5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Effectiveness of Antidepressants in Combination with Psychotherapy.

BACKGROUND: Consensus-guidelines for prescribing antidepressants recommend that clinicians should be vigilant to match antidepressants to patient's medical history but provide no specific advice on which antidepressant is best for a given medical history. AIMS OF THE STUDY: For patients with major depression who are in psychotherapy, this study provides an empirically derived guideline for prescribing antidepressant medications that fit patients' medical history. METHODS: This retrospective, observational, cohort study analyzed a large insurance database of 3,678,082 patients. Data was obtained from healthcare providers in the U.S. between January 1, 2001, and December 31, 2018. These patients had 10,221,145 episodes of antidepressant treatments. This study reports the remission rates for the 14 most commonly prescribed single antidepressants (amitriptyline, bupropion, citalopram, desvenlafaxine, doxepin, duloxetine, escitalopram, fluoxetine, mirtazapine, nortriptyline, paroxetine, sertraline, trazodone, and venlafaxine) and a category named "Other" (other antidepressants/combination of antidepressants). The study used robust LASSO regressions to identify factors that affected remission rate and clinicians' selection of antidepressants. The selection bias in observational data was removed through stratification. We organized the data into 16,770 subgroups, of at least 100 cases, using the combination of the largest factors that affected remission and selection bias. This paper reports on 2,467 subgroups of patients who had received psychotherapy. RESULTS: We found large, and statistically significant, differences in remission rates within subgroups of patients. Remission rates for sertraline ranged from 4.5% to 77.86%, for fluoxetine from 2.86% to 77.78%, for venlafaxine from 5.07% to 76.44%, for bupropion from 0.5% to 64.63%, for desvenlafaxine from 1.59% to 75%, for duloxetine from 3.77% to 75%, for paroxetine from 6.48% to 68.79%, for escitalopram from 1.85% to 65%, and for citalopram from 4.67% to 76.23%. Clearly these medications are ideal for patients in some subgroups but not others. If patients are matched to the subgroups, clinicians can prescribe the medication that works best in the subgroup. Some medications (amitriptyline, doxepin, nortriptyline, and trazodone) always had remission rates below 11% and therefore were not suitable as single antidepressant therapy for any of the subgroups. DISCUSSIONS: This study provides an opportunity for clinicians to identify an optimal antidepressant for their patients, before they engage in repeated trials of antidepressants. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: To facilitate the matching of patients to the most effective antidepressants, this study provides access to a free, non-commercial, decision aid at http://MeAgainMeds.com. IMPLICATIONS FOR HEALTH POLICIES:  Policymakers should evaluate how study findings can be made available through fragmented electronic health records at point-of-care. Alternatively, policymakers can put in place an AI system that recommends antidepressants to patients online, at home, and encourages them to bring the recommendation to their clinicians at their next visit. IMPLICATIONS FOR FURTHER RESEARCH:  Future research could investigate (i) the effectiveness of our recommendations in changing clinical practice, (ii) increasing remission of depression symptoms, and (iii) reducing cost of care. These studies need to be prospective but pragmatic. It is unlikely random clinical trials can address the large number of factors that affect remission.

Comparison of the Efficacy of Anti-Obesity Medications in Real-World Practice.

Purpose: Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the efficacy of AOMs has been reported, there have been no direct comparisons of these drugs. Therefore, in the present study, we aimed to compare the efficacy of all the AOMs available in Korea in a real-world setting. Patients and Methods: The body weight and composition of 205 adults treated with phentermine, phentermine/topiramate, liraglutide, naltrexone/bupropion, lorcaserin, or orlistat for at least 6 months were analyzed at 2 month intervals. The prevalence of the achievement of a ≥5% weight loss and the changes in body composition were compared between participants using each AOM at each visit. Results: A total of 132 (64.4%) participants achieved ≥5% weight loss within 6 months (prevalence of ≥5% weight loss after 6 months: phentermine, 87.2%; phentermine/topiramate, 67.7%; liraglutide, 58.1%; naltrexone/bupropion, 35.3%; lorcaserin, 75%; orlistat, 50%). At each visit, after adjustment for age, sex, and baseline body weight, phentermine use was associated with a significantly higher prevalence of ≥5% weight loss than the use of the other AOMs, except for liraglutide. There were significant differences in the body weight, body mass index and body fat mass among the AOM groups by visit (P for interaction <0.05), but not in their waist circumference, skeletal muscle mass, percentage body fat, or visceral fat area. Conclusion: All the AOMs were effective at inducing and maintaining weight loss, in the absence of significant changes in muscle mass, over a 6 month period, and the short-term use of phentermine and the long-term use of phentermine/topiramate or liraglutide would be practical choices for the treatment of obesity. However, further, large-scale studies are necessary to confirm these findings.

Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample.

Despite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of which were protective (CYP2B6 (rs1175607105), HTR3B (rs1413172952; rs1204720503), rs80210037 on chr15), and 2 of which were associated with reduced cessation (PARP15 (rs2173763), SCL18A2 (rs363222)). The others mapped to areas associated with cancer including FOXP1 (rs1288980) and ZEB1 (rs7349). Network analysis identified significant canonical pathways for the serotonin receptor signaling pathway, nicotine and bupropion metabolism, and several related to tumor suppression. Two novel markers (rs6749438; rs6718083) on chr2 are flanked by genes associated with regulation of bodyweight. The identification of novel loci in this study can provide new targets of pharmacotherapy and inform efforts to develop personalized treatments based on genetic profiles.

Coprolalia y copropraxia inducida por bupropión en un paciente autista y con trastorno obsesivo compulsivo / Bupropion-induced coprolalia and copropraxia in autistic and obsessive compulsive disorder patient

Se presenta el caso de un varón de 41 años, ingresado desde los 26 en la unidad residencial y rehabilitadora con los diagnósticos de trastorno del espectro autista y trastorno obsesivo compulsivo, en tratamiento con fluvoxamina, valproico, topiramato, risperidona y clonazepam. Tras un periodo de estabilidad, aparece un cuadro compatible con un episodio depresivo mayor, que se decide tratar con bupropión, para incidir en los síntomas de apatía y lentitud psicomotriz. Se produce una recuperación rápida en 2 semanas, pero comienza a presentar copropraxia y coprolalia, que nunca antes había presentado. Se retira el bupropión y desaparece la coprolalia en 2 semanas, pero mantiene parte de estas conductas, por lo se pauta acetato de ciproterona para controlarlas, con mejoría en una semana. Tres meses después de la retirada del bupropión, alcanzó la eutimia y ya no presentó ninguna alteración conductual de temática sexual, coprolalia ni copropraxia. La literatura confirma otros casos de aparición de tics en pacientes tratados con antidepresivos para un cuadro depresivo y comorbilidad con trastorno obsesivo compulsivo, pero casi ninguno por el uso de bupropión o con coprolalia y copropraxia. (AU)

The case is presented of a 41-year-old male, admitted since age 26 to the Residential and Rehabilitation Unit with the diagnoses of autism spectrum disorder and obsessive-compulsive disorder, and under treatment with fluvoxamine, valproic, topiramate, risperidone and clonazepam. After a period of stability, a picture compatible with a major depressive episode appear, which is treated with bupropion, in order to affect the symptoms of apathy and psychomotor slowness. There is a rapid recovery in two weeks, but he begins to present copropraxia and coprolalia, which he had never presented before. Bupropion is withdrawn and coprolalia disappears in two weeks, but he maintained some of these behaviors, so cyproterone acetate is prescribed to control them, with improvement in one week. Three months after withdrawal of bupropion, he reaches euthymia and no longer presented any sexual behavioral alteration, coprolalia or copropraxia. The literature confirms other cases of appearance of tics in patients treated with antidepressants for a depressive picture and comorbidity with obsessive-compulsive disorder, but almost none by the use of bupropion or with coprolalia and copropraxia. (AU)

Effect of smoking cessation interventions on abstinence and tuberculosis treatment outcomes among newly diagnosed patients: a randomized controlled trial.

