Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials
By
Martin Walter
Christine zu Eulenburg
Ani Damyanova
Karin Schmid
Isabel Schwienbacher
Evangelos Papanastasiou
Katarina Maiboe
Lars Arvastson
Caren Strote
Daniel Gehrlach
Hans Eriksson
June 24, 2026
Clinical Scorecard: Prolonged-Release Oral Ketamine for Managing Treatment-Resistant Depression: Results from Two Randomized Clinical Studies
At a Glance
Category Detail
Condition Treatment-Resistant Depression (TRD) Key Mechanisms Ketamine acts as a rapid-acting antidepressant with unique pharmacokinetic properties. Target Population Adults aged ≥18 years with TRD. Care Setting Clinical trials conducted in specialized settings.
Key Highlights
KET01 is a prolonged-release oral formulation of racemic ketamine. KET01 demonstrated limited dissociative properties compared to intranasal esketamine. The trials included a phase 1 head-to-head comparison and a phase 2 placebo-controlled study. Adverse effects included transient dissociative symptoms and cardiovascular changes. The primary outcome measures were changes in CADSS and MADRS scores. Guideline-Based Recommendations
Diagnosis
Diagnosis of TRD requires failure to respond to two different courses of antidepressant treatment during the current major depressive episode. Management
KET01 can be administered adjunctively to ongoing standard antidepressant therapy. Monitoring & Follow-up
Participants were monitored for 24 hours post-administration and followed up for 7 days after the second treatment period. Risks
Acute adverse effects include dissociative experiences and increased blood pressure. Patient & Prescribing Data
Adult outpatients with TRD.
KET01 was administered once daily for 3 weeks, with doses of 120 mg/d or 240 mg/d.
Clinical Best Practices
Conduct trials in accordance with ethical guidelines and obtain informed consent. Ensure double-blinding to minimize bias in treatment administration. Related Resources & Content
