New provocation test using MDMA (‘Ecstasy’) demonstrates Oxytocin deficiency in patients with central diabetes insipidus

C. Atila*^a (Dr), R. Murugesu^a (Mr), F. Holze^a (Dr), N. Varghese^a (Ms), A. Eckert^a (Prof), M. Liechti^a (Prof), M. Christ-Crain^a (Prof)

^a University Hospital Basel, Basel, SWITZERLAND

* cihan.atila@usb.ch

Introduction Arginine vasopressin (AVP) and Oxytocin (OT) are produced in the hypothalamus and released from the posterior pituitary. Central diabetes insipidus results from AVP deficiency, leading to polyuria and polydipsia. Whether patients with diabetes insipidus also have OT deficiency remains unclear since basal measurement of OT is not reliable, and no OT provocation test is available. Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) leads to a marked increase in circulating OT levels in healthy adults and could therefore be useful as a novel provocation test to reveal an OT deficiency in patients with diabetes insipidus.

Materials/Methods Randomized, double-blind, placebo-controlled, cross-over study in patients with diabetes insipidus and healthy controls. The primary objective was to investigate whether the oxytocin response (measured at baseline and after 90, 120, 150, 180, 300 minutes) to a single oral dose of MDMA (100mg) differentiates between diabetes insipidus and healthy controls. Psychological evaluation was performed using the State-Trait Anxiety Inventory (STAI) for anxiety and Toronto-Alexithymia-Scale 20 (TAS-20) for alexithymia at baseline. Emotion recognition was assessed using the Facial Emotion Recognition Test (FERT) at 150 minutes.

Results In total, 15 patients with diabetes insipidus and 15 healthy controls were included at the University Hospital Basel, Switzerland. In healthy controls, the median [IQR] OT level at baseline was 77 [59-94] pmol/ml and increased upon MDMA stimulation by 603 [335-914] pmol/ml, whereas, in patients with diabetes insipidus, the OT level at baseline was 60 pmol/ml [51-74] and remained stable i.e., only increased by 66 [14-94] pmol/ml, resulting in a group difference of 538 pmol/l (95%CI [359-716]; p<0.01). Psychological evaluation showed higher median scores for anxiety (40 points [30-46] vs 28 points [25-31], p<0.01) and alexithymia (47 points [37-59] vs 30 points [29-35], p<0.01), and lower rates of correct emotion recognition in ‘angry’ and ‘fearful’ faces in patients compared to healthy controls (p=0.04, p=0.03).

Discussion: We hereby prove for the first time an OT deficiency in patients with central diabetes insipidus correlating with psychopathological findings.

The author has declared no conflict of interest.