The renaissance of ketamine in psychiatry has opened both doors and debates. Among the most practical questions clinicians face is deceptively simple: how often should ketamine be administered? Whether delivered intravenously, subcutaneously, or intranasally, dosing frequency profoundly shapes both response and sustainability.

1. The science of timing

Ketamine’s antidepressant mechanism differs from traditional monoaminergic agents. It rapidly enhances glutamatergic signaling, activates AMPA receptors, and triggers synaptogenesis via BDNF and mTOR pathways. These molecular cascades emerge within hours, but their duration—how long the antidepressant effect lasts—varies widely between individuals. That variability is why there’s no single “ideal” frequency yet.

2. What clinical research shows

Most early studies used intravenous (IV) racemic ketamine at 0.5 mg/kg over 40 minutes, administered twice weekly for 2–4 weeks. This regimen became the de facto standard because it balanced efficacy and tolerability.

The subcutaneous (SC) route, now gaining attention for its simplicity and lower cost, shows similar response patterns. Clinical series suggest:

• Acute phase: 4–8 sessions, given once or twice weekly, typically at 0.1–0.5 mg/kg.
• Response window: Antidepressant effects usually emerge after 2–4 sessions and peak by 6–8.
• Maintenance: After remission, sessions may be spaced every 2–4 weeks based on symptom return.

In a 2022 case series (International Clinical Psychopharmacology), repeated SC ketamine twice weekly for 3 weeks led to remission in 80% of treatment-resistant depression patients. Other trials show durable benefit when shifted to once-weekly or fortnightly dosing after the initial phase.

3. The “wear-off” principle

A practical rule many clinicians follow is dosing just before the effect of the last session fades. For some, that means once weekly; for others, every 10–14 days. The principle is simple: avoid the relapse window while minimizing unnecessary exposure.

Too frequent dosing risks tolerance and dissociation; too infrequent risks relapse and patient discouragement. The optimal frequency is thus dynamic—responsive to the patient’s mood trajectory and functional improvement.

4. Beyond depression: tailoring frequency

• Bipolar depression: Similar schedules apply, but mood switching risk requires vigilance; weekly dosing tends to be safer than twice-weekly early on.
• OCD, PTSD, chronic pain: These conditions sometimes require longer induction phases (6–8 sessions) before spacing out.
• Maintenance responders: Some patients sustain remission with monthly boosters, others relapse after 2 weeks.

Tracking symptoms systematically with scales like MADRS or PHQ-9 helps determine when to repeat sessions objectively.

5. Practical guidance for clinicians

• Start low, go slow: 0.25 mg/kg SC once weekly is a conservative initiation point.
• Monitor response: Reassess after 4–6 sessions; if benefit stabilizes, extend interval.
• Maintain safety: Observe for dissociation, blood-pressure rise, urinary symptoms, and psychological craving.
• Taper thoughtfully: Avoid abrupt cessation; space out sessions gradually to test durability of benefit.

6. The way forward

The future of ketamine therapy likely lies in personalized dosing algorithms—potentially guided by biomarkers such as HRV, QEEG, or fNIRS changes. For now, clinical judgment remains the compass.

Weekly dosing strikes a pragmatic balance between efficacy, safety, and practicality in Indian clinical settings, especially for outpatient use. But the guiding maxim should always be: dose when needed, not when scheduled.

Author:
Dr. Srinivas Rajkumar T, MD (AIIMS Delhi), DNB, MBA (BITS Pilani)
Consultant Psychiatrist, Mind & Memory Clinic
Apollo Clinic Velachery (opposite Phoenix MarketCity), Chennai
📞 +91 85951 55808 | 🌐 srinivasaiims.com