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The Annals of Pharmacotherapy Jul 2024The objective of this study was to review the characteristics, efficacy, and safety of zuranolone in the management of postpartum depression (PPD). (Review)
Review
OBJECTIVE
The objective of this study was to review the characteristics, efficacy, and safety of zuranolone in the management of postpartum depression (PPD).
DATA SOURCES
Literature was identified using PubMed (1966-August 2023) and EMBASE (1973-August 2023) and clinicaltrials.gov. Search terms included zuranolone, SAGE-217, and PPD with further limitation of those published in English.
STUDY SELECTION AND DATA EXTRACTION
Articles selected for inclusion included trials evaluating zuranolone for the treatment of PPD.
DATA SYNTHESIS
Zuranolone was evaluated for the treatment of moderate to severe PPD in 2 phase III trials. Both studies resulted in statistically significant improvement in depressive symptoms at day 15 ( = 0.003 and < 0.001). Sustained differences in remission rates favoring zuranolone were found in both studies at day 45 compared with placebo ( = 0.01 and < 0.05). Zuranolone was well tolerated, with somnolence, dizziness, headache, and sedation reported as the most common side effects.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS
Zuranolone is only the second medication approved by the Food and Drug Administration (FDA) for PPD and offers an advantage over brexanolone in that it can administered orally in the outpatient setting. The rapid onset of effect of zuranolone is advantageous to traditional antidepressant therapy which can be weeks to months; however, limited information is available on safety during lactation.
CONCLUSIONS
The recent FDA approval of oral zuranolone for PPD offers a second rapid-acting treatment for PPD, extending the opportunity for treatment to patients in the outpatient setting.
Topics: Humans; Depression, Postpartum; Female; Administration, Oral; Drug Approval; United States Food and Drug Administration; United States; Antidepressive Agents; Treatment Outcome; Pregnanolone; Pyrazoles
PubMed: 37876133
DOI: 10.1177/10600280231204953 -
MMW Fortschritte Der Medizin Feb 2024
Topics: Humans; Nursing Homes; Psychotropic Drugs
PubMed: 38332264
DOI: 10.1007/s15006-023-3544-1 -
Drug Discovery Today Dec 2023Psychiatric disorders represent the largest cause of disability worldwide. Global interests in psychedelic substances as potentially therapeutic agents for psychiatric... (Review)
Review
Psychiatric disorders represent the largest cause of disability worldwide. Global interests in psychedelic substances as potentially therapeutic agents for psychiatric disorders has recently re-emerged. Here, we review progress in the development of psychedelic compounds that have potential therapeutic effects as well as the safety concerns. We include psilocybin, N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and the entactogen 3,4-methyl-enedioxy-methamphetamine (MDMA). We also review the potential interactive effects these compounds can have with psychotherapeutic approaches. We provide a cutting-edge review of active and recently completed clinical trials based on the published literature (from MEDLINE), published abstracts at citable conferences, clinical trials from the US Clinical Trials registry (clinicaltrials.gov) and media press releases.
Topics: Humans; Hallucinogens; Lysergic Acid Diethylamide; Mental Disorders; Psilocybin; N,N-Dimethyltryptamine
PubMed: 37925136
DOI: 10.1016/j.drudis.2023.103818 -
Frontiers in Psychiatry 2023
PubMed: 38045620
DOI: 10.3389/fpsyt.2023.1269307 -
Agri : Agri (Algoloji) Dernegi'nin... Oct 2023Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and...
OBJECTIVES
Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and neuropathic pain patients. PGB is often combined with anxiolytics and antidepressants. We aimed to investigate the antidepressant and anxiolytic effects of PGB and compare its effects with those of antidepressant and anxiolytic drugs and their combined use.
METHODS
Wistar Albino rats were used, and PGB (5, 10, 20, and 40 mg/kg), amitriptylin (AMT), fluoxetine (FLX), ketamine (KET), and diazepam (DZM), as well as combinations of PGB (20 mg/kg) with AMT, FLX, KET, and DZM, were administered. Elevated plus maze, forced swimming, and locomotor activity tests were performed.
