Prazosin Use in Adults With Anxiety Disorders

Anxiety Clinical Trial

Official title:

Open Label 8-Week Study of Prazosin Use in Adults With Anxiety Disorders

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03894345
• Other study ID #: HS21444 (B2018:002) PRA2051N
• Status: Suspended
• Phase: Phase 1
• Start date: May 24, 2019
• Est. completion date: December 2023

Study information

• Verified date: October 2022
• Source: University of Manitoba
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prazosin has shown effectiveness in treating Post-Traumatic Stress Disorder through improving sleep quality and global functioning. Given the significant evidence for its utility in treating PTSD, in combination with the fact that many anxiety symptoms overlap with PTSD (e.g.insomnia, hyperarousal, and irritability), it is essential to evaluate its potential effectiveness in treating symptoms of other anxiety disorder and patient tolerability.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 20
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Existing Diagnosis of any anxiety disorder according to DSM-5 criteria (i.e. GAD, Panic Disorder, Agoraphobia, Social Phobia or Specific phobias)

2. Newly diagnosed patients or patients who are either resistant or not adherent to their current treatment are eligible to be enrolled in the study.

3. If patient is on anti-hypertensive therapy, the dose of anti-hypertensive(s) must be stable for at least 4 weeks prior to the study and blood pressure must be well controlled.

Exclusion Criteria:

1. Patients with comorbid condition of psychosis, a diagnosis of PTSD, an active severe substance use disorder, or actively suicidal.

2. Patients actively enrolled in psychotherapy sessions at the time of the study.

3. Patients experiencing baseline systolic blood pressure =100 mmHg supine, orthostatic hypotension (a decrease in systolic blood pressure from a sitting position of 20 mmHg or more after 2 minutes standing accompanied with light-headedness), or a baseline diastolic blood pressure less than 60 mmHg.

4. Pregnant or lactating women.

5. Patients with acute medical or psychiatric conditions that require immediate hospital admission.

6. Patients with a history of allergic reaction to prazosin or any of its components.

7. Patients unable to communicate in English.

8. Patients who are scheduled to undergo cataract surgery are excluded from the study until after the surgery has been completed.

Related Conditions & MeSH terms

• Anxiety
• Anxiety Disorders

Intervention

Drug:
• Prazosin
Competitive alpha-1 adrenergic receptor blocker which has been used to treat PTSD and Benign Prostatic Hypertrophy

Locations

Country	Name	City	State
Canada	University of Manitoba - PsycHealth - Mood and Anxiety Disorders Clinic	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
University of Manitoba

Country where clinical trial is conducted

Canada, 

References & Publications (26)

Baldwin DS, Waldman S, Allgulander C. Evidence-based pharmacological treatment of generalized anxiety disorder. Int J Neuropsychopharmacol. 2011 Jun;14(5):697-710. doi: 10.1017/S1461145710001434. Epub 2011 Jan 7. Review. — View Citation

Birnbaum S, Gobeske KT, Auerbach J, Taylor JR, Arnsten AF. A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry. 1999 Nov 1;46(9):1266-74. — View Citation

Bland RC, Newman SC, Orn H. Period prevalence of psychiatric disorders in Edmonton. Acta Psychiatr Scand Suppl. 1988;338:33-42. — View Citation

Boynton L, Bentley J, Strachan E, Barbato A, Raskind M. Preliminary findings concerning the use of prazosin for the treatment of posttraumatic nightmares in a refugee population. J Psychiatr Pract. 2009 Nov;15(6):454-9. doi: 10.1097/01.pra.0000364287.63210.92. — View Citation

Carlozzi NE, Kratz AL, Downing NR, Goodnight S, Miner JA, Migliore N, Paulsen JS. Validity of the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in individuals with Huntington disease (HD). Qual Life Res. 2015 Aug;24(8):1963-71. doi: 10.1007/s11136-015-0930-x. Epub 2015 Jan 31. — View Citation

Clarke DE, Kuhl EA. DSM-5 cross-cutting symptom measures: a step towards the future of psychiatric care? World Psychiatry. 2014 Oct;13(3):314-6. doi: 10.1002/wps.20154. — View Citation

