Transitioning from Macro-Dosing to Microdosing Ketamine for Anxiety and Mood Enhancement: The Case of RK

Abstract
RK, a 51‑year‑old man with lifelong anxiety, depression, and ADHD, experienced worsening anxiety and dissociative side effects on a high‑dose sublingual ketamine regimen during a stressful divorce and custody battle. After switching to a structured microdosing protocol at AVYIA—carefully titrated downward from 750–1,000 mg twice weekly to low, frequent doses—he reported profound and sustained mood stabilization. Eight months in, RK described himself as “1,000 percent better… I don’t know how else to describe it,” having successfully tapered off Effexor and Wellbutrin with minimal residual anxiety.

Background

Ketamine’s efficacy in refractory mood disorders is well‑established, but high‑dose (“macro”) protocols often induce unpleasant dissociation or sedation. Emerging microdosing approaches aim to preserve therapeutic neuroplastic benefits while minimizing side effects—yet guidance on transitioning between these regimens remains limited.

Introducing the Research

This case study by Jason Chang, DNP, ARNP‑C at AVYIA details RK’s clinical journey from a dissociative, high‑dose sublingual ketamine protocol to a personalized microdosing schedule. It provides real‑world insights into dose‐adjustment strategies that maximize benefit and tolerability.

What You’ll Learn

• How to calculate and implement a gradual shift from macro‑ to microdosing ketamine.

• The clinical monitoring required to safely taper off adjunctive antidepressants.

• Evidence that microdosing can sustain mood improvements with fewer adverse effects.

Breaking Down the Research Article

A. The Big Question
Can a structured microdosing regimen maintain or enhance ketamine’s antidepressant and anxiolytic effects while reducing dissociative side effects in a patient transitioning from high‑dose therapy?

B. How They Did It (Study Design & Methods – Simplified)

• Patient Profile: 51‑year‑old male, history of generalized anxiety disorder (GAD‑7 score 7), major depression, and ADHD; under significant stress from divorce and custody proceedings.

• Previous Regimen: Sublingual ketamine 750–1,000 mg twice weekly, which provided moderate anxiety relief but caused troublesome dissociation. Concomitant Effexor (venlafaxine) and Wellbutrin (bupropion).

• Transition Protocol:

  1. Titration Calculation: Converted his total weekly dose into an equivalent low‑dose microdosing schedule (e.g., 10–20 mg oral ketamine, 5–7 times per week).

  2. Adjunctive Taper: Gradual reduction and eventual discontinuation of Effexor and Wellbutrin over 12 weeks under close supervision.

  3. Support: Weekly telehealth check‑ins and biweekly psychotherapy to monitor anxiety, mood, and cognitive side effects.

C. Key Findings (The Takeaway)

• Rapid Tolerability Gains: Within two weeks, RK reported virtually no dissociation or sedation.

• Sustained Mood Improvement: By month two, his anxiety and depressive symptoms stabilized at minimal levels (GAD‑7 < 5).

• Medication Reduction: Successfully weaned off Effexor and Wellbutrin, maintaining anxiety control solely on ketamine microdoses.

• Patient Quote: “I’m a thousand percent better… I don’t know how else to describe it.”

D. What Does This Mean For You? (Implications & Significance)

• For Patients: If high‑dose ketamine causes unwanted effects, transitioning to microdosing can preserve benefits and improve daily functioning.

• For Providers: Detailed conversion calculations and structured tapering of adjunct medications are essential to avoid withdrawal or relapse.

• For Treatment Planning: Microdosing protocols can be customized to individual stressors and life events, offering a more sustainable long‑term strategy.

E. Important Considerations & Limitations

• Single‑Case Data: Broader case series or trials are needed to validate generalizability.

• Clinical Oversight Required: Accurate dosing conversions and medication tapers demand close medical supervision.

• Individual Variability: Not all patients will tolerate or respond to microdosing equivalently; personalization is key.

Conclusion: Microdosing as a Path to Balanced Well‑Being

Recap
RK’s experience illustrates that a carefully calculated transition from high‑dose to microdosing ketamine can eliminate dissociative side effects, sustain antidepressant and anxiolytic efficacy, and allow safe discontinuation of other psychiatric medications.

Future Directions
Systematic studies should establish standardized dose‑conversion guidelines, evaluate long‑term outcomes, and explore patient selection criteria for microdosing protocols.

Call to Action
If you’re experiencing adverse effects on a high‑dose ketamine regimen or seeking a more tolerable maintenance strategy, consult a ketamine‑savvy clinician to discuss a personalized microdosing transition plan.