RESULTS
In the elevated plus maze, PGB10, 20, 40, AMT, FLX, and DZM increased open arm time. The PGB20+FLX combination increased compared to PGB20. In forced swimming, PGB doses increased immobility time. AMT, FLX, DZM, and KET decreased compared to control and PGB doses. Other combinations of PGB20 reversed immobility time, except FLX. In locomotor activity, PGB20, AMT, KET, and DZM decreased distance.
CONCLUSION
PGB had a depressant effect in all doses and a dose-dependently anxiolytic effect. In combinations of PGB with AMT, KET, and DZM, it reversed their antidepressant effects. We assumed FLX could be preferred instead of AMT in patients using PGB. When PGB is used in combination, drug interactions should be considered. These results are also very remarkable in terms of pharmacoeconomics.
Topics: Rats; Humans; Animals; Anti-Anxiety Agents; Pregabalin; Rats, Wistar; Antidepressive Agents; Fluoxetine; Amitriptyline; Ketamine; Epilepsy
PubMed: 37886867
DOI: 10.14744/agri.2022.98474 -
BMJ (Clinical Research Ed.) May 2024To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.
DATA SYNTHESIS AND STUDY QUALITY
Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges' g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies' sample sizes. Study quality was appraised using Cochrane's Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.
ELIGIBILITY CRITERIA
Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.
RESULTS
Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges' g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges' g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating.
CONCLUSION
Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023388065.
Topics: Humans; Antidepressive Agents; Depression; Hallucinogens; Psilocybin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38692686
DOI: 10.1136/bmj-2023-078084 -
Biology Direct Aug 2023Antipsychotic drugs are the mainstay of treatment for schizophrenia and provide adjunct therapies for other prevalent psychiatric conditions, including bipolar disorder...
Antipsychotic drugs are the mainstay of treatment for schizophrenia and provide adjunct therapies for other prevalent psychiatric conditions, including bipolar disorder and major depressive disorder. However, they also induce debilitating extrapyramidal syndromes (EPS), such as Parkinsonism, in a significant minority of patients. The majority of antipsychotic drugs function as dopamine receptor antagonists in the brain while the most recent 'third'-generation, such as aripiprazole, act as partial agonists. Despite showing good clinical efficacy, these newer agents are still associated with EPS in ~ 5 to 15% of patients. However, it is not fully understood how these movement disorders develop. Here, we combine clinically-relevant drug concentrations with mutliscale model systems to show that aripiprazole and its primary active metabolite induce mitochondrial toxicity inducing robust declines in cellular ATP and viability. Aripiprazole, brexpiprazole and cariprazine were shown to directly inhibit respiratory complex I through its ubiquinone-binding channel. Importantly, all three drugs induced mitochondrial toxicity in primary embryonic mouse neurons, with greater bioenergetic inhibition in ventral midbrain neurons than forebrain neurons. Finally, chronic feeding with aripiprazole resulted in structural damage to mitochondria in the brain and thoracic muscle of adult Drosophila melanogaster consistent with locomotor dysfunction. Taken together, we show that antipsychotic drugs acting as partial dopamine receptor agonists exhibit off-target mitochondrial liabilities targeting complex I.
Topics: Animals; Mice; Aripiprazole; Antipsychotic Agents; Depressive Disorder, Major; Drosophila melanogaster; Electron Transport
PubMed: 37528429
DOI: 10.1186/s13062-023-00375-9 -
Vortioxetine - pharmacological properties and use in mood disorders. The current state of knowledge.Psychiatria Polska Dec 2023Vortioxetine is an antidepressant with a unique profile of receptor activity. The pharmacodynamic spectrum of vortioxetine activity is linked to the modulation of not... (Review)
Review
Vortioxetine is an antidepressant with a unique profile of receptor activity. The pharmacodynamic spectrum of vortioxetine activity is linked to the modulation of not only serotoninergic but also noradrenergic and dopaminergic transmission. At the same time, its pharmacokinetic properties determine good tolerance and safety, which are also observed in elderly patients and those burdened with somatic comorbidity. This work aims to sum up the knowledge coming from the most recent studies assessing the efficacy of vortioxetine. The efficacy of vortioxetine in the treatment of depression was confirmed in a large number of open studies, randomized controlled studies with placebo control, and meta-analyses thereof. What is more, the latest research shows that this drug allows depressed patients to achieve not only symptomatic remission but also an improvement of anhedonia and recovery in cognitive and occupational function. Furthermore, there are studies showing that vortioxetine is efficacious in the treatment of elderly patients, as well as subjects who have experienced trauma or suffer from bipolar depression. Vortioxetine is characterized by a good tolerance profile and safety; rarely does it cause severe adverse effects.