The study evaluates the effectiveness of smoking cessation interventions [Behavioral Change Communication (BCC) and Behavioral Change Communication plus bupropion (BCC+)] compared to conventional Directly Observed Therapy Short Course (DOT) treatment in improving pulmonary tuberculosis treatment outcomes and abstinence among newly diagnosed pulmonary tuberculosis (PTB) patients, highlighting the scarcity of robust experimental studies. The current randomized controlled trial, conducted at Ojha Institute of Chest Diseases between October 2017 and June 2019, randomized 292 patients who were current smokers with newly diagnosed pulmonary tuberculosis into three arms: control (n = 97), BCC (n = 97), and BCC+ (n = 98) arms. The outcomes of the interventions were compared in terms of favorable treatment outcomes and abstinence achieved at the end of 6 months. Baseline characteristics were compared between groups. Cox regression quantified the effect size of interventions for both outcome variables and reported as (crude and adjusted) hazard ratios with 95% confidence intervals (CI). No statistically significant difference was observed in baseline characteristics in each arm. Both BCC+ and BCC showed a statistically significant effect in achieving favorable PTB outcomes at 6 months (aHR 2.37, 95% CI 1.52-3.70 and aHR 2.34, 95% CI 1.51-3.60), as well as for abstinence from smoking at 6 months (BCC+: aHR 4.03, 95% CI 2.18-7.44 and BCC: aHR 3.87, 95% CI 2.12-7.05) compared to the control arm. Both BCC and BCC+ aided by pharmacologic agents such as bupropion when incorporated with conventional DOTs were found to be significantly effective in attaining favorable tuberculosis treatment outcomes as well as in attaining smoking abstinence at the end of the 6-month treatment.This study shows that adding smoking cessation programs (with or without extra drugs like bupropion) to standard Directly Observed Treatment Short Course (DOTs) treatment for people who have recently been diagnosed with pulmonary tuberculosis has a great positive impact on how well the overall antituberculosis treatment works. Our trial shows very promising results for such a combined therapy (DOTs and smoking cessation) in a country where the burden of both tuberculosis and smoking is very high.

Evaluation of the effectiveness of cytisine for the treatment of smoking cessation: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Smoking is considered the main cause of preventable death world-wide. This study aimed to review the efficacy and safety of cytisine for smoking cessation. METHODS: This review included an exhaustive search of databases to identify randomized controlled trials (RCTs) in health centers of any level with smokers of any age or gender investigating the effects of cytisine at standard dosage versus placebo, varenicline or nicotine replacement therapy (NRT). RESULTS: We identified 12 RCTs. Eight RCTs compared cytisine with placebo at the standard dose covering 5922 patients, 2996 of whom took cytisine, delivering a risk ratio (RR) of 2.25 [95% confidence interval (CI) = 1.42-3.56; I2  = 88%; moderate-quality evidence]. The greater intensity of behavioral therapy was associated directly with the efficacy findings (moderate-quality evidence). The confirmed efficacy of cytisine was not evidenced in trials conducted in low- and middle-income countries. We estimate a number needed to treat (NNT) of 11. Two trials compared the efficacy of cytisine versus NRT, and the combination of both studies yields modest results in favor of cytisine. Three trials compared cytisine with varenicline, without a clear benefit for cytisine. Meta-analyses of all non-serious adverse events in the cytisine group versus placebo groups yielded a RR of 1.24 (95% CI = 1.11-1.39; participants = 5895; studies = 8; I2 = 0%; high-quality evidence). CONCLUSIONS: Cytisine increases the chances of successful smoking cessation by more than twofold compared with placebo and has a benign safety profile, with no evidence of serious safety concerns. Limited evidence suggests that cytisine may be more effective than nicotine replacement therapy, with modest cessation rates.

Update Lessons from PET Imaging Part II: A Systematic Critical Review on Therapeutic Plasma Concentrations of Antidepressants.

