Ketamine-Assisted Psychotherapy (Spravato® & Generic Protocols) protocol

Compound: Ketamine

Status: clinical

FDA-approved treatment for treatment-resistant depression with REMS protocol requirements

Dosing

Dose: 56mg or 84mg

Route: Spravato® (Esketamine) Nasal

Duration: 2-hour REMS observation

Sessions: Twice weekly x4 weeks (induction), then weekly/biweekly (maintenance)

Dose: 0.5 mg/kg over 40 minutes

Route: IV Ketamine Infusion

Duration: 40-minute infusion + 60-minute recovery

Sessions: 6 sessions over 2-3 weeks (induction)

Dose: 0.5-1.0 mg/kg

Route: IM Ketamine

Duration: 20-minute onset, 45-60 minute experience

Sessions: Per clinician protocol

Dose: 100-300mg sublingual

Route: Sublingual/Oral (Off-label)

Duration: 30-minute onset, 60-90 minute experience

Sessions: At-home protocols with telehealth supervision

Safety

Monitoring: Continuous observation during treatment. Blood pressure monitoring every 15 minutes. Pulse oximetry continuous. Emergency equipment accessible. Patient must not drive for 24 hours post-treatment.

Side effects

  • Dissociation
  • Elevated blood pressure
  • Nausea
  • Dizziness
  • Headache
  • Perceptual disturbances
  • Anxiety
  • Sedation

Abort criteria

  • Sustained BP >200/120 despite intervention
  • Severe respiratory depression (SpO2 <90%)
  • Severe agitation unresponsive to reassurance
  • Allergic reaction signs
  • Patient request to stop

Contraindications

  • Uncontrolled hypertension (>180/110)
  • Recent stroke or MI (<6 weeks)
  • Aneurysm or AV malformation
  • Active psychosis or mania
  • Pregnancy or breastfeeding
  • Known ketamine hypersensitivity

Rems requirements: Spravato® requires: REMS-certified healthcare setting, 2-hour post-dose monitoring, patient enrollment in REMS program, healthcare provider REMS certification

Overview

Mechanism: NMDA receptor antagonism leading to rapid glutamate surge, enhanced BDNF expression, and synaptogenesis. Dissociative properties may facilitate psychological flexibility during therapy.

Indications

  • Treatment-Resistant Depression (TRD)
  • Major Depressive Disorder with suicidal ideation
  • Acute suicidal ideation (Spravato REMS)

Evidence level: Level 1 - FDA Approved (Spravato), Level 2 - Off-label IV/IM

Contraindications

  • Uncontrolled hypertension
  • Aneurysmal vascular disease
  • Intracerebral hemorrhage history
  • Known hypersensitivity to ketamine/esketamine
  • Pregnancy
  • Current psychotic disorder

Citations

Doi: FDA Approval NDA 211243

Year: 2019

Title: Efficacy and Safety of Esketamine Nasal Spray (Spravato) - FDA Approval

Doi: 10.1016/j.biopsych.2020.01.027

Year: 2020

Title: Ketamine for Treatment-Resistant Depression: A Systematic Review

Doi: 10.1038/s41386-018-0023-y

Year: 2018

Title: NMDA Receptor Mechanisms in Depression

Doi: 10.3389/fpsyt.2021.672103

Year: 2021

Title: Music Selection for Ketamine-Assisted Psychotherapy

Doi: 10.1016/j.neuron.2019.01.021

Year: 2019

Title: Ketamine and Rapid-Acting Antidepressants: BDNF Signaling

Data export

Fields

  • Session date
  • Protocol used
  • Dosing
  • Vitals timeline
  • Mood pre/post
  • Therapeutic themes detected
  • Transcript excerpts (de-identified)
  • Integration notes

Formats

  • PDF (patient chart)
  • CSV (research)
  • JSON (EHR integration)

Fhir ready: true

Integration

Prompts

  • What insights from your session feel most significant?
  • How has your perspective on [presenting concern] shifted?
  • What practices help maintain the benefits?
  • Any challenges integrating the experience?

Homework

  • Daily mood tracking (0-10 scale)
  • Journaling: 10 minutes reflecting on session insights
  • Sleep hygiene optimization
  • Physical activity 30min/day

Framework: 24-48 hour follow-up session recommended. Integration focuses on processing insights, reinforcing perspective shifts, and connecting experiences to therapeutic goals. Use standardized mood scales to track progress.

Follow up structure

  • 24-48hr: Initial integration session (30-60 min)
  • 1 week: Progress assessment, PHQ-9/GAD-7
  • 2 weeks: Treatment response evaluation
  • Monthly: Maintenance and relapse prevention

Preparation

Screening

  • Complete psychiatric evaluation (PHQ-9, GAD-7, C-SSRS)
  • Medical history with focus on cardiovascular risk
  • Blood pressure baseline (seated and standing)
  • Pregnancy test for patients of childbearing potential
  • Review of concurrent medications (MAOIs, CNS depressants)
  • Informed consent documentation
  • REMS enrollment (Spravato only)
  • Designated driver/transport arranged

Set setting: Clinical setting with recliner/treatment chair, blood pressure monitoring equipment, pulse oximeter, crash cart access, quiet environment with adjustable lighting, optional music system with curated playlists

Consent template: Standard ketamine-assisted therapy informed consent covering: mechanism of action, expected effects (dissociation, perceptual changes), monitoring requirements, REMS obligations (Spravato), potential side effects, and transportation restrictions.

Clinical mode: true

Session execution

Music: Evidence-based playlists: Johns Hopkins Psilocybin Research playlist (adapted), Mendel Kaelen curated selections, or patient-selected calming instrumental music without lyrics

Timeline

  • T-30min: Baseline vitals, PHQ-9/GAD-7, set intentions
  • T-0: Medication administration
  • T+15min: Blood pressure check #1
  • T+30min: Blood pressure check #2, assess dissociation
  • T+45min: Blood pressure check #3
  • T+60min: Blood pressure check #4, begin integration discussion
  • T+90min: Final vitals, discharge assessment (Spravato: 2hr minimum)

Monitoring: Blood pressure every 15 minutes for first hour, then every 30 minutes. Document any BP >180/110 or symptoms of hypertensive crisis.

Environment: Eyeshades optional, comfortable reclined position, minimize external stimulation, therapist present but non-directive during peak experience

Voice logger integration

Prompts

  • What emotions are present right now?
  • Any shifts in perspective on your depression?
  • What body sensations are you noticing?
  • Any new insights about relationships or self-worth?
  • What would you like to remember from this experience?
  • Is there anything you feel ready to let go of?
  • What feels different about how you see yourself?
  • Any messages or realizations coming through?

Export pdf: true

Clinical mode: true

Hide archetypes: true

Pre session mood scale: true

Theme detection labels

  • grief
  • self-criticism
  • hope
  • acceptance
  • relationship patterns
  • self-worth
  • meaning
  • connection
  • release
  • insight

Post session mood scale: true

Reference material only. Nothing on this page is medical advice or a personal recommendation.

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