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The Journal of Family Practice Sep 2023YES. Low-dose naltrexone is as effective as amitriptyline in the treatment of painful diabetic neuropathy and has a superior safety profile (strength of recommendation... (Randomized Controlled Trial)
Randomized Controlled Trial
YES. Low-dose naltrexone is as effective as amitriptyline in the treatment of painful diabetic neuropathy and has a superior safety profile (strength of recommendation [SOR], B; single randomized controlled trial [RCT]). Low-dose naltrexone significantly reduced pain by 32% in inflammatory conditions and 44% in neuropathic conditions (SOR, B; single retrospective cohort study). Doses as low as 5.4 mg were found to reduce pain in 95% of patients with fibromyalgia (SOR, B; single prospective dose-response study).
Topics: Humans; Naltrexone; Pain Management; Amitriptyline; Fibromyalgia; Pain
PubMed: 37729143
DOI: 10.12788/jfp.0654 -
JAMA Mar 2024
Topics: Humans; Alcohol Drinking; Alcoholism; Alcohol Deterrents
PubMed: 38441587
DOI: 10.1001/jama.2023.28408 -
Hepatology (Baltimore, Md.) Feb 2024The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce.
APPROACH AND RESULTS
We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines on the efficacy of MAUD in patients with cirrhosis. A search was conducted in PubMed, Embase, and Scopus, including all studies until May 2022. The population was defined as patients with AUD and cirrhosis. The primary outcome was alcohol abstinence. Safety was a secondary outcome. We performed a random-effect analysis and expressed the results as relative risk of alcohol consumption. Heterogeneity was measured by I2 . Out of 4095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1), and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies, and 4 were RCTs. Only RCTs were included in the meta-analysis. MAUD was associated with a reduced rate of alcohol consumption [relative risk = 0.68 (CI: 0.48-0.97), P = 0.03], increasing alcohol abstinence by 32% compared to placebo or standard treatment, despite high heterogeneity ( I2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications.
CONCLUSION
MAUD in patients with cirrhosis is effective in promoting alcohol abstinence and has a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease.
Topics: Humans; Alcoholism; Alcohol Drinking; Acamprosate; Liver Cirrhosis, Alcoholic; Liver Cirrhosis
PubMed: 37625154
DOI: 10.1097/HEP.0000000000000570 -
Addictive Behaviors Aug 2024Exposure to alcohol-related cues is thought to elicit a conditional response characterized by increased craving in individuals with alcohol use disorder (AUD). In the...
PURPOSE
Exposure to alcohol-related cues is thought to elicit a conditional response characterized by increased craving in individuals with alcohol use disorder (AUD). In the context of AUD research, it is important to consider that not all individuals with an AUD are alcohol cue reactive. This study systematically examined subjective alcohol cue reactivity and its clinical and drinking correlates in individuals with an AUD enrolled in a human laboratory pharmacotherapy trial.
METHODS
Individuals with current moderate-to-severe AUD (N = 52) completed a standard alcohol cue exposure paradigm and individual difference assessments as part of a human laboratory pharmacotherapy trial (NCT04249882). We classified participants as cue reactive (CR+) and cue non-reactive (CR-), as indicated by self-reported, subjective alcohol urge, and examined group differences in baseline clinical characteristics and drinking outcomes over the course of the trial.
RESULTS
Twenty participants (38%) were identified as CR+, while 32 participants (62%) were identified as CR-. The CR+ and CR- groups did not differ in baseline drinking and AUD clinical characteristics, but the groups differed in race composition (p = 0.02) and smoking prevalence (p = 0.04) such that the CR+ group had lower prevalence of smokers. The CR+, compared with the CR-, group drank more during the trial titration period (p = 0.03). Both groups reduced drinking across the trial (p's < 0.001), but the CR+ group exhibited a smaller reduction in drinking, compared with the CR- group (time x group, p = 0.029; CR-, p < 0.0001; CR+: p = 0.01).
CONCLUSION
Results indicate that cue reactivity is a heterogenous construct. Recognizing this heterogeneity, and the clinical factors associated with it, is critical to advancing this paradigm as an early efficacy marker in AUD research.
Topics: Humans; Cues; Male; Female; Alcoholism; Craving; Adult; Middle Aged; Alcohol Deterrents; Alcohol Drinking
PubMed: 38640885
DOI: 10.1016/j.addbeh.2024.108028 -
CNS Drugs Aug 2023Naltrexone is a mu-opioid receptor antagonist with a long half-life compared with naloxone. Both of these drugs, along with others, were developed with the intention of...
Naltrexone is a mu-opioid receptor antagonist with a long half-life compared with naloxone. Both of these drugs, along with others, were developed with the intention of reversing the effects of opioid abuse or toxicity. Evidence has also shown that naltrexone has a benefit in preventing relapse by reducing opioid cravings and reducing symptoms of opioid withdrawal. The benefits of this drug were not only shown with opioid abuse. In 1984 this drug was also approved for alcohol abuse. Naltrexone has been proven to decrease alcohol relapse by decreasing the craving. Apart from these approved indications for the use of naltrexone, with time, it has been seen that this drug has a benefit in treating chronic pain. A number of studies have shown the benefits of this drug with inflammatory bowel disease, fibromyalgia, multiple sclerosis, diabetic neuropathy, and complex regional pain syndrome, among others. More studies are needed to approve this medication for specific chronic pain conditions.
