A UK-based Phase 2 clinical trial has found that a slow-release oral ketamine tablet significantly reduced the risk of relapse in patients with depression. The study, which enrolled 231 participants, reported that only 57% of those receiving ketamine relapsed after 13 weeks, compared to 71% in the placebo group. These findings mark a significant step toward more convenient and scalable delivery methods for ketamine-based antidepressant therapy.
Study Overview
- Location: United Kingdom
- Study Type: Phase 2, randomized, placebo-controlled trial
- Sample Size: 231 patients with major depressive disorder (MDD)
- Intervention: Slow-release oral ketamine tablet
- Comparator: Placebo tablet (matched appearance and schedule)
- Follow-up Duration: 13 weeks
- Primary Endpoint: Relapse of depressive symptoms
This trial represents one of the largest efforts to test oral ketamine formulations in a controlled clinical environment, offering insights into its potential for wider use beyond intravenous (IV) or intranasal administration.
Key Findings
1. Reduced Relapse Rates
- Ketamine group: 57% relapse after 13 weeks
- Placebo group: 71% relapse over the same period
- This represents a 20% relative reduction in relapse risk, demonstrating ketamine’s continued antidepressant effect in an oral formulation
2. Ease of Administration
- Slow-release tablets are more convenient than IV infusions or intranasal sprays
- Tablets may improve adherence, especially for patients in remote or underserved areas
- Potential for home-based treatment models under telehealth supervision
3. Sustained Antidepressant Effects
- Patients receiving oral ketamine remained in remission longer before any signs of relapse
- The delayed release design ensured steady plasma levels, minimizing side effects linked to peak serum concentrations
Scientific and Clinical Implications
A. New Era of Oral Psychedelic Medicine
- IV ketamine’s rapid-acting antidepressant properties are well known, but oral delivery methods have lagged behind
- This trial shows that oral ketamine may be a viable maintenance option, especially after successful IV induction therapy
- Could reduce healthcare system burden by lowering the need for recurrent clinic visits
B. Targeting Relapse Prevention
- Many antidepressants focus on acute symptom relief, but relapse remains a persistent challenge in major depressive disorder
- Ketamine’s ability to maintain neuroplasticity and regulate mood-related circuits could help “lock in” early treatment gains
Safety and Side Effects
- The study reported mild and transient side effects, including:
- Drowsiness
- Nausea
- Light-headedness
- No serious adverse events or misuse observed
- Low incidence of dissociation compared to parenteral forms
These findings support the notion that oral ketamine has fewer psychotomimetic side effects than IV or intranasal routes, enhancing tolerability.
Advantages of Slow-Release Tablet Formulation
- Extended therapeutic window due to gradual absorption
- Reduced “peaks and valleys” in blood concentration
- Easier to monitor and titrate compared to infusions
- Greater scalability in both primary care and psychiatric settings
Limitations and Considerations
- Short trial duration (13 weeks) — long-term efficacy and safety still need evaluation
- Unknown if higher or lower dosages might yield stronger or weaker outcomes
- Need for replication in diverse populations with comorbid conditions
Next Steps in Research
- Phase 3 trials with larger cohorts and extended follow-up
- Comparative studies with traditional SSRIs and SNRIs
- Evaluation of cost-effectiveness in health system integration
- Investigation into combination therapies using ketamine plus psychotherapy
Final Thoughts
The UK Phase 2 trial of slow-release oral ketamine tablets presents a promising new direction in depression treatment. With a 20% lower relapse rate than placebo over 13 weeks, oral ketamine offers a more practical, scalable option for maintaining remission in people with major depression. If future studies confirm these results, oral ketamine could become a frontline tool in relapse prevention, especially for patients seeking alternatives to invasive or hard-to-access treatments.
References
- The Guardian (2024). New trial shows oral ketamine helps prevent depression relapse. [theguardian.com]
Financial Times (2024). Ketamine tablet cuts relapse rates in depression. [ft.com]
