Movement Disorders and Mortality in Severely Mentally Ill Patients: The Curacao Extrapyramidal Syndromes Study XIV.

BACKGROUND AND HYPOTHESIS: There is a substantial gap in life expectancy between patients with severe mental illness (SMI) and the general population and it is important to understand which factors contribute to this difference. Research suggests an association between tardive dyskinesia (TD) and mortality; however, results are inconclusive. In addition, studies investigating associations between parkinsonism or akathisia and mortality are rare. We hypothesized that TD would be a risk factor for mortality in patients with SMI. STUDY DESIGN: We studied a cohort of 157 patients diagnosed predominantly with schizophrenia on the former Netherlands Antilles. TD, parkinsonism, and akathisia were assessed with rating scales on eight occasions over a period of 18 years. Twenty-four years after baseline, survival status and if applicable date of death were determined. Associations between movement disorders and survival were analyzed using Cox regression. Sex, age, antipsychotics, antidepressants and benzodiazepines at each measurement occasion were tested as covariates. STUDY RESULTS: Parkinsonism was a significant risk factor with an HR of 1.02 per point on the motor subscale of the Unified Parkinson's Disease Rating Scale (range 0-56). TD and akathisia were not significantly associated with mortality. CONCLUSIONS: Parkinsonism may be an important risk factor for mortality in SMI patients. This finding calls for more follow-up and intervention studies to confirm this finding and to explore whether treatment or prevention of parkinsonism can reduce excess mortality.

Prevalence of metabolic syndrome and its associated risk factors in an African-Caribbean population with severe mental illness.

This cross-sectional study aims to determine the prevalence of metabolic syndrome (MetS) in patients with severe mental illness (SMI) on a Caribbean island, Curaçao, using the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Among 350 patients (240 men and 110 women) with a mean age of 51.9 years (S.D.=13.5) MetS prevalence was 37.4%, significantly higher in female patients (63.6%) compared to male patients (25.4%). Increased waist circumference was present in 51.1%, low HDL in 50.6%, hypertension in 49.4%, hyperglycemia in 28.6% and 25.7% had hypertriglyceridemia. Except for hypertriglyceridemia, all criteria were more prevalent in female patients. Binary logistic regression analysis indicated that female gender, outpatient treatment setting and the absence of substance use disorder were all significant predictors for MetS. Compared to data from the general population obtained by the 2013 National Health Survey Curaçao, this study showed significantly higher prevalence of diabetes and hypertension in patients with SMI. Moreover, female patients had the highest prevalence of diabetes (28.2%), obesity (50.0%) and increased waist circumference (88.2%). This study demonstrates that African-Caribbean patients with SMI are at high-risk for MetS, especially female patients. Our data suggest to focus on modifiable lifestyle risk factors, as promoting physical activity and healthy dietary habits.

No Effect of Dose Adjustment to the CYP2D6 Genotype in Patients With Severe Mental Illness.

Background: The CYP2D6 enzyme is involved in the metabolism of numerous psychopharmacological drugs. Guidelines recommend how to adjust the dose of medication based on the CYP2D6 genotype. Aims: To evaluate the effect of dose adjustment to the CYP2D6 genotype and phenotype, in patients with severe mental illness (SMI) already receiving psychopharmacological treatment. Methods: A total of 269 psychiatric patients (on the island Curaçao) receiving antipsychotic treatment were genotyped for CYP2D6. Of these, 45 patients were included for dose adjustment according to the clinical guideline of the Royal Dutch Association for the Advancement of Pharmacy, i.e., 17 CYP2D6 poor metabolizers, 26 intermediate metabolizers, and 2 ultrarapid metabolizers. These 45 patients were matched for age, gender, and type of medication with a control group of 41 patients who were CYP2D6 extensive metabolizers (i.e., with a normal CYP2D6 function). At baseline and at 4 months after dose adjustment, subjective experience, psychopathology, extrapyramidal side-effects, quality of life, and global functioning were assessed in these two groups. Results: At baseline, there were no differences between the groups regarding the prescribed dosage of antipsychotics, the number of side-effects, psychiatric symptoms, global functioning, or quality of life. After dose adjustment, no significant improvement in these parameters was reported. Conclusion: In psychiatric patients with SMI already receiving antipsychotic treatment, dose adjustment to the CYP2D6 genotype or phenotype according to the guidelines showed no beneficial effect. This suggests that dose adjustment guidelines are currently not applicable for patients already using antipsychotics. ClinicalTrials.gov: Cost-effectiveness of CYP2D6 and CYP2C19 Genotyping in Psychiatric Patients in Curacao; Identifier: NCT02713672; https://clinicaltrials.gov/ct2/show/NCT02713672?term=CYP2D6&rank=5.

CYP2D6 and CYP2C19 genotyping in psychiatric patients on psychotropic medication in the former Dutch Antilles.

AIM: This study was aimed to asses the prevalence of CYP2D6 and CYP2C19 polymorphisms in psychiatric patients and in volunteers from Dutch caribbean origin. METHODS: In total, 435 individuals were genotyped for CYP2D6 and CYP2C19. Of these, 269 were psychiatric patients on psychotropic medication, living in Curaçao and 166 were volunteers from the Dutch Caribbean population. RESULTS: No differences in prevalence of alleles were found. CONCLUSION: Although prevalence of alleles appeared to be very different from African and Caucasian populations, the distribution into predicted phenotypes shows an equal distribution as in Caucasians.