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Pharmacology & Therapeutics Jan 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core impairments: impaired communication, impaired reciprocal social interaction,... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core impairments: impaired communication, impaired reciprocal social interaction, and restricted, repetitive, and stereotypical behavior patterns. Spectrum refers to the heterogeneity of presentation, severity of symptoms, and medical comorbidities associated with ASD. Among the most common underlying medical conditions are attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, epilepsy, digestive disorders, metabolic disorders, and immune disorders. At present, in the absence of an objective and accurate diagnosis of ASD, such as a blood test, pharmacological management remains a challenge. There are no approved medications to treat the core symptoms of the disorder and behavioral interventions are typically used as first line treatment. Additionally, psychotropic drugs with different mechanisms of action have been approved to reduce associated symptoms and comorbidities, including aripiprazole, risperidone, and haloperidol for irritability and aggression, methylphenidate, atomoxetine, clonidine, and guanfacine for ADHD, and melatonin for sleep disturbances. The purpose of this review is to emphasize that it is imperative to develop objective, personalized diagnostic kits in order to tailor and individualize treatment strategies, as well as to describe the current pharmacological management options available in clinical practice and new prospects that may be helpful in managing ASD's core symptoms.
Topics: Child; Humans; Autism Spectrum Disorder; Autistic Disorder; Psychotropic Drugs; Attention Deficit Disorder with Hyperactivity; Methylphenidate
PubMed: 38008401
DOI: 10.1016/j.pharmthera.2023.108564 -
PloS One 2023The evidence is insufficient regarding the association between organizational downsizing and employee mental health. Our aim was to analyze trajectories of prescribed... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The evidence is insufficient regarding the association between organizational downsizing and employee mental health. Our aim was to analyze trajectories of prescribed sedatives and anxiolytics with a sufficiently long follow-up time to capture anticipation, implementation and adaption to a downsizing event among stayers, changers and those who become unemployed compared to unexposed employees.
METHOD
Residents in Sweden aged 20-54 years in 2007, with stable employment between 2004 and 2007, were followed between 2005 and 2013 (n = 2,305,795). Employment at a workplace with staff reductions ≥18% between two subsequent years in 2007-2011 (n = 915,461) indicated exposure to, and timing of, downsizing. The unexposed (n = 1,390,334) were randomized into four corresponding sub-cohorts. With generalized estimating equations, we calculated the odds ratios (OR) of purchasing prescribed anxiolytics or sedatives within nine 12-month periods, from four years before to four years after downsizing. In order to investigate whether the groups changed their probability of purchases over time, odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated contrasting the prevalence of purchases during the first and the last 12-month period within four time periods for each exposure group.
RESULTS
The odds of purchasing psychotropic drugs increased more for changers (sedatives OR 1.08, 95% CI 1.05-1.11) and unemployed (anxiolytics OR 1.08, 95% CI 1.03-1.14), compared to unexposed before downsizing, while for stayers purchases increased more than for unexposed during and after downsizing. Among those without previous sickness absence, stayers increased their purchases of psychotropic drugs from the year before the event up to four years after the event.
CONCLUSION
This study indicates that being exposed to downsizing is associated with increased use of sedatives and anxiolytics, before the event among those who leave, but especially thereafter for employees who stay in the organization.
Topics: Humans; Anti-Anxiety Agents; Hypnotics and Sedatives; Longitudinal Studies; Personnel Downsizing; Psychotropic Drugs
PubMed: 38064436
DOI: 10.1371/journal.pone.0295383 -
Journal of Applied Gerontology : the... Nov 2023Individual state approaches to assisted living/residential care (AL/RC) licensing and oversight in the United States result in different practice standards and...
Individual state approaches to assisted living/residential care (AL/RC) licensing and oversight in the United States result in different practice standards and requirements, including psychotropic medication use. We examined 170 psychotropic medication deficiency citations issued to 152 Oregon AL/RC settings from 2015 to 2019. Applied thematic analysis resulted in the following themes: (1) documentation issues are primarily responsible for noncompliance, (2) unclear parameters place direct care workers in a role paradox, and (3) there is a persistent disconnect about when to seek qualified expertise before requesting psychotropic medications. AL/RC-specific mechanisms for medication prescription and administration are necessary to improve the structure and processes of care. Policymakers might consider how regulations unintentionally incentivize task-oriented versus person-centered care practices.
