Sleep-related adverse events of smoking cessation drugs: A network meta-analysis of randomized controlled trials.

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.

Insomnia and parasomnia induced by validated smoking cessation pharmacotherapies and electronic cigarettes: a network meta-analysis.

We aim to assess the relationship between validated smoking cessation pharmacotherapies and electronic cigarettes (e-cigarettes) and insomnia and parasomnia using a systematic review and a network meta-analysis. A systematic search was performed until August 2022 in the following databases: PUBMED, COCHRANE, CLINICALTRIAL. Randomized controlled studies against placebo or validated therapeutic smoking cessation methods and e-cigarettes in adult smokers without unstable or psychiatric comorbidity were included. The primary outcome was the presence of "insomnia" and "parasomnia." A total of 1261 studies were selected. Thirty-seven studies were included in the quantitative analysis (34 for insomnia and 23 for parasomnia). The reported interventions were varenicline (23 studies), nicotine replacement therapy (NRT, 10 studies), bupropion (15 studies). No studies on e-cigarettes were included. Bayesian analyses found that insomnia and parasomnia are more frequent with smoking cessation therapies than placebo except for bupropion. Insomnia was less frequent with nicotine substitutes but more frequent with bupropion than the over pharmacotherapies. Parasomnia are less frequent with bupropion but more frequent with varenicline than the over pharmacotherapies. Validated smoking cessation pharmacotherapies can induce sleep disturbances with different degrees of frequency. Our network meta-analysis shows a more favorable profile of nicotine substitutes for insomnia and bupropion for parasomnia. It seems essential to systematize the assessment of sleep disturbances in the initiation of smoking cessation treatment. This could help professionals to personalize the choice of treatment according to sleep parameters of each patient. Considering co-addictions, broadening the populations studied and standardizing the measurement are additional avenues for future research.

Multidimensional assessment of adverse events of bupropion: A large-scale data analysis from the FAERS database.

OBJECTIVE: Bupropion, a monocyclic antidepressant, aids in smoking cessation, treats major depression, and prevents severe depression in seasonal affective disorder patients. Yet, its adverse reactions remain insufficiently studied. METHODS: All data from the raw data packages for 78 quarters from the 1st quarter of 2004 to the 2nd quarter of 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database and imported into the SAS9.4 software for data cleaning and analysis. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods were used to analyze drug adverse events and assess their compliance with various screening criteria. RESULTS: The results showed a total of 36,862 reports related to Bupropion use, identifying 364 positive reaction terms (PT) covering 23 System Organ Classes (SOCs). In addition to known side effects, some new potential adverse reactions were found, such as Stool analysis abnormal, Oculocephalogyric reflex absent, Suspected suicide, and so on. At the same time, reactions like Encephalopathy neonatal, Hyponatraemic coma, and Electrocardiogram QRS complex prolonged were prominently ranked. Notably, occurrences such as Urine amphetamine positive and Amphetamines positive were relatively high, suggesting extra caution for these potential adverse reactions during clinical use of Bupropion. CONCLUSION: These findings highlight the potential health risks of long-term Bupropion use, especially concerning efficacy, positive drug tests, and suicidal tendencies. Therefore, it is recommended to monitor and assess patients using Bupropion more stringently to use this therapeutically potential drug more safely and effectively.

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)

Smoking Cessation Pharmacotherapy Efficacy in Comorbid Medical Populations: Secondary Analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) Randomized Clinical Trial.

