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The Cochrane Database of Systematic... Sep 2022Pharmacological interventions for disordered and problem gambling have been employed in clinical practice. Despite the availability of several reviews of the efficacy of... (Review)
Review
BACKGROUND
Pharmacological interventions for disordered and problem gambling have been employed in clinical practice. Despite the availability of several reviews of the efficacy of pharmacological interventions for disordered or problem gambling, few have employed systematic search strategies or compared different categories of pharmacological interventions. Systematic reviews of high-quality evidence are therefore essential to provide guidance regarding the efficacy of different pharmacological interventions for disordered or problem gambling.
OBJECTIVES
The primary aims of the review were to: (1) examine the efficacy of major categories of pharmacological-only interventions (antidepressants, opioid antagonists, mood stabilisers, atypical antipsychotics) for disordered or problem gambling, relative to placebo control conditions; and (2) examine the efficacy of these major categories relative to each other. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and PsycINFO (all years to 11 January 2022).
SELECTION CRITERIA
We included randomised trials evaluating a pharmacological intervention for the treatment of disordered or problem gambling. Eligible control conditions included placebo control groups or comparisons with another category of pharmacological intervention.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures, including systematic extraction of included study characteristics and results and risk of bias assessment. Our primary outcome was reduction in gambling symptom severity. Our secondary outcomes were reduction in gambling expenditure, gambling frequency, time spent gambling, depressive symptoms, anxiety symptoms, and functional impairment; and responder status. We evaluated treatment effects for continuous and dichotomous outcomes using standardised mean difference (SMD) and risk ratios (RR), respectively, employing random-effects meta-analyses. A minimum of two independent treatment effects were required for a meta-analysis to be conducted (with only meta-analytic findings reported in this abstract).
MAIN RESULTS
We included 17 studies in the review (n = 1193 randomised) that reported outcome data scheduled for end of treatment. Length of treatment ranged from 7 to 96 weeks. Antidepressants: Six studies (n = 268) evaluated antidepressants, with very low to low certainty evidence suggesting that antidepressants were no more effective than placebo at post-treatment: gambling symptom severity (SMD -0.32, 95% CI -0.74 to 0.09, n = 225), gambling expenditure (SMD -0.27, 95% CI -0.60 to 0.06, n = 144), depressive symptoms (SMD -0.19, 95% CI -0.60 to 0.23, n = 90), functional impairment (SMD -0.15, 95% CI -0.53 to 0.22, n = 110), and responder status (RR 1.24, 95% CI 0.93 to 1.66, n = 268). Opioid antagonists: Four studies (n = 562) evaluated opioid antagonists, with very low to low certainty evidence showing a medium beneficial effect of treatment on gambling symptom severity relative to placebo at post-treatment (SMD -0.46, 95% CI -0.74 to -0.19, n = 259), but no difference between groups in responder status (RR 1.65, 95% CI 0.86 to 3.14, n = 562). Mood stabilisers: Two studies (n = 71) evaluated mood stabilisers (including anticonvulsants), with very low certainty evidence suggesting that mood stabilisers were no more effective than placebo at post-treatment: gambling symptom severity (SMD -0.92, 95% CI -2.24 to 0.39, n = 71), depressive symptoms (SMD -0.15, 95% CI -1.14 to 0.83, n = 71), and anxiety symptoms (SMD -0.17, 95% CI -0.64 to 0.30, n = 71). Atypical antipsychotics:Two studies (n = 63) evaluated the atypical antipsychotic olanzapine, with very low certainty evidence showing a medium beneficial effect of treatment on gambling symptom severity relative to placebo at post-treatment (SMD -0.59, 95% CI -1.10 to -0.08, n = 63). Comparative effectiveness: Two studies (n = 62) compared antidepressants with opioid antagonists, with very low certainty evidence indicating that antidepressants were no more effective than opioid antagonists on depressive symptoms (SMD 0.22, 95% CI -0.29 to 0.72, n = 62) or anxiety symptoms (SMD 0.21, 95% CI -0.29 to 0.72, n = 62) at post-treatment. Two studies (n = 58) compared antidepressants with mood stabilisers (including anticonvulsants), with very low certainty evidence indicating that antidepressants were no more effective than mood stabilisers on depressive symptoms (SMD 0.02, 95% CI -0.53 to 0.56, n = 58) or anxiety symptoms (SMD 0.16, 95% CI -0.39 to 0.70, n = 58) at post-treatment. Tolerability and adverse events: Several common adverse effects were reported by participants receiving antidepressants (e.g. headaches, nausea, diarrhoea/gastrointestinal issues) and opioid antagonists (e.g. nausea, dry mouth, constipation). There was little consistency in the types of adverse effects experienced by participants receiving mood stabilisers (e.g. tiredness, headaches, concentration difficulties) or atypical antipsychotics (e.g. pneumonia, sedation, increased hypomania). Discontinuation of treatment due to these adverse events was highest for opioid antagonists (10% to 32%), followed by antidepressants (4% to 31%), atypical antipsychotics (14%), and mood stabilisers (13%).
