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Addiction Biology Nov 2022Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by...
Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption.
Topics: Animals; Humans; Hallucinogens; Psilocybin; Alcoholism; Lysergic Acid Diethylamide; Mescaline
PubMed: 36301215
DOI: 10.1111/adb.13229 -
Revista Espanola de Salud Publica Oct 2022Cannabis is an illegal drug whose use has increased in recent years, especially among adolescents. Despite its popularity, its use and abuse brings with it health... (Review)
Review
OBJECTIVE
Cannabis is an illegal drug whose use has increased in recent years, especially among adolescents. Despite its popularity, its use and abuse brings with it health consequences, being greater if consumption occurs in the adolescent stage, since the brain is in full development. The objective of this systematic review was to determine the effects of cannabis use on cognitive functions of attention and memory in adolescent population.
METHODS
A systematic review of the literature was carried out in the main search portals (Pubmed, Web of Science, SciELO, Cochrane) referring to the last 10 years, following the PRISMA criteria. The systematic search strategy was carried out in the period from March to May 2021, applying the PICO method and the PEDro scale to guarantee the methodological quality of the included studies.
RESULTS
Both attention and memory are affected by cannabis use; however, memory functions improve with abstinence, not being so for attention. Memory deficits are an indicator of therapeutic abandonment of addiction treatment. In relation to psychosocial interventions aimed at improving memory, the contingency management, educational interventions and motivational interviewing have not been shown to be effective on the effects of substances. Working memory training offers positive results, although not clinically significant. Finally, memory deficits are an indicator of therapeutic abandonment of pharmacological treatment for cannabis addiction. Therefore, research is needed aimed both at reducing the side effects of drugs on memory processes and at establishing to what extent memory deficits associated with cannabis use can facilitate therapeutic abandonment.
CONCLUSIONS
More research is necessary, considering the dual consumption of cannabis-tobacco and the effects that both substances may have jointly and separately on attention and memory processes.
Topics: Adolescent; Humans; Cannabis; Marijuana Abuse; Spain; Illicit Drugs; Memory Disorders
PubMed: 36300331
DOI: No ID Found -
Frontiers in Pharmacology 2022The skin is the largest organ of the body that protects from mechanical, thermal, and physical injury. However, the function and appearance of skin visibly degenerates... (Review)
Review
The skin is the largest organ of the body that protects from mechanical, thermal, and physical injury. However, the function and appearance of skin visibly degenerates with age due to its frequent exposure to harmful effects of the environment, including ultraviolet irradiation and hazardous substances, in addition to the progression of oxidative stress in aging. These factors result in phenotypic changes in the skin, including wrinkling, pigmentation, reduced elasticity, and hydration during aging. Many natural antioxidant compounds have been studied extensively to reverse the signs of aging skin. Tocotrienols are a subfamily of vitamin E with potent antioxidant activity. Therefore, supplementation with vitamin E in the form of tocotrienol may efficiently protect skin from aging. In this review, the effects of tocotrienol on skin health, including pigmentation, moisture, and wrinkles during aging and UV exposure, were systematically evaluated based on a literature search of the PubMed and Scopus databases. The present data showed that tocotrienols protect the skin from inflammation, UV radiation and melanin accumulation. As the therapeutic value of tocotrienols grows, the potential of these vitamin E analogs to the skin requires further investigation.
PubMed: 36299879
DOI: 10.3389/fphar.2022.1006198 -
Journal of Psychopharmacology (Oxford,... Dec 2022Preclinical research suggests that cannabidiol (CBD) may have therapeutic potential in pathological anxiety. Dosing guidelines to inform future human studies are however... (Review)
Review
BACKGROUND
Preclinical research suggests that cannabidiol (CBD) may have therapeutic potential in pathological anxiety. Dosing guidelines to inform future human studies are however lacking.
AIM
We aimed to predict the therapeutic window for anxiety-reducing effects of CBD in humans based on preclinical models.
METHODS
We conducted two systematic searches in PubMed and Embase up to August 2021, into pharmacokinetic (PK) and pharmacodynamic (PD) data of systemic CBD exposure in humans and animals, which includes anxiety-reducing and potential side effects. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. A control group was an inclusion criterion in outcome studies. In human outcome studies, randomisation was required. We excluded studies that co-administered other substances. We used the IB-de-risk tool for a translational integration of outcomes.