Topics: Humans; United States; Oregon; Psychotropic Drugs; Health Personnel; Patient Compliance
PubMed: 37268438
DOI: 10.1177/07334648231181517 -
Expert Opinion on Pharmacotherapy 2023A new era of treatment for adults with treatment-resistant depression (TRD), which involves psychedelic substances, is dawning. Emerging evidence indicates that... (Review)
Review
INTRODUCTION
A new era of treatment for adults with treatment-resistant depression (TRD), which involves psychedelic substances, is dawning. Emerging evidence indicates that psychedelics can exert antidepressant effects through multiple neurobiological and psychological mechanisms. However, it remains to be seen if these new treatments will revolutionize the treatment of TRD.
AREAS COVERED
The present review focuses on the efficacy of serotoninergic psychedelics psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and mescaline (3,4,5-trimethoxyphenethylamine), as well as 3,4-methylenedioxymethamphetamine (MDMA), for TRD. A systematic search was conducted for psilocybin in TRD as emerging trials had not yet been subject to review. A narrative review summarized findings on other psychedelics.
EXPERT OPINION
Psychedelic therapy has created a paradigm shift in the treatment of TRD, as it can maximize therapeutic benefits and minimize potential risks. Psilocybin holds promise as a potential game-changer in the treatment of TRD, with initial evidence suggesting a rapid antidepressant effect sustained for some responders for at least 3 months. Nevertheless, further adequately powered, double-blind, comparator-controlled trials are required to explore and clarify the mechanisms of action and long-term effects of psychedelics in TRD. Psychedelics also hold promise for other psychiatric conditions, such as bipolar depression and post-traumatic stress disorder.
Topics: Adult; Humans; Hallucinogens; Psilocybin; Depressive Disorder, Treatment-Resistant; Lysergic Acid Diethylamide; Mescaline; N,N-Dimethyltryptamine; Antidepressive Agents; Randomized Controlled Trials as Topic
PubMed: 37947195
DOI: 10.1080/14656566.2023.2281582 -
Journal of Voice : Official Journal of... Mar 2024To describe the burden of psychiatric illness and psychotropic medication usage among the subset of transgender patients who undergo gender-affirming laryngeal surgery...
OBJECTIVES
To describe the burden of psychiatric illness and psychotropic medication usage among the subset of transgender patients who undergo gender-affirming laryngeal surgery and describe some of the most commonly encountered conditions experienced by this population.
METHODS
An Institutional Review Board-approved chart review was conducted for the 18 patients who have undergone gender-affirming laryngeal procedures from August 2019 to June 2022 performed at a single institution. Patient demographic data, treatment details, and psychiatric diagnoses and prescriptions for psychotropic medications were recorded.
RESULTS
Of the 18 patients who underwent gender-affirming laryngeal surgery at this institution, 16 patients underwent these operations as part of a transition from male to female gender, while 2 patients were transitioning from female to male gender. In this cohort, 13 patients were diagnosed with a psychiatric comorbidity (72.2%). Of these patients, 11 were prescribed at least 1 psychotropic medication (61.1%). The most common psychiatric illnesses encountered in these patients were depression, anxiety, and post-traumatic stress disorder. Ten patients were diagnosed with more than 1 psychiatric comorbidity (55.6%). The most commonly prescribed psychotropic drugs were selective serotonin/norepinephrine reuptake inhibitors. Three patients in this cohort had a recorded history of at least one prior suicide attempt.
CONCLUSIONS
Multiple studies have demonstrated increased rates of mental illness in transgender individuals, however, this is the first study to describe the burden of these conditions specifically in the subset of patients who undergo gender-affirming laryngeal surgery.
