Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice.

BACKGROUND AND PURPOSE: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. METHODS: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. RESULTS: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. CONCLUSIONS: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

Validation of the predictive value of BDNF -87 methylation for antidepressant treatment success in severely depressed patients-a randomized rater-blinded trial.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE). METHODS: The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study's main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE. ETHICS AND DISSEMINATION: The trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals. TRIAL REGISTRATION: German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.

Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation - Clinical and safety results.

INTRODUCTION: We investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. MATERIAL AND METHODS: Patients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. For treatment group comparisons, we used ANOVA with pairwise least squares mean difference tests in a mixed model repeated measures analysis. RESULTS: Twenty-seven patients completed the double-blind protocol before trial premature termination due to poor recruitment during the COVID-19 pandemic. Mean (SD) MADRS scores on day 15 were 23 (10.32) in placebo, 25 (8.28) with 160 mg/day and 17 (10.32) with 240 mg/day KET01. MADRS change was numerically larger but statistically non-significant in the 240 mg/day KET01 group vs placebo on day 7 (-5.67; p = 00.106) and day 15 was (difference: 4.99; p = 00.15). In exploratory analysis, baseline leukocyte count correlated with response to KET01 (p = 00.01). Distribution of adverse event rates were comparable between the treatment arms. Safety analysis did not identify increased risk of suicidality, dissociation, hear rate, systolic and diastolic blood pressure associated with trial treatment. DISCUSSION: Our results suggest that adjunctive oral administration of prolonged-release ketamine at a dose of 240 mg/day shows a positive, although statistically non-significant, trend towards antidepressant efficacy, however, the benefit could not be confirmed due to premature trial termination. Given its ease of use and low side effects, further trials are warranted to investigate this route of ketamine administration as a promising potential treatment of TRD.

The risk of acute infections in new users of antidepressants: An observational cohort study.

BACKGROUND: Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity. METHODS: We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000-2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18-80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding. RESULTS: In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95-1.00), fluoxetine (0.94, 95 % CI, 0.92-0.95), and venlafaxine (0.90, 95 % CI, 0.87-0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82-0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen. LIMITATIONS: Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram. CONCLUSIONS: Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.

Recurrence of exostosis as a result of medication-induced bruxism: case study.

Introduction: Alveolar oral exostosis is a common, benign condition routinely found in dentistry. Clinical problems associated with exostoses are the maintenance of oral hygiene as well as the fabrication of prosthodontic appliances. Over time, exostoses may contribute to irritation and periodontal disease. Case description: The patient in this case study had a recurrence of exostoses and was bothered by consistent and prominent pain. She reported being a bruxer; her bruxism was exacerbated due to attention-deficit hyperactivity disorder and antidepressant medications. Discussion: The etiology behind the recurrence of exostosis is discussed. The most evident etiology seems to be persistence of medication-induced bruxism, specifically awake bruxism. Conclusion: It is necessary to take a proper history to identify the cause of the recurrence of exostosis. Dental hygienists can contribute to a better understanding of and provide better treatment options for patients who have medication-induced bruxism.

Introduction: L'exostose buccale alvéolaire est une affection bénigne courante couramment observée en dentisterie. Les problèmes cliniques associés aux exostoses sont le maintien de l'hygiène buccale ainsi que la fabrication d'appareils prosthodontiques. Avec le temps, les exostoses peuvent causer de l'irritation et des maladies parodontales. Description de cas: Dans cette étude de cas, la patiente présente des exostoses récurrentes et est dérangée par une douleur constante et proéminente. Elle a déclaré souffrir de bruxisme exacerbé par la prise de médicaments antidépresseurs et contre le trouble déficitaire de l'attention avec hyperactivité. Discussion: L'étiologie derrière la récurrence de l'exostose est abordée. L'étiologie la plus évidente semble être la persistance du bruxisme induit par les médicaments, en particulier le bruxisme diurne. Conclusion: Il est nécessaire d'obtenir les antécédents médicaux appropriés pour identifier la cause de la récurrence de l'exostose. Les hygiénistes dentaires peuvent contribuer à une meilleure compréhension et offrir de meilleures options de traitement aux patients atteints de bruxisme induit par les médicaments.