BACKGROUND: Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established. METHODS: We have discussed the literature on the relationship between plasma concentrations of antidepressant drugs and their target occupancy. Antidepressants reviewed in this work are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, duloxetine, milnacipran, tricyclic antidepressants (amitriptyline, nortriptyline, and clomipramine), bupropion, tranylcypromine, moclobemide, and vortioxetine. Four electronic databases were systematically searched. RESULTS: We included 32 articles published 1996-2022. A strong relationship between serotonin transporter (SERT) occupancy and drug concentration is well established for selective serotonin reuptake inhibitors. Lower limits of recommended therapeutic reference ranges largely corroborate with the findings from positron emission tomography studies (80% SERT occupancy). Only a few novel studies have investigated alternative targets, that is, norepinephrine transporters (NETs), dopamine transporters (DATs), or monoamine oxidase A (MAO-A). For certain classes of drugs, positron emission tomography study data are inconclusive. Low DAT occupancy after bupropion treatment speculates its discussed mechanism of action. For MAO inhibitors, a correlation between drug concentration and MAO-A occupancy could not be established. CONCLUSIONS: Neuroimaging studies are critical in TDM-guided therapy for certain antidepressants, whereas for bupropion and MAO inhibitors, the available evidence offers no further insight. Evidence for selective serotonin reuptake inhibitors is strong and justifies a titration toward suggested ranges. For SNRIs, duloxetine, and venlafaxine, NETs are sufficiently occupied, well above the SERT efficacy threshold. For these drugs, a titration toward higher concentrations (within the recommended range) should be considered in case of no response at lower concentrations.

Dextromethorphan/Bupropion: A Novel Treatment for Patients With Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) affects millions of people and is the leading cause of disability worldwide. Patients report decreased quality of life and ability to perform activities of daily living. It is estimated that the current standard of care, which includes pharmacologic therapy with a selective serotonin reuptake inhibitor, is effective in 40%-60%. Additional treatment options are warranted. The combination of dextromethorphan (DEX) and bupropion (BUP) (Auveulty) was approved for treatment in 2022. This unique combination offers an interesting mechanism of action and favorable onset of action for patients with MDD. PHARMACODYNAMICS AND PHARMACOKINETICS: The mechanism of action of DEX-BUP when used in combination is unique. DEX is a noncompetitive N-methyl-d-aspartate receptor antagonist rapidly metabolized through the CYP450 2D6. BUP is an aminoketone and CYP2D6 inhibitor, which results in increased plasma levels of DEX through competitive CYP2D6 inhibition. CLINICAL TRIALS: In a phase 2 clinical study, the efficacy of DEX-BUP was compared with BUP alone in patients with clinically diagnosed MDD. At baseline, participants had moderate-to-severe depression using the Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impressions Severity (CGI-S) scales. There was a significant overall reduction in MADRS and CGI-S scores in the treatment group compared with the BUP monotherapy with improvement observed as early as week 1 of treatment. Later, a phase 3 study was conducted comparing DEX-BUP 45 mg/105 mg with placebo in patients with moderate-to-severe MDD. Similarly, MADRS and CGI-S scores were significantly reduced in the treatment group. Adverse effects were similar in all groups. THERAPEUTIC ADVANCE: Clinical response to first line treatment options for MDD are reported to be 40%-60%. Availability of additional treatment options, particularly those with reduced time to efficacy, may improve overall treatment and patient quality of life. DEX-BUP is a combination option that has been shown to improve depression symptoms as early as 1 week after initiation.

A randomized, double-blind, placebo-controlled, multicentre trial on the efficacy of varenicline and bupropion in combination and alone for treatment of alcohol use disorder: Protocol for the COMB study.

