Adults with major depressive disorder have a new option to treat their depression. Auvelity, an extended-release fixed combination of dextromethorphan (45 mg) and bupropion (105 mg), was approved by the Food and Drug Administration in 2022. After initiation of therapy with one tablet each day for three days, the maintenance dose is one tablet twice a day.
Dextromethorphan is a noncompetitive N-methyl-D-aspartate receptor antagonist and a sigma-1 receptor agonist. Its inhibition of the excitatory neurotransmitter glutamate may contribute to its effect on depression. It also inhibits serotonin and norepinephrine reuptake. Bupropion is a norepinephrine and dopamine reuptake inhibitor.
Dextromethorphan-bupropion was studied in a clinical trial of 327 adult patients with major depressive disorder who were randomized to six weeks of treatment with either the drug or placebo. The primary end point was the reduction in depression from baseline to week 6 as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Patients randomized to dextromethorphan-bupropion had a statistically significantly greater reduction in the MADRS score than those given placebo (a decrease of 15.9 points versus 12.1 points). A second study compared the use of dextromethorphan-bupropion with bupropion 105 mg in patients with major depressive disorder. The mean change from baseline in the MADRS score was also statistically significantly greater with use of the combination drug than with bupropion monotherapy.
Like all antidepressants, dextromethorphan-bupropion carries a boxed warning that it may increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients. Seizures can also occur with its use and are more likely at higher doses. A history of seizure disorder is a contraindication for use, as is a current or prior diagnosis of bulimia or anorexia nervosa, as a higher incidence of seizures was seen in such patients who had been treated with other bupropion-containing products. The drug should be discontinued if seizures occur.
Concurrent use of dextromethorphan-bupropion with monoamine oxidase inhibitors (MAOIs) or its use within 14 days of stopping an MAOI is contraindicated. Because MAOIs increase levels of norepinephrine, serotonin, and dopamine, a drug interaction between MAOIs and dextromethorphan-bupropion is possible and can lead to hypertensive crisis or serotonin syndrome. Patients taking dextromethorphan-bupropion along with other drugs that increase serotonin levels, such as selective serotonin reuptake inhibitors or tricyclic antidepressants, are at increased risk for serotonin syndrome. (For signs and symptoms of serotonin syndrome, go to http://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes.)
Dextromethorphan is metabolized quickly by cytochrome P-450 (CYP) 2D6. Bupropion competitively inhibits CYP2D6, increasing circulating levels of dextromethorphan. Because any drug that affects CYP2D6 can alter the circulating levels of dextromethorphan, nurses should inquire about the concomitant use of any such drugs, as well as about other drugs containing dextromethorphan (including over-the-counter cough suppressants) or bupropion.
Other warnings and precautions in the drug's labeling include increased blood pressure and hypertension, activation of mania or hypomania, psychosis and other neuropsychiatric reactions, angle-closure glaucoma, dizziness, and embryo-fetal toxicity. The most common adverse effects are dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis (excessive sweating), anxiety, constipation, decreased appetite, and insomnia.
As dextromethorphan-bupropion causes mild pupillary dilation, patients who have untreated anatomically narrow angles can develop angle-closure glaucoma. If the patient suddenly develops symptoms such as headache, eye pain, nausea, rainbow around lights at night and very blurred vision, they should seek emergency medical care, as acute angle closure glaucoma can permanently damage vision if not treated quickly.
Patients should be told that the bupropion component of the drug may induce changes in mood (delusions, hallucinations, psychosis, concentration disturbances, paranoia, and confusion) and any symptoms should be promptly reported to their provider. Because of the risk of fetal harm, patients of childbearing age should use birth control and discontinue the drug before attempting to conceive. Patients who are breastfeeding should not take dextromethorphan-bupropion; breastfeeding should not be started until five days after the final dose.
For complete prescribing information for dextromethorphan-bupropion, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215430s000lblCorrect3.p.