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Journal of Cardiothoracic and Vascular... Mar 2024The potential risks associated with the use of levosimendan in the pediatric population has not been systematically evaluated. This study aimed to review the available... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The potential risks associated with the use of levosimendan in the pediatric population has not been systematically evaluated. This study aimed to review the available evidence regarding the safety of this treatment.
METHODS
Bio Med Central, PubMed, Embase, and the Cochrane Central Register of clinical trials were searched for studies describing levosimendan administration in the pediatric population in any setting. Relevant studies were independently screened, selected, and their data extracted by two investigators. The authors excluded: reviews, meta-analyses, as well as basic research and trials involving patients >18 years old. The primary outcome was the number and the type of adverse side effects reported during levosimendan administration.
RESULTS
The updated systematic review included 48 studies, enrolling a total of 1,271 pediatric patients who received levosimendan as treatment (790 patients in the 11 studies that reported side effects). The primary adverse effects of levosimendan administration were hypotension and cardiac arrhythmias, particularly tachycardia. Hypotension occurred in approximately 28.9% of patients, while arrhythmia occurred in about 12.3% of patients. Meta analysis of RCTs revealed a rate of all-cause mortality of 2.0% (8 out of 385) in the levosimendan group compared to 3.9% (15 out of 378) in the control group (dobutamine, milrinone or placebo) (risk ratio [RR] = 0.55; 95% confidence interval [CI] = 0.25-1.21; P = 0.14; I = 0%) CONCLUSIONS: Hypotension and cardiac arrhythmia are the most reported side effects of levosimendan in pediatric patients. However, adverse events remain underreported, especially in randomized trials.
Topics: Humans; Child; Adolescent; Simendan; Hydrazones; Pyridazines; Dobutamine; Arrhythmias, Cardiac; Hypotension
PubMed: 38135567
DOI: 10.1053/j.jvca.2023.11.020 -
Toxicology Letters Jan 2024This systematic review aimed to assess the association between neuropsychiatric effects of substance use and occurrence of ER stress and unfolded protein response (UPR)...
INTRODUCTION
This systematic review aimed to assess the association between neuropsychiatric effects of substance use and occurrence of ER stress and unfolded protein response (UPR) through comprehensive electronic search of existing literature and review of their findings.
METHODS
A comprehensive electronic literature search was carried out on research articles published between 1950 to July 2023 through major databases, such as Scopus, Web of Science, Google Scholar, PubMed, PsycINFO, EMBASE, Medline and Cochrane Library.
RESULTS
A total of 21 research articles were selected for review, which were comprised of sixteen animal studies, four human studies and one study on postmortem human brain samples. The selected studies revealed that alcohol, methamphetamine, cocaine, opioid and kratom exposures contributed to neuropsychiatric effects: such as decline in learning and memory function, executive dysfunction, alcohol, methamphetamine, opioid, and kratom dependence. These effects were associated with activation and persistent of ER stress and UPR with elevation of BiP and CHOP expression and the direction of ER stress is progressing towards the PERK-eIF2α-ATF4-CHOP pathway and neuronal apoptosis and neurodegeneration at various regions of the brain. In addition, regular kratom use in humans also contributed to elevation of p-JNK expression, denoting progress of ER stress towards the IRE1-ASK1-JNK-p-JNK pathway which was linked to kratom use disorder. However, treatment with certain compounds or biological agents could reverse the activation of ER stress.
CONCLUSIONS
The neuropsychiatric effects of alcohol, methamphetamine, cocaine, opioid and kratom use may be associated with persistent ER stress and UPR.
Topics: Animals; Humans; Endoplasmic Reticulum Stress; eIF-2 Kinase; Analgesics, Opioid; Unfolded Protein Response; Endoplasmic Reticulum; Apoptosis; Methamphetamine; Substance-Related Disorders; Cocaine
PubMed: 38101493
DOI: 10.1016/j.toxlet.2023.12.008 -
The Cochrane Database of Systematic... Dec 2023Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme... (Review)
Review
BACKGROUND
Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme deficiency; people with late-onset Pompe disease (LOPD) retain some residual enzyme activity. GAA deficiency is treated with an intravenous infusion of recombinant human acid alglucosidase alfa, an enzyme replacement therapy (ERT). Alglucosidase alfa and avalglucosidase alfa are approved treatments, but cipaglucosidase alfa with miglustat is not yet approved.
OBJECTIVES
To assess the effects of enzyme replacement therapies in people with late-onset Pompe disease.
SEARCH METHODS
We searched the Cochrane Inborn Errors of Metabolism Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched MEDLINE OvidSP, clinical trial registries, and the reference lists of relevant articles and reviews. Date of last search: 21 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of ERT in people with LOPD of any age.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias and the certainty of the evidence (using GRADE). We resolved disagreements through discussion and by consulting a third author.
