Weight Management in Adults with Obesity or Overweight

Medications for Weight Loss

• The American Gastroenterological Association (AGA) conditionally recommends naltrexone-bupropion ER (extended-release) with lifestyle interventions for adults with obesity or overweight with weight-related complications, based on moderate certainty evidence 1
• Naltrexone-bupropion ER (extended-release) produces modest weight loss of approximately 3.01% total body weight loss compared to lifestyle interventions alone 1
• The AGA recommends considering FDA-approved medications with stronger evidence, such as semaglutide 2.4mg, liraglutide 3.0mg, phentermine-topiramate ER, and naltrexone-bupropion ER, which have higher efficacy for weight loss 1
• Naltrexone-bupropion ER (extended-release) may be beneficial for patients attempting smoking cessation or with depression, but should be avoided in patients with seizure disorders or used concomitantly with opioid medications 1
• Treatment with naltrexone-bupropion ER (extended-release) requires blood pressure and heart rate monitoring, especially in the first 12 weeks, and has common adverse effects leading to discontinuation, including nausea, vomiting, headache, dizziness, and depression 1
• The American Gastroenterological Association recommends that Auvelity should not be used in patients with seizure disorders, current use of MAO inhibitors, uncontrolled hypertension, conditions that lower seizure threshold, anorexia or bulimia nervosa, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
• For patients with moderate to severe renal impairment, the bupropion dose should be reduced by 50%, and in patients with moderate to severe hepatic impairment, bupropion dosing should not exceed one tablet daily, as recommended by the Gastroenterology society guidelines 1, 3, 4

Contraindications and Warnings

• The use of MAO inhibitors with Auvelity is contraindicated due to the risk of hypertensive crisis, as stated by the Gastroenterology society guidelines 1
• Opioids may reduce the efficacy of opioid analgesics or precipitate withdrawal reactions due to the naltrexone component of Auvelity 1
• Bupropion is contraindicated for use with monoamine oxidase inhibitors (MAOIs), and the combination of bupropion and amitriptyline presents other risks, including increased risk of seizures and neuropsychiatric effects 5, 2, 4

Combination Therapy

• The American College of Physicians suggests that bupropion and atomoxetine can be used together for patients with comorbid MDD and ADHD, with careful monitoring for cardiovascular effects and neuropsychiatric symptoms 6
• Bupropion has strong evidence for efficacy comparable to SSRIs in treating MDD, according to the Annals of Internal Medicine 6
• Atomoxetine has well-established efficacy for ADHD, although bupropion's efficacy in treating ADHD is mixed 6
• Regular monitoring of blood pressure, heart rate, and neuropsychiatric symptoms is recommended when using the bupropion-atomoxetine combination, due to the increased risk of cardiovascular and neuropsychiatric effects 6

Adverse Effects and Monitoring

• Common adverse effects of bupropion include insomnia, dry mouth, anxiety/jitteriness, decreased appetite, headache, and potential for increased blood pressure and heart rate 7, 1
• Serious adverse effects include increased blood pressure and heart rate, seizures, severe skin reactions or anaphylaxis, and neuropsychiatric symptoms 8
• Monitoring for anxiety, agitation, insomnia, and increased vigilance for suicidal thoughts, especially in patients under 24 years, is crucial 8, 1
• Gradual tapering is recommended when discontinuing bupropion, with a reduction to 150mg once daily for 1-2 weeks before complete discontinuation, to minimize withdrawal symptoms, including neuropsychiatric symptoms, insomnia, headache, and mood changes 4, 1, 9, 10

Alternative Treatments

• For patients who do not tolerate or respond to the bupropion-atomoxetine combination, consider alternative treatments such as cognitive behavioral therapy with a second-generation antidepressant for predominant MDD, or stimulant medication with an SSRI for predominant ADHD 6
• Antidepressant combination therapy is a treatment approach that involves using multiple antidepressants or combining an antidepressant with another medication to manage depression, as recommended by the American College of Physicians 6
• The combination of venlafaxine and bupropion can be effective for treatment-resistant depression, but requires careful monitoring for potential adverse effects, particularly cardiovascular effects and seizure risk 8