Patient-centred education for ketamine and esketamine therapies in mood disorders

Introduction

Treatment-resistant depression (TRD) and bipolar depression (TRBD) are severe and disabling conditions associated with marked functional impairment, reduced quality of life, elevated suicide risk and substantial health-care utilization. ¹ Conventional antidepressants and mood stabilizers often provide incomplete or delayed benefit, leaving many individuals exposed to prolonged depressive morbidity and recurrent suicidal ideation. ² These limitations underscore the urgent need for effective treatments with more rapid and robust antidepressant effects. ³

Ketamine, initially developed as a dissociative anaesthetic, and its S-enantiomer esketamine, have demonstrated rapid antidepressant and anti-suicidal effects in patients with TRD and major depression with acute suicidal ideation or behaviour. ⁴ Intranasal esketamine has been approved by regulators in several jurisdictions as an add-on treatment for TRD and, in some regions, for depression with acute suicidal ideation or behaviour, with a clinic-based, monitored administration model. ⁵ A recent double‑blind, randomized clinical trial demonstrated that esketamine monotherapy is effective for TRD, supporting its use as a stand‑alone option. ⁶ Intravenous (IV), intramuscular, subcutaneous, oral and sublingual ketamine are widely used off-label in specialist settings – delivered either as a medically monitored administration or, in some services, integrated with structured psychotherapy (ketamine-assisted psychotherapy (KAP) or ketamine combined with psychotherapy (KCP)) – with psychoeducational needs differing accordingly. These treatments are characterized by:

While TRD constitutes the majority of the available evidence base, TRBD and schizoaffective treatment-resistant depression represent clinically important contexts in which ketamine is increasingly considered, often with distinct safety and tolerability implications. ⁹ Despite this clinical momentum, no consolidated patient-centred psychoeducational framework currently exists for ketamine-based care in mood disorders, and existing safety-monitoring tools such as the Ketamine Side Effect Tool address adverse-event capture but not the broader educational needs of patients. ¹⁰ Drawing on regulatory documents, clinical trials, observational studies and qualitative research, this narrative review uniquely synthesizes patient-relevant evidence into a practical psychoeducational framework (informational domains and tools) that clinicians can embed in routine ketamine/esketamine care pathways. Finally, it highlights gaps in the evidence base and outlines priorities for future research on psychoeducational interventions in ketamine-based treatment pathways.

Methods

A selective narrative review methodology was adopted to allow integrative synthesis and critical interpretation of heterogeneous evidence spanning regulatory, clinical and experiential domains, in accordance with established guidance for narrative reviews. The conduct and reporting of the review were informed by the Scale for the Assessment of Narrative Review Articles (SANRA) framework to enhance transparency, structure and interpretability. ¹¹ A completed SANRA checklist is available as Supplemental File 1.

A targeted literature search was conducted in MEDLINE (via PubMed) and Scopus in December 2025. Search terms were iteratively developed to capture evidence on therapeutic ketamine and intranasal esketamine across mood disorders and included combinations of the following keywords: (ketamine OR esketamine) AND (depression OR ‘treatment resistant depression’ OR ‘TRD’ OR ‘bipolar depression’ OR ‘bipolar disorder’ OR ‘TRBD’)

Eligible sources included:

Studies were excluded if they:

Rationale for patient-centred education in ketamine-based treatment

While the Ketamine Side Effect Tool (KSET) provides a rigorously developed, four-form instrument for systematic capture of acute and longer-term adverse events, it is limited to safety monitoring and does not address the broader educational needs of patients, such as treatment expectations, preparation procedures, substance-misuse counselling or family-involvement strategies that are essential for safe and effective ketamine/esketamine care. ¹⁰

Core content of psychoeducation

Preparation for the visit and treatment setting

While the core preparatory instructions outlined below apply across delivery models, the framing and emphasis of pre-session education differ meaningfully between medically monitored infusion settings and psychotherapy-integrated approaches (KAP or KCP). In the latter, preparation additionally encompasses intention-setting, a discussion of how to relate to emerging emotional or perceptual material, and clarification of the therapist’s role during the dosing session; these elements are addressed further in ‘Educational models and therapeutic context’ Section. Key preparatory instructions can be summarized for patients (Table 1).

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Table 1.

Practical patient instructions before, during and after (es)ketamine sessions.

