Umeå University's logo

Objective: This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised.

Methods: The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients' severity of depressed symptoms records were screened for MADRS-S scores.

Results: No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model.

Conclusion: Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.

Objective: This study aims to ascertain the effect of baseline IL-1Ra and IL-8 in the treatment response of patients with major depressive disorder (MDD) and to clarify the relationship between inflammation markers and depression.

Methods: We recruited 242 patients with a Beck Depression Inventory (BDI) score ≥ 17 referred to secondary care in Finland. The patients’ serum IL-1Ra and IL-8 concentrations were measured at baseline. Montgomery-Åsberg Depression Rating Scale (MADRS) tests and Alcohol Use Disorders Identification Tests (AUDIT) were administered at baseline and six weeks. The Antidepressant treatments varied: somewere started, others changed or continued their previous medication, and others had their doses adjusted. Patients started behavioral activation therapy. Linear regression was used with a relative MADRS score change during six weeks as the dependent variable and patient age, AUDIT score, BMI, daily number of cigarettes smoked, sex, and serum IL-1Ra and IL-8 concentrations as independent variables.

Results: Higher baseline serum IL-1Ra and IL-8 levels were associated with a smaller relative change in the MADRS-score within the first six weeks of treatment in linear regression analysis (p<0.001 and p=0.007, respectively). In further analysis comparing groups with ≤ 24 and > 24 MADRS score only the ≤ 24 MADRS score group showed a similar association.

Conclusion: Higher baseline IL-1Ra and IL-8 concentrations were associated with a lesser relative response to depression treatment, particularly in patients with mild depression. Results on IL-8 concur with earlier findings whereas the association between higher IL-1Ra serum concentrations reduced treatment response is a novel finding.

Background: Non-adherence and negative attitudes towards medication are major problems in treating psychotic disorders. Cytochrome P450 2D6 (CYP2D6) contributes to the metabolism of aripiprazole and risperidone. Variations in CYP2D6 activity may affect treatment response or adverse effects. The impact of these variations on adherence and medication attitudes is unclear.

Aims: This study investigates the relationships between CYP2D6 phenotype, self-reported adherence, adverse effects, and attitudes among aripiprazole and risperidone users.

Methods: This study analyzed data from the SUPER-Finland cohort of 10,474 adults with psychotic episodes, including 1,429 aripiprazole and 828 risperidone users. The Attitudes towards neuroleptic treatment (ANT) questionnaire assessed adherence and adverse effects in all patients, while medication-related attitudes were examined in a subgroup of 1,000 participants. Associations between CYP2D6 phenotypes and outcomes were analyzed using logistic regression and beta regression in aripiprazole and risperidone groups separately.

Results: Among risperidone users, we observed no association between CYP2D6 phenotypes and adherence, adverse effects, or attitudes. Similarly, no link was found between adherence and CYP2D6 phenotypes among aripiprazole users. However, aripiprazole users with the ultrarapid CYP2D6 phenotype had more adverse effects (OR = 1.71, 95 % CI 1.03–2.90, p = 0.041). Among aripiprazole users, CYP2D6 ultrarapid phenotype was associated with less favorable attitudes towards antipsychotic treatment (β = -0.48, p = 0.023).

Conclusions: We found preliminary evidence that the ultrarapid CYP2D6 phenotype is associated with increased adverse effects and negative attitudes towards antipsychotic medication among aripiprazole users. CYP2D6 phenotype did not influence adherence, adverse effects, or attitudes among risperidone users.

Objective: Associations between leptin (LEP) and leptin receptor (LEPR) gene polymorphisms and mood disorders have been found but not yet confirmed in multiple studies. The aim of our study was to study the associations between LEP and LEPR single nucleotide polymorphisms (SNPs) and treatment response of depression. Associations between leptin levels and depression severity were also investigated.

Methods: The data included 242 depressed patients in secondary psychiatric care. Symptoms of depression were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS). Previously found LEP and LEPR SNPs associated with depression and other mood disorders were studied. Furthermore, all available LEP and LEPR SNPs were clumped using proxy SNPs to represent gene areas in r2 > 0.2 linkage disequilibrium and their association with treatment response was analysed with logistic regression.

Results: Two proxy SNPs of LEPR gene, rs12564738 and rs12029311, were associated with MADRS response at 6 weeks (p adjusted = 0.024, p adjusted = 0.024). SNPs from previous studies were not associated with MADRS response, but LEPR rs12145690 from a previous study was strongly associated with rs12564738 (r2 = 0.94). The positive association between leptin levels and MADRS score at baseline after adjusting with age, sex, body mass index (BMI), Alcohol Use Disorders Identification Test score, and smoking was found (p = 0.011).

Conclusion: Our findings suggest that LEPR polymorphisms are associated with depression treatment response. We also found associations between leptin levels and depression independently of BMI. Further studies and meta-Analyses are needed to confirm the significance of found SNPs and the role of leptin in depression.

