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Pharmacology, Biochemistry, and Behavior Sep 2023Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications.... (Review)
Review
Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.
Topics: Humans; Cannabidiol; Cannabinoids; Cannabis; Hallucinogens; Attention Deficit Disorder with Hyperactivity; Dronabinol; Randomized Controlled Trials as Topic
PubMed: 37543051
DOI: 10.1016/j.pbb.2023.173607 -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
Journal of Affective Disorders Sep 2023Transcutaneous auricular vagus nerve stimulation (taVNS) is used for treating depression but the efficacy and safety have not been well assessed. This study was... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Transcutaneous auricular vagus nerve stimulation (taVNS) is used for treating depression but the efficacy and safety have not been well assessed. This study was conducted to evaluate the efficacy and safety of taVNS in depression.
METHODS
The retrieval databases included English databases of PubMed, Web of Science, Embase, the Cochrane Library and PsycINFO, and Chinese databases of CNKI, Wanfang, VIP and Sino Med, and the retrieval period was from their inception to November 10, 2022. The clinical trial registers (ClinicalTrials.gov and Chinese Clinical Trial Registry) were also searched. Standardized mean difference and the risk ratio were used as the effect indicator and the effect size was represented by the 95 % confidence interval. Revised Cochrane risk-of-bias tool for randomized trials and the Grades of Recommendation, Assessment, Development and Evaluation system were used to assess the risk of bias and quality of evidence respectively.
RESULTS
Totally, 12 studies of 838 participants were included. taVNS could significantly improve depression and reduce Hamilton Depression Scale scores. Low to very low evidence showed that taVNS had higher response rates than sham-taVMS and comparable response rates compared to antidepressants (ATD) and that taVNS combined with ATD had comparable efficacy to ATD with fewer side effects.
LIMITATIONS
The number of studies in subgroups was small and the evidence quality was low to very low.
CONCLUSIONS
taVNS is an effective and safe method for alleviating depression scores and had a comparable response rate to ATD.
Topics: Humans; Vagus Nerve Stimulation; Randomized Controlled Trials as Topic; Transcutaneous Electric Nerve Stimulation; Antidepressive Agents; Vagus Nerve; Depressive Disorder
PubMed: 37230264
DOI: 10.1016/j.jad.2023.05.048 -
The American Journal of Geriatric... Jan 2024Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a... (Meta-Analysis)
Meta-Analysis Review
AIM/HYPOTHESIS
Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a systematic review and meta-analysis to examine the antidepressant effects of GLP-1RAs.
METHODS
Randomized controlled trials and prospective cohort studies investigating the effects of GLP-1RAs versus placebo or other antidiabetic therapies on depressive symptoms were searched for using multiple electronic sources (CENTRAL, PubMed, EMBASE, PsycINFO, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, China Network Knowledge Infrastructure, China Biomedical Database, Wan Fang data, and Chinese Scientific Journals Database) from inception to February 16, 2023. We utilized a random effects model to analyze standardized mean differences for the change in depression rating scales comparing GLP-1RA treated groups with control treated groups.
RESULTS
The meta-analysis comprising 2,071 participants included 5 randomized controlled trials and 1 prospective cohort study. The meta-analysis indicated that the change from baseline in depression rating scale scores decreased significantly when patients received treatment with GLP-1RAs compared to control treatments (SMD = -0.12, 95% CI [-0.21, -0.03], p <0.01, I = 0%, p = 0.52). The subgroup analysis showed that the effects of GLP-1RAs on depressive symptoms were consistent in patients with Type 2 diabetes mellitus (SMD = -0.12, 95% CI [-0.21, -0.03], p <0.01, I = 2%, p = 0.40).
CONCLUSIONS
Adults treated with GLP-1RAs showed significant reductions in the depression rating scale scores compared to those treated with control substances. Our findings suggest that GLP-1RAs may be a potential treatment for alleviating depressive symptoms in humans.
Topics: Humans; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor Agonists; Prospective Studies; Hypoglycemic Agents; Antidepressive Agents
PubMed: 37684186
DOI: 10.1016/j.jagp.2023.08.010 -
Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y -
The Cochrane Database of Systematic... Aug 2023Prenatal exposure to certain anti-seizure medications (ASMs) is associated with an increased risk of major congenital malformations (MCM). The majority of women with... (Review)
Review
BACKGROUND
Prenatal exposure to certain anti-seizure medications (ASMs) is associated with an increased risk of major congenital malformations (MCM). The majority of women with epilepsy continue taking ASMs throughout pregnancy and, therefore, information on the potential risks associated with ASM treatment is required.
OBJECTIVES
To assess the effects of prenatal exposure to ASMs on the prevalence of MCM in the child.
SEARCH METHODS
For the latest update of this review, we searched the following databases on 17 February 2022: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to February 16, 2022), SCOPUS (1823 onwards), and ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP). No language restrictions were imposed.