Time point	Key instructions for patients
Before starting treatment	Share a full medical and psychiatric history, including heart diseases, high blood pressure, liver or kidney problems, bladder symptoms, seizures and substance use. Provide a complete list of prescribed medications, over-the-counter drugs and herbal supplements. Agree on a visit schedule you can realistically attend (including transport and support at home).
Day before each visit	Arrange for a family member, friend or carer to accompany you or collect you after treatment. Plan your day so you can stay in the clinic for about 3 h.
On the treatment day – before arrival	Do not drink alcohol or use recreational drugs. Do not take benzodiazepines or sedative medications on the morning of treatment unless your psychiatrist specifically approves this.
Immediately before dosing (in the clinic)	Avoid solid food for at least 2 h and liquids for 30 min before dosing to reduce nausea. If you use a nasal steroid or decongestant, take it at least 1 h before esketamine; do not use it immediately before or after dosing. Tell staff if you feel unwell (e.g. fever, chest pain, severe cold). Switch your phone to silent; you may be allowed to listen to quiet music with headphones.
During the session	Stay seated or reclined in the treatment chair or bed. Expect possible short-lived sensations such as feeling detached, light-headed, or as if time and space are distorted; try to observe these calmly. Tell staff immediately if you experience severe anxiety, chest pain, difficulty breathing or intense nausea.
Observation period after dosing	You will remain under supervision for at least 1.5–2 h. Staff will check your blood pressure, pulse, oxygen level and alertness regularly. Move slowly and ask for help before standing up. Avoid making major decisions or signing important documents while you still feel affected.
After discharge (rest of the day)	Do not drive, ride a bicycle in traffic, operate machinery or engage in hazardous activities until the next day after a full night’s sleep. Avoid alcohol and non-prescribed sedatives. Contact your treatment team urgently if you notice marked mood worsening, suicidal thoughts, severe urinary pain or persistent confusion.
Between visits	Take your regular antidepressants or mood stabilizers as prescribed unless your doctor advises otherwise. Monitor for new or worsening side effects (e.g. bladder symptoms, severe headaches, sudden mood elevation, craving for ketamine or changes in thinking or perception) and report them promptly. Ask family or carers to let you and your team know about any sudden changes in mood, behaviour or safety.

The physical setting should be a low-stimulation environment: dim lighting, minimal noise and limited interruptions. ¹⁹ Complete sensory deprivation is not recommended, as it can intensify dissociation; a balanced, calming environment is preferable.

How to deliver patient education: Modalities and models

Psychoeducation in ketamine- and esketamine-based treatment should be conceptualized as an ongoing, structured process rather than a single pre-treatment consent discussion. Given the rapid onset of effects, the distinctive subjective experiences and the clinic-based delivery model, effective education requires repetition, multimodal reinforcement and adaptation to patient characteristics and service context

Implementation and service-level considerations

From a service perspective, embedding patient education into ketamine pathways requires:

Staffing models typically rely on psychiatrists or other physicians experienced in ketamine treatment, supported by psychiatric nurses or other trained HCPs. Current safety data suggest that, in medically stable patients receiving sub-anaesthetic doses, routine involvement of an anaesthesiologist is not necessary if appropriate monitoring and emergency protocols are in place. Services offering psychotherapy-integrated models (KAP or KCP) in addition require staff trained in psychotherapeutic facilitation of altered states, including preparation, in-session support and structured post-session integration – competencies that extend beyond the medical and nursing training sufficient for monitored infusion settings.

Future directions

Key research gaps include:

More broadly, the field is increasingly moving toward precision psychiatry approaches, in which clinical, phenotypic and emerging biological markers may help identify which patients are most likely to benefit from ketamine-based therapies, although such approaches remain at an early stage of development. ³⁴

Discussion

This narrative review synthesizes evidence from regulatory documents, clinical trials, observational studies and qualitative research to propose a patient-centred psychoeducational framework for (es)ketamine-based treatment in mood disorders. The central finding is that psychoeducation is not a peripheral or optional component of care but a core clinical responsibility, one that is structurally underprovided in current service models. While existing instruments such as the KSET address adverse-event surveillance, ¹¹ no consolidated framework has previously defined the broader informational and relational needs of patients receiving these treatments – including expectation management, visit preparation, misuse risk counselling and tailored guidance for special populations.

What patients know, expect and are prepared for before and during treatment emerges as a consistent determinant of acceptability, engagement and perceived benefit. The acute dissociative and perceptual effects that accompany ketamine administration are not merely side effects to be monitored, but experiences that require contextualization and preparation. ²⁰ When inadequately explained, these effects may provoke anxiety, loss of trust or premature discontinuation; when anticipated and normalized, they are more likely to be tolerated and integrated into the overall treatment process. ³⁵ This reframes psychoeducation as a core clinical responsibility sitting at the intersection of prescribing practice and psychological care – yet one that current regulatory frameworks leave structurally under-specified. Prescribing authority is typically embedded within structures that emphasize medical oversight, safety monitoring, and risk mitigation, ⁵ with little guidance on preparation for acute psychoactive effects, management of distress during sessions or post-session integration. Where formal psychotherapeutic support is absent, the prescriber’s role consequently expands, often implicitly, beyond traditional biomedical boundaries. ²⁷