Recent genome wide association studies (GWAS) found associations between clozapine serum levels and single nucleotide polymorphisms (SNP) in intragenic region between cytochrome P450 1A1 (CYP1A1) and CYP1A2 and nuclear factor 1B (NFIB). The aim of this study was to perform another GWAS of polymorphisms associated with the serum levels of clozapine and norclozapine, their ratios, and to perform meta-analyses with two previous GWAS. Finnish clozapine patients (n = 170) with known smoking habits were genotyped. GWAS was performed with clozapine concentration/dose ratio (C/D), norclozapine C/D and clozapine/norclozapine-ratio as phenotypes, adjusting for age, sex and first four genetic principal components, and additionally for smoking and valproate use. The two other patient populations were from the British CLOZUK2 study (n = 2989) and Norwegian Diakonhjemmet Hospital study (n = 484). In the three population (n = 3643) meta-analyses the top SNP associated with the clozapine C/D ratio was rs2472297, located between the CYP1A1 and CYP1A2 genes. For the norclozapine C/D ratio, an association signal was found near uridine-5´-diphospho-glucunorosyltransferase (UGT) UGT2B10 gene. Additionally, rs3732218, an intron variant in the UGT1A family gene complex, was associated with norclozapine C/D. Lead SNP associated with the clozapine/norclozapine ratio was rs6827692, an intron variant near UGT2B7 gene. In the two population meta-analyses (n = 654) adjusting for smoking and valproate use, the UGT2B10 intron variant rs835309 was associated with the clozapine/norclozapine ratio. We suggest a UGT2B10 missense SNP rs61750900, in perfect linkage disequilibrium with UGT2B10 rs835309, as the probable causal variant. Our study confirms and extends the number of genetic variants affecting clozapine and norclozapine metabolism.

Background: Sleep problems are common in psychotic disorders and are associated with worse quality of life and disease prognosis. Genome-wide association studies (GWAS) have revealed genetic influences for schizophrenia and sleep, but polygenic scores (PGSs) for sleep traits have not been evaluated systematically in patients with psychotic disorders.

Methods: This study investigated the associations between PGSs for sleep traits (insomnia, PGSINS; sleep duration, PGSSD; short sleep duration, PGSSS; long sleep duration; PGSLS), diurnal preference (eveningness, PGSME), and schizophrenia (PGSSZ) with clinical features of psychotic disorders in the Finnish SUPER study comprising 8,232 patients with psychotic disorders. The measures included self-reported sleep and well-being, cognitive assessments, clozapine use, and functional outcomes. Using FinnGen data of 356,077 individuals, we analyzed the distributions of PGSs in psychotic and bipolar disorders and the general population.

Results: PGSINS associated with more sleep problems and worse well-being (e.g. worse health-related quality of life [β = -0.07, CI = -0.09, -0.05, p < .001]). High PGSSZ is associated with better sleep quality, worse clinical outcomes, and performance in cognitive tests (e.g. more errors in paired-associated learning [β = 0.07, CI = 0.04, 0.09, p < .001]). PGSINS was higher in affective psychotic and bipolar disorders, while PGSSD and PGSME were higher in schizophrenia as compared with individuals with no psychiatric disorders.

Conclusion: Genetic risks for sleep and diurnal preference vary between non-affective psychosis, affective psychosis, and the general population. The findings in this study emphasize the heterogeneity in genetic etiology of the objective features of disease severity and the more subjective measures related to well-being and self-reported measures of sleep.

Background: Common mental disorders (CMDs) are significant causes of work disability. Low socioeconomic status (SES) is a known risk factor for CMDs and work disability, one possible reason being poorer treatment adherence. We aimed to study the realization of pharmacological treatment and antidepressant adherence in patients with CMDs 3 years before and 3 years after being granted a disability pension (DP) and the role of SES in this. We also studied whether antidepressant adherence is associated with return to work (RTW) after a temporary DP.

Methods: Information on all persons granted a DP due to CMD between 2010 and 2012 in Finland (n = 12,388) was retrieved from national registers, which included medical, socioeconomic, and sociodemographic information of the subjects. We used the PRE2DUP method to estimate drug use periods and regression analyses to study associations between SES, taking medications, and RTW.

Results: Prevalence of taking antidepressants increased towards the DP grant and decreased thereafter, but 14.6% of subjects did not take antidepressants or antipsychotics at all during the study period. Of SES factors, only income was positively associated with antidepressant adherence, lasting over a year. Antidepressant adherence was not associated with RTW.

Conclusions: An alarming result was the absence of recommended medication in fewer than every seventh patient estimated to be disabled due to pharmacologically treatable psychiatric disorders. Contrary to expectations, SES had only a minor predictive role in antidepressant adherence in this patient group. Contrary to taking antidepressants, rehabilitation was associated with RTW. The results adduced the importance of CMD treatment optimization regardless of SES.

