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Author: Admin | 2025-04-28
1, although at the end of the study some patients did have clinically significant improvement.[1][3] In Study 2 (STRIDE-1), dextromethorphan/bupropion was compared with bupropion alone in another randomized controlled trial.[1] The dose of bupropion in the study was lower than the target dose recommended for clinical practice.[10] In this study, dextromethorphan/bupropion showed significantly greater improvement than bupropion alone in the first two weeks of treatment but not by week 6 of treatment in people with major depressive disorder.[1][11] The baseline scores were 33.4 points with dextromethorphan/placebo and 33.2 points with placebo, while the score reductions at week 1 were 5.2 points on the MADRS with dextromethorphan/bupropion and 3.6 points with bupropion (a 1.6-point difference), at week 2 were 8.0 points with dextromethorphan/bupropion and 6.1 points with bupropion (a 1.9-point difference), and at week 6 were 11.6 points with dextromethorphan/bupropion and 9.4 points with bupropion (a 2.2-point difference).[11][12] On the basis of this trial, the FDA concluded that dextromethorphan contributes to the apparent antidepressant effects of dextromethorphan/bupropion.[1]Side effects of dextromethorphan/bupropion include dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction (including abnormal orgasm, erectile dysfunction, decreased libido, and anorgasmia), hyperhidrosis, anxiety, constipation, decreased appetite, insomnia, arthralgia, fatigue, paresthesia, and blurred vision.[1] These side effects occurred at rates ≥2% and to a greater extent than with placebo in clinical trials.[1]Dextromethorphan acts as an NMDA receptor antagonist, σ1 receptor agonist, and serotonin–norepinephrine reuptake inhibitor, among other actions, while bupropion acts as a norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator.[1][13] Bupropion is also a potent inhibitor of CYP2D6, and thereby inhibits the metabolism of dextromethorphan.[13] Dextromethorphan/bupropion has less activity as an NMDA receptor antagonist than dextromethorphan alone.[11] This is because bupropion is a potent CYP2D6 inhibitor and prevents the bioactivation of dextromethorphan into dextrorphan, a much more potent NMDA receptor antagonist and weaker serotonin reuptake inhibitor than dextromethorphan itself.[11] The mechanism of action of dextromethorphan/bupropion in the treatment of depression is unknown, although the preceding pharmacological actions are assumed to be involved. When administered together as dextromethorphan/bupropion, the elimination half-life of dextromethorphan is 22 hours and the elimination half-life of bupropion is 15 hours.[1] The elimination half-lives of bupropion active metabolites are 35 hours for hydroxybupropion, 44 hours for erythrohydrobupropion, and 33 hours for threohydrobupropion.[1] Bupropion inhibits the metabolism of dextromethorphan by inhibiting the enzyme CYP2D6, the major enzyme responsible for the metabolism of dextromethorphan.[1] This in turn improves the bioavailability of dextromethorphan, prolongs its half-life, prevents its metabolism into dextrorphan, and increases the ratio of dextromethorphan to dextrorphan in the body.[1][13][14][6][15]Dextromethorphan/bupropion was developed by Axsome Therapeutics.[16] It was approved for the treatment of major depressive disorder by the US Food and Drug Administration in August 2022.[1]Society and culture[edit]Dextromethorphan/bupropion is sold
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