TABLE 2.

Recommendations aimed at improving patient safety and care in trials or off-label treatment with (es)ketamine.

Preparation
Instructions	Provide clear instructions on timing, nature, intensity, and unpredictability of a wide range of subjective effects
Neutral terminology	Use neutral terminology rather than verbiage with negative associations (“side effects”). It can be useful to remind patients to keep an open mind regarding any potential therapeutic effects
Promote acceptance	Instruct patients about the potential “loss of control” during the acute phase, and the value of accepting difficult emotions, thoughts, memories rather than resisting these
Calming techniques	Instruct and practice simple techniques related to surrendering to the experience: mindfulness or breathing exercises, hand holding etc.
Calm, open-minded	Support patients to enter each session calmly, and with a clear and open mind
Minimize anxiety	Remind patients about the transient nature of (negative) experiences, and the fact that they’re in safe hands and in a safe environment
Expectation management	Manage/minimize expectations about the content of the acute ketamine sessions, and about any potential outcomes of the treatment
Support
Therapeutic rapport	Establish rapport with staff or others who will be present during and after dosing sessions
Physical presence	Ensure physical presence of nursing staff, particularly during early (low-dose) sessions, and upon patient request
Partners or relatives	Partners, relatives or friends can be a source of comfort and calm during sessions (both clinically and for at-home use)
Debriefing/integration	Availability of clinical stuff to help patients debrief, remember fleeting experiences, and discuss potentially transformative or overwhelming experiences
Hand holding/touch	Holding hands can be reassuring when patients experience distress or anxiety (however: always discuss beforehand)
Validation	Take experiences seriously, either through integratory talks or by facilitating interaction or discussion with other patients
Setting
Music	Offer the use of calming music, and the possibility of (noise cancelling) headphones
Privacy, stimulus-free	Ensure privacy, minimize interruptions, and measurements around dosing sessions
Comfort	Provide a warm, comfortable environment (blankets, pleasant surroundings, possibility to lay down, etc.)
Optimizing home setting	Provide suggestions on ideal home setting (e.g., privacy, reducing external stimuli, avoiding distractions by others, the use of music, suggesting strategies on mitigating undesirable effects; acutely, post-acutely, and over the next days)