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Journal of Psychiatric Research Dec 2023Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and motor dysfunction in parkinsonism and/or cerebellar ataxia. Patients... (Clinical Trial)
Clinical Trial Observational Study
Comparison of tandospirone and escitalopram as a symptomatic treatment in Multiple System Atrophy-cerebellar ataxia: An open-label, non-controlled, 4 weeks observational study.
BACKGROUND
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and motor dysfunction in parkinsonism and/or cerebellar ataxia. Patients with MSA usually present with depression and anxiety symptoms. This observational study of patients with MSA-cerebellar subtype (MSA-C) with subthreshold depression/anxiety symptoms aimed to compare the efficacy of escitalopram oxalate (an antidepressant drug) and tandospirone citrate (an anxiolytic drug).
METHODS
Fifty-six MSA-C patients were included, with 28 patients in each treatment group. One group received escitalopram oxalate 10 mg/day and the other group received tandospirone citrate 30 mg/day. The patients were evaluated at baseline and after 4 weeks. Several psychiatric and neurological tests were performed, including the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), Scale for the Assessment and Rating of Ataxia (SARA), and the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT). Furthermore, post-void residual urine volume (PVR) and blood pressure were measured.
RESULTS
There was a more substantial reduction in the HAMA/HAMD, scores of stance, finger tracking, and finger nose test in the SARA, and PVR in the tandospirone group. There was a more substantial reduction in scores of dysuria, light-headed when standing up, syncope and hyperhidrosis in the SCOPA-AUT in the escitalopram group (p's < 0.05).
CONCLUSIONS
Tandospirone citrate was more effective in improving depression/anxiety and some cerebellar ataxia symptoms, whereas escitalopram was more effective in improving some autonomic symptoms in MSA-C patients over a short-term period in an open-label observational study without a control group. Further research is needed to evaluate the long-term effects of tandospirone and escitalopram in MSA-C in long-term placebo controlled trials.
Topics: Humans; Anti-Anxiety Agents; Cerebellar Ataxia; Citrates; Escitalopram; Multiple System Atrophy
PubMed: 37907036
DOI: 10.1016/j.jpsychires.2023.10.028 -
Nature Jun 2024Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders. These compounds...
Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT (ref. ). However, 5-HT also plays a part in the behavioural effects of tryptamine hallucinogens, particularly 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a psychedelic found in the toxin of Colorado River toads. Although 5-HT is a validated therapeutic target, little is known about how psychedelics engage 5-HT and which effects are mediated by this receptor. Here we map the molecular underpinnings of 5-MeO-DMT pharmacology through five cryogenic electron microscopy (cryo-EM) structures of 5-HT, systematic medicinal chemistry, receptor mutagenesis and mouse behaviour. Structure-activity relationship analyses of 5-methoxytryptamines at both 5-HT and 5-HT enable the characterization of molecular determinants of 5-HT signalling potency, efficacy and selectivity. Moreover, we contrast the structural interactions and in vitro pharmacology of 5-MeO-DMT and analogues to the pan-serotonergic agonist LSD and clinically used 5-HT agonists. We show that a 5-HT-selective 5-MeO-DMT analogue is devoid of hallucinogenic-like effects while retaining anxiolytic-like and antidepressant-like activity in socially defeated animals. Our studies uncover molecular aspects of 5-HT-targeted psychedelics and therapeutics, which may facilitate the future development of new medications for neuropsychiatric disorders.
Topics: Animals; Humans; Male; Mice; 5-Methoxytryptamine; Anti-Anxiety Agents; Antidepressive Agents; Cryoelectron Microscopy; Hallucinogens; Lysergic Acid Diethylamide; Methoxydimethyltryptamines; Models, Molecular; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Serotonin Receptor Agonists; Structure-Activity Relationship
PubMed: 38720072
DOI: 10.1038/s41586-024-07403-2 -
The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review.Journal of Psychopharmacology (Oxford,... Dec 2023Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this... (Review)
Review
BACKGROUND
Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this systematic review, we aimed to review the relationship between the 5-HT7 receptor system and mood and anxiety disorders, and to explore the pharmacology and therapeutic potential of medications that target the 5-HT7 receptor for their treatment.
METHODS
Medline, Cochrane Library, EMBASE, PsycINFO databases, the National Institute of Health website Clinicaltrials.gov, controlled-trials.com, and relevant grey literature were used to search for original research articles, and reference lists of included articles were then hand searched.
RESULTS
Sixty-four studies were included in the review: 52 animal studies and 12 human studies. Studies used a variety of preclinical paradigms and questionnaires to assess change in mood, and few studies examined sleep or cognition. Forty-four out of 47 (44/47) preclinical 5-HT7 modulation studies identified potential antidepressant effects and 20/23 studies identified potential anxiolytic effects. In clinical studies, 5/7 identified potential antidepressant effects in major depressive disorder, 1/2 identified potential anxiolytic effects in generalized anxiety disorder, and 3/3 identified potential antidepressant effects in bipolar disorders.