MAIN RESULTS
We included six trials (358 randomised participants) lasting from 12 to 78 weeks. A single trial reported on each comparison listed below. None of the included trials assessed two of our secondary outcomes: need for respiratory support and use of a walking aid or wheelchair. Certainty of evidence was most commonly downgraded for selective reporting bias. Alglucosidase alfa versus placebo (90 participants) After 78 weeks, alglucosidase alfa probably improves the six-minute walk test (6MWT) distance compared to placebo (mean difference (MD) 30.95 metres, 95% confidence interval (CI) 7.98 to 53.92; moderate-certainty evidence) and probably improves respiratory function, measured as the change in per cent (%) predicted forced vital capacity (FVC) (MD 3.55, 95% CI 1.46 to 5.64; moderate-certainty evidence). There may be little or no difference between the groups in occurrence of infusion reactions (risk ratio (RR) 1.21, 95% CI 0.57 to 2.61; low-certainty evidence), quality of life physical component score (MD -1.36 points, 95% CI -5.59 to 2.87; low-certainty evidence), or adverse events (RR 0.94, 95% CI 0.64 to 1.39; low-certainty evidence). Alglucosidase alfa plus clenbuterol versus alglucosidase alfa plus placebo (13 participants) The evidence is very uncertain about the effect of alglucosidase alfa plus clenbuterol compared to alglucosidase alfa plus placebo on: change in 6MWT distance after 52 weeks (MD 34.55 metres, 95% CI-10.11 to 79.21; very low-certainty evidence) and change in % predicted FVC (MD -13.51%, 95% CI -32.44 to 5.41; very low-certainty evidence). This study did not measure infusion reactions, quality of life, and adverse events. Alglucosidase alfa plus albuterol versus alglucosidase alfa plus placebo (13 participants) The evidence is very uncertain about the effect of alglucosidase alfa plus albuterol compared to alglucosidase alfa plus placebo on: change in 6MWT distance after 52 weeks (MD 30.00 metres, 95% CI 0.55 to 59.45; very low-certainty evidence), change in % predicted FVC (MD -4.30%, 95% CI -14.87 to 6.27; very low-certainty evidence), and risk of adverse events (RR 0.67, 95% CI 0.38 to 1.18; very low-certainty evidence). This study did not measure infusion reactions and quality of life. VAL-1221 versus alglucosidase alfa (12 participants) Insufficient information was available about this trial to generate effect estimates measured at one year or later. Compared to alglucosidase alfa, VAL-1221 may increase or reduce infusion-associated reactions at three months, but the evidence is very uncertain (RR 2.80, 95% CI 0.18 to 42.80). This study did not measure quality of life and adverse events. Cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo (125 participants) Compared to alglucosidase alfa plus placebo, cipaglucosidase alfa plus miglustat may make little or no difference to: 6MWT distance at 52 weeks (MD 13.60 metres, 95% CI -2.26 to 29.46); infusion reactions (RR 0.94, 95% CI 0.49 to 1.80); quality of life scores for physical function (MD 1.70, 95% CI -2.13 to 5.53) and fatigue (MD -0.30, 95% CI -2.76 to 2.16); and adverse effects potentially related to treatment (RR 0.83, 95% CI 0.49 to 1.40) (all low-certainty evidence). Cipaglucosidase alfa plus miglustat probably improves % predicted FVC compared to alglucosidase alfa plus placebo (MD 3.10%, 95% CI 1.04 to 5.16; moderate-certainty evidence); however, it may make little or no change in % predicted sniff nasal inspiratory pressure (MD -0.06%, 95% CI -8.91 to 7.71; low-certainty evidence). Avalglucosidase alfa versus alglucosidase alfa (100 participants) After 49 weeks, avalglucosidase alfa probably improves 6MWT compared to alglucosidase alfa (MD 30.02 metres, 95% CI 1.84 to 58.20; moderate-certainty evidence). Avalglucosidase alfa probably makes little or no difference to % predicted FVC compared to alglucosidase alfa (MD 2.43%, 95% CI -0.08 to 4.94; moderate-certainty evidence). Avalglucosidase alfa may make little or no difference to infusion reactions (RR 0.78, 95% CI 0.42 to 1.45), quality of life (MD 0.77, 95% CI -2.09 to 3.63), or treatment-related adverse events (RR 0.92, 95% CI 0.61 to 1.40), all low-certainty evidence.
