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Ketamine, originally an anesthetic, has emerged as a rapid-acting antidepressant for patients with Treatment-Resistant Depression (TRD) and Major Depressive Disorder (MDD), particularly when conventional antidepressants fail.
Clinical Effectiveness
Aspect Findings Onset of Action Relief seen within hours; peak effect usually within 24–72 hours. Response Rate 50–70% of TRD patients show significant symptom reduction after 1–2 infusions. Remission Rate Around 30–50% achieve remission (e.g., Montgomery–Åsberg Depression Rating Scale). Duration of Effect Single infusion may last 1–2 weeks; maintenance infusions help prolong effect. Suicidal Ideation Rapid reduction in suicidal thoughts within hours, sustained for several days.
Supporting Evidence
- NIH (2019) – Found ketamine effective in reducing depressive symptoms in TRD within 24 hours.
- ASH Clinical Practice Guidelines (2023) – Endorses intranasal esketamine (FDA-approved) for TRD.
- Cochrane Review (2022) – Ketamine superior to placebo in short-term mood improvement.
Mechanism of Action
Ketamine is a noncompetitive NMDA receptor antagonist. It:
- Enhances glutamate transmission
- Promotes synaptogenesis and neuroplasticity
- Modulates the mTOR pathway for rapid mood elevation
Modes of Administration
- IV Infusion (Racemic Ketamine) – Most studied, 0.5 mg/kg over 40 minutes.
- Intranasal Esketamine (Spravato) – FDA-approved for TRD, used with oral antidepressant.
- Oral/Sublingual/IM – Used off-label with varying results.
Safety & Side Effects
- Common: Dissociation, dizziness, elevated blood pressure, nausea.
- Rare: Hallucinations, bladder issues (with prolonged use), potential for abuse.
- Tolerability: Generally good under clinical supervision.
Indications for Use
- Failure of ≥2 antidepressant trials
- Chronic MDD with functional impairment
- Severe suicidality unresponsive to SSRIs/SNRIs
Maintenance Strategies
- Repeated IV infusions (e.g., 2-3 per week initially, then taper)
- Combination with psychotherapy and/or oral antidepressants
- Intranasal Esketamine twice weekly then weekly/monthly
Limitations
- Long-term safety data still evolving
- Cost and access issues
- Requires monitoring and infrastructure (e.g., for BP, dissociation)
Here is a comprehensive Ketamine Therapy Treatment Protocol tailored for your clinic — NeuroNext Brain & Mind Centre, Islamabad — for patients with Treatment-Resistant Depression (TRD)/MDD.
Ketamine Therapy Treatment Protocol – NeuroNext Brain & Mind Centre
1. Patient Selection Criteria
Inclusion:
- Diagnosis of Major Depressive Disorder (MDD) or Bipolar Depression (non-manic state)
- Failed ≥2 adequate antidepressant trials (TRD criteria)
- Significant functional impairment or suicidality
- Age 18–65 (with flexibility based on clinical judgement)
Exclusion:
- Uncontrolled hypertension or cardiovascular disease
- Active substance use disorder
- History of psychosis or mania (unless fully stabilized)
- Pregnancy or breastfeeding
- Unstable medical conditions
2. Pre-Treatment Assessment
- 🧠 Psychiatric Evaluation: Confirm diagnosis, review past treatments, assess suicidality
- ❤️ Medical Clearance: Vitals, ECG, CBC, LFTs, RFTs, urine drug screen if indicated
- 📄 Informed Consent: Document risks, benefits, alternatives, and expectations
3. Dosing & Administration
Route Initial Dose Frequency IV Infusion 0.5 mg/kg over 40 minutes 2–3 times/week × 2–3 weeks IM 0.5–0.7 mg/kg 1–2 times/week (alternative) Oral/Sublingual 1–2 mg/kg (lower bioavailability) Less preferred, off-label use
Monitoring Required:
- Administer in a quiet, medically equipped room
- Continuous pulse oximetry, BP, HR monitoring
- Monitor for 2 hours post-infusion
4. Monitoring & Assessment
During Infusion:
- Record vitals every 10–15 minutes
- Observe for dissociation, nausea, or distress
Post-Session:
- Clinician debrief
- No driving for 6–12 hours post-infusion
- Follow-up PHQ-9, MADRS, or QIDS score tracking
5. Maintenance Phase (If Responsive)
Phase Frequency Week 3–6 1 infusion/week Week 7–12 1 infusion every 10–14 days After 3 months Monthly or PRN
Concurrent Treatment:
- Keep oral antidepressants stable
- Integrate psychotherapy (CBT, ACT, etc.)
6. Adverse Effects Management
Symptom Management Transient Hypertension Monitor, lower dose next time if needed Dissociation/Anxiety Provide reassurance, reduce stimulation Nausea Pre-medicate with ondansetron if recurrent Headache Paracetamol post-infusion
7. Documentation
- Session logs: Dose, vitals, observations, side effects
- Response tracking: PHQ-9/MADRS scores pre and post each infusion
- Consent forms, medication chart, emergency contact list
8. Emergency Preparedness
Your ketamine therapy room must be equipped with:
- Oxygen, suction,
Conclusion
Ketamine therapy offers rapid, substantial, and sometimes life-saving relief in TRD and MDD, especially where traditional therapies have failed. It is not a first-line treatment, but a powerful adjunct or rescue intervention under proper psychiatric supervision.
