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Tobacco Induced Diseases 2024Smoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the...
Efficacy of bupropion and varenicline genetic markers in choosing pharmacological treatment for smoking cessation, and implications for combining drugs: A randomized controlled trial - GENTSMOKING.
INTRODUCTION
Smoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the genetically favorable markers to choose a smoking cessation drug treatment (precision medicine) was superior to using the most effective drug (varenicline) in terms of abstinence rates. Additionally, combination therapy was tested when monotherapy failed.
METHODS
This partially blind, single-center study randomized (1:1) 361 participants into two major groups. In the genetic group (n=184), CYP2B6 rs2279343 (genotype AA) participants started treatment with bupropion, and CHRNA4 rs1044396 (genotype CT or TT) participants started treatment with varenicline; when genetic favorable to both, participants started treatment with bupropion, and when favorable to neither, on both drugs. In the control group (n=177), participants started treatment with varenicline, regardless of genetic markers. Drug treatment lasted 12 weeks. Efficacy endpoints were abstinence rates at Weeks 4, and Weeks 8-12, biochemically validated by carbon monoxide in exhaled air. Participants who did not achieve complete abstinence at Week 4, regardless of group, were given the choice to receive combination therapy.
RESULTS
Abstinence rates were 42.9% (95% CI: 36-64) in the control group versus 30.4% (95% CI: 23-37) in the genetic group at Week 4 (p=0.01); and 74% (95% CI: 67-80) versus 52% (95% CI: 49-64) at Week 12 (p<0.001), respectively. The strategy of combining drugs after Week 4 increased abstinence rates in both groups and the significant difference between genetic and control groups was maintained.
CONCLUSIONS
Results show that using these selected genetic markers was inferior to starting treatment with varenicline (control group), which is currently the most effective smoking cessation drug; moreover, the addition of bupropion in cases of varenicline monotherapy failure improves the efficacy rate until the end of treatment.
CLINICAL TRIAL IDENTIFIER
NCT03362099.
PubMed: 38628555
DOI: 10.18332/tid/186072 -
CMAJ : Canadian Medical Association... Apr 2024
Topics: Humans; Transcranial Magnetic Stimulation; Smoking Cessation
PubMed: 38621778
DOI: 10.1503/cmaj.230806-f -
Expert Opinion on Emerging Drugs Apr 2024Alcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their... (Review)
Review
INTRODUCTION
Alcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their communities and society at large. Even though pharmacotherapy is an integral part of AUD treatment, the few available substances show limited efficacy and limited clinical impact. Thus, there is a need for new innovative pharmacotherapeutic approaches.
AREAS COVERED
This paper provides a comprehensive review of drugs approved for the treatment of AUD as well as those currently in phase II and III development. Data from recent clinical trials has been reviewed and supplemented by additional literature based on a systematic search of the PubMed database and clinical trials registries. Compounds discussed include disulfiram, naltrexone, nalmefene, acamprosat, baclofen, sodium oxybate, doxazosin, varenicline, zonisamide, gabapentin, apremilast, ibudilast, ivermectin, tolcapone, mifepristone, suvorexant, ketamine, psilocybin, semaglutide, oxytocin and cannabidiol.
EXPERT OPINION
Even though the majority of the discussed compounds lack sufficient evidence to support their efficacy, multiple promising new treatment options are currently under investigation. Future research has to consider specific phenotypes and subgroups of AUD as well as a possible enhancement of the effects of psychotherapy through combination with pharmacotherapy. Practitioners should be encouraged to use available compounds to support existing therapeutic regimens.
PubMed: 38606899
DOI: 10.1080/14728214.2024.2342951 -
Journal of Addiction Medicine Apr 2024Tobacco contributes to the leading causes of morbidity and mortality among persons with human immunodeficiency virus (PWHs). Nonetheless, medications for tobacco use...
INTRODUCTION
Tobacco contributes to the leading causes of morbidity and mortality among persons with human immunodeficiency virus (PWHs). Nonetheless, medications for tobacco use disorder are widely underused, particularly among PWHs. We sought to characterize the extent to which insurance barriers impacted access to medications for tobacco use disorder and, in comparison, to access to antiretroviral therapy (ART).
METHODS
This is a secondary analysis of data on individuals enrolled in a randomized clinical trial to address tobacco use involving nicotine replacement therapy and, for some, additionally, varenicline or bupropion. Medication prescriptions are transmitted electronically from the clinic to neighborhood pharmacies. Data sources included participant assessments and intervention visit tracking forms.
RESULTS
Of 93 participants enrolled from September 2020 to July 2021, 20 (22%) were unable to fill or had difficulty filling their nicotine replacement therapy (NRT) prescriptions because of insurance barriers. These fell into 2 broad categories: enrollment in a publicly insured managed care plan in which the pharmacy benefit manager excluded nonprescription NRT and lack of understanding by the pharmacy of the scope of coverage. Of these 20 participants, 5 (25%) were unable to obtain medications at all, and 3 of these participants dropped out of the study. One additional participant paid out-of-pocket to obtain NRT. No participant was denied coverage of ART, bupropion, or varenicline.
CONCLUSIONS
Gaps in insurance coverage may result in PWHs receiving ART without simultaneous medical management of their tobacco use. This may undermine the efficacy of antivirals. Mandated insurance coverage of nonprescription NRT may improve the health of PWHs who smoke.