SELECTION CRITERIA
We included prospective cohort controlled studies, cohort studies set within pregnancy registries, randomised controlled trials and epidemiological studies using routine health record data. Participants were women with epilepsy taking ASMs; the two control groups were women without epilepsy and untreated women with epilepsy.
DATA COLLECTION AND ANALYSIS
Five authors independently selected studies for inclusion. Eight authors completed data extraction and/or risk of bias assessments. The primary outcome was the presence of an MCM. Secondary outcomes included specific types of MCM. Where meta-analysis was not possible, we reviewed included studies narratively.
MAIN RESULTS
From 12,296 abstracts, we reviewed 283 full-text publications which identified 49 studies with 128 publications between them. Data from ASM-exposed pregnancies were more numerous for prospective cohort studies (n = 17,963), than data currently available for epidemiological health record studies (n = 7913). The MCM risk for children of women without epilepsy was 2.1% (95% CI 1.5 to 3.0) in cohort studies and 3.3% (95% CI 1.5 to 7.1) in health record studies. The known risk associated with sodium valproate exposure was clear across comparisons with a pooled prevalence of 9.8% (95% CI 8.1 to 11.9) from cohort data and 9.7% (95% CI 7.1 to 13.4) from routine health record studies. This was elevated across almost all comparisons to other monotherapy ASMs, with the absolute risk differences ranging from 5% to 9%. Multiple studies found that the MCM risk is dose-dependent. Children exposed to carbamazepine had an increased MCM prevalence in both cohort studies (4.7%, 95% CI 3.7 to 5.9) and routine health record studies (4.0%, 95% CI 2.9 to 5.4) which was significantly higher than that for the children born to women without epilepsy for both cohort (RR 2.30, 95% CI 1.47 to 3.59) and routine health record studies (RR 1.14, 95% CI 0.80 to 1.64); with similar significant results in comparison to the children of women with untreated epilepsy for both cohort studies (RR 1.44, 95% CI 1.05 to 1.96) and routine health record studies (RR 1.42, 95% CI 1.10 to 1.83). For phenobarbital exposure, the prevalence was 6.3% (95% CI 4.8 to 8.3) and 8.8% (95% CI 0.0 to 9277.0) from cohort and routine health record data, respectively. This increased risk was significant in comparison to the children of women without epilepsy (RR 3.22, 95% CI 1.84 to 5.65) and those born to women with untreated epilepsy (RR 1.64, 95% CI 0.94 to 2.83) in cohort studies; data from routine health record studies was limited. For phenytoin exposure, the prevalence of MCM was elevated for cohort study data (5.4%, 95% CI 3.6 to 8.1) and routine health record data (6.8%, 95% CI 0.1 to 701.2). The prevalence of MCM was higher for phenytoin-exposed children in comparison to children of women without epilepsy (RR 3.81, 95% CI 1.91 to 7.57) and the children of women with untreated epilepsy (RR 2.01. 95% CI 1.29 to 3.12); there were no data from routine health record studies. Pooled data from cohort studies indicated a significantly increased MCM risk for children exposed to lamotrigine in comparison to children born to women without epilepsy (RR 1.99, 95% CI 1.16 to 3.39); with a risk difference (RD) indicating a 1% increased risk of MCM (RD 0.01. 95% CI 0.00 to 0.03). This was not replicated in the comparison to the children of women with untreated epilepsy (RR 1.04, 95% CI 0.66 to 1.63), which contained the largest group of lamotrigine-exposed children (> 2700). Further, a non-significant difference was also found both in comparison to the children of women without epilepsy (RR 1.19, 95% CI 0.86 to 1.64) and children born to women with untreated epilepsy (RR 1.00, 95% CI 0.79 to 1.28) from routine data studies. For levetiracetam exposure, pooled data provided similar risk ratios to women without epilepsy in cohort (RR 2.20, 95% CI 0.98 to 4.93) and routine health record studies (RR 0.67, 95% CI 0.17 to 2.66). This was supported by the pooled results from both cohort (RR 0.71, 95% CI 0.39 to 1.28) and routine health record studies (RR 0.82, 95% CI 0.39 to 1.71) when comparisons were made to the offspring of women with untreated epilepsy. For topiramate, the prevalence of MCM was 3.9% (95% CI 2.3 to 6.5) from cohort study data and 4.1% (0.0 to 27,050.1) from routine health record studies. Risk ratios were significantly higher for children exposed to topiramate in comparison to the children of women without epilepsy in cohort studies (RR 4.07, 95% CI 1.64 to 10.14) but not in a smaller comparison to the children of women with untreated epilepsy (RR 1.37, 95% CI 0.57 to 3.27); few data are currently available from routine health record studies. Exposure in utero to topiramate was also associated with significantly higher RRs in comparison to other ASMs for oro-facial clefts. Data for all other ASMs were extremely limited. Given the observational designs, all studies were at high risk of certain biases, but the biases observed across primary data collection studies and secondary use of routine health records were different and were, in part, complementary. Biases were balanced across the ASMs investigated, and it is unlikely that the differential results observed across the ASMs are solely explained by these biases.