PubMed: 38556380
DOI: 10.1016/j.jvoice.2024.02.017 -
Pharmacological Reports : PR Dec 2023The desire to find a gold-standard therapy for depression is still ongoing. Developing one universal and effective pharmacotherapy remains troublesome due to the high... (Review)
Review
The desire to find a gold-standard therapy for depression is still ongoing. Developing one universal and effective pharmacotherapy remains troublesome due to the high complexity and variety of symptoms. Over the last decades, the understanding of the mechanism of pathophysiology of depression and its key consequences for brain functioning have undergone significant changes, referring to the monoaminergic theory of the disease. After the breakthrough discovery of ketamine, research began to focus on the modulation of glutamatergic transmission as a new pharmacological target. Glutamate is a crucial player in mechanisms of a novel class of antidepressants, including hallucinogens such as ketamine. The role of glutamatergic transmission is also suggested in the antidepressant (AD) action of scopolamine and psilocybin. Despite fast, robust, and sustained AD action hallucinogens belonging to a group of rapid-acting antidepressants (RAA) exert significant undesired effects, which hamper their use in the clinic. Thus, the synergistic action of more than one substance in lower doses instead of monotherapy may alleviate the likelihood of adverse effects while improving therapeutic outcomes. In this review, we explore AD-like behavioral, synaptic, and molecular action of RAAs such as ketamine, scopolamine, and psilocybin, in combination with mGlu2/3 receptor antagonists.
Topics: Ketamine; Hallucinogens; Psilocybin; Receptors, Metabotropic Glutamate; Antidepressive Agents; Depression; Scopolamine
PubMed: 37932583
DOI: 10.1007/s43440-023-00547-4 -
Current Opinion in Psychiatry Jul 2024New psychoactive substances (NPS) continue to emerge globally and present a threat to public health. This article summarizes the most recent literature on approaches for... (Review)
Review
PURPOSE OF REVIEW
New psychoactive substances (NPS) continue to emerge globally and present a threat to public health. This article summarizes the most recent literature on approaches for monitoring NPS use and adverse events related to use.
RECENT FINDINGS
A variety of approaches have recently been employed for surveillance of NPS use and associated harms, including the use of toxicology testing of patients in emergency departments, surveys of sentinel populations, drug checking and syringe services programs, wastewater-based epidemiology, and retrospective analyses of clinical samples and toxicology reports. These studies cover a range of time periods and NPS examined across numerous countries.
SUMMARY
Areas of particular interest for future research include the use of data from drug checking services to inform surveillance efforts of the illicit drug supply and the development of methods for wastewater-based monitoring of NPS. Studies that combine self-report data with toxicology testing in particular are important for capturing unintentional or unknown exposure to NPS including fentanyls and drugs like xylazine. Given the limitations associated with individual indicators of drug use and associated harms, the harmonization of multiple data sources can help present a more complete picture of both trends involving NPS to better inform public health responses.
Topics: Humans; Psychotropic Drugs; Public Health Surveillance; Illicit Drugs; Substance-Related Disorders; Substance Abuse Detection
PubMed: 38587019
DOI: 10.1097/YCO.0000000000000938 -
Nordic Journal of Psychiatry Oct 2023To survey trends of antipsychotic use during pregnancy and examine the associations between the use of quetiapine or any antipsychotic and adverse obstetric and neonatal...
PURPOSE
To survey trends of antipsychotic use during pregnancy and examine the associations between the use of quetiapine or any antipsychotic and adverse obstetric and neonatal outcomes.
METHODS
Birth register study of 36,083 women who gave birth at Kuopio University Hospital, Finland, between 2002 and 2016. Obstetric and neonatal outcomes between women using quetiapine ( = 152) or any antipsychotic ( = 227) were compared to controls ( = 35,133).
RESULTS
Altogether 246 (0.7%) women used antipsychotic medications during pregnancy and 153 (62,2%) of these women used quetiapine. Antipsychotic usage increased from 0.4% to 1.0% during the 15-year follow-up. Women using antipsychotics were more likely to smoke, drink alcohol, use illicit drugs, use other psychotropic medications, and have higher pre-pregnancy body mass index. Quetiapine use was associated with higher risk of increased postpartum bleeding in vaginal delivery (aOR 1.65; 95%CI 1.13-2.42), prolonged neonatal hospitalization (≥5 days) (aOR 1.54; 95%CI 1.10-2.15), and higher placental to birth weight ratio (PBW ratio) (aB 0.009; 95%CI 0.002-0.016). Use of any antipsychotic was associated with a higher risk of gestational diabetes mellitus (aOR 1.64; 95%CI 1.19-2.27), increased postpartum bleeding in vaginal delivery (aOR 1.50; 95%CI 1.09-2.07), prolonged neonatal hospitalization (≥5 days) (aOR 2.07; 95%CI 1.57-2.73), and higher PBW ratio (aB 0.007; 95%CI 0.001-0.012).
