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BioMed Research International 2021Migraine has a great impact on public health. Current acute therapies do not satisfy all migraineurs. The novel serotonin 5-HT receptor agonist appears more promising... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Migraine has a great impact on public health. Current acute therapies do not satisfy all migraineurs. The novel serotonin 5-HT receptor agonist appears more promising for aborting migraine attacks.
OBJECTIVE
To evaluate the clinical efficacy and safety of lasmiditan in treating acute migraine attacks.
METHODS
The literature search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) which assessed the effect and safety of lasmiditan on migraine. The risk of bias was assessed using the Cochrane Collaboration's risk of bias tool. Results were extracted and pooled as risk ratios (RRs) with a fixed or random-effects model.
RESULTS
Based on the four included RCTs, pooled estimates showed that lasmiditan with the 50 mg, 100 mg, and 200 mg doses was superior to placebo at 2 h after the first dose in terms of pain freedom, absence of migraine-associated symptoms, headache relief, no/mild disability, and global impression of change (very much/much better) (RRs ranged from 1.13 to 1.96), except for nausea-free and vomiting-free. Both lasmiditan 100 mg and 200 mg resulted in significantly fewer patients using rescue medication (100 mg: RR = 0.75, 95% CI (0.61, 0.92), = 0.007; 200 mg: RR = 0.81, 95% CI (0.66, 0.99), = 0.04) at 2-24 h postdose, compared with placebo. Safety data showed that the proportion of patients reporting at least one treatment-emergent adverse event (TEAE) and the incidence of most common TEAEs such as dizziness, paresthesia, fatigue, somnolence, and nausea was higher in the lasmiditan groups (50 mg, 100 mg, and 200 mg), compared with placebo. There was no significant difference between lasmiditan and placebo in terms of cardiovascular-related TEAEs (RR = 2.75, 95% CI (0.81, 9.37), = 0.11). Compared with lasmiditan 100 mg, lasmiditan 200 mg was more effective in pain freedom at 2 h after the first dose (RR = 0.83, 95% CI (0.74, 0.94), = 0.004) but associated with a higher risk of reporting at least one TEAE (RR = 0.88, 95% CI (0.81, 0.96), = 0.006).
CONCLUSIONS
Lasmiditan with the 50 mg, 100 mg, and 200 mg doses are effective and safe in acute migraine treatment. Lasmiditan 200 mg is more effective than lasmiditan 100 mg in pain freedom, while lasmiditan 100 mg is better tolerated in the short-term follow-up. Further larger sample-size RCTs are required to verify the applicability and tolerability in the long term.
Topics: Adult; Benzamides; Cardiovascular Diseases; Confidence Intervals; Disability Evaluation; Female; Humans; Male; Migraine Disorders; Piperidines; Publication Bias; Pyridines; Receptors, Serotonin; Risk; Serotonin Receptor Agonists; Treatment Outcome; Receptor, Serotonin, 5-HT1F
PubMed: 34660796
DOI: 10.1155/2021/6663591 -
The Cochrane Database of Systematic... Apr 2020Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly, nicotine withdrawal may produce depressive symptoms and antidepressants may relieve these. Additionally, some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
OBJECTIVES
To assess the evidence for the efficacy, safety and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Specialized Register, which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO, clinicaltrials.gov, the ICTRP, and other reviews and meeting abstracts, in May 2019.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that recruited smokers, and compared antidepressant medications with placebo or no treatment, an alternative pharmacotherapy, or the same medication used in a different way. We excluded trials with less than six months follow-up from efficacy analyses. We included trials with any follow-up length in safety analyses.
DATA COLLECTION AND ANALYSIS
We extracted data and assessed risk of bias using standard Cochrane methods. We also used GRADE to assess the certainty of the evidence. The primary outcome measure was smoking cessation after at least six months follow-up, expressed as a risk ratio (RR) and 95% confidence intervals (CIs). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. Similarly, we presented incidence of safety and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropout due to drug, as RRs (95% CIs).
