The COVID-19 pandemic and the use of benzodiazepines and benzodiazepine-related drugs in Estonia: an interrupted time-series analysis.

BACKGROUND: The COVID-19 pandemic has posed challenges that worsened people's mental health. We explored the impact of the COVID-19 pandemic on the mental well-being of the population, as indicated by the prevalence rates of benzodiazepine and benzodiazepine-related drug (BDZ) use. METHODS: This population-based, time-series analysis included all prescriptions of BDZs dispensed in Estonia between 2012 and 2021. The monthly prevalence rates of BDZ use were calculated. Autoregressive integrated moving average models with pulse and slope intervention functions tested for temporary and long-term changes in monthly prevalence rates after the onset of the COVID-19 pandemic. RESULTS: Throughout the 10-year study period, a total of 5,528,911 BDZ prescriptions were dispensed to 397,436 individuals. A significant temporary increase in the overall prevalence rate of BDZ use in March 2020 (2.698 users per 1000, 95% CI 1.408-3.988) was observed, but there was no statistically significant long-term change. This temporary increase affected all the examined subgroups, except for new users, individuals aged 15-29 years, and prescribing specialists other than general practitioners and psychiatrists. The long-term increase in BDZ use was confined to females aged 15-29 years (0.056 users per 1000 per month, 95% CI 0.033-0.079), while no significant change was observed among males of the same age (0.009 users per 1000 per month, 95% CI - 0.017 to 0.035). Among females aged 15-29 years, a significant long-term increase in BDZ use was observed for anxiety disorders (0.017 users per 1000 per month, 95% CI 0.010-0.023), depressive disorders (0.021 users per 1000 per month, 95% CI 0.012-0.030), and other mental and behavioral disorders (0.020 users per 1000 per month, 95% CI 0.010-0.030), but not for sleep disorders (- 0.008 users per 1000 per month, 95% CI - 0.018-0.002). CONCLUSION: The COVID-19 pandemic led to a short-term increase in BDZ use immediately after the pandemic was declared. In the long term, young females experienced a sustained increase in BDZ use. The prolonged effect on girls and young women suggests their greater vulnerability. These results underscore the need to effectively address the long-term effects of the pandemic among youth.

Subjective Well-Being Under Neuroleptics Scale short form (SWN-K): reliability and validity in an Estonian speaking sample.

BACKGROUND: The Subjective Well-Being Under Neuroleptic Treatment Scale short form (SWN-K) is a self-rating scale developed to measure mentally ill patients' well-being under the antipsychotic drug treatment. This paper reports on adaptation and psychometric properties of the instrument in an Estonian psychiatric sample. METHODS: In a naturalistic study design, 124 inpatients or outpatients suffering from the first psychotic episode or chronic psychotic illness completed the translated SWN-K instrument. Item content analysis, internal consistency analysis, exploratory principal components analysis, and confirmatory factor analysis were used to construct the Estonian version of the SWN-K (SWN-K-E). Additionally, socio-demographic and clinical data, observer-rated psychopathology, medication side effects, daily antipsychotic drug dosages, and general functioning were assessed at two time points, at baseline and after a 29-week period; the associations of the SWN-K-E scores with these variables were explored. RESULTS: After having selected 20 items for the Estonian adaptation, the internal consistency of the total SWN-K-E was 0.93 and the subscale consistencies ranged from 0.70 to 0.80. Good test-retest reliabilities were observed for the adapted scale scores, with the correlation of the total score over about 6 months being r = 0.70. Confirmatory factor analysis replicated the presence of a higher-order factor (general well-being) and five first-order factors (mental functioning, physical functioning, social integration, emotional regulation, and self-control); the model fitted the data well. The results indicated a moderate-high correlations r = 0.54 between the SWN-K-E total score and the evaluation how satisfied patients were with their lives in generally. No significant correlations were found between the overall subjective well-being score and age, severity of the psychopathology, drug adverse effects, or prescribed drug dosage. CONCLUSION: Taken together, the results demonstrated that the Estonian version of the SWN-K is a reliable and valid instrument with psychometric properties similar to the original English version. The potential uses of the scale in both research and clinical settings are considered.

Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.

