in particular received limited social support from others such as friends, family, or colleagues.22 Because of this lack of support, these patients could be vulnerable when using medication and fail to take it on time.
This study has clinical and political implications. Our results showed that suicide risk increased within the first 30 days of antipsychotic discontinuation; therefore, physicians and family members should pay greater attention to the need for continuous monitoring of schizophrenia patients after planned withdrawal of antipsychotic medication or when unplanned or sudden withdrawal is indicated. Furthermore, a specific methodology should be followed for suicide prevention in schizophrenia patients. Regular assessment and evaluation of suicide risk is necessary in clinical practice. In addition, development of a plan for suicide prevention during hospitalization and care should include deep observation. Following discharge, it is advisable to establish a concrete plan for managing unexpected behavior. In particular, patients recently discharged from hospital or admitted to hospital repeatedly should be observed, to ensure that in times of personal crisis, involving significant environmental changes, high levels of stress, and severe depression, schizophrenia patients or their family members arrange frequent outpatient visits. In addition, relevant risk factors, such as social isolation, substance abuse, and depression, should be removed to prevent suicide.
The strengths of this study were the population-based design and the acquisition of data from the NHIS-NSC, which is representative of the entire country. In addition, follow up was robust because of our use of unique personal identification numbers for Korean residents, which were linked to the national mortality database. Recall bias was not an issue, as we used data from prescriptions for antipsychotic medication, which were recorded prior to the occurrence of the outcomes. Despite these strengths, several limitations should be considered. First, as with other studies that used administrative claims data, there were some potentially key covariates that we were unable to identify, such as previous family suicide attempts, family structure, marital status, employment status, and previous suicide attempts. In addition, patients’ histories of self-harm, including drug overdose, poisoning, self-laceration, and non-fatal suicide attempts prior to entry into the study, were unknown. Second, there are some issues to consider when using administrative claims data. Reliance on ICD-10 codes for comorbidity could lead to misclassification due to activities such as miscoding behavior. Third, the study could have been subject to certain inherent limitations caused by the use of administrative data, which lack information on schizophrenia subtypes. Fourth, as the data source was a claim dataset, actual medication adherence rates were not reflected in the data.