PubMed: 38606851
DOI: 10.1097/ADM.0000000000001302 -
The Medical Letter on Drugs and... Apr 2024
Topics: Pregnancy; Female; Humans; Bupropion; Smoking Cessation; Varenicline
PubMed: 38576145
DOI: 10.58347/tml.2024.1699c -
Psychiatry Research May 2024Smoking cessation medications have the potential to affect the functioning of the nervous system, leading to sleep disturbances. Our study aimed to compare the... (Review)
Review
Smoking cessation medications have the potential to affect the functioning of the nervous system, leading to sleep disturbances. Our study aimed to compare the sleep-related side effects (such as insomnia, abnormal dreams, nightmares, and somnolence) induced by different smoking cessation medications in non-psychiatric smokers. We conducted a thorough search of five electronic databases (Cochrane, EMBASE, PubMed, PsycInfo, and Web of Science) for randomized controlled trials. This study was registered with the PROSPERO (registration number CRD42022347976). A total of 79 full-text articles, encompassing 36,731 participants, were included in our analysis. Individuals using bupropion, bupropion in combination with a nicotinic acetylcholine receptor agonist (NRA), and bupropion in conjunction with nicotine replacement therapy (NRT) exhibited a higher likelihood of experiencing insomnia compared to those using NRT alone. Bupropion plus NRA had the highest ranking on the surface under the cumulative ranking curve (SUCRA) for insomnia risk, while placebo had the lowest ranking. Additionally, NRA plus NRT ranked first for abnormal dream outcomes, NRA alone for nightmares, and nortriptyline for somnolence, based on the SUCRA results. Healthcare providers should exercise caution when prescribing smoking cessation drugs, particularly in consideration of their potential sleep-related side effects.
Topics: Humans; Smoking Cessation; Bupropion; Varenicline; Smoking; Network Meta-Analysis; Sleep Initiation and Maintenance Disorders; Sleepiness; Tobacco Use Cessation Devices; Randomized Controlled Trials as Topic; Nicotinic Agonists; Sleep
PubMed: 38564922
DOI: 10.1016/j.psychres.2024.115874 -
International Review of Neurobiology 2024New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options...
New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options for opioid and nicotine use disorders. So far, there has been little attention to substitution therapy for the treatment of AD. Here, we explain the mechanistic foundations of alcohol substitution maintenance therapy. Alcohol has many primary targets in the brain (and other organs) and the physical interaction of ethanol molecules with these specific ethanol-sensitive sites on a variety of ionotropic receptors (e.g. GABA-A, NMDA, and nicotinic acetylcholine (nACh) receptors) and ion channels provides the rationale for substitution. As such, a variety of compounds can interact with those ethanol-sensitive sites and can thus substitute for some of the effects of alcohol. For some of these compounds, alcohol discrimination studies have shown their substitution potential. Accordingly, potential substitution treatments include agonists acting at GABA receptors such as sodium oxybate, baclofen and benzodiazepines, NMDA receptor antagonists such as ketamine and memantine, or nAChRs agonists such as varenicline. All these compounds are already approved for other indications and we present clinical evidence for these drugs in the treatment of alcohol withdrawal syndrome (AWS) and in the long-term treatment of AD, and outline future steps for their acceptance as substitution treatment in AD. Finally, we discuss the substitution approach of managed alcohol programs for the most severely affected homeless populations. Results showed that sodium oxybate is probably the closest to a substitution therapy for AD and is already approved for the treatment of AWS and in the long-term treatment of AD in some countries. In conclusion, we argue that better AD treatment can be provided if substitution maintenance treatments for alcohol are implemented at a similar scale as for opioid and nicotine use disorder.
Topics: Humans; Alcoholism; Sodium Oxybate; Analgesics, Opioid; Substance Withdrawal Syndrome; Ethanol; Tobacco Use Disorder; Receptors, Nicotinic
PubMed: 38555116
DOI: 10.1016/bs.irn.2024.03.005 -
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 -
JAMA Internal Medicine May 2024
Notice of Retraction: Lin HX et al. Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial. JAMA Intern Med. 2024;184(3):291-299.
PubMed: 38551593
DOI: 10.1001/jamainternmed.2024.1125 -
Brain Sciences Mar 2024Previous research has indicated that anticipating positive effects from cannabis use may be linked with increased frequency of cannabis consumption, yet these...
Previous research has indicated that anticipating positive effects from cannabis use may be linked with increased frequency of cannabis consumption, yet these expectancies remain poorly understood in adults with social anxiety disorder (SAD). Thus, our study aimed to investigate the expectancies of the effects of cannabis use in 26 frequently using adults with SAD (age: 27.9 ± 7.3 years; 54% female) and 26 (age: 27.4 ± 6.7 years; 50% female) without. While no between-group differences were observed, both groups reported expecting tension reduction and relaxation (F = 0.001; = 0.974), cravings, and physical effects (F = 1.10; = 0.300), but denied global negative effects (F = 0.11; = 0.744). The trajectory of cannabis use perceptions (further investigated in 12/26 participants/group) also showed no between-group differences. Before the initial use, positive perceptions may have led to initial and continuous cannabis consumption, while the symptoms of cannabis use disorder may have contributed to repeated use. Our data indicate that, regardless of psychiatric history, frequent cannabis-using adults are more likely to report positive expectancies, which are often associated with increased patterns of cannabis consumption. Psychoeducational programs and openly discussing the risks of cannabis may be beneficial in preventing and/or reducing cannabis use in people with SAD.
PubMed: 38539634
DOI: 10.3390/brainsci14030246