Vagus Nerve Stimulation (VNS) Guide: Benefits, Risks & Candidate Assessment
Vagus Nerve Stimulation (VNS) is an implanted neuromodulation treatment used in selected adults with severe, chronic or recurrent treatment-resistant depression when multiple standard treatments have not provided enough improvement. A small pulse generator is surgically implanted beneath the skin of the chest and connected to the left vagus nerve in the neck, where it delivers programmed electrical signals that influence brain networks involved in mood regulation. This comprehensive guide explains how VNS works, who may be considered, the surgical procedure, expected treatment timeline, common side effects, device and anesthesia risks, long-term programming and follow-up, and important alternatives to consider before implantation. It also includes a scoreable candidate-discussion questionnaire with an automated summary to help patients prepare for consultation with a psychiatrist and VNS specialist.
Ketamine • Esketamine / Spravato • Treatment-Resistant Depression • Candidate Assessment
Complete Guide to Ketamine & Esketamine Treatment
A detailed patient guide to ketamine-based depression treatment, including IV racemic ketamine, FDA-approved intranasal esketamine (Spravato), treatment-resistant depression, rapid antidepressant effects, treatment schedules, dissociation, blood-pressure monitoring, abuse/misuse risk, medical contraindications, and a comprehensive scoreable candidate-discussion questionnaire.
Mark Zauss, BC-TMC, LMHC, LPC, CCMHC, NCC, ASDCS, CCTP, CCTP II, NATC, ADHD-CCSP, C-DBT, C-PD
Educational decision-support resource. This worksheet does not prescribe ketamine/esketamine, establish medical eligibility, or replace evaluation by a qualified prescriber.
Educational decision-support resource. This worksheet does not prescribe ketamine/esketamine, establish medical eligibility, or replace evaluation by a qualified prescriber.
Ketamine and esketamine are related—but not the same treatment
Racemic Ketamine
Ketamine is a Schedule III medication FDA-approved as an anesthetic. IV, IM, oral, or sublingual ketamine may be used off-label by clinicians for depression, but ketamine itself is not FDA-approved for a psychiatric disorder. Evidence is strongest for carefully monitored subanesthetic IV treatment in treatment-resistant depression.
Esketamine (Spravato)
Esketamine is one component of ketamine and is administered as a nasal spray. FDA labeling allows Spravato for adult treatment-resistant depression as monotherapy or with an oral antidepressant, and for depressive symptoms in adults with MDD and acute suicidal ideation or behavior in conjunction with an oral antidepressant. citeturn517284search17
Regulatory distinction: A clinic should clearly tell patients whether it is offering FDA-approved esketamine, off-label racemic ketamine, or a compounded preparation. These are not interchangeable from a regulatory, evidence, monitoring, or insurance standpoint.
The molecules are related, but the route, FDA status, evidence base, monitoring framework, and insurance coverage can differ substantially.
How may ketamine reduce depression?
Ketamine and esketamine act primarily through the glutamate system and NMDA-receptor modulation rather than through the serotonin reuptake mechanism used by many conventional antidepressants. Their downstream effects appear to involve AMPA signaling, synaptic plasticity, and changes in brain-network function. The exact antidepressant mechanism remains an active area of research.
Why are they considered?
Treatment Resistance
Ketamine/esketamine may be considered when adequate antidepressant strategies have not produced sufficient improvement.
Rapid Antidepressant Effect
Some patients improve much faster than with conventional antidepressants, although rapid response is not guaranteed and may not persist without continuation treatment.
Different Mechanism
The glutamatergic mechanism gives clinicians another treatment pathway when standard monoamine-based medications have been insufficient.