Background: Psychotic disorders, including schizophrenia (SZ), schizoaffective disorder (SZA), bipolar disorder (BD), psychotic depression (PD), and other nonaffective psychoses (ONAP), are associated with increased risk of suicidal acts. Few studies have compared suicidal act prevalence across psychotic disorders using both self-report and register data. The impact of hospitalization duration on subsequent suicidal acts is unclear.

Methods: We used data from the SUPER-Finland study, involving 7067 participants with register-based ICD-10 diagnoses of psychotic disorders (SZ, SZA, BD, PD, ONAP). Lifetime suicidal acts were identified through self-report and register-based records of intentional self-harm events requiring medical treatment. Associations between diagnostic categories and suicidal acts were assessed using logistic regression, adjusted for sex, duration of illness, socioeconomic status, childhood abuse, and substance use. Survival analysis was used to examine the impact of hospital stay length on postdischarge self-harm.

Results: Lifetime suicide attempts (39.1%) and register self-harm (19.3%) were prevalent. of those with self-reported suicide attempts, 40.5% also had register-based self-harm. Self-harm and suicide attempts were significantly more prevalent in SZA, BD, and PD compared to schizophrenia, with large differences between groups (24.1–46.4% for suicide attempts, 11.1–23.9% for self-harm). Adjusted odds of self-harm were higher for disorders with a mood component. Shorter hospitalizations were associated with an elevated hazard ratio for subsequent self-harm.

Conclusions: Prevalence of register-based self-harm and self-reported suicide attempts differ markedly. Suicidal acts are common in psychotic disorders, particularly in those with a mood component. Very short inpatient stays may not be adequate in these disorders.

BACKGROUND: This study evaluates the accuracy of different adherence assessment methods in first-episode psychosis (FEP), where long-term adherence is essential for relapse prevention. We compared self-reported adherence, pharmacy refill data, and therapeutic drug monitoring (TDM).

METHODS: In this one-year follow-up study, 78 FEP patients were assessed for adherence at two and twelve months using the Attitudes towards Neuroleptic Treatment (ANT) scale (self-report), pharmacy refill data (≥1 or ≥2 purchases in four months), and TDM as the reference standard. Statistical analyses included McNemar's test, sensitivity, specificity, Cohen's kappa, and Receiver Operating Characteristic (ROC) analysis.

RESULTS: At two months, adherence was 50.0% based on TDM, decreasing to 41.5% at twelve months. At two months, adherence rates were 73.3% for the ANT scale, 84.6% for at least one pharmacy refill, and 55.8% for at least two refills; by twelve months, these were 68.8%, 91.2%, and 52.9%, respectively. The ANT-attitude variable had weak predictive value for adherence (AUC: 0.607 at two months, 0.671 at twelve months). The ANT scale showed high sensitivity but low specificity, leading to adherence overestimation. Pharmacy refill adherence was more reliable, particularly when defined as at least two purchases within four months.

CONCLUSION: Medication non-adherence is common in FEP. Pharmacy refill data provided a more accurate adherence measure than self-report. Enhancing adherence requires psychoeducation, follow-up, and proactive monitoring. Measuring drug concentrations after hospital discharge could help detect early non-adherence and optimize treatment.

Background: Sleep problems are common and related to a worse quality of life in patients with schizophrenia. Almost all patients with schizophrenia use antipsychotic medications, which usually increase sleep. Still, the differences in subjective sleep outcomes between different antipsychotic medications are not entirely clear.

Methods: This study assessed 5466 patients with schizophrenia and is part of the nationwide Finnish SUPER study. We examined how the five most common antipsychotic medications (clozapine, olanzapine, quetiapine, aripiprazole, and risperidone) associate with questionnaire-based sleep problems in logistic regression analyses, including head-to-head analyses between different antipsychotic medications. The sleep problems were difficulties initiating sleep, early morning awakenings, fatigue, poor sleep quality, short (≤6 h) and long sleep duration (≥10 h).

Results: The average number of antipsychotic medications was 1.59 per patient. Clozapine was associated with long sleep duration (49.0 % of clozapine users vs 30.2 % of other patients, OR = 2.05, 95 % CI 1.83–2.30, p < .001). Olanzapine and risperidone were in head-to-head analyses associated with less sleep problems than patients using aripiprazole, quetiapine, or no antipsychotic medication. Aripiprazole and quetiapine were associated with more insomnia symptoms and poorer sleep quality. Patients without antipsychotic medications (N = 159) had poorer sleep quality than patients with antipsychotic use, and short sleep duration was common (21.5 % of patients using antipsychotics vs 7.8 % of patients using antipsychotics, OR = 2.97, 95 % CI 1.98–4.44, p < .001).

Conclusions: Prevalence of sleep problems is markedly related to the antipsychotic medication the patient uses. These findings underline the importance of considering and assessing sleep problems when treating schizophrenia patients with antipsychotics.