CONCLUSION
The use of antipsychotic medications increased among Finnish pregnant women from 2002 to 2016. Pregnant women using antipsychotics appear to have a higher risk for some adverse pregnancy and birth outcomes and may benefit from more frequent maternity care follow-ups.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Male; Quetiapine Fumarate; Antipsychotic Agents; Follow-Up Studies; Placenta; Maternal Health Services; Hospitals
PubMed: 37149788
DOI: 10.1080/08039488.2023.2205852 -
Journal of Affective Disorders Mar 2024The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy, acceptability, tolerability, and safety for acute mania in children and adolescents.
METHOD
We systematically reviewed the double-blinded, randomized controlled trials (RCTs) comparing drugs or placebo for acute manic episodes of bipolar disorder in children and adolescents using PRISMA guidelines. We searched PubMed/MEDLINE, EMBASE, Web of Science, EBSCO, Scopus, the Cochrane Central Register of Controlled Trials, and https://clinicaltrials.gov from inception until November 20, 2022. Response to treatment was the primary outcome, and random-effects network meta-analyses were conducted (PROSPERO 2022: CRD42022367455).
RESULTS
Of 10,134 citations, we included 15 RCTs, including 2372 patients (47 % female), 15 psychotropic drugs, and the placebo. Risperidone 0.5-2.5 mg/day, aripiprazole 30 mg/day olanzapine, quetiapine 400 mg/day, quetiapine 600 mg/day, asenapine 5 mg/day, asenapine 10 mg, ziprasidone, and aripiprazole 10 mg were found to be effective (in comparison with placebo) in children and adolescents, respectively (τ = 0.0072, I = 10.2 %). The tolerability of aripiprazole 30 mg/day was lower than risperidone 0.5-2.5 mg/day and olanzapine. Oxcarbazepine had the highest discontinuation due to the adverse effects risk ratio.
LIMITATIONS
Efficacy ranking of the treatments could be performed by evaluating relatively few RCT results, and only monotherapies were considered.
CONCLUSIONS
Efficacy, acceptability, tolerability, and safety are changing with the doses of antipsychotics for children and adolescents with acute bipolar manic episodes. Drug selection and optimum dosage should be carefully adjusted in children and adolescents.
Topics: Humans; Adolescent; Adult; Child; Risperidone; Olanzapine; Aripiprazole; Bipolar Disorder; Quetiapine Fumarate; Mania; Network Meta-Analysis; Antipsychotic Agents; Dibenzocycloheptenes
PubMed: 38211745
DOI: 10.1016/j.jad.2024.01.067 -
Expert Opinion on Drug Metabolism &... May 2024There is a large body of preclinical data implicating that grapefruit juice (GJ) inhibits many CYP 450 isoforms. The potential of GJ-to-drug is of high relevance to... (Review)
Review
INTRODUCTION
There is a large body of preclinical data implicating that grapefruit juice (GJ) inhibits many CYP 450 isoforms. The potential of GJ-to-drug is of high relevance to clinical psychiatry, because a wide range of psychotropic medicines undergo CYP 450 metabolism and P-gp transport.
AREAS COVERED
Relevant data were identified by searching the electronic databases up to February 2024. This work constitutes a summary of preclinical and clinical data on GJ impact on CYP 450 metabolism, P-glycoprotein, and organic anion-transporting polypeptides (OATPs), with focus on studies that assessed GJ-to-psychotropic drug interactions. Additionally, an unpublished case series of nine patients is provided.
EXPERT OPINION
The impact of GJ on CYP 3A4 appears to be the critical mechanism for the majority of GJ-to-psychopharmacotherapy interactions described in human studies or case reports. However, there are studies and cases of patients clearly showing that this is not the only route explaining the GJ effect, and at times, this particular is of no relevance and that other CYP 450 isoforms as well as drug transporting proteins might be involved. The risk of GJ-to-psychotropic drugs needs to be further evaluated in a 'real-world' setting and apply not only measures of pharmacokinetics but also treatment effectiveness and safety.
Topics: Citrus paradisi; Humans; Food-Drug Interactions; Psychotropic Drugs; Fruit and Vegetable Juices; Animals; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Organic Anion Transporters; ATP Binding Cassette Transporter, Subfamily B, Member 1
PubMed: 38721667
DOI: 10.1080/17425255.2024.2352468