Purpose & Clinical Rationale

Tulsa Family Psychiatry & Wellness (TFAM) provides intramuscular (IM) ketamine treatment as a medical intervention for treatment-resistant mood and anxiety disorders, modeled on the established IV ketamine literature.

This protocol intentionally distinguishes:

• Medical ketamine treatment (Track A)
• Ketamine-Assisted Psychotherapy (KAP) (Track B)

Psychotherapy is not required for antidepressant efficacy and is not routinely provided during medical ketamine sessions.

This distinction preserves:

• Clinical clarity
• Billing integrity
• Scope-of-practice alignment
• Audit defensibility

2. Treatment Tracks

Track A — IM Ketamine (Medical Only)

• Biologically focused intervention
• No psychotherapy during dosing session
• Target dissociation: Stages 1–2
• Session length: 90–120 minutes
• Patient-paid ketamine administration fee

Track B — Ketamine-Assisted Psychotherapy (KAP)

• Psychotherapeutic intervention using ketamine
• Therapist present during dosing
• Target dissociation: Stages 3–4
• Separate protocol (not covered in this document)

This document governs Track A only.

3. Indications

IM ketamine may be offered to adult patients with:

• Treatment-resistant major depressive disorder
• Bipolar II depression (no mixed or manic states)
• PTSD
• Severe anxiety disorders
• Chronic suicidal ideation (without imminent intent)
• OCD (case-by-case)

All patients must undergo a medical and psychiatric evaluation prior to initiation.

4. Contraindications & Exclusions

Absolute / Temporary Contraindications

• Uncontrolled hypertension
• Recent myocardial infarction (< 12 months)
• Recent stroke (< 12 months)
• Active psychosis
• Active mania or hypomania
• Pregnancy or breastfeeding
• Ketamine hypersensitivity
• Acute substance intoxication or withdrawal

Vital Sign Parameters

• BP must be ≤150/90 prior to administration
• Elevated BP may be managed per clinic protocol or treatment deferred

5. Pre-Treatment Requirements

Before first IM ketamine session:

• Comprehensive psychiatric evaluation
• Medical history review and medication reconciliation
• Baseline symptom assessment (e.g., PHQ-9, MADRS, QIDS-SR, GAD-7)
• Review of risks, benefits, and alternatives
• Informed consent signed
• Transportation arranged (no driving post-treatment)

6. Dosing Protocol (IM)

IM dosing is individualized and titrated to effect, modeled on IV ketamine pharmacodynamics.

Initial & Induction Dosing

Session	Typical Dose Range	Intended Dissociation
1	0.4–0.5 mg/kg	Stage 1–2
2–3	0.5–0.75 mg/kg	Stage 1–2
4–6	0.75–1.0 mg/kg	Stage 2

Dose Adjustments

Dose adjustments may be made based on:

• Symptom response
• Adverse effects
• Patient tolerance
• Prior dissociative response

Doses >1.0 mg/kg are not routinely used in Track A.

7. Dissociation Targeting Framework

Stage 1 — Light Dissociation

• Relaxation, emotional distance
• Preserved orientation
• Antidepressant response common

Stage 2 — Moderate Dissociation

• Altered perception, introspection
• Patient remains aware of environment
• Primary target for medical ketamine

Stage 3 — Deep Dissociation

• Vivid imagery, symbolic content
• Ego-boundary softening
• Requires therapist support

Stage 4 — Psychedelic / Ego Dissolution

• Full immersive experience
• Not appropriate without KAP framework

TFAM medical ketamine sessions intentionally target Stages 1–2 only.

8. Session Workflow (Track A)

Total Visit Time: approximately 90–120 minutes

1. Check-in and vital signs
2. Brief medical check-in (symptoms, side effects, safety)
3. IM ketamine administration by licensed prescriber via divided doses spaced 10 mins apart
4. Patient placed in quiet, monitored environment
5. Optional eye mask and calming music
6. Vitals rechecked mid-session (40 min)
7. Recovery period
8. Final vitals and discharge once criteria met

Psychotherapy, guided processing, or intentional facilitation is not provided during Track A sessions though appropriate grounding and reassurance may be provided by treating provider or proxy via trained unlicensed staff members under direct oversight provided by licensed provider.

9. Monitoring & Safety

Monitoring

• Baseline vitals
• 30-40 minutes post second-dose
• Prior to discharge
• Additional monitoring as clinically indicated

Staffing

• Prescriber (MD/DO/NP/PA) administers injection
• MA/CMA monitors vitals and patient status
• RN optional, not required

Adverse Effect Management

• Nausea → ondansetron
• Anxiety → reassurance, grounding
• Severe agitation → benzodiazepine per rescue protocol
• Hypertension → clonidine per protocol

10. Severe Agitation Rescue Protocol

For post-ketamine agitation, give 0.05 mg/kg IM midazolam 23 (typically 5 mg in adults), which reduces agitation and is well tolerated 23. If needed, repeat once after 5–10 minutes 2, and monitor for respiratory depression 22. IM onset is ≈10–15 minutes 22, so expect a delay and avoid IV or repeated dosing in agitated patients

Midazolam has been difficult to procure via our suppliers as of April 2026. Procurement pending.

