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CNS Drugs Nov 2022An oral, fixed-dose combination of dextromethorphan hydrobromide [an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist] and the... (Review)
Review
An oral, fixed-dose combination of dextromethorphan hydrobromide [an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist] and the antidepressant bupropion hydrochloride (an aminoketone and CYP2D6 inhibitor that increases dextromethorphan bioavailability) [AUVELITY; dextromethorphan/bupropion], is being developed by Axsome Therapeutics, Inc. for the treatment of major depressive disorder (MDD), Alzheimer's disease agitation and smoking cessation. Dextromethorphan/bupropion was approved in the USA in August 2022 for the treatment of MDD in adults. This article summarizes the milestones in the development of dextromethorphan/bupropion leading to this first approval for the treatment of adults with MDD.
Topics: Adult; Humans; Antidepressive Agents; Bupropion; Depressive Disorder, Major; Dextromethorphan; Receptors, N-Methyl-D-Aspartate; Drug Approval
PubMed: 36301443
DOI: 10.1007/s40263-022-00968-4 -
CNS Spectrums Oct 2022
Topics: Humans; Bupropion; Antidepressive Agents, Second-Generation
PubMed: 33843549
DOI: 10.1017/S1092852921000365 -
Drug Metabolism Reviews Aug 2019Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, associated with a wide interindividual variability. An extensive... (Review)
Review
Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, associated with a wide interindividual variability. An extensive pharmacokinetic and pharmacodynamic review of bupropion was performed, also focusing on chemical, pharmacological, toxicological, clinical and forensic aspects of this drug without a limiting period. Bupropion is a chiral, basic, highly lipophilic drug, clinically used as racemate that undergoes extensive stereoselective metabolism. Its major active metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion reach higher plasma concentrations than bupropion. Bupropion exerts its effects mainly by inhibiting dopamine and norepinephrine reuptake and by blocking several nicotinic receptors. Recent reports highlight recreational use of bupropion via intranasal insufflation and intravenous use. Seizures, insomnia, agitation, headache, dry mouth, and nausea are some of the reported adverse effects. Neurologic effects are major signs of intoxication that should be carefully managed. Finally, the characterization of the polymorphic enzymes involved in the metabolism of bupropion is essential to understand factors that may influence the interindividual and intraindividual variability in bupropion metabolite exposure, including the evaluation of potential drug-drug interactions and pharmacogenetic implications.
Topics: Animals; Antidepressive Agents, Second-Generation; Bupropion; Forensic Toxicology; Humans
PubMed: 31124380
DOI: 10.1080/03602532.2019.1620763 -
Biological Psychiatry Feb 2006Incomplete symptom remission and sexual side effects are common problems for which bupropion often is added to treatment with selective serotonin and... (Comparative Study)
Comparative Study Review
Incomplete symptom remission and sexual side effects are common problems for which bupropion often is added to treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs) for patients with major depressive disorder (MDD). This article reviews the literature on combining bupropion with SSRIs or SNRIs. We used MEDLINE to select studies that included patients diagnosed with MDD treated with any combination of bupropion and an SSRI or SNRI, either to enhance antidepressant response or to ameliorate antidepressant-associated sexual dysfunction. Bibliographies of located articles were searched for additional studies. Controlled and open-label studies support the effectiveness of bupropion in reversing antidepressant-associated sexual dysfunction, whereas open trials suggest that combination treatment with bupropion and an SSRI or SNRI is effective for the treatment of MDD in patients refractory to the SSRI, SNRI, or bupropion alone. The available data suggest that, although not an approved indication, the combination of bupropion and either an SSRI or an SNRI is generally well tolerated, can boost antidepressant response, and can reduce SSRI or SNRI-associated sexual side effects. Additional randomized controlled studies are needed to answer important questions, such as those regarding optimal dose and duration of treatment.