RESULTS
We synthesised data from 87 studies. For most observations (70.3%), CBD had no effect on anxiety outcomes. There was no identifiable relation between anxiety outcomes and drug levels across species. In all species (humans, mice, rats), anxiety-reducing effects seemed to be clustered in certain concentration ranges, which differed between species.
DISCUSSION
A straightforward dosing recommendation was not possible, given variable concentration-effect relations across species, and no consistent linear effect of CBD on anxiety reduction. Currently, these results raise questions about the broad use as a drug for anxiety. Meta-analytic studies are needed to quantitatively investigate drug efficacy, including aspects of anxiety symptomatology. Acute and (sub)chronic dosing studies with integrated PK and PD outcomes are required for substantiated dose recommendations.
Topics: Humans; Mice; Rats; Animals; Cannabidiol; Anxiety; Anxiety Disorders
PubMed: 36239014
DOI: 10.1177/02698811221124792 -
Plants (Basel, Switzerland) Sep 2022(L.) (Asteraceae) is an important annual medicinal herb and is widespread in Morocco and Algeria. Most of its parts are used in traditional medicine and the roots are... (Review)
Review
(L.) (Asteraceae) is an important annual medicinal herb and is widespread in Morocco and Algeria. Most of its parts are used in traditional medicine and the roots are the most important parts used. The present review gives an account of the updated information on its phytochemical and pharmacological properties. We have collected the essential characteristics and the different scientific data of the species, and reviewed its potential. It is seen from the literature that is a rich source of the phytochemical constituents such as alkaloids (pellitorin) and -alkylamides. This species also contains pyrethrins, sesamin, traces of essential oils and a wide range of other chemical compounds. These active substances possess antimicrobial and anti-inflammatory activities. The plant has an antidiabetic, insecticidal and immunostimulatory effect, as well as an aphrodisiac and antioxidant potentials, and various other important medicinal properties. Many traditional uses are also reported in previous research such as for rheumatism, sciatica, colds, neuralgia and paralysis. This species is considered to be a sialagogue, and used in the treatment of stomach ailments, diseases of inflammation of the mouth, against cysts in the genital tract and to relieve toothaches. Thus, further research must be carried out in order to establish any relationship between the traditional uses, phytochemistry and toxicity. Moreover, is quite promising as a medicinal agent, so further clinical trials should be performed to prove its efficacy.
PubMed: 36235444
DOI: 10.3390/plants11192578 -
International Journal of Molecular... Sep 2022This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment-psilocybin and... (Review)
Review
This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment-psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin's antidepressive effects occurred one day after intake and after 6-7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin's effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Treatment-Resistant; Hallucinogens; Humans; Ketamine; Psilocybin
PubMed: 36232748
DOI: 10.3390/ijms231911450 -
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 -
Cureus Aug 2022Anxiety is one of the most common mental disorders in the adolescent age group due to both physiological and psychological changes along with substance use in this age... (Review)
Review
Anxiety is one of the most common mental disorders in the adolescent age group due to both physiological and psychological changes along with substance use in this age group. Generalized anxiety disorder, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), and social phobia (or social anxiety disorder) constitute anxiety disorders as per the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. In India, the National Mental Health Survey was conducted to estimate the burden of different mental health disorders, but the adolescent age group was not included in that survey. A comprehensive search strategy was used to find out articles from PubMed and ProQuest, along with a risk of bias assessment using two components of the Quality in Prognosis Studies (QUIPS) tool. The 13 articles included in the meta-analysis were divided into two groups depending on sampling strategy and outcome measurement. Due to more than 99% heterogeneity, the random effect model is used to find the pooled estimate. The pooled prevalence of anxiety disorder among adolescents in India is found to be 0.41 (CI: 0.14-0.96) for studies with more than low risk and 0.29 (CI: 0.11-0.46) for studies with low risk. The Begg and Mazumdar rank correlation test revealed no publication bias in the included studies. One study was found to be an outlier using the Baujat test, but pooled estimate and heterogeneity did not change significantly after its removal from analysis. The weight of individual studies calculated using the random effect model did not show any gross difference. A significant burden of anxiety was found in adolescents in India. Effective intervention should be planned to reduce this burden.
PubMed: 36127986
DOI: 10.7759/cureus.28084 -
BMC Medicine Sep 2022Non-communicable diseases (NCDs) are a leading cause of maternal mortality and morbidity worldwide. The World Health Organization is developing new recommendations...