BACKGROUND: Alcohol Use Disorder (AUD) is a major cause of premature death, disability and suffering. Available treatments are of modest efficacy and under-prescribed so there is a pressing need for a well-tolerated and effective treatment option for AUD. Dopamine is hypothesized to be involved in the development of alcohol dependence. To challenge the low-dopamine hypothesis of addiction, this randomized, double-blind, placebo-controlled, 13-week, multicentre clinical trial with four parallel arms is designed to evaluate the efficacy of two substances raising dopamine levels, varenicline and bupropion, alone and in combination vs. placebo on alcohol consumption in AUD. Varenicline, a partial agonist at brain nicotinic acetylcholine receptors increases dopamine release, whereas bupropion is a centrally-acting, norepinephrine-dopamine reuptake inhibitor. Varenicline is previously shown to reduce alcohol intake in individuals with AUD. We hypothesize that the effect size of a combination of two drugs affecting dopamine levels in the brain will exceed that of approved AUD therapies. METHODS: Consenting individuals with AUD will be recruited via media advertisements. Those fulfilling the eligibility criteria (N = 380) will be randomized to one of four interventions (n = 95 per arm). Treatment will comprise one week of titration (varenicline 0.5‒2 mg; bupropion SR 150‒300 mg) plus 12 weeks at steady state. Efficacy will be evaluated using two primary endpoints of alcohol consumption: Heavy Drinking Days and blood levels of phosphatidylethanol. Secondary objectives, exploratory and subgroup analyses will be also performed. The modified Intention-to-Treat and Per Protocol datasets will be evaluated using Analysis of Covariance. Last patient out is estimated to occur in December, 2022. DISCUSSION: The COMB Study aims to evaluate the efficacy of the combination of varenicline and bupropion, two drugs affecting dopamine, on alcohol consumption, and to challenge the low-dopamine hypothesis of addiction. Study Code COMB-BO8, EudraCT 2018-000048-24, Version 3.2, Lidö & deBejczy, 2020-06-16; https://clinicaltrials.gov identifier NCT04167306.

Patient interest in acupuncture for smoking cessation: a survey.

BACKGROUND/OBJECTIVE: Tobacco use remains the leading cause of preventable death in the United States. The most widely available treatment options to assist patients in smoking cessation are limited by side effects and moderate efficacy at best. Acupuncture may be an effective option for smoking cessation. The goal of this study was to establish the need for and interest in acupuncture therapy to potentially assist with smoking cessation from a patient perspective. METHODS: We conducted a cross-sectional survey study among patients aged 18 years or older whose medical record reported current tobacco use with English as their preferred language. REDCap surveys were administered to patients during office visits and included questions regarding opinions and use of all treatments available for smoking cessation (including acupuncture) as well as perceived barriers to acupuncture treatment. RESULTS: A total of 57 surveys were distributed, and 42 (74%) were completed. Most patients reported previous attempts at quitting (76%) and had tried a variety of treatments including nicotine replacement (45%), Chantix (varenicline; 23%), Wellbutrin (bupriopion; 19%), "cold turkey" (65%) and hypnosis (3%). No respondents reported having tried acupuncture for smoking cessation. CONCLUSION: When comparing treatment options, patients reported more interest in acupuncture than other treatment options with a statistically significant difference in the level of interest between acupuncture and bupropion. All barriers (cost, time and effectiveness) were equally rated on a Likert-type scale with a median of 50 on a 101-point scale.

Real-world assessment of treatment inertia in the management of patients treated for major depressive disorder in the USA.

Aim: Major depressive disorder (MDD) is a debilitating illness in which depressive symptoms may persist after treatment. Treatment inertia is the continued use of the same pharmacotherapy regimen when treatment goals are not met. This study assessed the frequency of treatment inertia among adult patients with MDD treated in a real-world setting. Patients & methods: This was a retrospective, observational study of patients with MDD identified in the Decision Resources Group Real World Evidence US Data Repository from January 2014 to June 2018. Patients (≥18 years) had an elevated Patient Health Questionnaire-9 (PHQ-9) score (≥5) following 8 weeks of stable baseline antidepressant use with/without mental-health outpatient therapy. Treatment inertia, modification and discontinuation were evaluated over a 16-week follow-up period (timeline based on the APA Practice Guidelines). The primary outcome was the proportion of MDD patients experiencing treatment inertia. Results: 2850 patients (median age, 55 years; 74% female) met the study criteria. Of these patients, 834 (29%) had study-defined treatment inertia, 1534 (54%) received treatment modification and 482 (17%) discontinued treatment. Use of mirtazapine (Odd ratio [OR]: 0.63; 95% confidence interval [CI]: 0.50-0.79), selective serotonin reuptake inhibitors (OR: 0.64; 95% CI: 0.54-0.75) or bupropion (OR: 0.71; 95% CI: 0.60-0.84) in the baseline period was associated with an increased likelihood of treatment modification versus not receiving treatment with these medications. Frequency of treatment inertia may differ among those who do not have a documented PHQ-9 score. Conclusion: Effective symptom management is critical for optimal outcomes in MDD. Results demonstrate that treatment inertia is common in MDD despite guidelines recommending treatment modification in patients not reaching remission.