AUTHORS' CONCLUSIONS
One trial compared the effect of ERT to placebo in LOPD, showing that alglucosidase alfa probably improves 6MWT and respiratory function (both moderate-certainty evidence). Avalglucosidase alfa probably improves 6MWT compared with alglucosidase alfa (moderate-certainty evidence). Cipaglucosidase plus miglustat probably improves FVC compared to alglucosidase alfa plus placebo (moderate-certainty evidence). Other trials studied the adjunct effect of clenbuterol and albuterol along with alglucosidase alfa, with little to no evidence of benefit. No significant rise in adverse events was noted with all ERTs. The impact of ERT on some outcomes remains unclear, and longer RCTs are needed to generate relevant information due to the progressive nature of LOPD. Alternative resources, such as post-marketing registries, could capture some of this information.
Topics: Humans; Glycogen Storage Disease Type II; Enzyme Replacement Therapy; Clenbuterol; Albuterol
PubMed: 38084761
DOI: 10.1002/14651858.CD012993.pub2 -
The Korean Journal of Internal Medicine Jan 2024There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB.
METHODS
A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review.
RESULTS
We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc.
CONCLUSION
The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.
Topics: Humans; Anemia; Anticoagulants; Diltiazem; Gastrointestinal Hemorrhage; Gemfibrozil; Heart Failure; Helicobacter Infections; Helicobacter pylori; Myocardial Infarction; Risk Factors; Verapamil
PubMed: 38062723
DOI: 10.3904/kjim.2023.098 -
The International Journal on Drug Policy Jan 2024International efforts have reduced the availability of methamphetamine precursors, but its distribution and use continue to rise. Methamphetamine use can lead to short-... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
International efforts have reduced the availability of methamphetamine precursors, but its distribution and use continue to rise. Methamphetamine use can lead to short- and long-term adverse effects, including addiction, physical and psychosocial health problems, socioeconomic troubles, incarceration, overdose, and death. Gay, bisexual, and other men who have sex with men (MSM) have been shown to have an elevated prevalence of methamphetamine use.
METHODS
We conducted a systematic review and meta-analysis to estimate the prevalence of methamphetamine use among MSM. We searched electronic databases, such as PubMed, for peer-reviewed literature published between 2011 and 2022. Data on methamphetamine use were extracted, including study features, location, study design, sampling method, recruitment period, specific MSM subgroups, prevalence period, and demographics. Employing a random-effects model, we computed the pooled prevalence of methamphetamine use among MSM across two prevalence periods: recent use (i.e., one month, three months, six months, one year) and lifetime use.
RESULTS
The systematic review included 56 studies with a total of 25,953 MSM who use methamphetamine. Most studies were conducted in Europe, with the highest prevalence reported in the United Kingdom. The studies primarily used cross-sectional or cohort study designs with convenience sampling. The pooled prevalence rates across recent use (i.e., past month, past three months, past six months, and past year) was 15% (95% CI [11-19%]). Additionally, we pooled lifetime use, which was 23% (95% CI [9-38%]). High heterogeneity (I > 99%) was observed, indicating significant variation.
CONCLUSION
This systematic review and meta-analysis provide a pooled prevalence of methamphetamine use among MSM. The analysis accounts for study design, prevalence period, specific MSM subgroups, and geographical areas to estimate methamphetamine use in diverse settings and populations. The review highlights the need for targeted interventions and harm reduction strategies focused on prevention, education, healthcare access, and stakeholder collaboration to address the multifaceted challenges of methamphetamine use among MSM.
Topics: Humans; Male; Cohort Studies; Cross-Sectional Studies; HIV Infections; Homosexuality, Male; Methamphetamine; Prevalence; Sexual and Gender Minorities; Recreational Drug Use
PubMed: 38061224
DOI: 10.1016/j.drugpo.2023.104271 -
Psychiatry Research Jan 2024Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a... (Meta-Analysis)
Meta-Analysis
Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that reduces cravings by altering cortical excitability and connectivity in brain regions. This systematic review and meta-analysis was conducted (following the PRISMA guidelines) to evaluate the efficacy of tDCS in reducing cravings for substances. Our analysis included 43 randomized, sham-controlled trials involving 1,095 and 913 participants receiving tDCS and sham stimulation, respectively. We analyzed the changes in craving scores and found that tDCS led to a moderate reduction in cravings compared with the sham effects. This effect was particularly pronounced when bilateral stimulation was used, the anodal electrode was placed on the right dorsolateral prefrontal cortex, current intensities ranged from 1.5 to 2 mA, stimulation sessions lasted 20 minutes, and the electrodes size was ≥35 cm². Notably, tDCS effectively reduced cravings for opioids, methamphetamine, cocaine, and tobacco but not for alcohol or cannabis. Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco. Additional studies are warranted to refine stimulation parameters and evaluate the long-term efficacy of tDCS in managing substance cravings.