RATIONALE: Perphenazine, a classical antipsychotic drug, has the potential to induce extrapyramidal side effects (EPS). Dopaminergic and serotonergic pathways are involved in the therapeutic and adverse effects of the drug. OBJECTIVES: To evaluate the impact of polymorphisms in the dopamine D(2) and D(3) and serotonin 2A and 2C receptor genes (DRD2, DRD3, HTR2A, and HTR2C) on short-term effects of perphenazine monotherapy in schizophrenic patients. MATERIALS AND METHODS: Forty-seven Estonian inpatients were evaluated before and after 4-6 weeks of treatment by Simpson-Angus rating scale, Barnes scale, and Positive and Negative Symptom Scale. Genotyping was performed for common DRD2, DRD3, HTR2A, and HTR2C gene polymorphisms, previously reported to influence receptor expression and/or function. RESULTS: Most of the patients (n = 37) responded to the treatment and no significant association was observed between the polymorphisms and antipsychotic response. The 102C allele of HTR2A and the -697C and 23Ser alleles of HTR2C were more frequent among patients with EPS (n = 25) compared to patients without EPS (n = 22) (p = 0.02, 0.01, and 0.02, respectively). The difference between patients with and without EPS in variant allele frequencies remained significant after multiple model analyses including age, gender, and duration of antipsychotic treatment as covariants. There was no significant association between EPS occurrence and polymorphisms in the DRD2 and DRD3 genes. CONCLUSIONS: An association was observed between polymorphisms in HTR2A and HTR2C genes and occurrence of acute EPS in schizophrenic patients treated with perphenazine monotherapy. Larger study populations are needed to confirm our findings.

Case histories illustrating the utility of sertindole in clinical practice.

Many conventional and atypical antipsychotic agents are available for the treatment of schizophrenia. Matching individual patients to the medication that suits them best is often a matter of trial and error. Controlled clinical trials and extensive post-marketing research have shown that the atypical antipsychotic agent sertindole is a broadly efficacious and safe choice for the treatment of schizophrenia. Individual case reports emerging from the ongoing sertindole post-marketing clinical programme illustrate how, under normal conditions of clinical practice, a switch to sertindole can benefit patients who have, for various reasons, previously not been satisfactorily managed on conventional or other atypical antipsychotic agents. Such case reports have shown that a switch to sertindole has the potential to provide greater relief from positive, negative and affective symptoms than has been achieved with conventional and certain other atypical agents. Cognitive dysfunction evident during therapy with conventional antipsychotic agents has also been seen to improve in individuals switched to sertindole. These improvements have occurred without evidence of extrapyramidal symptoms or other poorly tolerated adverse events. After switching to sertindole, the five patients described in this report complied well with therapy, were generally able to perform daily activities more efficiently, and also had improved personal relationships and vocational potential, all of which contributed to improvements in their overall quality of life.

Maintenance therapy with zuclopenthixol decanoate: associations between plasma concentrations, neurological side effects and CYP2D6 genotype.

RATIONALE: Several antipsychotic drugs are metabolised by the polymorphic cytochrome P(450) CYP2D6. The impact of the polymorphism on the plasma levels and the occurrence of side effects have not been clearly established. OBJECTIVE: To investigate the impact of the CYP2D6 polymorphism on the steady-state plasma concentrations of zuclopenthixol and the occurrence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD) during treatment with zuclopenthixol-decanoate. METHODS: Fifty-two clinically stable schizophrenic outpatients on monotherapy with zuclopenthixol-decanoate (100-400 mg/4 weeks) were genotyped for the CYP2D6 variants CYP2D6*3 and CYP2D6*4. Steady-state plasma levels of zuclopenthixol were analysed using high-performance liquid chromatography. Assessments of EPS, TD and psychopathology were performed twice with an 8-week interval using the extrapyramidal symptoms rating scale, the abnormal involuntary movement scale and the brief psychiatric rating scale. RESULTS: Thirty-five patients were homozygous extensive metabolisers (EMs), 13 were heterozygous EMs and 4 were poor metabolisers (PMs). While there were no significant genotype-related differences in the doses of zuclopenthixol decanoate, PMs as well as heterozygous EMs had significantly higher steady-state plasma levels of zuclopenthixol than homozygous EMs (median 9.5 nmol/l; 8.2 nmol/l and 5.9 nmol/l, respectively, P<0.05). The median dose-corrected plasma concentrations were 0.029, 0.038 and 0.048 nmol.l(-1).mg(-1) in homozygous EMs, heterozygous EMs and PMs, respectively, with statistically significant differences between homozygous EMs and heterozygous EMs ( P=0.014) and homozygous EMs and PMs ( P=0.03). Patients with neurological side effects were significantly older than patients without ( P=0.02 in case of parkinsonism and P=0.04 in case of TD). Mutant CYP2D6*3 and *4 alleles tended to occur more frequently in patients with neurological side effects. An odds ratio (OR) of 2.3 (95% confidence interval 0.7-6.9) for development of parkinsonism and an OR of 1.7 (95% confidence interval 0.5-4.9) for TD was calculated in an individual with at least one mutated allele. However, the ORs were not statistically significant. CONCLUSIONS: The higher zuclopenthixol steady-state plasma concentrations in heterozygous EM and PM schizophrenic patients receiving monotherapy with zuclopenthixol-decanoate than in homozygous EMs indicates a significant role of CYP2D6 in the systemic elimination of zuclopenthixol. The tendencies for patients carrying at least one mutated CYP2D6 gene to have an increased risk of parkinsonism and TD are in accordance with previous studies. Age was a significant risk factor for neurological side effects.