CONCLUSION
While there is some evidence that the 5-HT7 receptor system may be a potential target for treating mood and anxiety disorders, many agents included in the review also bind to other receptors. Further research is needed using drugs that bind specifically to 5-HT7 receptors to examine treatment proof of concept further.
Topics: Animals; Humans; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major
PubMed: 37994803
DOI: 10.1177/02698811231211228 -
Naunyn-Schmiedeberg's Archives of... May 2024Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT receptor (5-HT2A) activation....
Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear. In this study, we ethopharmacologically analyzed the role of 5-HT2A in the occurrence of anxiolytic- and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice 24 h post-treatment. Mice with acute intraperitoneal psychedelic treatment exhibited significantly shorter immobility times in the forced swimming test (FST) and tail-suspension test (TST) than vehicle-treated control mice. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the novelty-suppressed feeding test (NSFT), the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not diminish this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. These results suggest that 5-HT2A contributes to the antidepressant effects of serotonergic psychedelics rather than anxiolytic effects.
Topics: Animals; Male; Antidepressive Agents; Hallucinogens; Mice, Inbred C57BL; Receptor, Serotonin, 5-HT2A; Amphetamines; Psilocybin; Behavior, Animal; Motor Activity; Mice; Anti-Anxiety Agents; Serotonin 5-HT2 Receptor Agonists; Swimming; Depression; Bridged Bicyclo Compounds; Methylamines
PubMed: 37874338
DOI: 10.1007/s00210-023-02778-x -
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 -
Journal of Forensic Sciences May 2024The increasing use and misuse of gabapentin pose a major risk to public health and traffic safety. Gabapentin has been approved by the Food and Drug Administration (FDA)...
The increasing use and misuse of gabapentin pose a major risk to public health and traffic safety. Gabapentin has been approved by the Food and Drug Administration (FDA) since 1993 for adjunctive therapy in the treatment of epilepsy and neuralgia but is increasingly being prescribed for numerous off-label uses including insomnia, anxiety, depression, and migraine. Reported side effects include blurred vision, drowsiness, and loss of coordination. Driving behaviors such as exiting the lane of travel and crashes have been reported in connection to drugged driving investigations concerning gabapentin. To further assist with the toxicological interpretation of gabapentin in driving under the influence of drugs (DUID) scenarios, a review of approximately 108,000 gabapentin-positive DUID cases was conducted. Of those, 858 cases met inclusion criteria and underwent additional evaluation. Blood specimens were screened via enzyme-linked immunosorbent assay (ELISA) and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for quantitation of gabapentin. This review found an overall DUID gabapentin positivity of 7.9% between January 2020 and December 2022; 17 states from various geographical regions had at least one positive gabapentin DUID case. Observations in six driving and human performance cases where gabapentin was the only drug reported were consistent with the known adverse effects of the medication. Half of the case histories reviewed involved crashes where the driver was determined to be at fault. Additionally, 94% of the cases in this review involved gabapentin in combination with other drugs. The most prevalent drug combinations were opioids and gabapentin present in 64% of cases.
Topics: Gabapentin; Humans; Driving Under the Influence; Tandem Mass Spectrometry; Chromatography, Liquid; Male; Enzyme-Linked Immunosorbent Assay; Adult; Female; Middle Aged; Forensic Toxicology
PubMed: 38402540
DOI: 10.1111/1556-4029.15500 -
Journal of Psychopharmacology (Oxford,... Aug 2023Ketamine may be effective in treating symptoms of anxiety, but the time profile of ketamine's anxiolytic effect is ill-defined. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ketamine may be effective in treating symptoms of anxiety, but the time profile of ketamine's anxiolytic effect is ill-defined. This systematic review and meta-analysis investigated the anxiolytic effect of ketamine at different time points across a range of clinical settings.
METHODS
Electronic databases were searched to capture randomised control trials measuring the anxiolytic effects of ketamine in contexts including mood disorders, anxiety disorders and chronic pain. Meta-analyses were conducted using a random-effects model. The correlations between (1) improvements in mean anxiety and depression scores, and (2) peak dissociation and improvements in mean anxiety scores were also assessed.
RESULTS
In all, 14 studies met inclusion criteria. Risk of bias was high in 11 studies. Ketamine significantly reduced anxiety scores compared to placebo at acute (<12 h; standard mean difference (SMD): -1.17, 95% confidence interval (CI) [-1.89, -0.44], < 0.01), subacute (24 h; SMD: -0.44, 95% CI [-0.65, -0.22], < 0.01) and sustained (7-14 days; SMD: -0.40, 95% CI [-0.63, -0.17], < 0.01) time points. Exploratory analyses revealed improvements in anxiety and depression symptoms correlated at both subacute ( = 0.621, = 0.035) and sustained time points ( = 0.773, = 0.021). The relationship between peak dissociation and improvement in anxiety was not significant.
CONCLUSIONS
Ketamine appears to offer rapid and sustained anxiety symptom relief across a range of clinical settings, with anxiolytic effects occurring within the first 12 h of administration and remaining effective for 1-2 weeks. Future studies could explore the effects of ketamine maintenance therapy on anxiety symptoms.