MAIN RESULTS
We included 115 studies (33 new to this update) in this review; most recruited adult participants from the community or from smoking cessation clinics. We judged 28 of the studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased long-term smoking cessation rates (RR 1.64, 95% CI 1.52 to 1.77; I = 15%; 45 studies, 17,866 participants). There was insufficient evidence to establish whether participants taking bupropion were more likely to report SAEs compared to those taking placebo. Results were imprecise and CIs encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I = 0%; 21 studies, 10,625 participants; moderate-certainty evidence, downgraded one level due to imprecision). We found high-certainty evidence that use of bupropion resulted in more trial dropouts due to adverse events of the drug than placebo (RR 1.37, 95% CI 1.21 to 1.56; I = 19%; 25 studies, 12,340 participants). Participants randomized to bupropion were also more likely to report psychiatric AEs compared with those randomized to placebo (RR 1.25, 95% CI 1.15 to 1.37; I = 15%; 6 studies, 4439 participants). We also looked at the safety and efficacy of bupropion when combined with other non-antidepressant smoking cessation therapies. There was insufficient evidence to establish whether combination bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.19, 95% CI 0.94 to 1.51; I = 52%; 12 studies, 3487 participants), or whether combination bupropion and varenicline resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I = 15%; 3 studies, 1057 participants). We judged the certainty of evidence to be low and moderate, respectively; in both cases due to imprecision, and also due to inconsistency in the former. Safety data were sparse for these comparisons, making it difficult to draw clear conclusions. A meta-analysis of six studies provided evidence that bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.71, 95% CI 0.64 to 0.79; I = 0%; 6 studies, 6286 participants), whilst there was no evidence of a difference in efficacy between bupropion and NRT (RR 0.99, 95% CI 0.91 to 1.09; I = 18%; 10 studies, 8230 participants). We also found some evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I = 16%; 6 studies, 975 participants), whilst there was insufficient evidence to determine whether bupropion or nortriptyline were more effective when compared with one another (RR 1.30 (favouring bupropion), 95% CI 0.93 to 1.82; I = 0%; 3 studies, 417 participants). There was no evidence that any of the other antidepressants tested (including St John's Wort, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs)) had a beneficial effect on smoking cessation. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression.
AUTHORS' CONCLUSIONS
There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion also increases the number of adverse events, including psychiatric AEs, and there is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with placebo. However, there is no clear evidence to suggest whether people taking bupropion experience more or fewer SAEs than those taking placebo (moderate certainty). Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo. Evidence suggests that bupropion may be as successful as NRT and nortriptyline in helping people to quit smoking, but that it is less effective than varenicline. There is insufficient evidence to determine whether the other antidepressants tested, such as SSRIs, aid smoking cessation, and when looking at safety and tolerance outcomes, in most cases, paucity of data made it difficult to draw conclusions. Due to the high-certainty evidence, further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over front-line smoking cessation aids already available. However, it is important that where studies of antidepressants for smoking cessation are carried out they measure and report safety and tolerability clearly.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Bupropion; Humans; Nortriptyline; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 32319681
DOI: 10.1002/14651858.CD000031.pub5 -
Schizophrenia Bulletin Nov 2016Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of... (Meta-Analysis)
Meta-Analysis Review
Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples (n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2-20, n = 81-2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ADRA2A], Adrenoceptor Beta 3 [ADRB3], Brain-Derived Neurotrophic Factor [BDNF], Dopamine Receptor D2 [DRD2], Guanine Nucleotide Binding Protein [GNB3], 5-Hydroxytryptamine (Serotonin) Receptor 2C [HTR2C], Insulin-induced gene 2 [INSIG2], Melanocortin-4 Receptor [MC4R], and Synaptosomal-associated protein, 25kDa [SNAP25]) were significantly associated with antipsychotic-related weight gain (P-values < .05-.001). SNPs in ADRA2A, DRD2, HTR2C, and MC4R had the largest effect sizes (Hedges' g's = 0.30-0.80, ORs = 1.47-1.96). Less prior antipsychotic exposure (pediatric or first episode patients) and short follow-up (1-2 mo) were associated with larger effect sizes. Individual antipsychotics did not significantly moderate effect sizes. In conclusion, antipsychotic-related weight gain is polygenic and associated with specific genetic variants, especially in genes coding for antipsychotic pharmacodynamic targets.