Topics: Humans; Transcranial Direct Current Stimulation; Craving; Prefrontal Cortex; Substance-Related Disorders; Methamphetamine; Cocaine; Double-Blind Method
PubMed: 38043411
DOI: 10.1016/j.psychres.2023.115621 -
The Cochrane Database of Systematic... Nov 2023A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines.
OBJECTIVES
To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses.
MAIN RESULTS
Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low.
AUTHORS' CONCLUSIONS
In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
Topics: Adult; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Fluoxetine; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Alprazolam; Clomipramine; Reboxetine; Clonazepam; Desipramine; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Tricyclic; Benzodiazepines; Diazepam
PubMed: 38014714
DOI: 10.1002/14651858.CD012729.pub3 -
Journal of Psychopharmacology (Oxford,... Jan 2024Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT),... (Review)
Review
Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug-drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.
Topics: Humans; Hallucinogens; Psilocybin; Mescaline; N,N-Dimethyltryptamine; Drug Interactions; Lysergic Acid Diethylamide
PubMed: 37982394
DOI: 10.1177/02698811231211219 -
Drug and Alcohol Dependence Dec 2023This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion efficacy and safety for amphetamine-type stimulant use disorder (ATSUD) treatment.
METHOD
Electronic databases were searched for records published to October 31st, 2022, including MEDLINE, CINAHL, PsycINFO, EBM Reviews, EMBASE, PubMed, Web of Science, trial registries. Inclusion criteria were RCTs comparing bupropion to placebo in ATSUD. Cochrane RoB2 tool and GRADE evidence certainty assessment were employed. Outcomes included amphetamine-type stimulant (ATS) use by urinalysis, retention in treatment, treatment adherence, ATS craving, addiction severity, depressive symptom severity, drop-out following adverse events (AEs), and serious AEs. Random-effect meta-analysis was conducted presenting standardized mean difference (SMD), risk ratio (RR), and risk difference (RD).
RESULTS
Eight RCTs (total N=1239 participants) were included. Bupropion compared to placebo was associated with reduced ATS use (RR: 0.90; 95% CI: 0.84, 0.96), end-of-treatment ATS craving (SMD: -0.38; 95%CI: -0.63, -0.13), and adherence (RR: 0.91; 95%CI: 0.84, 0.99). Subgroup analysis showed greater reduction in ATS use with longer trial duration (12 weeks) (RR: 0.85; 95%CI: 0.78, 0.93) and greater reduction in end-of-treatment ATS craving in studies with mixed ATS use frequency (SMD: -0.46; 95%CI: -0.70, -0.22) and male-only samples (SMD: -1.26; 95%CI: -1.87, -0.65).
CONCLUSION
Bupropion showed a significant modest reduction in ATS use and ATS craving (both rated as very low-quality evidence), larger in males (craving), and with longer treatment (ATS use). These results may inform future studies. More research is warranted on who might benefit from bupropion as ATSUD treatment.
Topics: Male; Humans; Bupropion; Randomized Controlled Trials as Topic; Substance-Related Disorders; Amphetamines
PubMed: 37979478
DOI: 10.1016/j.drugalcdep.2023.111018 -
Sexual Medicine Reviews Dec 2023Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions...
INTRODUCTION
Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions encompass pharmaceutical and psychological treatments. Unconventional therapies, like MDMA, offer hope for sexual dysfunction. This review delves into MDMA's effects on sexual responsiveness and its potential role in treating sexual dysfunction.
OBJECTIVES
The purpose of this review is to elucidate effects of MDMA on different domains of the female and male sexual response cycles.
METHODS
We conducted a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, MEDLINE, and EMBASE were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were "MDMA" or "ecstasy" in combination with "desire," "arousal," "lubrication," "orgasm," "pleasure," "libido," "erection," and "ejaculation." Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least 1 domain of the female and/or male sexual response cycles were described and measured. Randomized controlled trials, cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis.
RESULTS
We identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle and 8 met criteria for assessment of the male sexual response cycle. Four of 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of 4 studies, but they were not affected in 1 randomized control study. In men, 7 studies evaluated the effects of MDMA on desire and/or arousal, 5 studies measured impact on erection, 3 on orgasm, and 2 on ejaculation. Sixty percent of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies evaluating orgasm reported delay in achieving orgasm but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative.
CONCLUSION
Our findings suggest that MDMA generally increases sexual desire and intensifies orgasm when achieved. While producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile and ejaculatory function in men.
Topics: Female; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Prospective Studies; Retrospective Studies; Sexual Behavior; Sexual Dysfunction, Physiological
PubMed: 37888490
DOI: 10.1093/sxmrev/qead046