Falling through the cracks

September 2015

Clinical

Is there a role for prazosin in the treatment of post-traumatic stress disorder?

Volume 44, No.9, September 2015 Pages 647-649

John Togno

Scott Eaton

This article is the next in our series of occasional papers ‘At the cutting edge’, where we invite researchers to inform readers on where they believe clinical practice is heading. The material published in this article is not mainstream or part of standard clinical practice. However, we hope readers will be inspired and enjoy contemplating where clinical medicine may lead in the future – the Editor.

Background

Post-traumatic stress disorder (PTSD) is a common disorder with significant morbidity and associated comorbidities, including mood disorders and substance abuse, and is frequently misdiagnosed or under-diagnosed. Management of PTSD requires combined psychotherapy and pharmacotherapy, but some symptoms, particularly nightmares and sleep disturbance, are often resistant to treatment.

Objective/s

The aim of this article is to inform primary healthcare professionals of the prevalence and significance of PTSD, and to review the evidence that prazosin is a useful option for managing PTSD-associated nightmares and sleep disturbance.

Discussion

PTSD should be considered in patients with treatment-resistant mood disorders. A trauma history should be taken for these pa-tients and in recognised groups of patients who have a high incidence of PTSD. The treatment of PTSD is challenging, fre-quently requiring specialist input from psychiatrists. Prazosin has been proven to be safe and effective in the management of nightmares and sleep disturbances associated with PTSD and is indicated where these distressing symptoms are present.

Post-traumatic stress disorder (PTSD) is a common disorder, affecting 3–4% of the general population.1 The incidence of PTSD is higher in certain groups including Aboriginal and Torres Strait Islander peoples,2 people with substance abuse disorders,1,3 serving and ex-service military and emergency services personnel,1 and prisoners.4

Detection of PTSD in primary care is clinically important. PTSD is a significant psychological disorder associated with increased morbidity, increased use of healthcare services, functional disability, increased suicide risk and premature death.5 Significant comorbidities include anxiety and depression,1 tobacco smoking, alcohol and other substance abuse, poor diet and physical inactivity.1,5

Diagnostic criteria and screening tools for PTSD

The diagnostic criteria for PTSD are specified in the fifth edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-5).6 The criteria are specific for adults and adolescents, and children older than 6 years. Diagnostic criteria for PTSD include a history of exposure to an actual or threatened traumatic event involving death, serious injury or sexual violation, which may be direct, witnessed or vicariously experienced if the trauma occurs to a close family member or friend. Symptoms from each of the four symptom clusters listed below must occur:

  • intrusion
  • avoidance
  • negative alterations in cognitions and mood
  • alterations in arousal and reactivity.

Other criteria concern duration of symptoms and impairment in important areas of functioning, and clarify that symptoms are not attributable to a substance or co-occurring medical condition.6

PTSD is frequently misdiagnosed or under-diagnosed.7 A useful screening tool is the Primary Care Post-Traumatic Stress Disorder Screen8 (Box 1). This screening tool can be supplemented by the PTSD checklist for DSM-5 (PCL 5)9 and structured diagnostic interviews such as the Clinician Administered PTSD Scale (CAPS), to confirm the diagnosis.10 CAPS should be reserved for use by health professionals with appropriate training in the delivery and interpretation of the scoring for this tool.

Box 1 Primary Care Post-Traumatic Stress Disorder Screen8

In your life, have you ever had any experience that was so frightening, horrible or upsetting that, in the past month, you:

1. Have had nightmares about it or thought about it when you did not want to?

Yes

No

2. Tried hard not to think about it or went out of your way to avoid situations that reminded you of it?

Yes

No

3. Were constantly on guard, watchful, or easily startled?

Yes

No

4. Felt numb or detached from others, activities or your surroundings?

Yes

No

If a patient answers ‘YES’ to 2 or more questions, a diagnosis of PTSD is highly likely.

Initial approach to treatment of PTSD

PTSD is a difficult condition to treat and requires an integrated approach using disorder-specific psychological treatments such as trauma-focused cognitive behavioural therapy and eye movement desensitisation and reprocessing, and pharmacotherapy.11,12 In primary care, the recommended first-line pharmacotherapy agents for treating PTSD are selective serotonin reuptake inhibitors, such as paroxetine 20–40 mg once daily for at least 10 weeks. Second-line pharmacological interventions include the use of mirtazapine or phenelzine. It is recommended that only mental health professionals should initiate the use of phenelzine. Where symptoms have not responded adequately, consideration should be given to increasing the dose of antidepressants (within approved limits), switching antidepressant or adding risperidone or olanzapine as an adjunct.11