Topics: Antipsychotic Agents; Humans; Pharmacogenetics; Psychotic Disorders; Weight Gain
PubMed: 27217270
DOI: 10.1093/schbul/sbw058 -
Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis.The Egyptian Heart Journal : (EHJ) :... Jul 2023Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for...
BACKGROUND
Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for controlling nausea. However, ondansetron is linked with a number of adverse effects, including prolongation of the QT interval. Therefore, the purpose of this meta-analysis was to assess the occurrence of QT prolongation in pediatric, adult, and elderly patients receiving oral or intravenously administered ondansetron.
METHODS
A thorough electronic search was conducted on PubMed (Medline) and Cochrane Library from the databases' inception to August 10, 2022. Only those studies were considered in which ondansetron was administered orally or intravenously to participants for the treatment of nausea and vomiting. The prevalence of QT prolongation in multiple predefined age groups was the outcome variable. Analyses were conducted using Review manager 5.4 (Cochrane collaboration, 2020).
RESULTS
A total of 10 studies involving 687 ondansetron group participants were statistically analyzed. The administration of ondansetron was associated with a statistically significant prevalence of QT prolongation in all age groups. An age-wise subgroup analysis was conducted which revealed that the prevalence of QT prolongation among participants younger than 18 years was not statistically significant, whereas it was statistically significant among participants aged 18-50 years and among patients older than 50 years.
CONCLUSIONS
The present meta-analysis provides further evidence that oral or intravenous administration of Ondansetron may lead to QT prolongation, particularly among patients older than 18 years of age.
PubMed: 37395900
DOI: 10.1186/s43044-023-00385-y -
Journal of Applied Oral Science :... 2022This study aimed to investigate if SNP rs6313, SNP rs2770304, SNP rs4941573, and SNP rs1923884 of the 5-HT2A receptor gene and SNP rs6295 of the 5-HT1A receptor gene are...
UNLABELLED
This study aimed to investigate if SNP rs6313, SNP rs2770304, SNP rs4941573, and SNP rs1923884 of the 5-HT2A receptor gene and SNP rs6295 of the 5-HT1A receptor gene are associated with bruxism etiology.
METHODOLOGY
This systematic review was registered in PROSPERO (CRD42018094561). A search was conducted for articles published in or before May 2021. To qualify for eligibility in this review, the studies had to be case-controls, cohort or cross-sectional. The inclusion criteria were the articles with a group of patients with bruxism and a control group in which the presence of these SNPs was evaluated. The exclusion criteria were the investigations of other polymorphisms, the studies that did not consider a control group for comparison, case reports, and reviews. The NOS and JBI were used to evaluate the methodological quality of studies.
RESULTS
We conducted this study with databases, such as Web of Science, Scopus, Embase, PubMed/MEDLINE, and ProQuest. We considered four studies eligible. A total of 672 participants were included,187 with sleep bruxism, 105 with awake bruxism, 89 with sleep and awake bruxism, and 291 controls. One study found a strong association between the SNPs rs6313, rs2770304 and rs4941573 of the 5-HT2A receptor gene and sleep bruxism. In one study, we considered the C allele of the SNP rs2770304 a risk factor for sleep bruxism. We found no significant results of other SNPs in sleep bruxers compared to controls. We found no positive association concerning the SNPs and groups of awake bruxism and sleep and awake bruxism.
CONCLUSION
The different results regarding the SNPs in sleep bruxers could be explained by the genetic distinction between Chilean, Mexican, Japanese, and Polish population. More clinical trials and prospective studies must be conducted with larger sample size and in different ethnicities to confirm the results of this review.
Topics: Humans; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT1A; Sleep Bruxism
PubMed: 35019025
DOI: 10.1590/1678-7757-2021-0262 -
Schizophrenia Research. Cognition Dec 2023In a previous meta-analysis, the use of serotonin(5-HT) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on...
BACKGROUND
In a previous meta-analysis, the use of serotonin(5-HT) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on positive symptoms and attention/processing speed in schizophrenia patients. This meta-analysis builds on that study by examining the effects of adjunctive treatment with 5-HT partial agonists in improving other domains of neurocognitive function in schizophrenia patients.