BACKGROUND
Non-communicable diseases (NCDs) are a leading cause of maternal mortality and morbidity worldwide. The World Health Organization is developing new recommendations focusing on the management of NCDs for pregnant, intrapartum, and postnatal women. Thus, to support the development of new guidelines and recommendations, we aimed to determine the availability, focus, and scope of recommendations of current guidelines for the management of NCDs during pregnancy, intrapartum, and postnatal period.
METHODS
PubMed, Global Index Medicus, TRIP, and Guideline International Network databases were searched on 31 May 2021, to identify any NCD-related guidelines published between 2011 and 2021 with no language or country restrictions. Websites of 165 professional organizations were also searched. Characteristics of included guidelines were analyzed, and recommendations were extracted from guidelines of five high-priority NCD conditions (diabetes, chronic hypertension, respiratory conditions, hemoglobinopathies and sickle cell disease, and mental and substance use disorders).
RESULTS
From 6026 citations and 165 websites, 405 guidelines were included of which 132 (33%) were pregnancy-specific and 285 (88%) were developed in high-income countries. Among pregnancy-specific guidelines, the most common conditions for which recommendations were provided were gestational diabetes, circulatory diseases, thyroid disorders, and hypertensive disorders of pregnancy. For the five high-priority conditions, 47 guidelines were identified which provided 1834 recommendations, largely focused on antenatal care interventions (62%) such as early detection, screening tools, pharmacological treatment, and lifestyle education. Postnatal recommendations largely covered postnatal clinical assessments, lifestyle education, and breastfeeding. Health system recommendations largely covered multidisciplinary care teams and strengthening referral pathways.
CONCLUSIONS
This study provides a robust assessment of currently available guidelines and mapping of recommendations on NCD management within maternal health services, which will inform the scope of the World Health Organization's future guideline development activities. This study identified a need to develop guidelines that consider NCDs holistically, with an integrated approach to antenatal, intrapartum, and postnatal care, and that are relevant for resource-limited contexts. Any such guidelines should consider what interventions are most essential to improving outcomes for women with NCDs and their newborns, and how variations in quality of NCD-related care can be addressed.
Topics: Diabetes, Gestational; Female; Global Health; Humans; Infant, Newborn; Noncommunicable Diseases; Postnatal Care; Pregnancy; World Health Organization
PubMed: 36123668
DOI: 10.1186/s12916-022-02508-9 -
The Cochrane Database of Systematic... Sep 2022Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events... (Review)
Review
BACKGROUND
Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events (AEs) of treatment for pain in cancer and palliative care, resulting in increased morbidity and reduced quality of life. This review is a partial update of a 2008 review, and critiques as previous update (2018) trials only for people with cancer and people receiving palliative care.
OBJECTIVES
To assess for OIBD in people with cancer and people receiving palliative care the effectiveness and safety of mu-opioid antagonists (MOAs) versus different doses of MOAs, alternative pharmacological/non-pharmacological interventions, placebo, or no treatment.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science (December 2021), clinical trial registries and regulatory websites. We sought contact with MOA manufacturers for further data.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the effectiveness and safety of MOAs for OIBD in people with cancer and people at a palliative stage irrespective of the type of terminal disease.
DATA COLLECTION AND ANALYSIS
Two review authors assessed risk of bias and extracted data. The appropriateness of combining data from the trials depended upon sufficient homogeneity across trials. Our primary outcomes were laxation response, effect on analgesia, and AEs. We assessed the certainty of evidence using GRADE and created summary of findings tables.