INTRODUCTION: This study sought to compare medication efficacy in participants with medical comorbidities who smoke in the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) trial, a double-blind, triple-dummy, placebo- and active-controlled randomized controlled trial. AIMS AND METHODS: Participants were from the U.S. cohort of the main trial and randomized (1:1:1:1) to varenicline, bupropion, nicotine replacement therapy (NRT) patch, or placebo for 12 weeks with follow-up through week 24. Medical comorbidity data were derived from the baseline medical screening questionnaire and categorized into four subgroups (cardiac, respiratory, vascular, and diabetes). Within each comorbidity, generalized linear mixed models were used to assess the association between treatment and continuous abstinence rates from weeks 9-12 to 9-24. Similar models were used to test the effect of number of comorbidities on abstinence. RESULTS: Varenicline resulted in the highest week 12 abstinence rates across all pharmacotherapies and compared to placebo in all comorbidity subgroups: Cardiac (40.0% vs. 3.6%; odds ratios [OR] = 23.3 [5.1-107.1]), respiratory (24.7% vs. 12.8%; OR = 2.2 [1.3-3.8]), vascular (29.1% vs. 10.4%; OR = 3.6 [2.3-5.7]), and diabetes (30.9% vs. 8.3%; OR = 6.5 [2.3-19.0]). This was maintained at week 24 for those with cardiac (23.3% vs. 1.8%; OR = 21.7 [2.7-178.2]), vascular (18.9% vs. 7.1%; OR = 3.1 [1.8-5.3]), and diabetes (20.6% vs. 4.2%; OR = 8.4 [2.1-33.7]) comorbidities. Treatment contrasts within some comorbidity subgroups revealed superior efficacy of varenicline over other pharmacotherapies. All pharmacotherapies increased the odds of abstinence regardless of number of comorbidities. CONCLUSIONS: Varenicline is the most efficacious option for patients with manageable cardiac, respiratory, vascular, and diabetes conditions to quit smoking, supporting recent clinical practice guidelines that recommend varenicline as first-line pharmacotherapy. Bupropion and NRT demonstrated efficacy for some comorbidity subgroups. IMPLICATIONS: This secondary analysis of the EAGLES trial demonstrated that varenicline is the most efficacious option for patients with cardiac, respiratory, vascular, and diabetes diagnoses to quit smoking. This demonstration of varenicline efficacy among individuals with comorbid medical conditions supports recent clinical practice guidelines that recommend varenicline as a first-line pharmacotherapy for smoking cessation.

Lo clásico y lo nuevo en el tratamiento del sobrepeso y la obesidad / The classic and the new in the treatment of overweight and obesity

Así como planteamos en la primera entrega de esta serie de artículos de actualización sobre la obesidad, resulta urgente revisar el abordaje tradicional que la comunidad médica le ofrece a las personas con cuerpos gordos. En este segundo artículo desarrollaremos en profundidad diferentes alternativas terapéuticas para los pacientes que desean bajar de peso:plan alimentario, actividad física, tratamiento farmacológico y cirugía metabólica. (AU)

As we proposed in the first issue of this series of articles, it is urgent to review the traditional approach that the medical community offers to people with fat bodies. This second article will develop different therapeutic alternatives for patients who want to lose weight: eating plans, physical activity, pharmacological treatment, and metabolic surgery. (AU)

Bupropion for treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND: This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion efficacy and safety for amphetamine-type stimulant use disorder (ATSUD) treatment. METHOD: Electronic databases were searched for records published to October 31st, 2022, including MEDLINE, CINAHL, PsycINFO, EBM Reviews, EMBASE, PubMed, Web of Science, trial registries. Inclusion criteria were RCTs comparing bupropion to placebo in ATSUD. Cochrane RoB2 tool and GRADE evidence certainty assessment were employed. Outcomes included amphetamine-type stimulant (ATS) use by urinalysis, retention in treatment, treatment adherence, ATS craving, addiction severity, depressive symptom severity, drop-out following adverse events (AEs), and serious AEs. Random-effect meta-analysis was conducted presenting standardized mean difference (SMD), risk ratio (RR), and risk difference (RD). RESULTS: Eight RCTs (total N=1239 participants) were included. Bupropion compared to placebo was associated with reduced ATS use (RR: 0.90; 95% CI: 0.84, 0.96), end-of-treatment ATS craving (SMD: -0.38; 95%CI: -0.63, -0.13), and adherence (RR: 0.91; 95%CI: 0.84, 0.99). Subgroup analysis showed greater reduction in ATS use with longer trial duration (12 weeks) (RR: 0.85; 95%CI: 0.78, 0.93) and greater reduction in end-of-treatment ATS craving in studies with mixed ATS use frequency (SMD: -0.46; 95%CI: -0.70, -0.22) and male-only samples (SMD: -1.26; 95%CI: -1.87, -0.65). CONCLUSION: Bupropion showed a significant modest reduction in ATS use and ATS craving (both rated as very low-quality evidence), larger in males (craving), and with longer treatment (ATS use). These results may inform future studies. More research is warranted on who might benefit from bupropion as ATSUD treatment.

Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials.

BACKGROUND: A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as first-generation monoamine-based antidepressants. OBJECTIVES: The objective of this systematic review was to assess the efficacy, safety, and mechanisms of action of AXS-05, a combination of the NMDA-receptor antagonist dextromethorphan with bupropion, in adults with MDD. METHODS: We searched PubMed, Embase, Google Scholar, and ClinicalTrials.gov for current studies reporting on efficacy and/or safety of AXS-05 in patients with MDD. The search terms included: "AXS-05" OR "dextromethorphan and bupropion" AND "depression". Studies from database inception to January 2023 were evaluated. Risk of bias was assessed using the Cochrane Risk of Bias tool. RESULTS: The search yielded 54 studies of which 5 were included. All studies had low risk of bias. Depression severity, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) significantly decreased as early as 1-week post-treatment from baseline when compared to a placebo-controlled group (LS mean difference 2.2; 95% CI 0.6-3.9; p = 0.007) and at 2 weeks compared to an active control group (LS mean difference 4.7; 95% CI 0.6-8.8; p = 0.024). Treatment efficacy could be maintained for up to 12 months with mean MADRS score reduction of 23 points from baseline. Clinical remission and response rates also improved at week 1 and were maintained for 12 months. The treatment was well-tolerated, with some transient adverse events reported. CONCLUSION: Current evidence suggests that the combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults with MDD. Initial success with AXS-05 supports the mechanistic role of glutamatergeric and sigma 1 signaling in the pathophysiology of MDD.

Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression.

BACKGROUND: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied. METHODS: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression. RESULTS: Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups. CONCLUSIONS: In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.).

Efficacy and safety of antidepressants for smoking cessation: A systematic review and network meta-analysis.

To evaluate the effectiveness, safety and tolerability of antidepressants in helping smokers quit tobacco dependence, five databases were searched for randomized controlled trials (RCTS ) on different antidepressant interventions involving smoking cessation in populations (September 2022). The STATA 15.1 software was used to perform network meta-analysis. The Cochrane bias risk tool was used to assess the risk of bias, and CINeMA was used to evaluate the evidence credibility for the effect of different interventions on smoking cessation. In all, 107 RCTs involving 42 744 patients were included. Seven studies were rated as having a low risk of bias. All trials reported 18 interventions and 153 pairwise comparisons were generated. The network meta-analysis showed that compared with placebo, varenicline + bupropion (OR = 3.53, 95% CI [2.34, 5.34]), selegiline + nicotine replacement therapy (NRT) (OR = 3.78, 95% CI [1.20, 11.92]), nortriptyline + NRT (OR = 2.33, 95% CI [1.21, 4.47), nortriptyline (OR = 1.58, 95% CI [1.11,2.26]), naltrexone + bupropion (OR = 3.84, 95% CI [1.39, 10.61]), bupropion + NRT (OR = 2.29, 95% CI [1.87, 2.81]) and bupropion (OR = 1.70, 95% CI [1.53, 1.89]) showed benefits with respect to smoking cessation. In addition, bupropion + NRT showed better effects than bupropion (OR = 1.35, 95% CI [1.12, 1.64]) and NRT (OR = 1.38, 95% CI [1.13, 1.69]) alone. The final cumulative ranking curve showed that varenicline + bupropion was the most likely to be the best intervention. There was moderate- to very-low-certainty evidence that most interventions showed benefits for smoking cessation compared with placebo, including monotherapy and combination therapies. Varenicline + bupropion had a higher probability of being the best intervention for smoking cessation.

Nicotine receptor partial agonists for smoking cessation.

BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). This is an update of a Cochrane Review first published in 2007. OBJECTIVES: To assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register in April 2022 for trials, using relevant terms in the title or abstract, or as keywords. The register is compiled from searches of CENTRAL, MEDLINE, Embase, and PsycINFO.  SELECTION CRITERIA: We included randomised controlled trials that compared the treatment drug with placebo, another smoking cessation drug, e-cigarettes, or no medication. We excluded trials that did not report a minimum follow-up period of six months from baseline. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Our main outcome was abstinence from smoking at longest follow-up using the most rigorous definition of abstinence, preferring biochemically validated rates where reported. We pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. We also reported the number of people reporting serious adverse events (SAEs). MAIN RESULTS: We included 75 trials of 45,049 people; 45 were new for this update. We rated 22 at low risk of bias, 18 at high risk, and 35 at unclear risk. We found moderate-certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I2 = 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I2 = 0%; 3 studies, 3781 participants; low-certainty evidence). SAE evidence was limited by imprecision. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I2 = 60%, 41 studies, 17,395 participants), and moderate-certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I2 = 0%; 26 studies, 14,356 participants). While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; I2 = 0%; 18 studies, 7151 participants; low-certainty evidence), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; I2 = 0%; 22 studies, 7846 participants; low-certainty evidence), in both cases evidence was limited by imprecision, and confidence intervals were compatible with both benefit and harm. Pooled results from studies that randomised people to receive cytisine or varenicline showed that more people in the varenicline arm quit smoking (RR 0.83, 95% CI 0.66 to 1.05; I2 = 0%; 2 studies, 2131 participants; moderate-certainty evidence) and reported SAEs (RR 0.67, 95% CI 0.44 to 1.03; I2 = 45%; 2 studies, 2017 participants; low-certainty evidence). However, the evidence was limited by imprecision, and confidence intervals incorporated the potential for benefit from either cytisine or varenicline. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than bupropion (RR 1.36, 95% CI 1.25 to 1.49; I2 = 0%; 9 studies, 7560 participants), and no clear evidence of difference in rates of SAEs (RR 0.89, 95% CI 0.61 to 1.31; I2 = 0%; 5 studies, 5317 participants), neuropsychiatric SAEs (RR 1.05, 95% CI 0.16 to 7.04; I2 = 10%; 2 studies, 866 participants), or cardiac SAEs (RR 3.17, 95% CI 0.33 to 30.18; I2 = 0%; 2 studies, 866 participants). Evidence of harms was of low certainty, limited by imprecision. We found high-certainty evidence that varenicline helps more people to quit than a single form of nicotine replacement therapy (NRT) (RR 1.25, 95% CI 1.14 to 1.37; I2 = 28%; 11 studies, 7572 participants), and low-certainty evidence, limited by imprecision, of fewer reported SAEs (RR 0.70, 95% CI 0.50 to 0.99; I2 = 24%; 6 studies, 6535 participants). We found no data on neuropsychiatric or cardiac SAEs. We found no clear evidence of a difference in quit rates between varenicline and dual-form NRT (RR 1.02, 95% CI 0.87 to 1.20; I2 = 0%; 5 studies, 2344 participants; low-certainty evidence, downgraded because of imprecision). While pooled point estimates suggested increased risk of SAEs (RR 2.15, 95% CI 0.49 to 9.46; I2 = 0%; 4 studies, 1852 participants) and neuropsychiatric SAEs (RR 4.69, 95% CI 0.23 to 96.50; I2 not estimable as events only in 1 study; 2 studies, 764 participants), and reduced risk of cardiac SAEs (RR 0.32, 95% CI 0.01 to 7.88; I2 not estimable as events only in 1 study; 2 studies, 819 participants), in all three cases evidence was of low certainty and confidence intervals were very wide, encompassing both substantial harm and benefit. AUTHORS' CONCLUSIONS: Cytisine and varenicline both help more people to quit smoking than placebo or no medication. Varenicline is more effective at helping people to quit smoking than bupropion, or a single form of NRT, and may be as or more effective than dual-form NRT. People taking varenicline are probably more likely to experience SAEs than those not taking it, and while there may be increased risk of cardiac SAEs and decreased risk of neuropsychiatric SAEs, evidence was compatible with both benefit and harm. Cytisine may lead to fewer people reporting SAEs than varenicline. Based on studies that directly compared cytisine and varenicline, there may be a benefit from varenicline for quitting smoking, however further evidence could strengthen this finding or demonstrate a benefit from cytisine. Future trials should test the effectiveness and safety of cytisine compared with varenicline and other pharmacotherapies, and should also test variations in dose and duration. There is limited benefit to be gained from more trials testing the effect of standard-dose varenicline compared with placebo for smoking cessation. Further trials on varenicline should test variations in dose and duration, and compare varenicline with e-cigarettes for smoking cessation.