METHODS
A literature search was performed from 1987 to May 2023 to identify randomized controlled trials. The standardized mean difference (SMD) with 95 % confidence intervals (CI) was calculated when there were two or more studies. Four studies, involving 313 patients, met the inclusion criteria and were used in the analysis.
RESULTS
5-HT partial agonists (buspirone or tandospirone) did not have a significant effect on verbal learning (SMD = 0.08, 95 % CI = -0.31 to 0.47) or working memory (SMD = 0.15, 95 % CI = -0.09 to 0.39). Regarding executive functions (Wisconsin Card Sorting Test), positive but non-significant results were seen with the category number (SMD = 0.26, 95 % CI = -0.81 to 1.32), while non-significant effects were noted for percent preservation errors (SMD = -0.10, 95 % CI = -0.53 to 0.33).
CONCLUSIONS
The absence of any significant benefits in the cognitive domains studied here may have been due to the variance in the concomitant medication (typical vs atypical antipsychotic drugs), the level of cognition at baseline, or other factors. Further studies with various types of 5-HT agonists are warranted to examine the potential cognitive efficacy of stimulating these receptors.
PubMed: 37732133
DOI: 10.1016/j.scog.2023.100290 -
Evidence-based Complementary and... 2019Despite the wide use of acupuncture for the management of visceral pain and the growing interest in the pathophysiology of visceral pain, there is no conclusive... (Review)
Review
BACKGROUND/AIMS
Despite the wide use of acupuncture for the management of visceral pain and the growing interest in the pathophysiology of visceral pain, there is no conclusive elucidation of the mechanisms behind the effects of acupuncture on visceral pain. This systematic review aims to provide an integrative understanding of the treatment mechanism of acupuncture for visceral pain.
METHODS
Electronic and hand searches were conducted to identify studies that involved visceral pain and acupuncture.
RESULTS
We retrieved 192 articles, out of which 46 studies were included in our review. The results of our review demonstrated that visceral pain behaviors were significantly alleviated in response to acupuncture treatment in groups treated with this intervention compared to in sham acupuncture or no-treatment groups. Changes in the concentrations of -endorphin, epinephrine, cortisol, and prostaglandin E2 in plasma, the levels of c-Fos, substance P, corticotropin-releasing hormone, P2X3, acetylcholinesterase (AchE), N-methyl-D-aspartate (NMDA) receptors, and serotonin in the gut/spinal cord, and the neuronal activity of the thalamus were associated with acupuncture treatment in visceral pain.
CONCLUSIONS
Acupuncture reduced visceral pain behavior and induced significant changes in neuronal activity as well as in the levels of pain/inflammation-related cytokines and neurotransmitters in the brain-gut axis. Further researches on the thalamus and on a standard animal model are warranted to improve our knowledge on the mechanism of acupuncture that facilitates visceral pain modulation.
PubMed: 31186654
DOI: 10.1155/2019/1304152 -
Annals of Palliative Medicine Apr 2021Researchers have not clearly determined whether adding aprepitant (ADH) to dexamethasone and one 5-HT3 receptor antagonist (DH) is clinically effective at preventing... (Meta-Analysis)
Meta-Analysis
Use of dexamethasone and a 5-HT3 receptor antagonist with or without aprepitant to prevent chemotherapy-induced nausea and vomiting among patients with lung cancer who are treated with platinum-based chemotherapy: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Researchers have not clearly determined whether adding aprepitant (ADH) to dexamethasone and one 5-HT3 receptor antagonist (DH) is clinically effective at preventing chemotherapy-induced nausea and vomiting (CINV) among patients with lung cancer (LC) treated with platinum-based chemotherapy (PBC). Therefore, we conducted a meta-analysis to examine the efficacy and safety of ADH and DH.
METHODS
We searched the PubMed, ScienceDirect, Cochrane Library, and Scopus databases, among others, for relevant studies. The primary outcomes were the complete response (CR) and the no nausea rate (NNR). The secondary endpoints were the number of patients who needed rescue antiemetic treatment (RAT), adverse events (AEs), and the Functional Living Index Emesis (FLIE) score.