Emotional Blunting in Depression in the PREDDICT Clinical Trial: Inflammation-Stratified Augmentation of Vortioxetine With Celecoxib.

BACKGROUND: Emotional symptoms are recognized as a key feature in individuals with major depressive disorder. Previously, emotional blunting has been described both as a side effect of antidepressant treatment and as a symptom of depression. Little is known about the change of emotional blunting during antidepressant treatment. METHODS: The PREDDICT trial is a randomized, placebo-controlled, 6-week trial on the augmentation of vortioxetine with the anti-inflammatory agent celecoxib or placebo. Presently we report on exploratory secondary outcomes of changes in emotional blunting in depression assessed with the Oxford Depression Questionnaire (ODQ) total score and subscores from baseline to 8-week, 3-month, and 6-month follow-up assessments. RESULTS: In the whole group, there was a significant improvement in the ODQ total score and all subscores after 8 weeks. After stratification of participants into the treatment groups, the ODQ total score as well as subscores related to emotional blunting as a symptom of depression (reduction in positive emotions, not caring) improved between baseline and all follow-up time points in both treatment groups. Changes in subscores considered as a side effect of antidepressants (general reduction in emotions, emotional detachment) were inconclusive in both treatment groups. Overall, the placebo-augmented group showed slightly better results in changes of emotional blunting scores than the celecoxib group as did those with elevated inflammation at screening, regardless of treatment group. CONCLUSIONS: This analysis suggests favorable effects of vortioxetine on emotional blunting in both short- and long-term course. The beneficial impact of vortioxetine on emotional blunting was weaker in celecoxib-augmented patients compared with placebo, possibly due to pharmacokinetic interactions. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p.

La depresión como factor de riesgo de la demencia: fisiopatología y modelos preclínicos de estudio / Depression as a risk factor for dementia: Pathophysiology and preclinical study models

El aumento de la esperanza de vida ha llevado a un incremento en la incidencia de enfermedades crónicas como la demencia. Tratar los factores de riesgo de la demencia, como la depresión, podría reducir su incidencia. Sin embargo, el tratamiento con antidepresivos no ha sido eficaz en el manejo de este síntoma, lo que aumenta el riesgo de demencia en el futuro. Es fundamental investigar las causas y el tratamiento de la depresión, y el uso de modelos animales es importante en este sentido. Este estudio busca analizar la relación entre la depresión y el riesgo de desarrollar demencia, así como los modelos preclínicos más relevantes para estudiar la depresión en roedores. (AU)

The increase in life expectancy has led to a rise in the incidence of chronic diseases, such as dementia. Treating the risk factors of dementia, such as depression, could help reduce its occurrence. However, antidepressant treatment has not proven effective in managing this symptom, thereby increasing the risk of dementia in the future. It is essential to investigate the causes and treatment of depression, and in this regard, the use of animal models is of great significance. This study aims to analyze the evidence supporting the relationship between depression and the risk of developing dementia, while also providing an update on the most relevant preclinical models for studying depression in rodents. (AU)

Coprolalia y copropraxia inducida por bupropión en un paciente autista y con trastorno obsesivo compulsivo / Bupropion-induced coprolalia and copropraxia in autistic and obsessive compulsive disorder patient

Se presenta el caso de un varón de 41 años, ingresado desde los 26 en la unidad residencial y rehabilitadora con los diagnósticos de trastorno del espectro autista y trastorno obsesivo compulsivo, en tratamiento con fluvoxamina, valproico, topiramato, risperidona y clonazepam. Tras un periodo de estabilidad, aparece un cuadro compatible con un episodio depresivo mayor, que se decide tratar con bupropión, para incidir en los síntomas de apatía y lentitud psicomotriz. Se produce una recuperación rápida en 2 semanas, pero comienza a presentar copropraxia y coprolalia, que nunca antes había presentado. Se retira el bupropión y desaparece la coprolalia en 2 semanas, pero mantiene parte de estas conductas, por lo se pauta acetato de ciproterona para controlarlas, con mejoría en una semana. Tres meses después de la retirada del bupropión, alcanzó la eutimia y ya no presentó ninguna alteración conductual de temática sexual, coprolalia ni copropraxia. La literatura confirma otros casos de aparición de tics en pacientes tratados con antidepresivos para un cuadro depresivo y comorbilidad con trastorno obsesivo compulsivo, pero casi ninguno por el uso de bupropión o con coprolalia y copropraxia. (AU)