Do medications increase the efficacy of digital interventions for smoking cessation? Secondary results from the iCanQuit randomized trial.

BACKGROUND AND AIMS: iCanQuit is a smartphone application (app) proven efficacious for smoking cessation in a Phase III randomized controlled trial (RCT). This study aimed to measure whether medications approved by the US Food and Drug Administration (FDA) for smoking cessation would further enhance the efficacy of iCanQuit, relative to its parent trial comparator-the National Cancer Institute's (NCI's) QuitGuide app. DESIGN: Secondary analysis of the entire parent trial sample of a two-group (iCanQuit and QuitGuide), stratified, doubled-blind RCT. SETTING: United States. PARTICIPANTS: Participants who reported using an FDA-approved cessation medication on their own (n = 619) and those who reported no use of cessation medications (n = 1469). INTERVENTIONS: Participants were randomized to receive iCanQuit app or NCI's QuitGuide app. MEASUREMENTS: Use of FDA-approved medications was measured at 3 months post-randomization. Smoking cessation outcomes were measured at 3, 6 and 12 months. The primary outcome was 12-month self-reported 30-day point prevalence abstinence (PPA). FINDINGS: The data retention rate at the 12-month follow-up was 94.0%. Participants were aged 38.5 years, 71.0% female, 36.6% minority race/ethnicity, 40.6% high school or less education, residing in all 50 US States and smoking 19.2 cigarettes/day. The 29.6% of all participants who used medications were more likely to choose nicotine replacement therapy (NRT; 78.8%) than other cessation medications (i.e. varenicline or bupropion; 18.3 and 10.5%, respectively) and use did not differ by app treatment assignment (all P > 0.05). There was a significant (P = 0.049) interaction between medication use and app treatment assignment on PPA. Specifically, 12-month quit rates were 34% for iCanQuit versus 20% for QuitGuide [odds ratio (OR) = 2.36, 95% confidence interval (CI) = 1.59, 3.49] among participants reporting any medication use, whereas among participants reporting no medication use, quit rates were 28% for iCanQuit versus 22% for QuitGuide (OR = 1.41, 95% CI = 1.09, 1.82). Results were stronger for those using only NRT: 40% quit rates for iCanQuit versus 18% quit rates for QuitGuide (OR = 3.57, 95% CI = 2.20, 5.79). CONCLUSIONS: The iCanQuit smartphone app for smoking cessation was more efficacious than the QuitGuide smartphone app, regardless of whether participants used medications to aid cessation. Smoking cessation medications, especially nicotine replacement therapy, might enhance the efficacy of the iCanQuit app.

The effects of bupropion alone and combined with naltrexone on blood pressure and CRP concentration: A systematic review and meta-regression analysis of randomized controlled trials.