MAIN RESULTS
We included 10 studies (two new trials) randomising in-total 1343 adults with cancer irrespective of stage, or at palliative care stage of any disease. The MOAs were oral naldemedine and naloxone (alone or in combination with oxycodone), and subcutaneous methylnaltrexone. The trials compared MOAs with placebo, MOAs at different doses, or in combination with other drugs. Two trials of naldemedine and three of naloxone with oxycodone were in people with cancer irrespective of disease stage. The trial on naloxone alone was in people with advanced cancer. Four trials on methylnaltrexone were in palliative care where most participants had advanced cancer. All trials were vulnerable to biases; most commonly, blinding of the outcome assessor was not reported. Oral naldemedine versus placebo Risk (i.e. chance) of spontaneous laxations in the medium term (over two weeks) for naldemedine was over threefold greater risk ratio (RR) 2.00, 95% confidence interval (CI) 1.59 to 2.52, 2 trials, 418 participants, I² = 0%. Number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 3 to 4; moderate-certainty evidence). Earlier risk of spontaneous laxations and patient assessment of bowel change was not reported. Very low-certainty evidence showed naldemedine had little to no effect on opioid withdrawal symptoms. There was little to no difference in the risk of serious (non-fatal) AEs (RR 3.34, 95% CI 0.85 to 13.15: low-certainty evidence). Over double the risk of AEs (non-serious) reported with naldemedine (moderate-certainty evidence). Low-dose oral naldemedine versus higher dose Risk of spontaneous laxations was lower for the lower dose (medium term, 0.1 mg versus 0.4 mg: RR 0.69, 95% CI 0.53 to 0.89, 1 trial, 111 participants (low-certainty evidence)). Earlier risk of spontaneous laxations and patient assessment of bowel change not reported. Low-certainty evidence showed little to no difference on opioid withdrawal symptoms (0.1 mg versus 0.4 mg mean difference (MD) -0.30, 95% CI -0.85 to 0.25), and occurrences of serious AEs (0.1 mg versus 0.4 mg RR 0.25, 95% CI 0.03 to 2.17). Low-certainty evidence showed little to no difference on non-serious AEs. Oral naloxone versus placebo Risk of spontaneous laxations and AEs not reported. Little to no difference in pain intensity (very low-certainty evidence). Full data not given. The trial reported that no serious AEs occurred. Oral naloxone + oxycodone versus oxycodone Risk of spontaneous laxations within 24 hours and in the medium term not reported. Low-certainty evidence showed naloxone with oxycodone reduced the risk of opioid withdrawal symptoms. There was little to no difference in the risk of serious (non-fatal) AEs (RR 0.68, 95% CI 0.44 to 1.06), 3 trials, 362 participants, I² = 55%: very low-certainty evidence). There was little to no difference in risk of AEs (low-certainty evidence). Subcutaneous methylnaltrexone versus placebo Risk of spontaneous laxations within 24 hours with methylnaltrexone was fourfold greater than placebo (RR 2.97, 95% CI 2.13 to 4.13. 2 trials, 287 participants, I² = 31%. NNTB 3, 95% CI 2 to 3; low-certainty evidence). Risk of spontaneous laxations in the medium term was over tenfold greater with methylnaltrexone (RR 8.15, 95% CI 4.76 to 13.95, 2 trials, 305 participants, I² = 47%. NNTB 2, 95% CI 2 to 2; moderate-certainty evidence). Low-certainty evidence showed methylnaltrexone reduced the risk of opioid withdrawal symptoms, and did not increase risk of a serious AE (RR 0.59, 95% CI 0.38 to 0.93. I² = 0%; 2 trials, 364 participants). The risk of AEs was higher for methylnaltrexone (low-certainty evidence). Lower-dose subcutaneous methylnaltrexone versus higher dose There was little to no difference in risk of spontaneous laxations in the medium-term (1 mg versus 5 mg or greater: RR 2.91, 95% CI 0.82 to 10.39; 1 trial, 26 participants very low-certainty evidence), or in patient assessment of improvement in bowel status (RR 0.98, 95% CI 0.71 to 1.35, 1 trial, 102 participants; low-certainty evidence). Medium-term assessment of spontaneous laxations and serious AEs not reported. There was little to no difference in symptoms of opioid withdrawal (MD -0.25, 95% CI -0.84 to 0.34, 1 trial, 102 participants) or occurrence of AEs (low-certainty evidence).
AUTHORS' CONCLUSIONS
This update's findings for naldemedine and naloxone with oxycodone have been strengthened with two new trials, but conclusions have not changed. Moderate-certainty evidence for oral naldemedine on risk of spontaneous laxations and non-serious AEs suggests in people with cancer that naldemedine may improve bowel function over two weeks and increase the risk of AEs. There was low-certainty evidence on serious AEs. Moderate-certainty evidence for methylnaltrexone on spontaneous laxations over two weeks suggests subcutaneous methylnaltrexone may improve bowel function in people receiving palliative care, but certainty of evidence for AEs was low. More trials are needed, more evaluation of AEs, outcomes patients rate as important, and in children.
Topics: Adult; Analgesics, Opioid; Child; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Neoplasms; Opioid-Induced Constipation; Oxycodone; Palliative Care; Quaternary Ammonium Compounds; Substance Withdrawal Syndrome
PubMed: 36106667
DOI: 10.1002/14651858.CD006332.pub4