Ketamine has re-emerged as one of the most versatile molecules in psychiatry—rapid-acting, robust, and lifesaving for patients with treatment-resistant depression and suicidal ideation. Yet, in many low- and middle-income countries, the practical challenge lies not in whether ketamine works, but how to administer it safely, affordably, and ethically. Intramuscular (IM) and subcutaneous (SC) ketamine protocols offer precisely that: a feasible alternative where intravenous infusions are impractical or unaffordable.

1. Why Alternative Routes Matter

IV ketamine remains the gold standard in most trials, typically 0.5 mg/kg over 40 minutes. However, maintaining infusion pumps, continuous cardiac monitoring, and trained staff may be unrealistic in smaller hospitals or outpatient clinics in India and other resource-limited settings.

The IM and SC routes bypass this barrier—they require minimal equipment, can be administered in outpatient settings, and still deliver predictable antidepressant effects. For psychiatrists working outside tertiary centers, these routes democratize access to a potentially life-saving intervention.

2. Pharmacology and Mechanism

Regardless of route, ketamine acts as an NMDA receptor antagonist, enhancing glutamate signaling and downstream neuroplasticity via AMPA receptor activation and BDNF release. IM and SC administration both achieve adequate plasma concentrations for these neurobiological effects, though the onset and duration vary slightly.

• IM Ketamine: Rapid onset (5–10 minutes), peak effect by 20 minutes, lasting 45–90 minutes.
• SC Ketamine: Slower absorption (15–20 minutes to onset), smoother peak, fewer dissociative symptoms.

Both routes deliver the same mechanism—modulation of glutamatergic tone and restoration of synaptic connectivity in mood circuits.

3. Practical Dosing and Frequency

Most clinics use 0.5–1 mg/kg IM or 0.3–0.5 mg/kg SC, typically once or twice weekly for 4–6 sessions.
A test dose (0.25 mg/kg) may be administered initially to assess tolerance. Subsequent sessions can be titrated based on response and dissociation severity.

Session essentials:

• Quiet room with medical supervision
• Baseline BP and pulse, repeat monitoring post-dose
• Observation for 60–90 minutes
• No driving or operating machinery for the next 6 hours

4. Comparative Effectiveness

Multiple studies (Domino, 2020; Al Shirawi et al., J Affect Disord, 2017; Loo et al., Int J Neuropsychopharmacol, 2016) show that IM and SC ketamine have comparable antidepressant efficacy to IV infusion when delivered in equivalent bioavailability.

SC administration, in particular, offers smoother pharmacokinetics and fewer dissociative side effects, making it suitable for elderly or anxious patients. IM remains favored for emergency or inpatient setups due to faster onset and ease of dose control.

5. Safety and Monitoring

Common transient effects:

• Dizziness, mild dissociation, perceptual changes
• Elevated BP or pulse (self-limiting)
• Nausea or fatigue

Rare adverse effects include prolonged dissociation, anxiety, or transient headache. Serious complications like cystitis or hepatic dysfunction are associated only with chronic misuse, not therapeutic courses.

Contraindications include uncontrolled hypertension, psychosis, recent substance misuse, and pregnancy (relative).

All patients should be pre-screened for cardiovascular status, substance use history, and psychiatric stability.

6. Implementation in Resource-Limited Settings

Advantages:

• Minimal infrastructure: a basic clinic setup suffices.
• Low cost: each session can be delivered at a fraction of IV infusion costs.
• Feasibility for district hospitals, teaching institutions, or community psychiatry models.
• Safe when protocols are standardized and clinicians trained in basic resuscitation and observation.

Even with limited budgets, IM/SC ketamine can be integrated into treatment-resistant depression clinics, especially when combined with psychotherapy and follow-up care.

7. Future Directions

As India and similar regions expand psychiatric services beyond tertiary centers, task-shared ketamine protocols using IM or SC routes could transform access to care. Integration with digital monitoring tools, AI-assisted mood tracking, and telepsychiatry supervision could make this a sustainable, evidence-based model for low-resource healthcare ecosystems.

8. Conclusion

Intramuscular and subcutaneous ketamine are not inferior compromises—they are pragmatic innovations. When implemented thoughtfully, they combine the biological precision of modern psychiatry with the accessibility needed in public mental health. The future of ketamine therapy lies not only in cutting-edge clinics but in community psychiatry—where healing reaches those who need it most.

Author:
Dr. Srinivas Rajkumar T, MD (AIIMS Delhi), DNB, MBA (BITS Pilani)
Consultant Psychiatrist, Mind & Memory Clinic
Assistant Professor, Dept. of Psychiatry, Sree Balaji Medical College & Hospital
Apollo Clinic Velachery (opposite Phoenix MarketCity), Chennai

📞 +91 85951 55808 | 🌐 srinivasaiims.com

Dr. Srinivas specializes in treatment-resistant depression, neuromodulation, and ketamine-assisted therapy, with a focus on safe, affordable, and evidence-based interventions in the Indian context.