Topics: Humans; Naltrexone; Chronic Pain; Analgesics, Opioid; Narcotic Antagonists; Opioid-Related Disorders; Chronic Disease; Recurrence
PubMed: 37505425
DOI: 10.1007/s40263-023-01018-3 -
Pain Medicine (Malden, Mass.) Nov 2023At low doses, naltrexone (LDN) has been shown to modulate inflammation through the interruption of microglial cell activation within the central nervous system. One of... (Review)
Review
BACKGROUND
At low doses, naltrexone (LDN) has been shown to modulate inflammation through the interruption of microglial cell activation within the central nervous system. One of the most likely contributors to centralized pain is changes in microglial cell processing. Therefore, it has been postulated that LDN can be used to manage patients with pain resulting from central sensitization due to this relationship. This scoping review aims to synthesize the relevant study data for LDN as a novel treatment strategy for various centralized pain conditions.
METHODS
A comprehensive literature search was conducted in PubMed, Embase, and Google Scholar, guided by the Scale for Assessment of Narrative Review Articles (SANRA) criteria.
RESULTS
Forty-seven studies related to centralized pain conditions were identified. Many of the studies were case reports/series and narrative reviews, but a few randomized control trials have been conducted. Overall, the body of evidence revealed improvement in patient-reported pain severity and in outcomes related to hyperalgesia, physical function, quality of life, and sleep. Variability in dosing paradigms and the time to patient response was present in the reviewed studies.
CONCLUSIONS
Evidence synthesized for this scoping review supports the ongoing use of LDN for the treatment of refractory pain in various centralized chronic pain conditions. Upon review of the currently available published studies, it is apparent that further high-quality, well-powered randomized control trials need to be conducted to establish efficacy, standardization for dosing, and response times. In summary, LDN continues to offer promising results in the management of pain and other distressing symptoms in patients with chronic centralized pain conditions.
Topics: Humans; Naltrexone; Chronic Pain; Quality of Life; Chronic Disease; Inflammation
PubMed: 37302106
DOI: 10.1093/pm/pnad074 -
Obesity (Silver Spring, Md.) Nov 2023Binge-eating disorder (BED) is a prevalent psychiatric disorder associated with obesity. Few evidence-based treatments exist for BED, particularly pharmacological... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Binge-eating disorder (BED) is a prevalent psychiatric disorder associated with obesity. Few evidence-based treatments exist for BED, particularly pharmacological options. This study tested the efficacy of naltrexone/bupropion for BED.
METHODS
A randomized, double-blind, placebo-controlled, 12-week trial tested naltrexone/bupropion for BED with and without obesity. Eighty-nine patients (70.8% women, 69.7% White, mean age 45.7 y, mean BMI 35.1 kg/m , 77.5% with BMI ≥ 30 kg/m ) were randomized to placebo (n = 46) or naltrexone/bupropion (n = 43), with randomization stratified by obesity status and gender; 92.1% completed post-treatment assessments.
RESULTS
Mixed models of binge-eating frequency revealed significant reductions that did not differ significantly between naltrexone/bupropion and placebo. Logistic regression of binge-eating remission rates revealed that naltrexone/bupropion and placebo did not differ significantly. Obesity status did not predict, or moderate, binge-eating outcomes considered either continuously or categorically. Mixed models revealed that naltrexone/bupropion was associated with significantly greater percentage weight loss than placebo. Logistic regression revealed that naltrexone/bupropion had significantly higher rates of attaining ≥5% weight loss than placebo (27.9% vs. 6.5%). Obesity status did not predict or moderate weight-loss outcomes.
CONCLUSIONS
Naltrexone/bupropion did not demonstrate effectiveness for reducing binge eating relative to placebo but showed effectiveness for weight reduction in patients with BED. Obesity status did not predict or moderate medication outcomes.
Topics: Humans; Female; Middle Aged; Male; Bupropion; Naltrexone; Binge-Eating Disorder; Obesity; Bulimia; Weight Loss; Double-Blind Method; Treatment Outcome
PubMed: 37751990
DOI: 10.1002/oby.23898 -
International Review of Neurobiology 2024Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in... (Review)
Review
Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.
Topics: Humans; Alcoholism; Acamprosate; Naltrexone; Disulfiram; Sodium Oxybate; Baclofen; Drug Repositioning; Substance Withdrawal Syndrome; Alcohol Drinking
PubMed: 38555115
DOI: 10.1016/bs.irn.2024.02.002 -
The Cochrane Database of Systematic... Jan 2024Cocaine is a psychostimulant used by approximately 0.4% of the general population worldwide. Cocaine dependence is a chronic mental disorder characterised by the... (Review)
Review
BACKGROUND
Cocaine is a psychostimulant used by approximately 0.4% of the general population worldwide. Cocaine dependence is a chronic mental disorder characterised by the inability to control cocaine use and a host of severe medical and psychosocial complications. There is current no approved pharmacological treatment for cocaine dependence. Some researchers have proposed disulfiram, a medication approved to treat alcohol use disorder. This is an update of a Cochrane review first published in 2010.
