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 forsurgical treatment

• 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, manicdepression)

• 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-steroidal anti-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 and pregabalin, the usage may also be continued during this study.