The case is presented of a 41-year-old male, admitted since age 26 to the Residential and Rehabilitation Unit with the diagnoses of autism spectrum disorder and obsessive-compulsive disorder, and under treatment with fluvoxamine, valproic, topiramate, risperidone and clonazepam. After a period of stability, a picture compatible with a major depressive episode appear, which is treated with bupropion, in order to affect the symptoms of apathy and psychomotor slowness. There is a rapid recovery in two weeks, but he begins to present copropraxia and coprolalia, which he had never presented before. Bupropion is withdrawn and coprolalia disappears in two weeks, but he maintained some of these behaviors, so cyproterone acetate is prescribed to control them, with improvement in one week. Three months after withdrawal of bupropion, he reaches euthymia and no longer presented any sexual behavioral alteration, coprolalia or copropraxia. The literature confirms other cases of appearance of tics in patients treated with antidepressants for a depressive picture and comorbidity with obsessive-compulsive disorder, but almost none by the use of bupropion or with coprolalia and copropraxia. (AU)

VigiBase Pharmacovigilance Studies on Antidepressant-Related Adverse Reactions: A Scoping Review.

VigiBase, the World Health Organization's collaborative global pharmaco-vigilance database, provides storage for millions of adverse drug reaction (ADR) reports. Pharmacovigilance scientists use the database to detect signals, assess, and understand trends in ADRs so that potential harms can be communicated. A search for pharmacovigilance studies on psychotropic-related ADR reports published over the past 5 years in VigiBase identified the majority to be antipsychotic-related ADRs, and within the antipsychotic class, clozapine-related. The nine antidepressant-related ADR reports were reviewed in more detail and provide an example of how the science of pharmacovigilance identifies and communicates medication risks. [Journal of Psychosocial Nursing and Mental Health Services, 62(3), 7-10.].

What Is Perinatal Depression?

This JAMA Patient Page describes perinatal depression screening and diagnosis and available treatment options.

Bidirectional associations between mental disorders, antidepressants and cardiovascular disease.

BACKGROUND: Mental disorders have a high comorbidity with cardiovascular disease (CVD), but the causality between them has not been fully appreciated. OBJECTIVE: This study aimed to systematically explore the bidirectional causality between the two broad categories of diseases. METHODS: We conducted Mendelian randomisation (MR) and multivariable MR (MVMR) analyses to evaluate potential causal links between 10 mental disorders, the use of antidepressants and 7 CVDs. FINDINGS: We discovered that major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and insomnia exhibit connections with elevated risks of two or more CVDs. Moreover, the use of antidepressants is linked to heightened risks of each CVD. Each distinct CVD is correlated with a greater probability of taking antidepressants. Our MVMR analysis demonstrated that the use of antidepressants is correlated with the elevation of respective risks across all cardiovascular conditions. This includes arrhythmias (OR: 1.28), atrial fibrillation (OR: 1.44), coronary artery disease (OR: 1.16), hypertension (OR: 1.16), heart failure (OR: 1.16), stroke (OR: 1.44) and entire CVD group (OR: 1.35). However, MDD itself was not linked to a heightened risk of any CVD. CONCLUSIONS: The findings of our study indicate that MDD, insomnia and ADHD may increase the risk of CVD. Our findings highlight the utilisation of antidepressants as an independent risk factor for CVD, thus explaining the influence of MDD on CVD through the mediating effects of antidepressants. CLINICAL IMPLICATIONS: When treating patients with antidepressants, it is necessary to take into consideration the potential beneficial and detrimental effects of antidepressants.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Psilocybin.

