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Number of antidepressant users, events (hospitalizations due to psychosis), and person-years per exposure among antidepressant users.
Source publication
The aim of this study was to investigate the real-world effectiveness of antidepressant use in persons with schizophrenia. The register-based study cohort included all 61,889 persons treated in inpatient care due to schizophrenia during 1972–2014 in Finland. The main outcome was hospitalization due to psychosis and secondary outcomes included non-p...
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Purpose
This study aims to examine the prevalence and CAC distribution and to evaluate the association of each CAC classifications with major adverse cardiovascular event (MACE).
Method
This study was a retrospective observational cohort. We included patient aged above 35 years who underwent CAC testing. The absolute and age-sex specific percentil...
It is currently unknown whether the complexity and variability of cardiac dynamics predicts future depression and whether within-subject change herein precedes the recurrence of depression. We tested this in an innovative repeated single-subject study in individuals who had a history of depression and were tapering their antidepressants. In 50 indi...
Citations
... Nevertheless, antidepressants may increase the probable benefits in many cases [72]. Adding antidepressants to schizophrenia patients was linked to a lower likelihood of hospitalization for psychosis and a lower mortality rate among schizophrenia patients, according to a recent real-world, long-term cohort study conducted in Finland [73]. ...
Inappropriate prescription patterns and polypharmacy are critical challenges facing the optimal management of schizophrenia patients, especially in regard to patient safety. Background/Objectives: The purpose of this study was to examine the relationship between patient safety and the existence of incorrect prescription patterns and/or polypharmacy in the medications prescribed to individuals with schizophrenia. This issue is addressed in a broad context, highlighting the purpose of this study. Methods: A cross-sectional study was adopted, involving a prospective analysis of the prescriptions of schizophrenia patients receiving treatment. Prescription patterns deemed inappropriate were evaluated based on evidence-based guidelines. Antipsychotic maximum allowable daily doses were calculated using the British National Formulary Maximum Daily Dose (BNFmax), an online tool. Patient safety outcomes were assessed using the Glasgow Antipsychotic Side-effect Scale (GASS). Results: A total of 198 patients diagnosed with schizophrenia and receiving treatment consented to participate in the GASS survey. A total of 116 (58.6%) males participated. The mean age of patients was 40.1 (±12.7). Thirty-one (66.2%) reported mild side effects, while 67 (33.8%) reported moderate side effects. Polypharmacy was detected in 103 (52%) patients’ prescriptions. The correlation between GASS and BNFmax was positive and statistically significant (p < 0.001). The elevation in GASS score was associated with polypharmacy prescriptions (OR 3.21; 95% CI 1.64–6.29), the presence of first-generation antipsychotics (FGAP) (OR 2.79; 95% CI 0.236–5.951), any combination of antipsychotics containing haloperidol (OR 3.22; 95% CI 1.11–9.32), and olanzapine (OR 3.46; 95% CI 1.36–8.79). Conclusions: The safety of patients with schizophrenia has been proven to be impacted by the improper use of psychotropic drugs. Following evidence-based guidelines is a cornerstone to ensuring optimal, effective, and safe patient treatment plans.
... However, it can be useful in specific situations, depending on the presentation of symptoms or the severity of side effects. Concomitant prescription of drugs for depression such as SERTs is common to treat negative symptoms, although the reported effect is often small (Helfer et al., 2016;Galderisi et al., 2021;Lako et al., 2012;Mao and Zhang, 2015;Puranen et al., 2023;Singh et al., 2010;Terevnikov et al., 2015). 'Antipsychotic polypharmacy', when two or more drugs for psychosis are prescribed, may even be more effective than monotherapy without increased risk of side effects (Lähteenvuo and Tiihonen, 2021;Taipale et al., 2023;Tiihonen et al., 2019). ...
Background
Pharmacogenetics is considered a promising avenue for improving treatment outcomes, yet evidence arguing for the use of pharmacogenetics in the treatment of psychotic disorders is mixed and clinical usefulness is under debate. Many patients with psychosis use multiple medications, which can alter the metabolic capacity of CYP enzymes, a process called phenoconversion. In clinical studies, treatment outcomes of drugs for psychosis management may have been influenced by phenoconversion.
Aim
Here we evaluate the impact and predictive value of CYP2D6 phenoconversion in patients with psychotic disorders under pharmacological treatment.
Method
Phenoconversion-corrected phenotype was determined by accounting for inhibitor strength. Phenoconversion-corrected and genotype-predicted phenotypes were compared in association with side effects, subjective well-being and symptom severity.
Results
Phenoconversion led to a large increase in poor metabolizers (PMs; 17–82, 16% of sample), due to concomitant use of the serotonin reuptake inhibitors fluoxetine and paroxetine. Neither CYP2D6-predicted nor phenoconversion-corrected phenotype was robustly associated with outcome measures. Risperidone, however, was most affected by the CYP2D6 genotype.
Conclusion
Polypharmacy and phenoconversion were prevalent and accounted for a significant increase in PMs. CYP2D6 may play a limited role in side effects, symptoms and well-being measures. However, due to the high frequency of occurrence, phenoconversion should be considered in future clinical trials.
The human brain is an energetically costly organ, consuming 20–25% of all biochemical energy produced in the body, despite comprising only 2–3% of total body mass. Most energy in the brain is consumed to support synaptic neurotransmission, which is the primary means of neuron-to-neuron communication between. This energy is in the form of adenosine triphosphate (ATP), and within neural cells, nearly all ATP is produced by mitochondria via the process of oxidative phosphorylation (OXPHOS). To ensure that ATP is readily available, mitochondria are trafficked to areas of greater energy use, such as neuronal synapses. The balance between energetic supply and synaptic communication is essential for proper brain functioning. This chapter begins with a brief introduction to key features of neuronal synapses and mitochondrial energy production in the cerebral cortex. Next, the tight and bidirectional coupling of neuronal synaptic activity and mitochondrial OXPHOS is examined from functional, ultrastructural, and molecular perspectives. The effects of brain and non-brain organ system perturbations on synaptic-mitochondrial coupling are then examined within the context of (1) primary brain disorders, such as schizophrenia and bipolar disorder, and (2) primary peripheral disorders, such as diabetes and obesity. Finally, a discussion of potential intervention strategies that may restore neural communication and mitochondrial bioenergetics, within the framework of the brain-body connection, is provided.
Psychiatric disorders are a common source of disease morbidity with high rates of refractoriness to first‐line treatments. As such, many have investigated the utility of neurosurgical interventions for treatment‐resistant forms of these conditions. More recently among these, functional neurosurgical techniques using high‐ and low‐intensity focused ultrasound (FUS) have emerged as promising options in this arena, largely due to their minimally‐invasive nature and encouraging early safety and efficacy data. Existing clinical data have thus far demonstrated FUS to be a potentially useful intervention for treatment‐refractory forms of obsessive–compulsive disorder, major depressive disorder, various anxiety disorders, substance‐use disorder, and schizophrenia. This report presents a comprehensive review of existing clinical trial data, summarizing key findings, study specifications, and providing critical analysis. In addition to giving the most complete summary of modern clinical research on this topic to date, this report characterizes the current state of this body of literature using bibliometric analysis, succinctly highlighting the most investigated topics and the most promising areas of modern investigation. Based on our review of the literature, current work on this topic is highly heterogeneous with regard to specific treatment protocols and anatomic targets for FUS – targeting multiple nuclei at a wide variety of intensities. We recommend that future studies aim to clarify more precise therapeutic targets and specific treatment protocols which optimize the efficacy of these techniques.
Importance
The use of antipsychotics, antidepressants, and benzodiazepines may influence the risk of mortality in people with schizophrenia. However, many observational studies have not accounted for immortal time bias (ITB), which occurs when there is a period during which patients in the exposed group are necessarily alive and misclassified as exposed (the period between start of follow-up and initiation of drug). Ignoring ITB may lead to misinterpretation of the association between these drugs and mortality.
Objectives
To examine whether the cumulative dose of antipsychotics, antidepressants, and benzodiazepines is associated with mortality risk in patients with schizophrenia and discuss the potential impacts of ignoring ITB.
Design, Setting, and Participants
This cohort study used administrative data from Québec, Canada, including patients aged 17 to 64 years diagnosed with schizophrenia between January 1, 2002, and December 31, 2012. Data analysis was performed from June 22, 2022, to September 30, 2024.
Main Outcomes and Measures
The primary outcome was all-cause mortality, with follow-up from January 1, 2013, to December 31, 2017, or until death. Mortality risk was assessed for low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines. Cox proportional hazards regression models with time-fixed exposure (not controlling for ITB) and time-dependent exposure (controlling for ITB) were performed.
Results
The cohort included 32 240 patients (mean [SD] age, 46.1 [11.6] years; 19 776 [61.3%] men), of whom 1941 (6.0%) died during follow-up. No dose-response association was found for antipsychotics with mortality using the time-fixed method. However, high-dose antipsychotic use was associated with increased mortality after correcting for ITB (adjusted hazard ratio [AHR], 1.28; 95% CI, 1.07-1.55; P = .008). Antidepressants showed a reduced mortality risk using the time-fixed method, but only at high doses when correcting for ITB (AHR, 0.86; 95% CI, 0.74-1.00; P = .047). Benzodiazepines were associated with increased mortality risk regardless of the method.
Conclusions and Relevance
The findings of this study do not dispute the known efficacy of antipsychotics in schizophrenia, but they call into question the magnitude of long-term mortality benefits.
Excess mortality observed in people with schizophrenia may persist in later life. The specific causes of increased mortality observed in older adults with schizophrenia and the potential influence of psychotropic medications remain partly unknown. We compared 5-year mortality and its causes of older adults with schizophrenia to bipolar disorder (BD) or major depressive disorder (MDD). We used a 5-year prospective cohort, including 564 older inpatients and outpatients with schizophrenia, BD or MDD (mean age: 67.9 years, SD = 7.2 years). Causes of death were cardiovascular disorder (CVD) mortality, non-CVD disease-related mortality (e.g., infections), suicide, and unintentional injury. The primary analysis was a multivariable logistic model with inverse probability weighting (IPW) to reduce the effects of confounders, including sociodemographic factors, duration and severity of the disorder, and psychiatric and non-psychiatric comorbidity. Five-year all-cause mortality among older participants with schizophrenia and with BD or MDD were 29.4% (n = 89) and 18.4% (n = 45), respectively. Following adjustments, schizophrenia compared to MDD or BD was significantly associated with increased all-cause mortality (AOR = 1.35; 95%CI = 1.04–1.76; p = 0.024) and cardiovascular mortality (AOR = 1.50; 95%CI = 1.13–1.99; p = 0.005). These associations were significantly reduced among patients taking antidepressants [interaction odds ratio (IOR) = 0.42; 95%CI = 0.22–0.79; p = 0.008 and IOR = 0.39: 95%CI = 0.16–0.94; p = 0.035, respectively]. Schizophrenia was associated with higher mortality compared to BD or MDD. Cardiovascular diseases explained most of this excess mortality. Exploratory analyses suggested that psychotropic medications did not influence this excess mortality, except for antidepressants, which were associated with significantly reduced between-group difference in all-cause and cardiovascular mortality.