BACKGROUND: Considering the conflicting effects of bupropion on parameters related to cardiovascular system including blood pressure and inflammation, in this meta-analysis study, we investigated the effects of this drug alone or in combination with naltrexone on systolic (SBP) and diastolic blood pressure (DBP) and C-reactive protein (CRP). METHODS: Scopus, PubMed/Medline, Web of Science and Embase databases were searched using standard keywords to identify all controlled trials investigating effects of bupropion alone and combined with naltrexone on the BP and CRP. Pooled weighted mean difference and 95% confidence intervals (CIs) were achieved by random-effects model analysis for the best estimation of outcomes. RESULTS: The pooled findings showed that that bupropion alone or in combination with naltrexone would significantly increase SBP (weighted mean difference (WMD): 1.34 mmHg, 95% CI: 0.38-2.29) and DBP (WMD: 0.93 mmHg, 95% CI 0.88-0.99) as well as decrease CRP (WMD: -0.89 mg/L, 95% CI -1.09 to -0.70). The findings of the subgroup also show the greater effect of bupropion on blood pressure (SBP and DBP) increase in a dose greater than 360 mg and a duration of intervention less equal to 26 weeks. In addition, the subgroup analysis showed that changes in SBP after receiving bupropion together with naltrexone were more compared to bupropion alone. CONCLUSIONS: The addition of combination therapies such as bupropion and naltrexone can significantly improve CRP levels. However, its effect on blood pressure requires proper management of this drug.

Effect of severity of depression on augmentation of antidepressant medication in young adults with depression.

BACKGROUND: Antipsychotics (AP) have been used to augment antidepressant (AD) medication in treatment-resistant depression. In this study we examined factors (including severity of depression and initial antidepressant) affecting AP augmentation, as well as which APs were initiated as augmentation in young adults. METHODS: Data were extracted from Finnish nationwide registers. Of persons aged 18-29 years diagnosed with a depression during 2004-2017 we focused on incident AD users (who initiated AD 6 months before and after the diagnosis) whose severity level of depression was recorded (N = 21,966). AP augmentation was studied during 1 year after diagnosis of depression. Persons diagnosed with severe depression with psychotic features (n = 1486) were excluded from main analyses and analyzed separately. RESULTS: Overall, 8.4% of new antidepressant users initiated AP augmentation. Risk of augmentation increased with severity of depression as 3.9%, 5.8%, and 14.0% of persons with mild, moderate, and severe depression, respectively, initiated augmentation. Male sex, comorbid anxiety and personality disorders, substance abuse and selfharm/suicide attempt were positively associated with augmentation. Compared to citalopram, use of tricyclic antidepressant, paroxetine and venlafaxine were associated with increased risk of augmentation, while use of bupropion was associated with a decreased risk. Quetiapine and risperidone were the most common APs used in augmentation. Among persons with severe depression with psychotic features, use of sertraline was associated with AP augmentation, whereas use of fluoxetine decreased risk of augmentation. CONCLUSIONS: Use of APs as augmentation of AD therapy was common in severe depression. Comorbidities had only a small effect to augmentation, but selection of initial AD was more closely associated to risk of augmentation. Interestingly, use of bupropion decreased risk of augmentation, which warrants further studies, as well as the decrease in risk of augmentation when fluoxetine in case of psychotic depression was used.

Competitive inhibition of nicotine acetylcholine receptors using microneedles of nicotine and varenicline for smoking withdrawal therapy.

Current strategies for smoking withdrawal conditions involve monotherapy of nicotine and combinational therapy of nicotine with varenicline or bupropion as per the CDC and FDA. The available dosage forms for nicotine are patches, gums, inhalers and nasal sprays, bupropion and varenicline are available in tablet form. This research work focused on developing a microneedle delivery system to deliver combination drug for overcoming the obstacles encountered by oral route of administration of varenicline such as severe side effects (mood swings, agitation, depressed behaviour, seizures, etc), and nicotine therapy challenges such as short half-life, repeated dosing, nausea, and vomiting. The nanoparticles of nicotine prepared by nanoprecipitation method showed particle size PTZ (356.6 ± 65.98), percentage entrapment efficiency (35.55 % ± 0.007), in-vitro drug release (47.89 % ± 0.7) for 72 h. Microneedles showed height (600 µm), width (350 µm), and tip diameter (10 µm). The nanoparticles encapsulated in microneedles showed in-vitro sustained delivery of nicotine (67.00 % ± 4.92) and varenicline (79.78 % ± 1.09) in 48 h. Nicotine released in a sustained manner attaches to the nicotine acetylcholine receptors (nAchR) to release dopamine for controlling the withdrawal challenges such as anxiety, irritability, cravings, disturbed sleep pattern, etc. The varenicline released from microneedles binds to the nAchR and inhibits dopamine release responsible for the euphoric effect induced by nicotine, and thus assists in curbing the nicotine withdrawal symptoms. This combination microneedle system offers prolonged treatment in a single application for smoking withdrawal conditions wherein patients are not in stage of oral dosing because of repeated dosing resulting in adverse effects like seizures, hypertension, sleep disturbances, insomnia, and nausea.