BACKGROUND: The primary psychoactive drug in magic mushrooms, psilocybin, induces profound alterations in consciousness through the 5-HT2A receptor. This review consolidates current research findings to elucidate the pharmacology, safety profile, and clinical applications of psilocybin. AREAS OF UNCERTAINTY: Despite initial concerns that psilocybin could cause psychosis, contemporary research has demonstrated that psilocybin is generally safe. The most common adverse effects are nausea and headache, yet both tend to be transient. Serious adverse events can generally be avoided in controlled settings such as clinical trials. However, in the largest clinical trial to date, there were a total of 7 reported cases of suicidal ideation, up to 12 weeks after receiving a single 25 mg dose of psilocybin. That being said, all 7 cases did not respond to the treatment. Although selective serotonin reuptake inhibitors may blunt the hallucinogenic qualities of psilocybin, preliminary research suggests that they may enhance its antidepressant effects. THERAPEUTIC ADVANCES: In clinical trials, psilocybin has shown promise for treating major depressive disorder and treatment-resistant depression. Initial studies indicated that 42%-57% of patients underwent remission after psilocybin-assisted therapy, which suggests that psilocybin is more effective than existing antidepressant medications. Clinical data have also demonstrated that psilocybin can manage substance use disorders and end-of-life anxiety with clinical outcomes that are sustained for months and sometimes years after 1 or 2 doses. LIMITATIONS: However, larger Phase II trials with more than 100 depressed participants have shown a much smaller remission rate of 25%-29%, though these studies still observed that psilocybin causes a significant reduction in depressive symptoms. CONCLUSIONS: Aside from ketamine, psilocybin is the most clinically well-researched psychedelic drug, with trials that have enrolled hundreds of participants and multiple therapeutic applications. Phase III trials will determine whether psilocybin lives up to the promise that it showed in previous clinical trials.

Association between antidepressants and the risk of diabetic foot ulcers and amputation in antidepressant-naïve type 2 diabetes mellitus patients: A nested case-control study.

AIMS: Antidepressants are widely used by individuals with type 2 diabetes mellitus (T2DM). This study aimed to explore the correlation between antidepressant use, considering specific antidepressant subclasses or cumulative doses, and diabetic foot ulcer (DFU) risk. METHODS: This nested case-control study was conducted using a representative population-based Korean cohort database from 2002 to 2019. Participants with DFUs were matched with participants without DFUs based on age, sex, date of T2DM diagnosis, and follow-up duration. In total, 791 DFUs and 3900 controls were included. The association between antidepressant use or cumulative dose of each antidepressant subclass, DFU risk and amputation risk was examined using a conditional logistic regression model. RESULTS: Antidepressant ever-use was associated with an increased incidence of DFUs compared with non-use. Furthermore, an increase in DFU risk was evident with increasing cumulative antidepressant dosage, particularly among tricyclic antidepressant (TCA) ever-users and selective serotonin reuptake inhibitors (SSRIs) ever-users. Additionally, antidepressant ever-users displayed a higher risk of DFUs requiring amputation, which was consistently observed when the cumulative dosages of overall antidepressants and TCAs were considered. CONCLUSION: Caution is advised when administering TCAs and SSRIs in antidepressant-naïve T2DM patients to reduce DFU and the consequent amputation risk.

Association between depression, antidepressant use, and the incidence of atherosclerotic cardiovascular diseases.

OBJECTIVE: To examine the association between depression, the use of antidepressants, and atherosclerotic cardiovascular disease (ASCVD). METHODS: The South Korean national claims data was used. Among a nationally representative population, 273,656 subjects who had been diagnosed with depression and prescribed antidepressants ("DEP with antidepressants") and 78,851 subjects who had been diagnosed with depression but not prescribed antidepressants ("DEP without antidepressants") were identified to be eligible. Healthy controls (HCs) were 1:1 matched with DEP with antidepressants group for age and sex. We followed up on the occurrence of ASCVD including ischemic heart diseases and ischemic stroke. RESULTS: The risk of ASCVD was increased in the DEP with antidepressants group and decreased in the DEP without antidepressants group compared to HCs. Among those under antidepressants, tricyclic antidepressant users showed the highest risk of ASCVD compared to HCs. Among young adults, the risk of ASCVD was increased in both groups. CONCLUSION: The risk of ASCVD increased in depression patients taking antidepressants, while it decreased in depression patients not taking antidepressants. However, the relationship showed differences according to drug class and age group.

Current level of evidence for improvement of antidepressant efficacy and tolerability by pharmacogenomic-guided treatment: A Systematic review and meta-analysis of randomized controlled clinical trials.

