AVP-786 · program

AVP-786 (deudextromethorphan-quinidine) for Treatment-resistant depression

DiscontinuedDiscontinuedOtsuka Pharmaceutical Co., Ltd. (4578)

Indications for AVP-786: Agitation in Alzheimer's disease · Discontinued Schizophrenia · Discontinued Treatment-resistant depression · Discontinued

AVP-786 (deudextromethorphan/ultra-low-dose quinidine) as adjunctive treatment for major depressive disorder with inadequate response to standard antidepressants (SSRIs/SNRIs) - treatment-resistant depression. DISCONTINUED, SILENTLY, WITH RESULTS NEVER DISCLOSED. The single Phase 2 study (14-AVP-786-201, NCT02153502) was a 10-week, multicenter, randomized, double-blind, placebo-controlled proof-of-concept study using the sequential parallel comparison design (SPCD, the Fava/Schoenfeld anti-placebo-response design), primary endpoint MADRS total score, 206 enrolled at ~30 US sites; it started July 2014 - announced by Avanir shortly before Otsuka's acquisition closed - and completed February 2016. No topline was ever announced, no publication has been found, and no results were posted to ClinicalTrials.gov in the ten years since (still hasResults=false as of 2026-08-14). No further depression study of AVP-786 was ever registered, and Otsuka terminated the molecule across all indications in May 2024. Historically notable as one of the first oral dextromethorphan-based products taken into depression - the concept that later succeeded as Axsome's dextromethorphan-bupropion (AXS-05/AUVELITY, FDA-approved for MDD in 2022, tracked separately) - and as a deliberately captured example of a silently abandoned program: the absence of any disclosure after a completed 206-patient study is itself competitive intelligence.

Data current as of

Development timeline

DiscontinuedMay 2024
  1. Terminal state anchored to Otsuka's molecule-wide termination of AVP-786 development (announced 2024-05-22 after the Alzheimer's-agitation Phase 3 failure) - the first and only citable sponsor statement ending all AVP-786 development. In practice the depression program was de facto abandoned after the 2016 study completion (no disclosure, no follow-on study in eight years), but no source dates that decision, so the citable upper bound is used rather than an invented earlier date.↗
Phase 2Jul 2014 – Feb 2016
  1. Study 201 completed per ClinicalTrials.gov (February 2016, 206 enrolled). No topline was ever announced, no publication found, and no results were ever posted to the registry - the program went silent from this point.
  2. Phase 2 study 201 (NCT02153502) started per ClinicalTrials.gov (start July 2014; month precision). Avanir's initiation announcement described a 10-week, ~200-patient, ~30-site US, SPCD proof-of-concept study of AVP-786 as adjunctive therapy in major depression with inadequate response to SSRIs/SNRIs, primary endpoint MADRS total score.↗
  3. Trial startedAvanir starts the Phase 2 study of adjunctive AVP-786 in treatment-resistant major depression

Clinical trials in Treatment-resistant depression

NCT0215350214-AVP-786-201Phase 2Completedn=206

Phase 2 SPCD proof-of-concept study of adjunctive AVP-786 in major depressive disorder with inadequate response to antidepressant treatment (treatment-resistant depression)

Started Jul 2014· Primary completion Feb 2016· 📍 32 sites across 1 country (United States)

Formulations

FormulationRouteRegimenPharmacokinetics
AVP-786 oral capsule (d6-DM 18/28/42.63 mg + quinidine sulfate 4.9 mg)
Capsules combining deudextromethorphan hydrobromide with ultra-low-dose quinidine sulfate 4.9 mg. The Phase 2 depression study administered AVP-786 (d6-dextromethorphan hydrobromide and quinidine sulfate combination) orally over a 10-week adjunctive, placebo-controlled design; the registry record does not disclose the mg strengths used.
OralTwice daily—

Mechanism of action (compound-wide)

Deudextromethorphan (d6-DM) is deuterated dextromethorphan: selective replacement of six hydrogens with deuterium at the O- and N-methyl positions increases metabolic stability at CYP2D6 without altering the parent molecule's receptor pharmacology - uncompetitive NMDA receptor antagonism, sigma-1 receptor agonism, and inhibition of the serotonin and norepinephrine transporters. Ultra-low-dose quinidine sulfate (4.9 mg) is included purely as a CYP2D6 inhibitor to sustain plasma exposure of the active moiety. In treatment-resistant depression the rationale was the NMDA-antagonist antidepressant hypothesis (the same glutamatergic mechanism later validated by ketamine/esketamine and by dextromethorphan-bupropion): adjunctive rapid-acting glutamatergic modulation in patients with inadequate response to SSRIs/SNRIs.

TargetActionAffinity
NMDA receptorprimaryGRIN1Antagonist—ⓘ
Norepinephrine transporter (NET)SLC6A2Reuptake inhibitor—ⓘ
Serotonin transporter (SERT)SLC6A4Reuptake inhibitor—ⓘ
Sigma-1 receptorSIGMAR1Agonist—ⓘ

← Full AVP-786 compound page (identity, identifiers, all indications)

Sources

  1. Avanir Pharmaceuticals Announces Initiation of Phase II Study of AVP-786 for the Adjunctive Treatment of Major Depressive Disorder (2014) — Avanir Pharmaceuticals, Inc. (via PR Newswire)
  2. Deuterated dextromethorphan/quinidine for agitation in Alzheimer's disease (open-access review: AVP-786 composition, deuteration rationale, mechanism) — PubMed Central (NCBI)
  3. NCT02153502 (14-AVP-786-201) - Phase 2 study of AVP-786 in treatment-resistant depression: completed February 2016, no results ever posted (hasResults=false as of 2026-08-14) — ClinicalTrials.gov (U.S. National Library of Medicine)
  4. Otsuka to Terminate Development of AVP-786 (2024-05-22) - the molecule-wide termination used as the citable terminal anchor for this silently abandoned program — Otsuka Pharmaceutical Co., Ltd. / Otsuka America