Frequently asked questions about treatment-resistant depression and esketamine
What is treatment-resistant depression?
Treatment-resistant depression is generally defined as an inadequate clinical response after trying at least two different antidepressants at adequate doses and duration, under medical supervision. In these situations, a more comprehensive evaluation is recommended to reassess diagnosis, contributing factors, and advanced strategies.
How do I know if my case may be treatment-resistant depression?
It is usually considered when two well-conducted medication trials (or combinations) have not provided sufficient improvement and symptoms continue to impair functioning. Confirmation requires a clinical evaluation, including history, adherence, comorbidities, differential diagnosis, and review of the treatment plan.
What is esketamine and what role can it play in treatment-resistant depression?
Esketamine has a different mechanism compared to traditional antidepressants, involving NMDA receptors and neuroplasticity pathways. In selected patients, it may be considered as part of an individualized strategy for treatment-resistant depression, after careful medical assessment.
What is the difference between parenteral esketamine and intranasal esketamine (Spravato®)?
Esketamine can be administered through different routes. Intranasal esketamine (Spravato®) is an approved formulation for specific indications. Parenteral routes (IV/IM/SC) may be used off-label when carefully indicated, supported by scientific rationale, documented in the medical record, and accompanied by informed consent, with appropriate monitoring and a safe clinical setting.
Is parenteral esketamine “off-label”? Is it allowed?
Yes, parenteral esketamine for treatment-resistant depression may be off-label. Off-label use is not inherently prohibited, but it requires careful indication, clinical justification, proper documentation, and informed consent, as well as safety protocols and monitoring in an appropriate medical environment.
Does Intrador replace my psychiatrist?
No. Treatment-resistant depression should be managed through integrated care. Intrador focuses on medical evaluation, safety, monitoring, and, when indicated, supervised administration of advanced therapies, in coordination with ongoing psychiatric care.
What happens during the evaluation before considering esketamine?
The evaluation includes reviewing medical history, prior treatments, comorbidities, risk factors, differential diagnosis, and discussing alternatives. The goal is to determine whether esketamine may be appropriate and what safety measures are needed. Not every patient is a candidate.
How does supervised administration work and why is observation required afterward?
When indicated, administration should occur in a clinical setting with trained staff and monitoring. Observation is required because transient effects may occur, such as sedation, dizziness, perceptual changes/dissociation, or temporary increases in blood pressure, and to ensure safe discharge.
What are the most common side effects?
Possible effects include dizziness, nausea, sleepiness/sedation, perceptual changes/dissociation, and transient increases in blood pressure. Severity and duration vary. Monitoring protocols and guidance (including not driving on the day of treatment) are part of safety standards.
Who should not use esketamine?
Eligibility depends on medical evaluation. Caution is generally required in uncontrolled hypertension and active cerebrovascular conditions, and in patients with a history of psychosis, bipolar disorder, or substance misuse. Decisions are individualized.
How soon might improvement occur?
Some studies suggest a faster onset in selected patients, but response varies. There is no guaranteed outcome, and ongoing follow-up is essential to assess benefits, risks, and next steps.
How can I schedule a medical evaluation?
The first step is scheduling a specialized medical evaluation to review your history and define the most appropriate plan. The team can guide you on preparation and the information needed for the appointment.
Clinically Reviewed by:
Dr. Helio Widson Alves Pinheiro
Pain Medicine | Acupuncture
CRM/PE 21167 | RQE 2217, 2808
This content is informative and does not replace individual medical evaluation.
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Fundador da Clínica Intrador, médico especialista em Medicina da Dor e Acupuntura, com atuação em tratamentos intervencionistas e neuromodulação.
Note: This content is for educational and informational purposes only. The information is based on scientific evidence and the clinical practice of the Intrador team, but it does not replace individualized medical evaluation. Conduct, indications, and treatments must be defined after medical consultation.
Clinical reviewer: Dr. Helio Widson Alves Pinheiro · Pain Medicine | Acupuncture · CRM/PE 21167 | RQE 2217, 2808
Published on: January 17, 2026
Reviewed on: January 29, 2026
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