The aim of the study was to assess the clinical utility of currently available pharmacogenomic (PGx) tools compared with treatment as usual (TAU), using a meta-analysis of dichotomous and continuous antidepressant efficacy and tolerability data from previously published clinical trials. MEDLINE, clinicaltrial.gov, EU Clinical Trials Register, WHO ICTRP and CENTRAL were systematically searched; of the 962 results originally reviewed, 15 trials were included. Antidepressant efficacy was quantified by relative and absolute changes in symptom severity after eight weeks of treatment and by response and remission rates, while tolerability was estimated by the rate of study discontinuation for any reason. In the PGx-guided patients, symptom severity reduced by an average of 31.0% after eight weeks of treatment, compared to an average reduction of 26.8% in the TAU group. Accordingly, PGx-guided patients experienced a greater reduction in symptom severity of 3.4% (95%CI: 1.6-5.3%), which corresponded to a reduction in the Hamilton Depression score of 0.75 (0.30-1.21), a 37% (15-63%) higher remission rate, and an 18% (5-33%) higher response rate compared with TAU patients, while no difference was observed in discontinuation rate between groups. Notably, the majority of associations lost statistical significance when restricting the dataset to low risk of bias studies, while certain funnel plots suggested a potential publication bias favoring the reporting of statistically significant results. In summary, PGx tools marginally enhance antidepressant efficacy, but not antidepressant tolerability; thus, additional research and advancement of PGx tools are needed to improve integration of PGx in clinical pharmacotherapy of depression.

Cortical thickness of the posterior cingulate cortex is associated with the ketamine-induced altered sense of self: An ultra-high field MRI study.

Subanesthetic doses of ketamine induce an antidepressant effect within hours in individuals with treatment-resistant depression while it furthermore induces immediate but transient psychotomimetic effects. Among these psychotomimetic effects, an altered sense of self has specifically been associated with the antidepressant response to ketamine as well as psychedelics. However, there is plenty of variation in the extent of the drug-induced altered sense of self experience that might be explained by differences in basal morphological characteristics, such as cortical thickness. Regions that have been previously associated with a psychedelics-induced sense of self and with ketamine's mechanism of action, are the posterior cingulate cortex (PCC) and the pregenual anterior cingulate cortex (pgACC). In this randomized, placebo-controlled, double-blind cross-over magnetic resonance imaging study, thirty-five healthy male participants (mean age ± standard deviation (SD) = 25.1 ± 4.2 years) were scanned at 7 T. We investigated whether the cortical thickness of two DMN regions, the PCC and the pgACC, are associated with disembodiment and experience of unity scores, which were used to index the ketamine-induced altered sense of self. We observed a negative correlation between the PCC cortical thickness and the disembodiment scores (R = -0.54, p < 0.001). In contrast, no significant association was found between the pgACC cortical thickness and the ketamine-induced altered sense of self. In the context of the existing literature, our findings highlight the importance of the PCC as a structure involved in the mechanism of ketamine-induced altered sense of self that seems to be shared with different antidepressant agents with psychotomimetic effects operating on different classes of transmitter systems.

Association of antidepressant and benzodiazepine use, and anticholinergic burden with cognitive performance in schizophrenia.

Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016-2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use.

The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds.

BACKGROUND: Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs between antidepressants. This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes. METHODS: A PRISMA-compliant systematic search of Web of Science and PubMed databases was performed from inception until Jan 5, 2023, for original studies reporting incidences or risks of hypoNa in adults using antidepressants. We modelled random-effects meta-analyses to compute overall event rates and odds ratios of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa event rates. We conducted subgroup analyses for geriatric populations and sodium cut-off value. The study is registered with PROSPERO, CRD42021269801. RESULTS: We included 39 studies (n = 8,175,111). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (95%CI 1.911-5.225)). The highest event rates were found for SNRIs (7.44%), SSRIs (5.59%), and TCAs (2.66%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). Compared to SSRIs, SNRIs were significantly more likely (k = 10, OR = 1.292 (1.120 - 1.491), p < 0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 - 0.957), p = 0.032) to be associated with hypoNa. CONCLUSION: Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin.

BACKGROUND: Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period. METHODS: Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466). FINDINGS: Participants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p < 0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline. CONCLUSIONS: PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity. FUNDING: This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific.