-
Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta-analysis.Birth Defects Research Aug 2020Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital... (Meta-Analysis)
Meta-Analysis
Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital malformations (MCM), cardiac defects and orofacial clefts associated with first trimester exposure to ondansetron using a meta-analytic approach. MEDLINE, ClinicalTrials.gov and Scopus were searched until November 2019. All comparative cohort and case-control studies on MCM, cardiac or orofacial defects and use of ondansetron during pregnancy were included. A team of paired reviewers independently extracted data using a proprietary collaborative WEB-based meta-analysis platform (metaPreg.org). Pooled odd ratios with corresponding 95% CIs were calculated using random effects models. From 214 records initially retrieved, 12 studies were included. Using all available information to date, first trimester exposure to ondansetron was found to be associated with an increased risk of (a) ventricular septal defects (VSD) (OR 1.11, 95% CI 1.00-1.23; p < .05; n = 6 studies; I = 0%) and (b) oral clefts (OR 1.22, 95% CI 1.00-1.49; p < .05; n = 4 studies; I = 0%). No significant association was observed for the risk of cleft palate but, when excluding the study that contributed to the study heterogeneity, we found an OR of 1.48 (95% CI 1.19-1.84; p < .01; n = 5 studies; I = 0%). No statistically significant association was found for MCM, overall cardiac malformations, atrial septal defects and cleft lip with or without cleft palate. Exploratory investigations of other malformations showed an increased risk of diaphragmatic hernia, hypoplastic left heart and "respiratory system anomalies."
Topics: Abnormalities, Drug-Induced; Antiemetics; Cleft Lip; Cleft Palate; Female; Humans; Ondansetron; Pregnancy
PubMed: 32420702
DOI: 10.1002/bdr2.1705 -
Scientific Reports Nov 2023Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in augmentation with selective serotonin reuptake inhibitors (SSRIs) in the treatment of moderate to severe obsessive-compulsive disorder: a systematic review and meta-analysis of randomized clinical trials.
Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its pharmacological treatment. About 40-60% of the cases are treatment-refractory, and this makes searching for second-line treatment necessary. 5-Hydroxytryptamine-3 (5-HT3) antagonists are among the many medications that have been used in augmentation with SSRIs. In this systematic review and meta-analysis, we assessed the efficacy and safety of 5-HT3 receptor antagonists in augmentation with SSRIs in treating moderate to severe OCD. We searched PubMed, Web of Science, Scopus, Cochrane library, and Google Scholar for relevant trials published up to December 2022. The effect size was the mean difference in Yale-Brown obsessive compulsive scale (Y-BOCS) scores before and after receiving 5-HT3 receptor antagonist drugs in augmentation with SSRIs in moderate to severe OCD patients. We included 6 randomized-controlled trails (RCTs) with 334 patients assessing the effect of the augmentation of SSRIs with ondansetron, granisetron, and tropisetron on treating moderate to severe OCD. Our results were in favor of the experimental group in total (Z = 8.37, P < 0.00001), in the compulsion subgroup (Z = 5.22, P < 0.00001), and in the obsession subgroup (Z = 8.33, P < 0.00001). They are well-tolerated, and have mild side effects and do not result in withdrawal. Augmentation of 5-HT3 antagonists with SSRIs can be beneficial in treating moderate to severe OCD. Further multi-center trials under adequate conditions in longer periods are needed to help come up with a comprehensive action plan.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Serotonin; Receptors, Serotonin, 5-HT3; Treatment Outcome; Randomized Controlled Trials as Topic; Obsessive-Compulsive Disorder; Drug Therapy, Combination
PubMed: 38012263
DOI: 10.1038/s41598-023-47931-x -
Frontiers in Pharmacology 2023Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of...
Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of chemotherapy-induced nausea and vomiting (CINV) is of main concern. Ondansetron is a selective serotonin 5-HT3 receptor antagonist that has emerged as an essential medication against CINV in adult cancer patients. Ondansetron efficacy and tolerability have made it a primary medication in CINV prophylaxis and treatment regimens. The study aims to offer a detailed overview of ondansetron's effectiveness, safety, and impact on patients' lives, ultimately contributing to the ongoing research to enhance the quality of cancer care. On 4 September 2023, a search was conducted of the ClinicalTrials.gov database using the search terms "cancer," "ondansetron," and "Zofran." Inclusion and exclusion criteria were defined to select relevant clinical trials. Included trials were completed with results and interventional studies that assessed the preventive effects of ondansetron on CINV in adult cancer patients. A total of 23 clinical trials were identified, with only 13 of them focusing on investigating the preventive effects of ondansetron on CINV in adult cancer patients. The collective findings from these trials showed an effective management of CINV using ondansetron. Through a comprehensive overview of clinical trials, the use of ondansetron in adult cancer patients represents a significant improvement in CINV management.
PubMed: 38074143
DOI: 10.3389/fphar.2023.1310455 -
Anesthesia and Analgesia Jan 2024Pruritus is a frequently reported and unpleasant side effect following intrathecal opioid use with frequency further increased among parturients. We have performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pruritus is a frequently reported and unpleasant side effect following intrathecal opioid use with frequency further increased among parturients. We have performed a systematic review to assess the overall efficacy of ondansetron for the prevention of pruritus in patients receiving intrathecal opioid as part of spinal anesthesia for cesarean delivery.
METHODS
A literature search of MEDLINE, Embase, Cochrane, and Web of Science databases was conducted from date of inception to September 2022. Studies that included patients undergoing cesarean delivery with spinal anesthesia using intrathecal opioid were included. The primary outcome was the presence of pruritus, and the secondary outcome was time to onset of pruritus. Data from included studies were pooled for analysis using an appropriately determined random-effects model. Outcomes were presented using forest plots and 95% confidence intervals. Additional sensitivity and subgroup analysis were performed. Trial sequential analysis was conducted for the primary outcome.
RESULTS
Twenty-three randomized controlled trials with a total of 2586 patients were included: 1219 received ondansetron, 1030 received a placebo, and a further 337 received a different study drug and were excluded from analysis. Opioids used in the included studies were morphine, fentanyl, and sufentanil. Patients who received ondansetron showed a significant reduction in the incidence of pruritus compared to the control group (RR, 0.81; 95% confidence interval [CI], 0.71-0.92; I 2 = 64%). There was no significant difference in pruritus onset between the groups (mean difference [MD], 17.54 minutes; 95% CI, -2.18 to 37.26; I 2 = 83%). The overall Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment of quality of evidence was low.
CONCLUSIONS
This systematic review has demonstrated a significant reduction in the incidence of pruritus following the use of ondansetron. This is in contrast to previously published meta-analyses. Studies included were of varying quality and some at high risk of bias with a high degree of statistical heterogeneity. Furthermore, high-quality and well-powered studies are required to confirm these findings.
Topics: Pregnancy; Humans; Female; Ondansetron; Analgesics, Opioid; Postoperative Nausea and Vomiting; Pruritus; Fentanyl; Morphine; Randomized Controlled Trials as Topic
PubMed: 37167702
DOI: 10.1213/ANE.0000000000006526 -
Clinical Pharmacology and Therapeutics May 2022Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to...
Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically-based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug-specific model inputs were parameterized using data from the literature. Population-specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure (CUDDLE) study. The final model predicted breast milk and plasma exposures following a single 4 mg dose of intravenous ondansetron in 1,000 simulated women who were 2 days postpartum. Model predictions showed good agreement with observed data. Breast milk median prediction error (MPE) was 18.4% and median absolute prediction error (MAPE) was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model-predicted daily and relative infant doses were 0.005 mg/kg/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open-source and can be adapted to other drugs.
Topics: Female; Humans; Infant; Breast Feeding; Lactation; Milk, Human; Ondansetron; Postpartum Period
PubMed: 35076931
DOI: 10.1002/cpt.2530 -
The Cochrane Database of Systematic... Jun 2024Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are available to control postburn pruritus; however, it remains unclear how effective these are.
OBJECTIVES
To assess the effects of interventions for treating postburn pruritus in any care setting.
SEARCH METHODS
In September 2022, we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched clinical trials registries and scanned references of relevant publications to identify eligible trials. There were no restrictions with respect to language, publication date, or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that enrolled people with postburn pruritus to compare an intervention for postburn pruritus with any other intervention, placebo or sham intervention, or no intervention.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 25 RCTs assessing 21 interventions with 1166 randomised participants. These 21 interventions can be grouped into six categories: neuromodulatory agents (such as doxepin, gabapentin, pregabalin, ondansetron), topical therapies (such as CQ-01 hydrogel, silicone gel, enalapril ointment, Provase moisturiser, beeswax and herbal oil cream), physical modalities (such as massage therapy, therapeutic touch, extracorporeal shock wave therapy, enhanced education about silicone gel sheeting), laser scar revision (pulsed dye laser, pulsed high-intensity laser, fractional CO2 laser), electrical stimulation (transcutaneous electrical nerve stimulation, transcranial direct current stimulation), and other therapies (cetirizine/cimetidine combination, lemon balm tea). Most RCTs were conducted at academic hospitals and were at a high risk of performance, attrition, and detection bias. While 24 out of 25 included studies reported change in burn-related pruritus, secondary outcomes such as cost-effectiveness, pain, patient perception, wound healing, and participant health-related quality of life were not reported or were reported incompletely. Neuromodulatory agents versus antihistamines or placebo There is low-certainty evidence that doxepin cream may reduce burn-related pruritus compared with oral antihistamine (mean difference (MD) -2.60 on a 0 to 10 visual analogue scale (VAS), 95% confidence interval (CI) -3.79 to -1.42; 2 studies, 49 participants). A change of 2 points represents a minimal clinically important difference (MCID). Due to very low-certainty evidence, it is uncertain whether doxepin cream impacts the incidence of somnolence as an adverse event compared to oral antihistamine (risk ratio (RR) 0.64, 95% CI 0.32 to 1.25; 1 study, 24 participants). No data were reported on pain in the included study. There is low-certainty evidence that gabapentin may reduce burn-related pruritus compared with cetirizine (MD -2.40 VAS, 95% CI -4.14 to -0.66; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that gabapentin reduces the incidence of somnolence compared to cetirizine (RR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants). No data were reported on pain in the included study. There is low-certainty evidence that pregabalin may result in a reduction in burn-related pruritus intensity compared with cetirizine with pheniramine maleate (MD -0.80 VAS, 95% CI -1.24 to -0.36; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that pregabalin reduces the incidence of somnolence compared to cetirizine (RR 0.04, 95% CI 0.00 to 0.69; 1 study, 40 participants). No data were reported on pain in the included study. There is moderate-certainty evidence that ondansetron probably results in a reduction in burn-related pruritus intensity compared with diphenhydramine (MD -0.76 on a 0 to 10 numeric analogue scale (NAS), 95% CI -1.50 to -0.02; 1 study, 38 participants). A change of 2 points represents a MCID. No data were reported on pain and adverse events in the included study. Topical therapies versus relevant comparators There is moderate-certainty evidence that enalapril ointment probably decreases mean burn-related pruritus compared with placebo control (MD -0.70 on a 0 to 4 scoring table for itching, 95% CI -1.04 to -0.36; 1 study, 60 participants). No data were reported on pain and adverse events in the included study. Physical modalities versus relevant comparators Compared with standard care, there is low-certainty evidence that massage may reduce burn-related pruritus (standardised mean difference (SMD) -0.86, 95% CI -1.45 to -0.27; 2 studies, 166 participants) and pain (SMD -1.32, 95% CI -1.66 to -0.98). These SMDs equate to a 4.60-point reduction in pruritus and a 3.74-point reduction in pain on a 10-point VAS. A change of 2 VAS points in itch represents a MCID. No data were reported on adverse events in the included studies. There is low-certainty evidence that extracorporeal shock wave therapy (ESWT) may reduce burn-related pruritus compared with sham stimulation (SMD -1.20, 95% CI -1.65 to -0.75; 2 studies, 91 participants). This equates to a 5.93-point reduction in pruritus on a 22-point 12-item Pruritus Severity Scale. There is low-certainty evidence that ESWT may reduce pain compared with sham stimulation (MD 2.96 on a 0 to 25 pressure pain threshold (PPT), 95% CI 1.76 to 4.16; 1 study, 45 participants). No data were reported on adverse events in the included studies. Laser scar revision versus untreated or placebo controls There is moderate-certainty evidence that pulsed high-intensity laser probably results in a reduction in burn-related pruritus intensity compared with placebo laser (MD -0.51 on a 0 to 1 Itch Severity Scale (ISS), 95% CI -0.64 to -0.38; 1 study, 49 participants). There is moderate-certainty evidence that pulsed high-intensity laser probably reduces pain compared with placebo laser (MD -3.23 VAS, 95% CI -5.41 to -1.05; 1 study, 49 participants). No data were reported on adverse events in the included studies.
AUTHORS' CONCLUSIONS
There is moderate to low-certainty evidence on the effects of 21 interventions. Most studies were small and at a high risk of bias related to blinding and incomplete outcome data. Where there is moderate-certainty evidence, practitioners should consider the applicability of the evidence for their patients.
Topics: Humans; Pruritus; Burns; Randomized Controlled Trials as Topic; Bias; Antipruritics
PubMed: 38837237
DOI: 10.1002/14651858.CD013468.pub2 -
Turkish Journal of Obstetrics and... Jun 2022This investigation examined the efficacy of ondansetron (intervention) versus metoclopramide (control) in managing parturient females with hyperemesis gravidarum (HG),...
This investigation examined the efficacy of ondansetron (intervention) versus metoclopramide (control) in managing parturient females with hyperemesis gravidarum (HG), by pooling data from randomized controlled trials (RCTs) using a meta-analysis approach. From inception until January 2022, five information sources were screened: Cochrane Central Register of Controlled Trials, Google Scholar, Scopus, PubMed and Web of Science. Quality assessment was done through the Cochrane Risk of Bias (version 2) assessment tool. The mean difference (MD) with 95% confidence interval (CI) was used to summarize the continuous data in a fixed- or random-effects model, depending on the extent of between-study heterogeneity. Five RCTs were included, comprising a total of 695 patients (355 and 340 females were assigned to ondansetron and metoclopramide, respectively). Four RCTs had an overall "low" risk of bias, whereas one RCT had an overall "some concerns" due to lack of sufficient information about randomization. There was no significant difference between both groups regarding the pregnancy-unique quantification of emesis and nausea score [MD=0.23, 95% CI (-0.42, 0.88), p=0.49], length of hospital stay [MD=-0.17 days, 95% CI (-0.35, 0.02), p=0.08], the number of doses of drug received [MD=0.45, 95% CI (-0.08, 0.98), p=0.10], and duration of intravenous fluids [MD=-1.73 hours, 95% CI (-5.79, 2.33), p=0.40]. Among parturient females with HG, there was no substantial difference in efficacy between both agents. Nevertheless, ondansetron is favored over metoclopramide in view of its trending therapeutic efficacy and better safety profile.
PubMed: 35770443
DOI: 10.4274/tjod.galenos.2022.14367 -
European Journal of Pediatrics Jul 2020This review aimed to meta-analyze evidence of efficacy and safety of one single dose of ondansetron for vomiting in children and adolescents with acute gastroenteritis.... (Meta-Analysis)
Meta-Analysis
This review aimed to meta-analyze evidence of efficacy and safety of one single dose of ondansetron for vomiting in children and adolescents with acute gastroenteritis. Database searches of MEDLINE (PubMed), Scopus (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up to November 2019 were performed. Only randomized clinical trials versus placebo were considered. Fixed and random effect models were used for the analyses of pooled data. Thirteen randomized clinical trials (2146 patients) were finally included. One single dose of ondansetron showed to produce (1) higher chance of vomiting cessation within 8 h (RR 1.41, 95% CI 1.19-1.68; low-quality evidence); (2) lower chances of oral rehydration therapy failure (RR 0.43, 95% CI 0.34-0.55; high-quality evidence), intravenous hydration needs (RR 0.44, 95% CI 0.34-0.57; high-quality evidence), and hospitalization rates within 8 h (RR 0.49, 95% CI 0.32-0.75; high-quality evidence); and (3) no statistically significant differences in return visits to emergency department (RR 1.14, 95% CI 0.74-1.76; high-quality evidence) compared with placebo. Further studies are necessary to better assess long term efficacy and safety of ondansetron in this context.Conclusions: Mixed evidence was found via few studies about the efficacy and safety of a single dose of ondansetron in the pediatric population.What is known:• Ondansetron use for vomiting in pediatric acute gastroenteritis is increasing worldwide.• Actual convictions come from studies evaluating one and more than one dose of the drug.What is new:• This is the first review to collect data about the effects of one single dose of ondansetron on strong and temporally homogeneous clinical outcomes.• This study supports the use of one dose of ondansetron in pediatric acute gastroenteritis.• Further studies are necessary to assess its long-term efficacy and safety.
Topics: Acute Disease; Adolescent; Antiemetics; Child; Drug Administration Schedule; Gastroenteritis; Humans; Models, Statistical; Ondansetron; Treatment Outcome; Vomiting
PubMed: 32382791
DOI: 10.1007/s00431-020-03653-0 -
Journal of Perianesthesia Nursing :... Aug 2019Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via... (Meta-Analysis)
Meta-Analysis
PURPOSE
Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via 5HT3 receptor antagonism.
DESIGN
Systematic review and meta-analysis.
METHODS
We identified seven randomized controlled trials by systematically searching electronic databases that compare the efficacy of mirtazapine versus placebo or ondansetron in reducing PONV.
FINDINGS
Mirtazapine reduced PONV overall versus placebo in three studies (risk ratio [RR] = 0.44; 95% confidence interval [CI] 0.32 to 0.62) both on conventional meta-analysis and trial sequential analysis. One study comparing mirtazapine with ondansetron found similar rates of PONV (RR = 0.96; 95% CI 0.48 to 1.94). Mirtazapine reduced preoperative anxiety versus placebo or ondansetron (standardized mean difference -1.4; 95% CI -2.56 to -0.23) but increased sedation (RR = 22.47; 95% CI 5.61 to 89.93). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality of evidence was moderate to low.
CONCLUSIONS
This meta-analysis suggests that mirtazapine reduces PONV overall versus placebo. We found evidence of reduction in preoperative anxiety, although mirtazapine increased the risk of sedation.
Topics: Antiemetics; Humans; Mirtazapine; Postoperative Nausea and Vomiting
PubMed: 30879907
DOI: 10.1016/j.jopan.2018.11.006 -
The Cochrane Database of Systematic... May 2023Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services.
OBJECTIVES
To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs.
SEARCH METHODS
We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies.
SELECTION CRITERIA
All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use. Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition.
AUTHORS' CONCLUSIONS
In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.
Topics: Humans; Male; Acamprosate; Alcoholism; Amitriptyline; Developing Countries; Disulfiram; Mirtazapine; Naltrexone; Ondansetron; Topiramate
PubMed: 37158538
DOI: 10.1002/14651858.CD013350.pub2