Dick CL, Bland RC, Newman SC. Epidemiology of psychiatric disorders in Edmonton. Panic disorder. Acta Psychiatr Scand Suppl. 1994;376:45-53. — View Citation

George KC, Kebejian L, Ruth LJ, Miller CW, Himelhoch S. Meta-analysis of the efficacy and safety of prazosin versus placebo for the treatment of nightmares and sleep disturbances in adults with posttraumatic stress disorder. J Trauma Dissociation. 2016 Jul-Sep;17(4):494-510. doi: 10.1080/15299732.2016.1141150. Epub 2016 Feb 2. — View Citation

Hieble JP, Ruffolo RR Jr. The use of alpha-adrenoceptor antagonists in the pharmacological management of benign prostatic hypertrophy: an overview. Pharmacol Res. 1996 Mar;33(3):145-60. Review. — View Citation

Issa SA, Hadid OH, Baylis O, Dayan M. Alpha antagonists and intraoperative floppy iris syndrome: A spectrum. Clin Ophthalmol. 2008 Dec;2(4):735-41. — View Citation

Kessler RC, Nelson CB, McGonagle KA, Edlund MJ, Frank RG, Leaf PJ. The epidemiology of co-occurring addictive and mental disorders: implications for prevention and service utilization. Am J Orthopsychiatry. 1996 Jan;66(1):17-31. — View Citation

Maier W, Buller R, Philipp M, Heuser I. The Hamilton Anxiety Scale: reliability, validity and sensitivity to change in anxiety and depressive disorders. J Affect Disord. 1988 Jan-Feb;14(1):61-8. — View Citation

Morin CM, Belleville G, Bélanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011 May 1;34(5):601-8. — View Citation

Opbroek A, Delgado PL, Laukes C, McGahuey C, Katsanis J, Moreno FA, Manber R. Emotional blunting associated with SSRI-induced sexual dysfunction. Do SSRIs inhibit emotional responses? Int J Neuropsychopharmacol. 2002 Jun;5(2):147-51. doi: 10.1017/S1461145702002870. — View Citation

Pickworth WB, Sharpe LG, Nozaki M, Martin WR. Sleep suppression induced by intravenous and intraventricular infusions of methoxamine in the dog. Exp Neurol. 1977 Dec;57(3):999-1011. — View Citation

Raskind MA, Peskind ER, Chow B, Harris C, Davis-Karim A, Holmes HA, Hart KL, McFall M, Mellman TA, Reist C, Romesser J, Rosenheck R, Shih MC, Stein MB, Swift R, Gleason T, Lu Y, Huang GD. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. N Engl J Med. 2018 Feb 8;378(6):507-517. doi: 10.1056/NEJMoa1507598. — View Citation

Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, Dobie DJ, Hoff D, Rein RJ, Straits-Tröster K, Thomas RG, McFall MM. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003 Feb;160(2):371-3. — View Citation

Raskind MA, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, Homas D, Hill J, Daniels C, Calohan J, Millard SP, Rohde K, O'Connell J, Pritzl D, Feiszli K, Petrie EC, Gross C, Mayer CL, Freed MC, Engel C, Peskind ER. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013 Sep;170(9):1003-10. doi: 10.1176/appi.ajp.2013.12081133. — View Citation

Rodgman C, Verrico CD, Holst M, Thompson-Lake D, Haile CN, De La Garza R 2nd, Raskind MA, Newton TF. Doxazosin XL reduces symptoms of posttraumatic stress disorder in veterans with PTSD: a pilot clinical trial. J Clin Psychiatry. 2016 May;77(5):e561-5. doi: 10.4088/JCP.14m09681. — View Citation

Ruiz MA, Zamorano E, García-Campayo J, Pardo A, Freire O, Rejas J. Validity of the GAD-7 scale as an outcome measure of disability in patients with generalized anxiety disorders in primary care. J Affect Disord. 2011 Feb;128(3):277-86. doi: 10.1016/j.jad.2010.07.010. Epub 2010 Aug 9. — View Citation

Simpson TL, Malte CA, Dietel B, Tell D, Pocock I, Lyons R, Varon D, Raskind M, Saxon AJ. A pilot trial of prazosin, an alpha-1 adrenergic antagonist, for comorbid alcohol dependence and posttraumatic stress disorder. Alcohol Clin Exp Res. 2015 May;39(5):808-17. doi: 10.1111/acer.12703. Epub 2015 Apr 1. — View Citation

