Ketamine for Depression and Conversion Disorder
Ketamine is recommended as a treatment option for patients with treatment-resistant depression (TRD) who have not responded to several adequate pharmacologic trials, but there is insufficient evidence to recommend its use for conversion disorder. 1
Role in Treatment-Resistant Depression
- Ketamine (IV infusion) and esketamine (intranasal) have demonstrated significant improvement in depressive symptoms in patients with major depressive disorder (MDD) for whom at least 2 previous adequate trials of antidepressant medications have failed 1
- Ketamine provides rapid antidepressant effects, with improvements appearing within 24 hours and lasting 3-7 days after administration 2
- When used as an adjunct to ongoing antidepressant treatment, ketamine's effects can persist for up to 7 days, while ketamine monotherapy effects may diminish after 7 days 1, 2
- Ketamine has also shown efficacy in reducing suicidal ideation in patients with MDD and acute suicidal ideation, making it valuable for emergency management of suicidality 1, 2
Administration and Dosing Considerations
- IV ketamine is the best-studied administration route, with a typical dose of 0.5 mg/kg infused over 40 minutes 1, 3
- Intranasal esketamine has FDA approval for TRD and requires pharmacy and healthcare setting certification with mandatory monitoring for 2 hours after treatment 1
- Oral ketamine administration offers greater accessibility but has less robust evidence compared to IV administration 4
- Monitoring for adverse effects such as psychotomimetic experiences and hypertension is essential during ketamine administration 2, 4
Efficacy and Duration of Effect
- Meta-analyses of randomized controlled trials have shown that ketamine, compared to placebo or midazolam, results in significant improvement in depressive symptoms after 24 hours 1, 3
- These improvements typically persist at 3-4 day follow-up visits 1, 3
- Twice-weekly dosing of esketamine as augmentation to ongoing oral antidepressant use improved depressive symptoms and remission rates in TRD patients at up to 28 days of follow-up 1
- Maintenance ketamine treatment appears promising for sustaining antidepressant effects, though optimal dosing schedules have yet to be determined 5, 6
Safety Considerations and Limitations
- Ketamine and esketamine are not recommended as initial treatments but are reserved for patients who have failed or not tolerated previous therapies 1, 4
- Ketamine lacks long-term efficacy and safety trials in MDD, with most evidence focusing on short-term (7-day) efficacy 1
- Common side effects include dissociative symptoms, dizziness, nausea, sedation, and transient blood pressure increases 7
- Concerns exist regarding the potential for abuse, dependence, and cognitive effects with repeated administration, though these appear uncommon in controlled clinical settings 5, 7
Ketamine for Conversion Disorder
- There is no specific evidence in the provided literature regarding ketamine's efficacy for conversion disorder
- Current clinical guidelines do not mention ketamine as a treatment option for conversion disorder 1
- Treatment decisions for conversion disorder should follow established guidelines for functional neurological disorders, which typically emphasize psychotherapy approaches
Clinical Decision Algorithm
- Confirm diagnosis of treatment-resistant depression (failure of ≥2 adequate antidepressant trials) 1
- Assess for contraindications to ketamine (uncontrolled hypertension, history of psychosis, substance use disorders) 2
- For patients with TRD:
- Monitor closely during and after administration for cardiovascular and psychotomimetic effects 2, 4
- Develop a maintenance strategy if initial response is positive, recognizing the limited evidence for long-term use 5