Topics: Bupropion; Clinical Trials as Topic; Depressive Disorder, Major; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological
PubMed: 16165100
DOI: 10.1016/j.biopsych.2005.06.027 -
Profiles of Drug Substances,... 2016Bupropion hydrochloride is a norepinephrine-dopamine disinhibitor (NDDI) approved for the treatment of depression and smoking cessation. Bupropion is a trimethylated... (Review)
Review
Bupropion hydrochloride is a norepinephrine-dopamine disinhibitor (NDDI) approved for the treatment of depression and smoking cessation. Bupropion is a trimethylated monocyclic phenylaminoketone second-generation antidepressant, which differs structurally from most antidepressants, and resides in a novel mechanistic class that has no direct action on the serotonin system. Comprehensive chemical, physical, and spectroscopic profiles are presented. This analytical profile provides an extensive spectroscopic investigation utilizing mass spectrometry, one- and two-dimensional NMR, solid-state NMR, IR, NIR, Raman, UV, and X-ray diffraction. The profile also includes significant wet chemistry studies for pH, solubility, solution, and plasma stability. Both HPLC and UPLC methodology are presented for bupropion and its related impurities or major metabolites. The profile concludes with an overview of biological properties that includes toxicity, drug metabolism, and pharmacokinetics.
Topics: Animals; Antidepressive Agents, Second-Generation; Bupropion; Chemistry, Pharmaceutical; Humans
PubMed: 26940167
DOI: 10.1016/bs.podrm.2015.12.001 -
CNS Spectrums Oct 2019Although currently available antidepressants increase monoamine levels soon after the start of treatment, therapeutic benefits are often delayed by several weeks and the... (Review)
Review
Although currently available antidepressants increase monoamine levels soon after the start of treatment, therapeutic benefits are often delayed by several weeks and the majority of patients with major depressive disorder fail to achieve an adequate response to first- or second-line therapies targeting monoamines. The recent approval of the NMDA (N-methyl-d-aspartate) antagonist esketamine given intranasally for treatment-resistant depression has reinforced the need for agents with rapid onset with alternate mechanisms of action. Dextromethorphan/bupropion, an investigational medicine currently in development, is one such candidate.
Topics: Administration, Oral; Animals; Antidepressive Agents, Second-Generation; Bupropion; Dextromethorphan; Dopamine; Humans; Norepinephrine; Receptors, N-Methyl-D-Aspartate
PubMed: 31566163
DOI: 10.1017/S1092852919001470 -
Drug and Therapeutics Bulletin Nov 2017Naltrexone/bupropion (Mysimba - Orexigen Therapeutics Ireland Limited) is a fixed-dose combination product for the treatment of adults who are obese or overweight with... (Review)
Review
Naltrexone/bupropion (Mysimba - Orexigen Therapeutics Ireland Limited) is a fixed-dose combination product for the treatment of adults who are obese or overweight with at least one weight-related comorbidity, as an adjunct to diet and lifestyle modifications. Originally licensed by the European Medicines Agency (EMA) in 2015, it has recently been launched in the UK. Here, we review the evidence for its efficacy and safety and consider its place in therapy.
Topics: Anti-Obesity Agents; Bupropion; Chemotherapy, Adjuvant; Drug Combinations; Humans; Naltrexone; Obesity, Morbid; Randomized Controlled Trials as Topic
PubMed: 29117992
DOI: 10.1136/dtb.2017.11.0550 -
The Primary Care Companion For CNS... Sep 2017To evaluate data on birth outcomes following bupropion use during pregnancy. (Review)
Review
OBJECTIVE
To evaluate data on birth outcomes following bupropion use during pregnancy.
DATA SOURCES
A systematic literature review of PubMed and PsycINFO was performed through June 2017 for clinical studies published in English. The following keywords were used: bupropion, pregnancy, depression, smoking cessation, birth outcomes, miscarriage, and spontaneous abortion. References and related articles were also searched to yield additional publications. With the exception of limiting the search to human subjects, no other limitations were applied in an effort to capture all relevant published studies.
STUDY SELECTION/DATA EXTRACTION
No studies were excluded. A total of 8 studies were included in this review.
RESULTS
Bupropion's use in the first trimester has been linked with a small elevation in the risk of cardiovascular defects, although the absolute risk was low and confounding by indication (eg, use for smoking cessation) cannot be excluded. While the risk of miscarriage following prenatal bupropion exposure was higher than that of a control group of women in one study, it remained within the general population rate.
CONCLUSIONS
While more studies are needed, research to date suggests that bupropion may be a reasonable treatment option for depressed pregnant women who require pharmacotherapy, particularly when they also are attempting to reduce nicotine use during pregnancy.
