treating nightmares in posttraumatic stress disorder with clonidine and doxazosin

Conditions: Posttraumatic Stress Disorder

Summary: this randomized controlled trial will test the hypothesis that oral clonidine or doxazosin improves nightmares (primary outcome), other ptsd symptoms and psychopathology (secondary outcomes) to a greater extent than placebo over a ten week intervention phase in a parallel group design.


Eligibility criteria:
inclusion criteria: 1. diagnosis of posttraumatic stress disorder (ptsd) according to dsm 5 with a 20 item caps-5 total score ≥ 26 2. at least two nightmares a week, an intensity score ≥ 2, with a caps-iv b2 (frequency and intensity for the last week) score ≥ 5 3. men and women between 18 and 65 years of age 4. written informed consent 5. the patient has the capacity to give consent (he/she is able to understand the nature and anticipated effects/side effects of the proposed medical intervention) 6. the patient is not breastfeeding 7. women of child-bearing potential must have a negative urine or serum pregnancy test 8. all participants must use highly effective contraception 9. the patient received stable pharmacological medication for at least 4 weeks or at least five times the value of a elimination half-life prior to study baseline (any changes in medication dose or frequency of therapy must be answered with no). exclusion criteria: 1. disturbances of cardiac impulse formation and conduction, for example sick sinus syndrome or atrioventricular block second and third degree 2. bradycardia, with a heart rate less than 50 beats per minute 3. current major depressive episode and a madrs score \> 34 4. the patient does have a known allergy, hypersensitivity or contraindication against clonidine, doxazosin, or other types of quinazolines 5. history of severe orthostatic hypotension 6. benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary tract infection or bladder stones, hypotension (for benign prostate hyperplasia only) 7. either overflow bladder or anuria with or without progressive renal insufficiency 8. planned cataract surgery (risk of 'intraoperative floppy iris syndrome') 9. intake of phosphodiesterase-5-inhibitors 10. intake of methylphenidate 11. severe hepatic impairment (asat or alat greater than two times normal) 12. acute or unstable medical illness 13. known hiv- and/or active hepatitis-b- or hepatitis-c-infection 14. current or past malignant illness 15. the patient does have clinically significant abnormalities in 12-lead ecg 16. the patient does have clinically significant laboratory abnormalities 17. epilepsy 18. dementia 19. current substance/alcohol use disorder (≤ 3 months) 20. psychotic disorder 21. bipolar disorder 22. current anorexia nervosa 23. acute suicidality (any suicidal ideation of type of 5 in the c-ssrs in the past month) 24. intake of alpha adrenergic agents (clonidine, doxazosin, or others) within 4 weeks prior to baseline (randomization) 25. trauma-focused psychotherapy four weeks before the trial 26. initiation of sleep medication 4 weeks prior to baseline 27. the patient is unwilling to consent to saving, processing and propagation of pseudonymized medical data for study reasons 28. patients, who may be dependent on the sponsor, the investigator or the trial sites 29. the patient is legally detained in an official institution 30. the patient did participated in other interventional trials during the 3 months before and at the time of this trial

Keywords: nightmares posttraumatic stress disorder clonidine doxazosin