Is microdosing of ketamine (a medication used for anesthesia and treatment-resistant depression) effective for treating psychological disorders?

Microdosing Ketamine for Psychological Disorders: Current Evidence

The evidence provided does NOT support microdosing of ketamine for psychological disorders—all high-quality data examines standard subanesthetic doses (0.2-0.5 mg/kg IV), not microdoses, and these standard doses show robust efficacy for treatment-resistant depression and acute suicidal ideation. 1, 2, 3

Critical Distinction: Microdosing vs. Therapeutic Subanesthetic Dosing

The term "microdosing" in your question likely refers to very low, repeated doses similar to psychedelic microdosing protocols. However, no evidence exists for true microdosing of ketamine in the psychiatric literature provided. The studies examine subanesthetic doses which are therapeutically active but below anesthetic levels:

• Standard therapeutic dose: 0.5 mg/kg IV infused over 40 minutes 1, 2, 3
• Lower therapeutic dose: 0.2-0.25 mg/kg for emergency settings 1, 3
• True microdoses: Not studied in the provided evidence

The systematic review on microdosing 4 exclusively examines psychedelics (LSD, psilocybin), not ketamine, and shows mixed results with significant methodological limitations including lack of placebo controls and heavy reliance on self-report data.

Evidence-Based Ketamine Dosing for Psychological Disorders

Treatment-Resistant Depression

The American Psychiatric Association supports 0.5 mg/kg IV ketamine infused over 40 minutes for treatment-resistant depression after at least 2 failed adequate antidepressant trials. 3

• Efficacy timeline: Significant improvement in depressive symptoms within 24 hours, lasting 3-4 days after single infusion 2
• Serial infusion protocol: Twice weekly until remission or 4-6 total infusions completed 1, 3
• Response criteria: ≥50% reduction in depressive symptoms at 24 hours post-infusion 3

Acute Suicidal Ideation

Lower doses (0.2-0.25 mg/kg) administered in emergency settings show rapid antisuicidal effects beginning within 40 minutes and lasting up to 10 days. 1, 3

• Effect size: Largest at 40 minutes (d=1.05 overall; d=2.36 in high-baseline suicidal ideation) 1
• Duration: Effects persist for 2-10 days following single infusion 1, 3
• Mechanism: May be partially independent of general antidepressant effects, though this requires further investigation 4, 1, 3

Other Psychiatric Disorders

Ketamine shows promise for PTSD and OCD, but evidence is more limited:

• PTSD: Statistically significant reductions in PCL-5 scores (pooled estimate = -28.07) and CAPS-5 scores (pooled estimate = -14.07) 5
• OCD: Significant reduction in Y-BOCS scores (pooled estimate = -8.08) 5
• Alcohol use disorders: Decreased urge to drink, increased abstinence rates, longer time to relapse 5

Safety Profile and Dose-Dependent Effects

Psychotomimetic effects are dose-dependent, with higher incidence at doses approaching or exceeding 0.5 mg/kg:

• At 0.5 mg/kg: Hallucinations in ~20%, nightmares in ~12% of patients 1, 3
• Lower doses (0.2-0.25 mg/kg): Provide antisuicidal benefits while minimizing psychotomimetic effects 1
• Common adverse effects: Nausea, ataxia, transient dissociation, increased blood pressure 2
• Serious concerns: Dissociative side effects, abuse potential, possible excitotoxic neuronal injury with repeated use 6

Critical Limitations and Clinical Caveats

Long-term efficacy and safety data remain severely limited, with most evidence from small sample sizes and short-term follow-up (≤7 days). 2, 3

• Maintenance strategies: Not well-established; optimal frequency determined by monitoring symptom return typically 2-7 days after infusion 3
• Pseudospecificity concern: Whether ketamine's effects on suicidal ideation are independent of general antidepressant effects remains inconclusive 4
• Behavioral outcomes: All studies examined suicidal ideation, not suicidal behavior—whether effects translate to preventing actual suicide attempts is unknown 4
• Esketamine requirements: REMS certification and mandatory 2-hour post-treatment monitoring required 1, 3

Clinical Implementation Algorithm

For treatment-resistant depression:

1. Verify ≥2 failed adequate antidepressant trials (4-6 weeks at therapeutic doses) 3
2. Confirm moderately severe depression on standardized scales 3
3. For bipolar depression: Add concurrent mood stabilizer (lithium or valproate) to prevent manic switch 1, 3
4. Administer 0.5 mg/kg IV over 40 minutes, twice weekly 3
5. Assess response at 24 hours (target ≥50% symptom reduction) 3
6. Continue until remission or 4-6 total infusions 3

For acute suicidal ideation in emergency settings:

1. Consider lower dose (0.2-0.25 mg/kg over 1-2 minutes) 1, 3
2. Monitor for rapid onset (effects begin within 40 minutes) 1, 3
3. Use as bridge treatment until traditional therapies take effect 1

The evidence does not support "microdosing" ketamine—all therapeutic benefits occur at subanesthetic but pharmacologically active doses that produce measurable dissociative effects. 7, 8, 6