AUTHORS' CONCLUSIONS
This review provides preliminary support for the use of opioid antagonists (naltrexone, nalmefene) and atypical antipsychotics (olanzapine) to produce short-term improvements in gambling symptom severity, although a lack of available evidence precludes a conclusion regarding the degree to which these pharmacological agents can improve other gambling or psychological functioning indices. In contrast, the findings are inconclusive with regard to the effects of mood stabilisers (including anticonvulsants) in the treatment of disordered or problem gambling, and there is limited evidence to support the efficacy of antidepressants. However, these conclusions are based on very low to low certainty evidence characterised by a small number of included studies, high risk of bias, modest pooled sample sizes, imprecise estimates, moderate between-study heterogeneity, and exclusion of participants with psychiatric comorbidities. Moreover, there were insufficient studies to conduct meta-analyses on many outcome measures; to compare efficacy across and within major categories of interventions; to explore dosage effects; or to examine effects beyond post-treatment. These limitations suggest that, despite recommendations related to the administration of opioid antagonists in the treatment of disordered or problem gambling, pharmacological interventions should be administered with caution and with careful consideration of patient needs. A larger and more methodologically rigorous evidence base with longer-term evaluation periods is required before definitive conclusions can be drawn about the effectiveness and durability of pharmacological treatments for disordered or problem gambling.
Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Gambling; Headache; Humans; Naltrexone; Narcotic Antagonists; Nausea; Olanzapine
PubMed: 36130734
DOI: 10.1002/14651858.CD008936.pub2 -
Drug and Alcohol Dependence Dec 2022While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids... (Review)
Review
BACKGROUND
While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects.
METHODS
We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality.
RESULTS
Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline.
CONCLUSIONS
Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics.
Topics: Humans; Male; Female; Cannabis; Dronabinol; Cannabinoids; Cannabinoid Receptor Agonists; Hallucinogens; Substance Withdrawal Syndrome; Narcotics; Analgesics, Opioid
PubMed: 36434879
DOI: 10.1016/j.drugalcdep.2022.109702 -
International Journal of Environmental... Dec 2023Language development starts during the fetal period when the brain is sensitive to endocrine disruptions from environmental contaminants. This systematic review aims to... (Review)
Review
Language development starts during the fetal period when the brain is sensitive to endocrine disruptions from environmental contaminants. This systematic review aims to systematically summarize the existing literature on early-life exposure to PFAS and children's language and communication development, which is an indicator of neurocognitive development. A structured literature search was conducted using three databases, PubMed, Scopus, and CINAHL, last updated in April 2023. The population was defined as children and young adults. PFAS exposure was assessed pre- or postnatally. The outcome was defined as a language and communication ability assessed with validated instruments, parental self-reports, or clinical language disorder diagnoses. In total, 15 studies were identified for subsequent analyses. Thirteen were performed in background-exposed populations and two in highly exposed populations. There were some indications of potential adverse effects; however, these were not consistent across child sex, age of assessment, or PFAS exposure levels. No systematic effect of early-life PFAS exposure on language and communication development was found. These inconclusive findings may partly be explained by the use of general test instruments with limited validity as to children's language and communication development. Further studies over a wider exposure range using specific language test instruments are needed.