Topics: Humans; Ketamine; Anti-Anxiety Agents; Depression; Anxiety Disorders; Mood Disorders
PubMed: 37005739
DOI: 10.1177/02698811231161627 -
Current Pain and Headache Reports Sep 2023Almost half of people diagnosed with diabetes mellitus will develop painful diabetic neuropathy (PDN), a condition greatly impacting quality of life with complicated... (Review)
Review
PURPOSE OF REVIEW
Almost half of people diagnosed with diabetes mellitus will develop painful diabetic neuropathy (PDN), a condition greatly impacting quality of life with complicated pathology. While there are different FDA approved forms of treatment, many of the existing options are difficult to manage with comorbities and are associated with unwanted side effects. Here, we summarize the current and novel treatments for PDN.
RECENT FINDINGS
Current research is exploring alternative pain management treatments from the first line options of pregabalin, gabapentin, duloxetine, and amitriptyline which often have side effects. The use of FDA approved capsaicin and spinal cord stimulators (SCS) has been incredibly beneficial in addressing this. In addition, new treatments looking at different targets, such as NMDA receptor and the endocannabinoid system, show promising results. There are several treatment options that have been shown to be successful in helping treat PDN, but often require adjunct treatment or alterations due to side effects. While there is ample research for standard medications, treatments such as palmitoylethanolamide and endocannabinoid targets have extremely limited clinical trials. We also found that many studies did not evaluate additional variables other than pain relief, such as functional changes nor were there consistent measurement methods. Future research should continue trials comparing treatment efficacies along with more quality of life measures.
Topics: Humans; Diabetic Neuropathies; Quality of Life; Endocannabinoids; Gabapentin; Pregabalin; Diabetes Mellitus
PubMed: 37392335
DOI: 10.1007/s11916-023-01126-1 -
Drug Design, Development and Therapy 2024Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on... (Review)
Review
Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.
Topics: Humans; Anti-Anxiety Agents; Amidohydrolases; Monoacylglycerol Lipases; Animals; Endocannabinoids; Enzyme Inhibitors; Anxiety Disorders
PubMed: 38882045
DOI: 10.2147/DDDT.S462785 -
JAMA Network Open Oct 2023Children and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications...
IMPORTANCE
Children and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications are a common cost-effective approach to alleviating psychiatric symptoms, but evidence regarding their dispensation to children and adolescents with T1D remains lacking.
OBJECTIVE
To examine the trends and patterns of psychotropic medication dispensation among children and adolescents with T1D in Sweden between 2006 and 2019.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from multiple Swedish registers. The main study cohort included children and adolescents residing in Sweden from 2006 to 2019 and was followed up until the earliest of December 31, 2019, 18th birthday, emigration, or death. Data analyses were conducted from November 1, 2022, to April 30, 2023.
EXPOSURES
Type 1 diabetes.
MAIN OUTCOMES AND MEASURES
The primary outcomes were trends and patterns of psychotropic medication dispensation (including antipsychotics, antidepressants, anxiolytics, hypnotics, mood stabilizers, and medications for attention-deficit/hyperactivity disorder [ADHD]), psychotropic medication initiation, and history of neurodevelopmental and psychiatric diagnosis. Cumulative incidence curves and Cox proportional hazard models were used to estimate the aggregated incidence and hazard ratios of medication initiation after diabetes onset.
RESULTS
Of 3 723 745 children and adolescents (1 896 199 boys [50.9%]), 13 200 (0.4%; 7242 boys [54.9%]) had T1D (median [IQR] age at diagnosis, 11.1 [7.6-14.7] years). Between 2006 and 2019, psychotropic medication dispensation increased from 0.85% (95% CI, 0.65%-1.10%) to 3.84% (3.11%-4.69%) among children and from 2.72% (95% CI, 2.15%-3.39%) to 13.54% (95% CI, 12.88%-14.23%) among adolescents with T1D, consistently higher than their peers without T1D. The most commonly dispensed medications included hypnotics, ADHD medications, anxiolytics, and selective serotonin reuptake inhibitors, and all exhibited increasing trends. For those with T1D, psychiatric care was the primary prescription source, and up to 50.1% of treatments lasted more than 12 months. In addition, children and adolescents with T1D showed higher cumulative incidence and hazard ratios of medication initiation after diabetes onset than their same-age and same-sex counterparts.
CONCLUSIONS AND RELEVANCE
This cohort study found an increasing trend in psychotropic medication dispensation among children and adolescents with T1D from 2006 to 2019, persistently higher than those without T1D. These findings call for further in-depth investigations into the benefits and risks of psychotropic medications within this population and highlight the importance of integrating pediatric diabetes care and mental health care for early detection of psychological needs and careful monitoring of medication use.
Topics: Male; Child; Humans; Adolescent; Diabetes Mellitus, Type 1; Anti-Anxiety Agents; Cohort Studies; Psychotropic Drugs; Antidepressive Agents; Hypnotics and Sedatives
PubMed: 37787995
DOI: 10.1001/jamanetworkopen.2023.36621