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Depression and Physical Symptoms Linked to Adverse Outcomes in Schizophrenia Patients in Japan

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A recent study has identified key risk factors associated with death, hospitalisation, resignation, and sick leave among patients with schizophrenia in Japan. In order to examine the effects of various factors on crucial clinical outcomes in schizophrenia patients, Ken Inada and colleagues from Kitasato University School of Medicine used a sizable claims database. The findings, published in the journal BMC Psychiatry, highlight the significant role of depression and physical symptoms in exacerbating the condition and complicating treatment efforts.

The researchers conducted a nested case-control study using data from a Japanese health insurance claims database. The study included patients diagnosed with schizophrenia between January 2005 and January 2022. To ensure accuracy, the study excluded patients with other psychiatric or neurodevelopmental disorders, such as bipolar affective disorder or pervasive developmental disorders.

Four cohorts were established to evaluate different outcomes: death, hospitalisation, resignation, and sick leave. Each case was matched with up to four controls based on age, sex, index year, and enrolment status (employee or dependent family member). Potential risk factors were identified through prescriptions or diagnoses within three months prior to or in the month of the event. The associations between these risk factors and each outcome were analysed using multivariable conditional logistic regression.

The study’s results revealed that depression is a significant risk factor for death, hospitalisation, and sick leave from work among patients with schizophrenia. The odds ratio (OR) for death was 1.92, for hospitalisation it was 1.22, and for sick leave it was 1.46, indicating a strong correlation between depressive symptoms and adverse outcomes. Additionally, physical symptoms such as constipation and extrapyramidal symptoms (EPS) were found to increase the risk of these adverse outcomes.

For the outcome of death, the study identified several risk factors besides depression, including a history of hospitalisation and a higher Charlson Comorbidity Index (CCI) score. Patients prescribed laxatives also had a higher risk of death. Interestingly, prescriptions for antidyslipidemics were associated with a reduced risk of death, suggesting a protective effect that warrants further investigation.

Hospitalisation was another critical outcome where depression played a significant role. Patients with schizophrenia who also suffered from depression were more likely to be hospitalised. Other risk factors included prescriptions for hypnotics, laxatives, and anticholinergics. These medications, often used to manage the side effects of antipsychotic drugs, indicate that managing physical symptoms is crucial for preventing hospitalisations .

While depression was not directly associated with resignation, prescriptions for hypnotics and anticholinergics were identified as risk factors. This suggests that sleep disturbances and EPS, common side effects of antipsychotic medication, may lead to job resignations among patients with schizophrenia.

Depression emerged as a significant risk factor for sick leave from work. Patients with higher CCI scores and those prescribed hypnotics, laxatives, and antidiabetics were also more likely to take sick leave. The study found that a substantial proportion of patients with schizophrenia on sick leave eventually returned to work, indicating the potential for recovery and the importance of managing depressive symptoms and physical comorbidities effectively.

The findings underscore the necessity of addressing both psychiatric and physical symptoms in the treatment of schizophrenia. Healthcare professionals should monitor patients for signs of depression and physical complications, such as constipation and EPS, to improve clinical outcomes. By identifying and managing these risk factors, it may be possible to reduce the rates of death, hospitalisation, resignation, and sick leave among patients with schizophrenia.

The study has some limitations, including its reliance on claims data, which may not capture all relevant factors affecting outcomes. The definitions of some outcomes, such as resignation, were based on withdrawal from health insurance, which may not accurately reflect employment status changes. Additionally, the study did not account for social and lifestyle factors that could influence outcomes, such as physical activity, diet, and support services.

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