Topics: Child; Female; Young Adult; Humans; Child Language; Prenatal Exposure Delayed Effects; Fluorocarbons; Language Development; Communication; Environmental Pollutants; Alkanesulfonic Acids
PubMed: 38131721
DOI: 10.3390/ijerph20247170 -
Journal of Studies on Alcohol and Drugs Jul 2022This article reviews research on post-acute alcohol withdrawal syndrome (PAWS) management.
OBJECTIVE
This article reviews research on post-acute alcohol withdrawal syndrome (PAWS) management.
METHOD
We conducted a PRISMA (Preferred Reporting Items for Systematic Revision and Meta-Analyses)-guided scoping review of the published PAWS literature, searching six electronic databases (from their inception through December 2020) for English-language randomized and nonrandomized studies.
RESULTS
A total of 16 treatment studies met the inclusion criteria. The strength of evidence overall for pharmacologic treatments is low, with often only short-term results being reported, small treatment samples used, or inconsistent results found. However, for negative affect and sleep symptoms, more evidence supports using gabapentinoids (gabapentin and pregabalin) and anticonvulsants (carbamazepine and oxcarbazepine). Although preliminary data support acamprosate, there were no controlled trials. Despite an older treatment trial showing some positive data for amitriptyline for mood, the clinical measures used were problematic, and side effects and safety profile limit its utility. Finally, there is no evidence that melatonin and other agents (homatropine, Proproten-100) show PAWS symptoms.
CONCLUSIONS
Although there is some evidence for targeted pharmacotherapy for treating specific PAWS symptoms, there are few recent, robust, placebo-controlled trials, and the level of evidence for treatment efficacy is low.
Topics: Alcoholism; Anticonvulsants; Benzodiazepines; Gabapentin; Humans; Substance Withdrawal Syndrome
PubMed: 35838423
DOI: 10.15288/jsad.2022.83.470 -
International Journal of Molecular... Jul 2022One of the possible alternatives for creating materials for the regeneration of bone tissue supporting comprehensive reconstruction is the incorporation of active... (Review)
Review
One of the possible alternatives for creating materials for the regeneration of bone tissue supporting comprehensive reconstruction is the incorporation of active substances whose controlled release will improve this process. This systematic review aimed to identify and synthesize in vitro studies that assess the suitability of polyphenolics as additives to polymer-ceramic composite bone regeneration materials. Data on experimental studies in terms of the difference in mechanical, wettability, cytocompatibility, antioxidant and anti-inflammatory properties of materials were synthesized. The obtained numerical data were compiled and analyzed in search of percentage changes of these parameters. The results of the systematic review were based on data from forty-six studies presented in nineteen articles. The addition of polyphenolic compounds to composite materials for bone regeneration improved the cytocompatibility and increased the activity of early markers of osteoblast differentiation, indicating a high osteoinductive potential of the materials. Polyphenolic compounds incorporated into the materials presumably give them high antioxidant properties and reduce the production of reactive oxygen species in macrophage cells, implying anti-inflammatory activity. The evidence was limited by the number of missing data and the heterogeneity of the data.
Topics: Antioxidants; Biocompatible Materials; Bone Regeneration; Ceramics; Polyphenols; Tissue Engineering
PubMed: 35806482
DOI: 10.3390/ijms23137473 -
The International Journal of... Jul 2021Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is...
BACKGROUND
Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is less clear. This study aimed to assess the efficacy and tolerability of ketamine for bipolar depression.