Three mutually reinforcing mechanisms explain how psychoeducation may determine whether ketamine’s rapid pharmacological effects translate into sustained, acceptable clinical benefit. First, drawing on predictive-processing frameworks, psychoeducation recalibrates patients’ prior expectations about the likely time-course and variability of response and the meaning of acute dissociative experiences, reducing the likelihood that expected, time-limited drug effects are misinterpreted as danger or treatment failure. ²⁹ Second, consistent with the concept of set and setting, psychoeducation optimizes the treatment context by making the monitoring environment and session structure predictable, thereby reducing uncertainty during periods when dissociation and haemodynamic effects are most prominent. ³¹ Third, because ketamine and esketamine are delivered through repeated, supervised sessions, psychoeducation functions as a longitudinal relationship-building process that supports the therapeutic alliance, sustaining engagement and continuity across visits rather than operating as a one-time consent event. ³⁰ Through these mutually reinforcing mechanisms, psychoeducation may determine whether pharmacological effects translate into sustained and clinically meaningful benefit. ³²

Importantly, existing safety-focused instruments such as the KSET provide robust frameworks for adverse-event monitoring ¹¹ but do not address broader psychoeducational domains, including expectation management, visit preparation, family involvement or substance misuse counselling. ²³ The present review suggests that this gap reflects a broader structural divide between regulatory priorities, often centred on pharmacovigilance and controlled access, and the lived realities of patient care, which require a more relational and context-sensitive approach. Bridging this divide may require clearer delineation of roles within interdisciplinary teams, including how responsibilities for psychological safety and patient education are distributed between prescribers, nurses and mental health professionals. ²⁷

Qualitative studies consistently demonstrate that patients approach ketamine treatment with a complex mixture of hope, desperation and apprehension, frequently framing it as a ‘last resort’ intervention.^9,16 Media portrayals and direct-to-consumer messaging further shape expectations, often emphasizing dramatic benefits while minimizing uncertainty or limitations. ¹³ In this context, psychoeducation serves several critical functions: correcting unrealistic beliefs, contextualizing ketamine within broader treatment pathways, normalizing transient dissociative experiences and supporting informed consent and shared decision-making. Studies exploring patient experiences with intranasal and oral esketamine suggest that clarity, continuity of care and a predictable treatment environment enhance perceived safety and acceptability. ¹⁹

The structured educational framework proposed in this review aligns with principles of shared decision-making and informed consent, while also acknowledging the practical realities of clinic-based ketamine delivery. ⁵ Embedding psychoeducation into standard operating procedures, staff training and service-level quality indicators may reduce preventable adverse experiences, improve adherence and support more sustainable treatment engagement. ⁹ At the same time, integrating education with psychotherapy or psychological support may help bridge biological and experiential models of care, particularly in patients who seek meaning-making around their ketamine experiences. Future models of care may benefit from more explicitly defined interdisciplinary structures in which prescribing authority, psychological support and patient education are coordinated rather than siloed, thereby enhancing both safety and therapeutic coherence. ²⁷

Conclusions

Ketamine and esketamine represent important additions to the therapeutic armamentarium for mood disorders, particularly for individuals with TRD. Their safe, ethical and effective use, however, depends not only on pharmacological efficacy but also on the quality of patient education that accompanies treatment delivery.

This narrative review synthesizes current evidence to outline a structured, patient-centred approach to psychoeducation in ketamine-based care, encompassing expectation setting, practical preparation, adverse-event management, substance misuse risk and tailored counselling for special populations. Key elements include a clear explanation of indications and treatment goals, practical guidance on visit scheduling and preparation, a detailed discussion of common AEs and how to cope with them, explicit attention to substance misuse risk and suicidality, and tailored counselling for pregnancy, breastfeeding and comorbid medical conditions.

Beyond identifying gaps, the findings support several practical recommendations. Policymakers and professional bodies should consider defining minimum psychoeducation standards for ketamine services, incorporating core informational domains into routine care. Training frameworks should include not only medical management but also communication about psychoactive effects and management of psychological distress. Clearer delineation of interdisciplinary roles is needed to ensure responsibility for both medical and psychological safety. In addition, more standardized service models or accreditation pathways may help reduce variability in care delivery.

Standardizing these educational components and embedding them into service protocols can help clinicians deliver ketamine/esketamine therapy that is safer, more acceptable to patients and more likely to result in sustained benefit.

Supplemental Material