11. Documentation Standards

Each session note must include:

• Dose administered
  • Lot, expiration date
• Injection sights and time of each injection
• Patient response
• Vital signs
• Standardized depression screener scoring per selected screener
• Adverse effects (if any)
• Clinical impression
• Plan for next session

Documentation must clearly distinguish:

• Medical ketamine administration
• Any separately identifiable E&M, if billed

 

12. Billing Framework (Track A)

Ketamine Administration

• Patient-paid, non-covered service
• Covers medication, administration, monitoring, room use
• Charged as a flat fee of $300

E&M Billing

• Not routine on dosing days
• May be billed only when a medically necessary, separately identifiable evaluation occurs
• Typically billed:
  • At intake
  • Periodically during treatment course
  • At transition points
  • When new clinical decisions are made

Symptom Rating Scales

• Standardized tools (e.g., PHQ-9) may be administered at each visit when clinically appropriate

13 Clinical Philosophy Statement

TFAM recognizes ketamine as a powerful biological intervention that does not inherently require psychotherapy for antidepressant benefit.

When deeper psychological exploration is clinically indicated, patients may be referred to Ketamine-Assisted Psychotherapy, which follows a separate protocol and staffing model.

This separation ensures patient safety, ethical clarity, and regulatory compliance.

14 Inventory Control and Waste

Controlled Substance Handling and Disposal

Ketamine is a Schedule III controlled substance and must be handled, documented, and disposed of in accordance with applicable federal and state regulations.

Per 21 CFR §1317.90 (Destruction of Controlled Substances), all controlled substances designated for disposal must be rendered “non-retrievable,” meaning the substance is permanently altered to a condition or state from which it cannot be transformed for further use.

Once there is no remaining controlled substance, the vial itself is no longer regulated under controlled substance disposal requirements and may be discarded as medical waste (e.g., in an approved sharps container).

Wasting of Partial Quantities

Any remaining ketamine following dose preparation or administration must be promptly wasted in compliance with controlled substance requirements.

Per DEA regulations and standard controlled substance practices:

• Wasting must be performed immediately after dose administration or preparation
• The remaining quantity must be rendered non-retrievable
• The waste must be witnessed by two authorized individuals (e.g., licensed clinical staff)
• Both individuals must document and attest to the waste

Documentation must include:

• Patient identifier (if applicable)
• Date and time of waste
• Drug name and concentration
• Amount administered
• Amount wasted

DEA Form Requirements

• DEA Form 41 (Registrants Inventory of Drugs Surrendered) is required when controlled substances are:
  • Destroyed in bulk
  • Transferred to a reverse distributor for destruction

• Routine point-of-care wasting (e.g., partial vial waste during patient care)
  does NOT require DEA Form 41, provided:
  • The waste is documented internally
  • The substance is rendered non-retrievable
  • Appropriate witnessing procedures are followed

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Document Control

Draft Version: 1.10

Status: In-use

Intended Use: Clinical operations & policy

Works Cited / References

1. American Society of Anesthesiologists. Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018. Anesthesiology. 2018;128(3):437–479.
2. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd ed. Arlington, VA: APA; 2010 (and updates).
3. U.S. Food and Drug Administration. Ketamine Hydrochloride Injection Prescribing Information.
4. U.S. Food and Drug Administration. Spravato (esketamine) Nasal Spray Prescribing Information. Janssen Pharmaceuticals; 2019.

Core Ketamine Clinical Trials & Foundational Evidence

1. Carlos A. Zarate Jr. et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856–864.
2. Gerard Sanacora et al. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017;74(4):399–405.
3. Samuel T. Wilkinson et al. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2018;175(2):150–158.
4. Gerard Sanacora et al. Intravenous ketamine for treatment-resistant depression: A systematic review of clinical effectiveness. Biol Psychiatry. 2017.
5. James W. Murrough et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134–1142.
6. Jaskaran B. Singh et al. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry. 2016;173(8):816–826.
7. Daly EJ, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression. JAMA Psychiatry. 2018.

Mechanism, Safety, and Translational Science

1. Rebecca L. Price et al. Effects of ketamine on explicit and implicit suicidal cognition. Biol Psychiatry. 2009;66(5):522–526.
2. Matthew W. Johnson, Roland R. Griffiths. Potential therapeutic effects of psychedelics. Neurotherapeutics. 2017;14(3):734–740.
3. Bahji A, Vazquez GH, Zarate CA Jr. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. J Affect Disord. 2021.

Clinical Guidelines, Safety Frameworks, and Practice Standards

1. American College of Emergency Physicians. Clinical Policy: Procedural Sedation and Analgesia in the Emergency Department. Ann Emerg Med. 2014.
2. American Society of Ketamine Physicians, Psychotherapists, and Practitioners. Standards of Practice for Ketamine Therapy.
3. Department of Veterans Affairs & Department of Defense. VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder.
4. World Health Organization. Guidelines for the Management of Physical Health Conditions in Adults With Severe Mental Disorders. 2018.
5. Substance Abuse and Mental Health Services Administration. Treatment Improvement Protocols for Behavioral Health.
6. National Institute of Mental Health. Ketamine and Rapid-Acting Antidepressants: Research Overview.
7. American Society of Anesthesiologists. Practice Guidelines for Preoperative Fasting. Anesthesiology. 2017.
8. Lang, E. S., Spaite, D. W., Oliver, Z. J., Gotschall, C. S., Swor, R. A., Dawson, D. E., & Hunt, R. C. (2012). A national model for developing, implementing, and evaluating evidence-based guidelines for prehospital care. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 19(2), 201–209.https://doi.org/10.1111/j.1553-2712.2011.01281.
9. Akhlaghi, N., Payandemehr, P., Yaseri, M., Akhlaghi, A. A., & Abdolrazaghnejad, A. (2019). Premedication With Midazolam or Haloperidol to Prevent Recovery Agitation in Adults Undergoing Procedural Sedation With Ketamine: A Randomized Double-Blind Clinical Trial. Annals of emergency medicine, 73(5), 462–469. https://doi.org/10.1016/j.annemergmed.2018.11.016