Efficacy and safety of pharmacological intervention for smoking cessation in smokers with diseases: A systematic review and network meta-analysis.

OBJECTIVE: To investigate the most effective and best-tolerated drugs for treating diseased smokers. METHODS: Eight databases were searched for randomized controlled trials (RCTs) involving different pharmacological interventions for smoking cessation in disease patients (January 2023). Network meta-analysis was performed using STATA 15.1 software. The Cochrane Risk of Bias Tool assessed the risk of bias, and confidence in evidence was assessed using CINeMA. RESULTS: A total of 60 RCTs involving 13,009 patients of 12 disease categories were included. All trials reported 13 interventions, resulting in 78 comparisons. Network meta-analysis showed that varenicline (OR = 2.30, 95% CI (1.77, 3.00)) and bupropion (OR = 1.65, 95% CI (1.29, 2.11)) showed favorable abstinence effects compared to placebo in the cardiovascular disease population. Nicotine replacement therapy (NRT) had better withdrawal advantages than placebo (OR = 11.18, 95% CI (2.25, 55.54)) in the chronic obstructive pulmonary disease (COPD) population. Some combination treatments showed better results than monotherapy, such as bupropion + NRT was superior to bupropion (OR = 8.45, 95% CI (1.84, 38.89)) and NRT (OR = 4.98, 95% CI (1.25, 19.78)) in mental illness population. The final surface under the cumulative ranking curve indicated that bupropion + NRT achieved the best smoking cessation effect. Overall confidence in the evidence was low. In a comparison of drugs, the results showed that bupropion + NRT had the best safety. CONCLUSIONS: Most interventions show the benefit of quitting smoking compared with placebo, including monotherapy and combination therapy. Moreover, varenicline or bupropion combined with NRT is superior to some monotherapies.

Clinical Practice Guideline of Spanish Society of Pneumology and Thoracic Surgery (SEPAR) on Pharmacological Treatment of Tobacco Dependence 2023

Introduction: There are multiple systematic reviews and meta-analyses on the efficacy and safety of pharmacological treatments against nicotine dependence. However, there are few guidelines to answer frequent questions asked by a clinician treating a smoker. Therefore, the aim of this paper is to facilitate the treatment of tobacco addiction. Material and methods: 12 PICO questions are formulated from a GLOBAL PICO question: “Efficacy and safety of pharmacological treatment of tobacco dependence”. A systematic review was carried out to answer each of the questions and recommendations were made. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system was used to grade the certainty of the estimated effects and the strength of the recommendations. Results: Varenicline, nicotine replacement therapy (NRT), bupropion and cytisine are more effective than placebo. Varenicline and combined nicotine therapy are superior to the other therapies. In smokers with high dependence, a combination of drugs is recommended, being more effective those associations containing varenicline. Other optimization strategies with lower efficacy consist of increasing the doses, the duration, or retreat with varenicline. In specific populations varenicline or NRT is recommended. In hospitalized, the treatment of choice is NRT. In pregnancy it is indicated to prioritize behavioral treatment. The financing of smoking cessation treatments increases the number of smokers who quit smoking. There is no scientific evidence of the efficacy of pharmacological treatment of smoking cessation in adolescents. Conclusions: The answers to the 12 questions allow us to extract recommendations and algorithms for the pharmacological treatment of tobacco dependence. (AU)

Naltrexone/bupropion for binge-eating disorder: A randomized, double-blind, placebo-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/m2 , 77.5% with BMI ≥ 30 kg/m2 ) 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.