Bupropion: Does Its Efficacy Outweigh Potential Morbidity and Lethality?

Bupropion is a structurally and biochemically unique antidepressant that inhibits the neuronal uptake of dopamine and norepinephrine. Often prescribed for children and adolescents, bupropion displays both neurologic and cardiac toxicities in overdose more serious than toxicities resulting from poisonings by tricyclic antidepressants and selective serotonin reuptake inhibitors. Bupropion was briefly removed from the market in the 1980s. The incidence of bupropion poisonings in the United States, and resultant morbidity and mortality in children and adolescents, has been steadily increasing since 2012. Antidepressants less toxic than bupropion in overdose should be considered in the vulnerable 6- to 19-year-old patient population. [Pediatr Ann. 2023;52(5):e178-e180.].

BUPROPION MISUSE BY NASAL INSUFFLATION WITH A FATAL OUTCOME: CASE REPORT AND REVIEW.

Bupropion is the only FDA - approved synthetic cathinone, with increasing popularity in clinical practice due to its wide range of action, and lack of sexual side effects. However, its stimulant effect similar to amphetamines has growing the concern regarding its recreational use.

Antidepressants for smoking cessation.

BACKGROUND: The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short-term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction. OBJECTIVES: To assess the evidence for the efficacy, harms, and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, most recently on 29 April 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow-up from efficacy analyses. We included trials with any follow-up length for our analyses of harms. DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow-up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropouts due to treatment. We carried out meta-analyses where appropriate. MAIN RESULTS: We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results.  There was high-certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I2 = 16%; 50 studies, 18,577 participants). There was moderate-certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I2 = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I2 = 43%; 15 studies, 4117 participants; low-certainty evidence). There was moderate-certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I2 = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I2 = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I2 = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high-certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I2 = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I2 = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I2 = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I2 = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I2 = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single-form NRT (RR 1.03, 95% CI 0.93 to 1.13; I2 = 0%; 10 studies, 7613 participants). We also found evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I2 = 16%; 6 studies, 975 participants), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I2 = 0%; 3 studies, 417 participants), although this result was subject to imprecision. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression. AUTHORS' CONCLUSIONS: There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion may increase SAEs (moderate-certainty evidence when compared to placebo/no pharmacological treatment). There is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single-form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. Further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability.

Bayesian regularization to predict neuropsychiatric adverse events in smoking cessation with pharmacotherapy.

BACKGROUND: Research on risk factors for neuropsychiatric adverse events (NAEs) in smoking cessation with pharmacotherapy is scarce. We aimed to identify predictors and develop a prediction model for risk of NAEs in smoking cessation with medications using Bayesian regularization. METHODS: Bayesian regularization was implemented by applying two shrinkage priors, Horseshoe and Laplace, to generalized linear mixed models on data from 1203 patients treated with nicotine patch, varenicline or placebo. Two predictor models were considered to separate summary scores and item scores in the psychosocial instruments. The summary score model had 19 predictors or 26 dummy variables and the item score model 51 predictors or 58 dummy variables. A total of 18 models were investigated. RESULTS: An item score model with Horseshoe prior and 7 degrees of freedom was selected as the final model upon model comparison and assessment. At baseline, smokers reporting more abnormal dreams or nightmares had 16% greater odds of experiencing NAEs during treatment (regularized odds ratio (rOR) = 1.16, 95% credible interval (CrI) = 0.95 - 1.56, posterior probability P(rOR > 1) = 0.90) while those with more severe sleep problems had 9% greater odds (rOR = 1.09, 95% CrI = 0.95 - 1.37, P(rOR > 1) = 0.85). The prouder a person felt one week before baseline resulted in 13% smaller odds of having NAEs (rOR = 0.87, 95% CrI = 0.71 - 1.02, P(rOR < 1) = 0.94). Odds of NAEs were comparable across treatment groups. The final model did not perform well in the test set. CONCLUSIONS: Worse sleep-related symptoms reported at baseline resulted in 85%-90% probability of being more likely to experience NAEs during smoking cessation with pharmacotherapy. Treatment for sleep disturbance should be incorporated in smoking cessation program for smokers with sleep disturbance at baseline. Bayesian regularization with Horseshoe prior permits including more predictors in a regression model when there is a low number of events per variable.