Esketamine as Treatment for Chronic Pain Due to Endometriosis: a RCT Study

Inclusion Criteria:

• Women
• All pre-menopausal women aged above 18 years
• Diagnosed with endometriosis (ultrasound, MRI or previous laparoscopic and/ordiagnostic surgery) according to the #Enzian classification [52]. This means thatendometriosis is present in the following compartments:
• Rectovaginal space (minimal A1) and/or
• Sacrouterine ligaments, cardinal ligaments, pelvic sidewall (minimal B1) and/or
• Rectum (minimal C1) and/or
• Endometriosis of the intestines, diaphragm and/or
• Adenomyosis (according to the morphological uterus sonographic assessment (MUSA)or evident adenomyosis on the MRI) [53, 54] and/or
• Peritoneal / superficial endometriosis (diagnosed laparoscopically and nottreated during surgery).
• Mild to severe chronic pelvic pain (NRS scale >= 6). The 11-point NRS scale rangesfrom '0' representing no pain to '10' representing the worst pain imaginable.
• Resistant to current recommended lines of analgesics (paracetamol, NSAIDs)
• Usage of strong opioids must not have been prescribed or otherwise have beendiscontinued for more than 1 week.
• An indication for endometriosis resection surgery or on the waiting list for surgicaltreatment
• Ability to understand the patient information letter and to give oral and writteninformed consent
• No alteration in the utilization of hormonal therapy ≤1 months prior to inclusion.

Exclusion Criteria:

• Pain score <6 out of 10 (NRS) for chronic pelvic pain
• Endometriosis affecting the bladder and ureter
• Increased intracranial pressure
• Poorly regulated hypertension, >180/100mmHg at rest
• Patients with thyroid disease
• Patients with cancer
• History of psychiatric illness (schizophrenia, psychosis, delirium, manic depression)
• Serious medical disease (e.g., cardiovascular, renal , pulmonary or liver disease)
• Severe liver disease
• Patients with glaucoma
• Usage of strong opioid medication
• Usage of xanthine derivatives or ergometrine
• Unstable angina, heart failure, history of cerebral vascular accident (CVA)
• Patients suffering from an active infection
• Patients with epilepsy
• Patients trying to achieve pregnancy and or patients who are breastfeeding
• Not being able to answer questionnaires (in Dutch)
• Mentally incompetent (patients not able to make decisions that are in their bestinterests, this will be evaluated by their treating physician (e.g. patients with anintellectual disability or mental retardation))
• Alcohol or drug abuse
• Patient with a known (es)ketamine allergy
• Abnormal liver enzyme levels at baseline (ASAT, ALAT, GGT, AF, Bilirubin total) Patients are allowed to continue the following pain medications: paracetamol, non-steroidalanti-inflammatory drugs as described previously by Sigtermans et al. (Trial NL466 (NTR507))* according to their stable use in dose and frequency.

*in case of tramadol, amitriptylin, selective serotonin reuptake-inhibitors, gabapentin andpregabalin, the usage may also be continued during this study.