Spravato safety and monitoring
The FDA label carries warnings for sedation, dissociation, respiratory depression, abuse/misuse, and suicidal thoughts/behaviors in certain younger patients. Spravato is dispensed and administered through a restricted REMS program, and patients are monitored for at least two hours after administration. citeturn170939view3
| Issue | Why it matters |
|---|---|
| Blood pressure | Esketamine can temporarily raise blood pressure; BP is assessed before dosing and again after treatment. |
| Dissociation / sedation | Altered perception, detachment, sleepiness, dizziness, or feeling “drunk” can occur temporarily. |
| Driving | Spravato labeling instructs patients not to drive or operate machinery until the next day after a restful sleep. |
| Respiratory monitoring | Patients are observed for respiratory changes during the required monitoring period. |
| Abuse / misuse | Ketamine and esketamine are Schedule III controlled substances and require careful assessment in people at higher risk of misuse. |
Important contraindications and medical cautions
For Spravato, formal contraindications include aneurysmal vascular disease or arteriovenous malformation, a history of intracerebral hemorrhage, and hypersensitivity to esketamine/ketamine or product ingredients. Other cardiovascular and cerebrovascular conditions, elevated baseline blood pressure, pregnancy, liver impairment, medications, and substance-use history may alter treatment planning. citeturn170939view1turn170939view2
Ketamine/esketamine is not a substitute for emergency psychiatric care. FDA labeling specifically notes that improvement after Spravato does not eliminate the need for hospitalization when hospitalization is clinically warranted. citeturn170939view2
What treatment may feel like
Perception
Some patients experience detachment, altered time or space perception, dreamlike sensations, or changes in sensory experience.
Physical Effects
Dizziness, nausea, sedation, numbness/tingling, temporary blood-pressure elevation, or headache can occur.
After Treatment
Patients may feel tired or cognitively slowed for a period afterward. Transportation planning is important.
Psychological Integration
Some clinics pair treatment with psychotherapy or integration sessions, but ketamine-assisted psychotherapy is not the same as FDA-approved Spravato treatment and evidence varies by approach.
Patient information
Ketamine / Esketamine Candidate-Discussion Questionnaire
Rate each statement based on your current situation. Higher scores indicate a stronger discussion profile for a formal medical consultation—not medical eligibility, insurance authorization, or likelihood of response.
0 = Not at all1 = A little2 = Moderately3 = Strongly4 = Very strongly
Safety, Medical & Differential Screening
These items are not included in the score. They identify issues requiring direct prescriber review.
Results
Complete the questionnaire and calculate your profile.
| Profile | Interpretation |
|---|---|
| 0–39% | Limited current fit based on answered items; standard-treatment optimization, medical factors, or expectations may need attention. |
| 40–59% | Mixed profile; formal consultation may still be reasonable depending on diagnosis and prior treatment. |
| 60–79% | Strong discussion profile for a qualified ketamine/esketamine clinician if safety screening is acceptable. |
| 80–100% | Very strong discussion profile while still requiring individualized medical evaluation and product/route-specific eligibility. |
Automated AI-Style Summary
This summary organizes answers; it does not prescribe treatment, determine eligibility, or replace a qualified prescriber.
No summary generated yet.
Questions to ask a ketamine/esketamine clinic
Which Treatment?
Are you recommending IV ketamine, IM ketamine, compounded oral/sublingual ketamine, or Spravato? Is the use FDA-approved or off-label?
Monitoring
How are blood pressure, oxygenation, dissociation, sedation, and psychiatric symptoms monitored?
Evidence & Schedule
What induction and maintenance schedule do you use, and what evidence supports that protocol?
Safety & Follow-up
How do you screen for bipolar disorder, psychosis, cardiovascular disease, substance-use risk, pregnancy, urinary problems, and relapse?
APA-style clinical resources
- U.S. Food and Drug Administration. (2025). Spravato (esketamine) nasal spray prescribing information.
- U.S. Food and Drug Administration. (2025). Supplement approval: Spravato (esketamine) for treatment-resistant depression as monotherapy.
- U.S. Food and Drug Administration. (2026). Warning letters concerning unapproved ketamine products marketed for psychiatric treatment.
- American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.; DSM-5-TR). American Psychiatric Association Publishing.
- Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., Summergrad, P., & Nemeroff, C. B. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry, 74(4), 399–405.
- McIntyre, R. S., Rosenblat, J. D., Nemeroff, C. B., et al. (2021). Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: An international expert opinion on the available evidence and implementation. American Journal of Psychiatry, 178(5), 383–399.