Playing with a full dex of cards: Treatment resistant depression with suicidality responds to inpatient dextromethorphan therapy

Shapira, Itamar; Burk, Bradley; Hill, Harrison; Pruett, Brandon S.

doi:10.1016/j.psycr.2023.100105

Cited by 1 publication

(2 citation statements)

References 23 publications

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“…The possible utility of adding BUP to DEX has been revealed by case reports of rapid-acting antidepressant effects in a patient with TRD, 25 1 of them in a patient with relapse of MDD with aggravating intense and frequent suicidal thoughts. 26 Pharmacokinetics DEX-BUP displays nonlinear pharmacokinetics with steady state achieved within 8 days. 10 DEX is quickly and effectively absorbed from the gastrointestinal tract, but the first pass effects significantly limits its oral bioavailability.…”

Section: Mechanism Of Action and Pharmacodynamicsmentioning

confidence: 99%

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Dextromethorphan/Bupropion: A Novel Treatment for Patients With Major Depressive Disorder

Willett,

Bond,

Morrill

et al. 2024

American Journal of Therapeutics

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Background: Major depressive disorder (MDD) affects millions of people and is the leading cause of disability worldwide. Patients report decreased quality of life and ability to perform activities of daily living. It is estimated that the current standard of care, which includes pharmacologic therapy with a selective serotonin reuptake inhibitor, is effective in 40%–60%. Additional treatment options are warranted. The combination of dextromethorphan (DEX) and bupropion (BUP) (Auveulty) was approved for treatment in 2022. This unique combination offers an interesting mechanism of action and favorable onset of action for patients with MDD. Pharmacodynamics and Pharmacokinetics: The mechanism of action of DEX–BUP when used in combination is unique. DEX is a noncompetitive N-methyl-d-aspartate receptor antagonist rapidly metabolized through the CYP450 2D6. BUP is an aminoketone and CYP2D6 inhibitor, which results in increased plasma levels of DEX through competitive CYP2D6 inhibition. Clinical Trials: In a phase 2 clinical study, the efficacy of DEX-BUP was compared with BUP alone in patients with clinically diagnosed MDD. At baseline, participants had moderate-to-severe depression using the Montgomery–Asberg Depression Rating Scale (MADRS) and Clinical Global Impressions Severity (CGI-S) scales. There was a significant overall reduction in MADRS and CGI-S scores in the treatment group compared with the BUP monotherapy with improvement observed as early as week 1 of treatment. Later, a phase 3 study was conducted comparing DEX-BUP 45 mg/105 mg with placebo in patients with moderate-to-severe MDD. Similarly, MADRS and CGI-S scores were significantly reduced in the treatment group. Adverse effects were similar in all groups. Therapeutic Advance: Clinical response to first line treatment options for MDD are reported to be 40%–60%. Availability of additional treatment options, particularly those with reduced time to efficacy, may improve overall treatment and patient quality of life. DEX–BUP is a combination option that has been shown to improve depression symptoms as early as 1 week after initiation.

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Section: Mechanism Of Action and Pharmacodynamicsmentioning

confidence: 99%

Section: Pharmacodynamics and Pharmacokineticsmentioning

confidence: 99%