OBJECTIVES
To evaluate the efficacy and safety of disulfiram for the treatment of cocaine dependence.
SEARCH METHODS
We updated our searches of the following databases to August 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO. We also searched for ongoing and unpublished studies via two trials registries. We handsearched the references of topic-related systematic reviews and included studies. The searches had no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials that evaluated disulfiram alone or associated with psychosocial interventions versus placebo, no intervention, other pharmacological interventions, or any psychosocial intervention for the treatment of cocaine dependence.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Thirteen studies (1191 participants) met our inclusion criteria. Disulfiram versus placebo or no treatment Disulfiram compared to placebo may increase the number of people who are abstinent at the end of treatment (point abstinence; risk ratio (RR) 1.58, 95% confidence interval (CI) 1.05 to 2.36; 3 datasets, 142 participants; low-certainty evidence). However, compared to placebo or no pharmacological treatment, disulfiram may have little or no effect on frequency of cocaine use (standardised mean difference (SMD) -0.11 standard deviations (SDs), 95% CI -0.39 to 0.17; 13 datasets, 818 participants), amount of cocaine use (SMD -0.00 SDs, 95% CI -0.30 to 0.30; 7 datasets, 376 participants), continuous abstinence (RR 1.23, 95% CI 0.80 to 1.91; 6 datasets, 386 participants), and dropout for any reason (RR 1.20, 95% CI 0.92 to 1.55; 14 datasets, 841 participants). The certainty of the evidence was low for all these outcomes. We are unsure about the effects of disulfiram versus placebo on dropout due to adverse events (RR 12.97, 95% CI 0.77 to 218.37; 1 study, 67 participants) and on the occurrence of adverse events (RR 3.00, 95% CI 0.35 to 25.98), because the certainty of the evidence was very low for these outcomes. Disulfiram versus naltrexone Disulfiram compared with naltrexone may reduce the frequency of cocaine use (mean difference (MD) -1.90 days, 95% CI -3.37 to -0.43; 2 datasets, 123 participants; low-certainty evidence) and may have little or no effect on amount of cocaine use (SMD 0.12 SDs, 95% CI -0.27 to 0.51, 2 datasets, 123 participants; low-certainty evidence). We are unsure about the effect of disulfiram versus naltrexone on dropout for any reason (RR 0.86, 95% CI 0.56 to 1.32, 3 datasets, 131 participants) and dropout due to adverse events (RR 0.50, 95% CI 0.07 to 3.55; 1 dataset, 8 participants), because the certainty of the evidence was very low for these outcomes.
AUTHORS' CONCLUSIONS
Our results show that disulfiram compared to placebo may increase point abstinence. However, disulfiram compared to placebo or no pharmacological treatment may have little or no effect on frequency of cocaine use, amount of cocaine use, continued abstinence, and dropout for any reason. We are unsure if disulfiram has any adverse effects in this population. Caution is required when transferring our results to clinical practice.
Topics: Humans; Disulfiram; Cocaine-Related Disorders; Naltrexone; Alcoholism; Cocaine
PubMed: 38180268
DOI: 10.1002/14651858.CD007024.pub3 -
Expert Review of Neurotherapeutics Apr 2024Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment... (Review)
Review
INTRODUCTION
Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment options include psychological and pharmacological interventions.
AREAS COVERED
This narrative review explores existing pharmacological treatments for GD. The following classes of medications were considered: opioid-receptor antagonists (e.g. naltrexone and nalmefene), serotonin reuptake inhibitors (e.g. fluvoxamine, paroxetine, sertraline, escitalopram, and citalopram), glutamatergic agents (e.g. N-acetylcysteine (NAC), acamprosate, and memantine), mood stabilizers (e.g. topiramate, carbamazepine, lithium), and other medications (e.g. modafinil, nefazodone, olanzapine, haloperidol, tolcapone, and bupropion).
EXPERT OPINION
Due to the limitations of the studies reviewed, solid conclusions regarding the optimal choice of pharmacotherapy for individuals with GD are challenging to draw at this time. Despite some medications, such as naltrexone and nalmefene, showing promising results, efficacy has varied across studies. The review highlights current gaps/limitations, including small sample sizes, limited diversity in participant demographics, the need for exploring different gambling subtypes and treatment responses, high placebo response rates, lack of longer-term longitudinal information, limited investigation of neurobiological correlates and co-occurring disorders, and the importance of implementation research. Further research is needed to address these gaps and explore additional medications, as well as interventions like neuromodulation.
Topics: Humans; Gambling; Naltrexone; Behavior, Addictive; Narcotic Antagonists; Selective Serotonin Reuptake Inhibitors
PubMed: 38357896
DOI: 10.1080/14737175.2024.2316833