Topics: Abortion, Spontaneous; Bupropion; Dopamine Uptake Inhibitors; Female; Humans; Pregnancy; Pregnancy Complications; Smoking Cessation
PubMed: 28973846
DOI: 10.4088/PCC.17r02160 -
The Cochrane Database of Systematic... Oct 2017Attention deficit hyperactivity disorder (ADHD) is a prevalent neurobiological condition, characterised by behavioral and cognitive symptoms such as inattention,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a prevalent neurobiological condition, characterised by behavioral and cognitive symptoms such as inattention, impulsivity and/or excessive activity. The syndrome is commonly accompanied by psychiatric comorbidities and is associated with educational and occupational underachievement.Although psychostimulant medications are the mainstay of treatment for ADHD, not all adults respond optimally to, or can tolerate, these medicines. Thus, alternative non-stimulant treatment approaches for ADHD have been explored. One of these alternatives is bupropion, an aminoketone antidepressant and non-competitive antagonism of nicotinic acetylcholine receptors. Bupropion is registered for the treatment of depression and smoking cessation, but is also used off-label to treat ADHD.
OBJECTIVES
To assess the effects and safety of bupropion for the treatment of adults with ADHD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and seven other databases in February 2017. We also searched three trials registers and three online theses portals. In addition, we checked references of included studies and contacted study authors to identify potentially relevant studies that were missed by our search.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that evaluated the effects (including adverse effects) of bupropion compared to placebo in adults with ADHD.
DATA COLLECTION AND ANALYSIS
Two review authors (WV, GB) independently screened records and extracted data using a data extraction sheet that we tested in a pilot study. We extracted all relevant data on study characteristics and results. We assessed risks of bias using the Cochrane 'Risk of bias' tool, and assessed the overall quality of evidence using the GRADE approach. We used a fixed-effect model to pool the results across studies.
MAIN RESULTS
We included six studies with a total of 438 participants. Five studies were conducted in the USA, and one in Iran. All studies evaluated a long-acting version of bupropion, with the dosage ranging from 150 mg up to 450 mg daily. Study intervention length varied from six to 10 weeks. Four studies explicitly excluded participants with psychiatric comorbidity and one study included only participants with opioid dependency. Four studies were funded by industry, but the impact of this on study results is unknown. Two studies were publicly funded and in one of these studies, the lead author was a consultant for several pharmaceutical companies and also received investigator-driven funding from two companies, however none of these companies manufacture bupropion. We judged none of the studies to be free of bias because for most risk of bias domains the study reports failed to provide sufficient details. Using the GRADE approach, we rated the overall quality of evidence as low. We downgraded the quality of the evidence because of serious risk of bias and serious imprecision due to small sample sizes.We found low-quality evidence that bupropion decreased the severity of ADHD symptoms (standardised mean difference -0.50, 95% confidence interval (CI) -0.86 to -0.15, 3 studies, 129 participants), and increased the proportion of participants achieving clinical improvement (risk ratio (RR) 1.50, 95% CI 1.13 to 1.99, 4 studies, 315 participants), and reporting an improvement on the Clinical Global Impression - Improvement scale (RR 1.78, 95% CI 1.27 to 2.50, 5 studies, 337 participants). There was low-quality evidence that the proportion of participants who withdrew due to any adverse effect was similar in the bupropion and placebo groups (RR 1.20, 95% CI 0.35 to 4.10, 3 studies, 253 participants). The results were very similar when using a random-effects model and when we analysed only studies that excluded participants with a psychiatric comorbidity.
AUTHORS' CONCLUSIONS
The findings of this review, which compared bupropion to placebo for adult ADHD, indicate a possible benefit of bupropion. We found low-quality evidence that bupropion decreased the severity of ADHD symptoms and moderately increased the proportion of participants achieving a significant clinical improvement in ADHD symptoms. Furthermore, we found low-quality evidence that the tolerability of bupropion is similar to that of placebo. In the pharmacological treatment of adults with ADHD, extended- or sustained-release bupropion may be an alternative to stimulants. The low-quality evidence indicates uncertainty with respect to the pooled effect estimates. Further research is very likely to change these estimates. More research is needed to reach more definite conclusions as well as clarifying the optimal target population for this medicine. Treatment response remains to be reported in a DSM5-diagnosed population. There is also a lack of knowledge on long-term outcomes.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Bupropion; Central Nervous System Stimulants; Delayed-Action Preparations; Female; Humans; Male; Off-Label Use; Patient Dropouts; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 28965364
DOI: 10.1002/14651858.CD009504.pub2 -
The Primary Care Companion For CNS... Jan 2020
Topics: Adult; Antidepressive Agents; Bupropion; Dysthymic Disorder; Ejaculation; Humans; Male
PubMed: 31917530
DOI: 10.4088/PCC.19l02453