Topics: Aged; Humans; Antidepressive Agents; Mood Disorders; Treatment Outcome; Vortioxetine; Randomized Controlled Trials as Topic; Meta-Analysis as Topic
PubMed: 36571300
DOI: 10.12740/PP/OnlineFirst/151570 -
Pharmacopsychiatry Nov 2023In patients with a pre-existing mental disorder, an increased risk for a first manifestation of a psychiatric disorder in COVID-19 patients, a more severe course of...
INTRODUCTION
In patients with a pre-existing mental disorder, an increased risk for a first manifestation of a psychiatric disorder in COVID-19 patients, a more severe course of COVID-19 and an increased mortality have been described. Conversely, observations of lower COVID-19 incidences in psychiatric in-patients suggested protective effects of psychiatric treatment and/or psychotropic drugs against COVID-19.
METHODS
A retrospective multi-center study was conducted in 24 German psychiatric university hospitals. Between April and December 2020 (the first and partly second wave of COVID-19), the effects of COVID-19 were assessed on psychiatric in-patient care, the incidence and course of a SARS-CoV-2 infection, and treatment with psychotropic drugs.
RESULTS
Patients (n=36,322) were admitted to the hospitals. Mandatory SARS-CoV-2 tests before/during admission were reported by 23 hospitals (95.8%), while 18 (75%) conducted regular testing during the hospital stay. Two hundred thirty-two (0.6%) patients were tested SARS-CoV-2-positive. Thirty-seven (16%) patients were receiving medical treatment for COVID-19 at the psychiatric hospital, ten (4.3%) were transferred to an intermediate/intensive care unit, and three (1.3%) died. The most common prescription for SARS-CoV-2-positive patients was for second-generation antipsychotics (n=79, 28.2%) and antidepressants (SSRIs (n=38, 13.5%), mirtazapine (n=36, 12.9%) and SNRIs (n=29, 10.4%)).
DISCUSSION
Contrary to previous studies, our results showed a low number of infections and mortality in SARS-CoV-2-positive psychiatric patients. Several preventive measures seem effective to protect this vulnerable group. Our observations are compatible with the hypothesis of a protective effect of psychotropic drugs against COVID-19 as the overall mortality and need for specific medical treatment was low.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; Prevalence; Psychotropic Drugs; SARS-CoV-2; Retrospective Studies
PubMed: 37944561
DOI: 10.1055/a-2177-3056 -
Neuropharmacology Aug 2023Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many... (Review)
Review
Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks. Preliminary evidence suggests that some psychedelics may be effective for certain types of pain and/or improved quality of life with increased functionality and reduced disability and distress in people whose pain may never be completely relieved. Efficacy in these quality-of-life related outcomes would be consistent with the 'reset in thinking' about chronic pain management being increasingly called for as a more realistic goal for some people as compared to complete elimination of pain. This commentary summarizes the rationale for conducting more basic research and clinical trials to further explore the potential for psychedelics in chronic pain management. Additionally, if shown to be effective, to then determine whether the effects of psychedelics are primarily due to direct antinociceptive or anti-inflammatory mechanisms, or via increased tolerability, acceptance, and sense of spirituality, that appear to at least partially mediate the therapeutic effects of psychedelics observed in psychiatric disorders such as major depression. This commentary represents a collaboration of clinical and more basic scientists examining these issues and developing recommendations for research ranging from neuropharmacology to the biopsychosocial treatment factors that appear to be as important in pain management as in depression and other disorders in which psychedelic medicines are under development. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".
Topics: Humans; United States; Hallucinogens; Lysergic Acid Diethylamide; Chronic Pain; Quality of Life; Psilocybin; Depressive Disorder, Major
PubMed: 37015315
DOI: 10.1016/j.neuropharm.2023.109528