METHODS
We conducted a systematic review of experimental studies using ketamine for the treatment of bipolar depression. We searched PubMed, MEDLINE, Embase, PsycINFO, and the Cochrane Central Register for relevant studies published since each database's inception. We synthesized evidence regarding efficacy (improvement in depression rating scores) and tolerability (adverse events, dissociation, dropouts) across studies.
RESULTS
We identified 6 studies, with 135 participants (53% female; 44.7 years; standard deviation, 11.7 years). All studies used 0.5 mg/kg of add-on intravenous racemic ketamine, with the number of doses ranging from 1 to 6; all participants continued a mood-stabilizing agent. The overall proportion achieving a response (defined as those having a reduction in their baseline depression severity of at least 50%) was 61% for those receiving ketamine and 5% for those receiving a placebo. The overall response rates varied from 52% to 80% across studies. Ketamine was reasonably well tolerated; however, 2 participants (1 receiving ketamine and 1 receiving placebo) developed manic symptoms. Some participants developed significant dissociative symptoms at the 40-minute mark following ketamine infusion in 2 trials.
CONCLUSIONS
There is some preliminary evidence supporting use of intravenous racemic ketamine to treat adults with bipolar depression. There is a need for additional studies exploring longer-term outcomes and alterative formulations of ketamine.
Topics: Bipolar Disorder; Excitatory Amino Acid Antagonists; Humans; Ketamine
PubMed: 33929489
DOI: 10.1093/ijnp/pyab023 -
Drug and Alcohol Review Jan 2023Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to... (Meta-Analysis)
Meta-Analysis Review
ISSUES
Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta-analysis since 2008.
APPROACH
MEDLINE (1966-2020), CINAHL (1982-2020), PsychINFO (1806-2020) and EMBASE (1947-2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta-analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted.
KEY FINDINGS
Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta-analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD -0.49, 95% CI -0.80, -0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established.
CONCLUSIONS
There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high-quality trials.
Topics: Male; Humans; Female; Substance Withdrawal Syndrome; Methamphetamine; Randomized Controlled Trials as Topic
PubMed: 35862266
DOI: 10.1111/dar.13511 -
International Journal of Environmental... Jan 2020There is evidence that sex- and gender-related factors are involved in cannabis patterns of use, health effects and biological mechanisms. Women and men report different...
There is evidence that sex- and gender-related factors are involved in cannabis patterns of use, health effects and biological mechanisms. Women and men report different cannabis use disorder (CUD) symptoms, with women reporting worse withdrawal symptoms than men. The objective of this systematic review was to examine the effectiveness of cannabis pharmacological interventions for women and men and the uptake of sex- and gender-based analysis in the included studies. Two reviewers performed the full-paper screening, and data was extracted by one researcher. The search yielded 6098 unique records-of which, 68 were full-paper screened. Four articles met the eligibility criteria for inclusion. From the randomized clinical studies of pharmacological interventions, few studies report sex-disaggregated outcomes for women and men. Despite emergent evidence showing the influence of sex and gender factors in cannabis research, sex-disaggregated outcomes in pharmacological interventions is lacking. Sex- and gender-based analysis is incipient in the included articles. Future research should explore more comprehensive inclusion of sex- and gender-related aspects in pharmacological treatments for CUD.