RESULTS
We initially screened 2,118 articles; ultimately, four randomized controlled trials (RCTs) with 518 patients were included. The ADH group had a superior overall CR [risk ratio (RR): 1.16 (1.06, 1.27), P=0.002] and a lower number of patients who needed RAT [RR: 0.44 (0.29, 0.65), P<0.0001]. The ADH group also had a better overall NNR [RR: 1.11 (0.97, 1.26), P=0.12] and delayed CR [RR: 1.12 (0.97, 1.31), P=0.13]. No significant differences were observed in acute CR, acute NNR, or delayed NNR. In the subgroup analysis of the overall CR and NNR, ADH was superior in certain clinical characteristics (China, cisplatin-based chemotherapy, 2nd-generation 5-HT3 receptor antagonist, ADC <50%, and Eastern Cooperative Oncology Group (ECOG) score of 0-2). No significant differences in the AEs characterized as hematological or nonhematological toxicity were observed between the groups.
CONCLUSIONS
Compared with DH, ADH appears to be superior at preventing CINV and achieving a better CR among patients with LC treated with PBC.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; China; Dexamethasone; Humans; Lung Neoplasms; Morpholines; Nausea; Platinum; Randomized Controlled Trials as Topic; Receptors, Serotonin, 5-HT3; Vomiting
PubMed: 33894731
DOI: 10.21037/apm-20-2290 -
Cureus Oct 2022Irritable bowel syndrome (IBS) is a common pathology in middle-aged patients and a regular consultation in the gastroenterology office. The prevalence is high in females... (Review)
Review
Irritable bowel syndrome (IBS) is a common pathology in middle-aged patients and a regular consultation in the gastroenterology office. The prevalence is high in females with a ratio of 2:1, and due to its multifactorial etiology, it is difficult to address the symptomatology. On the other hand, fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome also prevalent in the female population, characterized by systemic symptoms. It is proven that 28-59 % of patients with FMS develop IBS at some point in their illness; on the other hand, 32-77% of those with IBS will develop FMS. Our study aims to compile information about the pathogenesis of these diseases and highlight their common processes to target these two illnesses potentially. This systematic review comprises twenty-three studies published between 2017 and 2022, selected by electronic research with keywords and Medical Subject Headings (MESH) strategy. The articles were taken from PubMed, Pubmed Central (PMC), Medline, and Cochrane libraries and met the inclusion and exclusion criteria and the pertinent quality checklists. Of the reviewed studies, 10 were case-control, six were narrative reviews, three were systematic reviews, three were cross-sectional, and one was a cohort study. They investigated the correlation and similitudes in the pathogenic process between FMS and IBS. There are some similar mechanisms in the physiopathologies of IBS and FMS, where the immune system, especially the mast cells (MCs), along with their products, receptors, the inflammatory cells with their intermediaries, hormones, and neurotransmitters such as serotonin, act together pathologically. Also, the role of the microbiota is very important in this pathogenesis since dysbiosis alters the levels of serotonin in the body and can produce hyperstimulation of the autonomic nervous system. There are common associated factors in IBS and FMS, with evident symptoms presented in both syndromes such as fatigue, pain, hypersensitivity, depression, anxiety, and others, that could be correlated in a certain way. After this systematic review, we can conclude that the most accepted theories of the common pathogenesis are the role of serotonin and MCs with their inflammatory biomarkers, which can affect different parts of the body producing the characteristic symptomatology. Moreover, other pathogenic mechanisms such as the involvement of microbiota and dysregulation of the gut-brain axis have shown promising results, and further investigation should be made to support their role.
PubMed: 36381861
DOI: 10.7759/cureus.29923 -
The Cochrane Database of Systematic... Jan 2019Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014.
OBJECTIVES
To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use.
SEARCH METHODS
We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.Abstinence at end of treatment was no more likely with Δ-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness.
AUTHORS' CONCLUSIONS
There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.
Topics: Acetylcysteine; Adult; Anticonvulsants; Antidepressive Agents; Buspirone; Dronabinol; Female; Humans; Male; Marijuana Abuse; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Selective Serotonin Reuptake Inhibitors; Young Adult
PubMed: 30687936
DOI: 10.1002/14651858.CD008940.pub3