Skelly MJ, Weiner JL. Chronic treatment with prazosin or duloxetine lessens concurrent anxiety-like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety-related alcohol use. Brain Behav. 2014 Jul;4(4):468-83. doi: 10.1002/brb3.230. Epub 2014 Apr 14. — View Citation

Taylor FB, Martin P, Thompson C, Williams J, Mellman TA, Gross C, Peskind ER, Raskind MA. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008 Mar 15;63(6):629-32. Epub 2007 Sep 14. — View Citation

Wittchen HU, Carter RM, Pfister H, Montgomery SA, Kessler RC. Disabilities and quality of life in pure and comorbid generalized anxiety disorder and major depression in a national survey. Int Clin Psychopharmacol. 2000 Nov;15(6):319-28. — View Citation

Zaider TI, Heimberg RG, Fresco DM, Schneier FR, Liebowitz MR. Evaluation of the clinical global impression scale among individuals with social anxiety disorder. Psychol Med. 2003 May;33(4):611-22. — View Citation

Zuithoff NP, Vergouwe Y, King M, Nazareth I, van Wezep MJ, Moons KG, Geerlings MI. The Patient Health Questionnaire-9 for detection of major depressive disorder in primary care: consequences of current thresholds in a crosssectional study. BMC Fam Pract. 2010 Dec 13;11:98. doi: 10.1186/1471-2296-11-98. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Anxiety Symptoms	The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items, each defined by a series of, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	To be completed at baseline and weekly during weeks 2,3,4,5,6,7, 8 to assess changes over the last week
Primary	Change in Anxiety Symptoms	Generalized Anxiety Disorder 7 Item Scale (GAD-7) objectively determines initial symptoms severity and monitor symptom changes/effect of treatment over time. Each item is scored on a scale of "0" (not at all) to "3" (nearly every day). Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.	To be completed at baseline and weekly during weeks 2,3,4,5,6,7,8 to assess changes over the last week
Secondary	Change in Depressive Symptoms	To examine depressive symptoms following the use of prazosin as measured by the Patient Health Questionnaire (PHQ-9).Each item is scored on a scale of "0" (not at all) to "3" (nearly every day). Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.	To be completed at baseline,weeks 2, 4 and 8 to assess changes since last previous 2 weeks
Secondary	Change in Level of Disability	To examine levels of disability following the use of prazosin as measured by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)	To be completed at baseline, weeks 2, 4 and 8 to assess changes over the previous 2 weeks
Secondary	Change in Overall Symptom Severity	To examine overall symptom severity following the use of prazosin as measured by the DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure for Adults (DSM-5).	Previous 2 weeks
Secondary	Changes in Experienced Symptoms	To examine improvement in symptoms as measured by the Clinical Global Impression-Improvement Scale (CGI-I). Scale ranges from 1 (very much improved since initiation of treatment) to 7 (very much worse since initiation of treatment)	Completed at Baseline, and at weeks 2, 3, 4, 5, 6, 7, 8 to assess changes over the past week
Secondary	Tolerability of Medication (Heart Rate)	To examine the overall tolerability of prazosin by recording heart rate at each visit	To be assessed at Baseline, and at weeks 2, 3, 4, 5, 6, 7, 8 to monitor changes since last visit
Secondary	Tolerability of Medication (blood pressure)	To examine the overall tolerability of prazosin by recording blood pressure at each visit in the sitting and standing positions	To be assessed at Baseline, and at weeks 2, 3, 4, 5, 6, 7, 8
Secondary	Side Effects	To examine the overall tolerability and side effects of prazosin by recording potential adverse symptoms using a Vital Signs and Adverse Symptoms Checklist.	To be assessed at Baseline, and at weeks 2, 3, 4, 5, 6, 7, 8
Secondary	Change in Sleep Impairment	To examine sleep quality following the use of prazosin as measured by the Insomnia Severity Index (ISI).	Will be completed by patients at baseline, weeks 2,4 and 8 to assess changes over the previous 2 weeks