Topics: Cannabis; Female; Humans; Male; Marijuana Abuse; Sex Factors; Substance Withdrawal Syndrome
PubMed: 32019247
DOI: 10.3390/ijerph17030872 -
Medicina (Kaunas, Lithuania) Sep 2023Oxidative stress is involved in the alterations at the level of salivary glands, being the cause of oral pathologies like xerostomia, periodontitis, gingivitis,... (Review)
Review
Oxidative stress is involved in the alterations at the level of salivary glands, being the cause of oral pathologies like xerostomia, periodontitis, gingivitis, leucoplakia, and cancer. It is known that antioxidants can reverse changes induced by drugs or other chemicals in some organs, but the question is whether these substances can reduce or revert the effects of oxidative stress at the salivary gland level. Our aim was to find histopathological data at the level of salivary glands supporting the hypothesis of the reversal of oxidative stress-induced changes after the treatment with substances with antioxidant effect. : A systematic search was conducted in PubMed, Science Direct, and Springer databases, including research articles on oxidative stress histological aspects and oxidative stress biomarkers induced by drugs or other chemicals on salivary glands. : Out of 1756 articles, 25 articles were selected with data on tissue homogenate used for biochemical analysis of oxidative and antioxidative markers, along with routine hematoxylin eosin (HE) and immunohistochemical analysis used for histopathological and immunohistochemical diagnosis. Drugs (antineoplastic drugs, antibiotics, and analgesics), alcohol, heavy metals, and fluoride can cause oxidative stress, resulting in morphological changes in different tissues, including in salivary glands. There are many antioxidants but only a few were evaluated regarding the effects on salivary glands in animal studies, such as hesperidin and selenium, which can reverse the damage induced by cyclophosphamide; 10-dehydrogingerdione (10-DHGD), a compound extracted from ginger, which has a protective effect against the oxidative stress and apoptosis induced by tramadol; and glycyrrhizic acid, which may repair the injuries incurred after the administration of sodium nitrite. : Substances such as hesperidin, selenium, 10-dehydrogingerdione, and glycyrrhizic acid are antioxidants with proven restorative effects on salivary glands for the damage induced by oxidative stress after exposure to drugs and other chemical substances; however, demonstrating their similar effects in human salivary glands is challenging.
PubMed: 37763811
DOI: 10.3390/medicina59091692 -
Addiction (Abingdon, England) Apr 2022Up to 95% of pregnant women seeking treatment for alcohol and other drug (AOD) use smoke tobacco. Previous reviews indicate few effective smoking cessation treatments... (Review)
Review
BACKGROUND AND AIMS
Up to 95% of pregnant women seeking treatment for alcohol and other drug (AOD) use smoke tobacco. Previous reviews indicate few effective smoking cessation treatments for this group. This updated review aimed to identify and measure the efficacy of smoking cessation interventions trialled among pregnant women in AOD treatment settings who smoke tobacco.
METHODS
A narrative synthesis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies involving psychological, behavioural or pharmacological interventions used to treat tobacco use, including electronic nicotine delivery systems, for pregnant women of any age, who smoked tobacco and were seeking/receiving treatment, or in post-treatment recovery for AOD concerns, were reviewed. MEDLINE, PsycINFO, CINAHL, EMBASE and ProQuest databases, grey literature and reference lists were searched, and field experts were contacted for unpublished study data. The Effective Public Health Practice Project tool assessed study quality. The review was pre-registered with PROSPERO no. CRD42018108777.
RESULTS
Seven interventions (two randomised controlled trials, two single-arm pilot studies, two program evaluations and one causal comparative study) treating 875 women were identified. All were United States (US)-based and targeted women with drug dependence, but not alcohol dependence. Three interventions used contingency management, five provided behavioural counselling, and one offered nicotine replacement therapy. All reported reductions in cigarette consumption; one contingency management-based study demonstrated higher abstinence rates compared with controls at treatment-end that were not maintained at follow-up. Four of six studies were rated as methodologically weak and one unpublished study was not rated.
CONCLUSIONS
Conclusions about the efficacy of smoking interventions for pregnant women with alcohol and other drug concerns who also smoke tobacco are hindered by the paucity of available data and poor methodological quality of included studies.
Topics: Alcoholism; Behavior Therapy; Female; Humans; Male; Pregnancy; Pregnant Women; Randomized Controlled Trials as Topic; Smoking Cessation; Substance-Related Disorders; Tobacco Use Cessation Devices; United States
PubMed: 34374145
DOI: 10.1111/add.15663