AUTHORS' CONCLUSIONS
Exposure in the womb to certain ASMs was associated with an increased risk of certain MCMs which, for many, is dose-dependent.
Topics: Pregnancy; Child; Female; Humans; Male; Prospective Studies; Topiramate; Lamotrigine; Phenytoin; Cohort Studies; Prenatal Exposure Delayed Effects; Epilepsy
PubMed: 37647086
DOI: 10.1002/14651858.CD010224.pub3 -
The Cochrane Database of Systematic... Sep 2023Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies.
OBJECTIVES
To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco.
SEARCH METHODS
We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), cluster-RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e-cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co-interventions (e.g. behavioural support) were eligible if the co-intervention was provided equally to study arms.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta-analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta-regression. We evaluated certainty using GRADE.
MAIN RESULTS
Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e-cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high-certainty evidence that nicotine e-cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high-certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate-certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low-certainty evidence), equating to one additional quitter (95% CrI -2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non-nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low-certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e-cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e-cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2).
AUTHORS' CONCLUSIONS
The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.
Topics: Adult; Female; Humans; Pregnancy; Bupropion; Electronic Nicotine Delivery Systems; Network Meta-Analysis; Nicotine; Nortriptyline; Smoking Cessation; Varenicline
PubMed: 37696529
DOI: 10.1002/14651858.CD015226.pub2 -
Cannabis and Cannabinoid Research Apr 2024One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these...
One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. and have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual. PROSPERO no. 135886.
Topics: Humans; Cannabinoids; Cannabis; Chronic Pain; Cannabinoid Receptor Agonists; Hallucinogens; Sleep Wake Disorders
PubMed: 36971587
DOI: 10.1089/can.2021.0156 -
Schizophrenia Bulletin Jan 2024Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. (Meta-Analysis)
Meta-Analysis
Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.
BACKGROUND AND HYPOTHESIS
Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia.
STUDY DESIGN
We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1.
STUDY RESULTS
Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations.
CONCLUSIONS
SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Aripiprazole; Olanzapine; Risperidone; Delayed-Action Preparations; Schizophrenia
PubMed: 37350486
DOI: 10.1093/schbul/sbad089 -
Biological Psychiatry Apr 2024Understanding the interactions between the gut microbiome and psychotropic medications (psycho-pharmacomicrobiomics) could improve treatment stratification strategies in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Understanding the interactions between the gut microbiome and psychotropic medications (psycho-pharmacomicrobiomics) could improve treatment stratification strategies in psychiatry. In this systematic review and meta-analysis, we first explored whether psychotropics modify the gut microbiome; second, we investigated whether the gut microbiome affects the efficacy and tolerability of psychotropics.
METHODS
Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched (November 2022) for longitudinal and cross-sectional studies that investigated the effect of psychotropics on the gut microbiome. The primary outcome was the difference in diversity metrics (alpha and beta) before and after treatment with psychotropics (longitudinal studies) and in medicated compared with unmedicated individuals (cross-sectional studies). Secondary outcomes included the association between gut microbiome and efficacy and tolerability outcomes. Random effect meta-analyses were conducted on alpha diversity metrics, while beta diversity metrics were pooled using distance data extracted from graphs. Summary statistics included standardized mean difference and Higgins I for alpha diversity metrics and F and R values for beta diversity metrics.
RESULTS
Nineteen studies were included in our synthesis; 12 investigated antipsychotics and 7 investigated antidepressants. Results showed significant changes in alpha (4 studies; standard mean difference: 0.12; 95% CI: 0.01-0.23; p = .04; I: 14%) and beta (F = 15.59; R = 0.05; p < .001) diversity metrics following treatment with antipsychotics and antidepressants, respectively. Altered gut microbiome composition at baseline was associated with tolerability and efficacy outcomes across studies, including response to antidepressants (2 studies; alpha diversity; standard mean difference: 2.45; 95% CI: 0.50-4.40; p < .001, I: 0%).
CONCLUSIONS
Treatment with psychotropic medications is associated with altered gut microbiome composition, and the gut microbiome may in turn influence the efficacy and tolerability of these medications.
Topics: Humans; Cross-Sectional Studies; Psychotropic Drugs; Antidepressive Agents; Antipsychotic Agents; Gastrointestinal Microbiome
PubMed: 37567335
DOI: 10.1016/j.biopsych.2023.07.019