The role of prazosin in treating PTSD

Two significant distressing symptoms of PTSD, nightmares (intrusion) and sleep disturbance (alteration in arousal), are often resistant to pharmacological treatment.13 The mechanism for these symptoms appears to be enhanced postsynaptic adrenoceptor responsiveness to central nervous system (CNS) noradrenaline.13 Randomised clinical trials provide evidence that the off-label use of prazosin, a brain-active alpha-1 adrenoceptor antagonist, is effective and safe in the treatment of nightmares and sleep disturbance associated with PTSD, and contributes to an improvement in overall clinical status without affecting blood pressure.13–16

Introducing prazosin into the treatment of a patient with PTSD is guided by the ‘start low, go slow’ rule. The recommended starting dose to minimise the risk of adverse drug reactions (ADRs) is 1 mg before bed, increasing by 1 mg every 2–3 nights until a clinical response is obtained. Average doses of prazosin in the treatment of PTSD achieved daily doses of 19.6 mg for males and 8.7 mg for females,12 although there are reports of higher doses being used.17 Prazosin is well tolerated and common ADRs include dizziness (10%), headache (8%), drowsiness (8%), lack of energy (7%), weakness (7%), palpitations (5%) and nausea (5%). A significant potential ADR is ‘first-dose syncope’ (1%), which occurs with doses of 2 mg or higher. Treatment, therefore, should always commence at a dose of 1 mg.18

Summary

This article provides a review of a role for prazosin as safe and effective pharmacotherapy for the distressing symptoms of nightmares and sleep disturbance in patients with PTSD.13 The authors recommend that treating practitioners consider and screen for PTSD in patients who are unresponsive to treatment for diagnoses such as bipolar disorders, anxiety and depression. Patients with common conditions such as alcohol and substance abuse should be screened for PTSD. This condition should be actively considered as a critical diagnosis in all Aboriginal and Torres Strait Islander patients, serving and ex-service military and emergency personnel, and prisoners. Consultation with a psychiatrist is recommended when any or all of the following factors are present:11,12

  • diagnostic uncertainty
  • comorbid conditions
  • severe or complex PTSD and concern about patient safety
  • treatment resistance requiring sophisticated pharmacological strategies.

Authors

John Togno MBBS, FRACGP, general practitioner, associate professor, Social and Preventive Medicine, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD; medical educator, International Medical Graduate Program, Australian College of Rural and Remote Medicine, Brisbane, QLD. jtogno@gmail.com

Scott Eaton MB ChB, MRCPsych, FRANZCP, consultant psychiatrist, Bendigo Health and Sternberg Clinic, Bendigo, VIC.

Competing interests: None.
Provenance and peer review: Commissioned, externally peer reviewed.

References

  1. Creamer M, Burgess P, McFarlane AC. Post-traumatic stress disorder: findings from the Australian National Survey of Mental Health and Well-being. Psychol Med 2001;31:1237–47.
  2. Nadew GT. Exposure to traumatic events, prevalence of posttraumatic stress disorder and alcohol abuse in Aboriginal communities. Rural Remote Health 2012;4:1667. Available at www.rrh.org.au/articles/subviewnew.asp?ArticleID=1667 [Accessed 14 May 2015].
  3. Ross J, Teesson M, Darke S, et al. The characteristics of heroin users entering treatment: findings from the Australian Treatment Outcome Study. Drug Alcohol Rev 2005;24:411–18.
  4. Goff A, Rose E, Rose S, Purves D. Does PTSD occur in sentenced prison populations? A systematic literature review. Crim Behav Ment Health 2012;17:152–62.
  5. McFall M, Cook J. PTSD and health risk behaviour. The National Center for Posttraumatic Stress Disorder. PTSD Research Quarterly 2006;17:1–8.
  6. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th edn. Washington, DC: APA, 2013.
  7. Sher L. Recognizing post-traumatic stress disorder (Editorial). Q J Med 2004;97:1–5.
  8. Prins A, Ouimette P, Kimerling R, et al. The primary care PTSD screen (PC-PTSD): development and operating characteristics. Prim Care Psychiatry 2003;9:9–14.
  9. Weathers FW, Litz BT, Keane TM, Palmieri PA, Marx BP, Schnurr PP. PTSD Checklist for DSM-5 (PCL-5) 2014. Available at www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp [Accessed 14 May 2015].
  10. Weathers FW, Blake DD, Schnurr PP, Marx BP, Keane TM. Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) 2014. Available at www.ptsd.va.gov/professional/assessment/adult-int/caps.asp [Accessed 14 May 2015].
  11. Australian Centre for Posttraumatic Mental Health. Australian guidelines for the treatment of acute stress disorder and posttraumatic stress disorder. Melbourne: Australian Centre for Posttraumatic Mental Health, 2013. Available at www.nhmrc.gov.au/_files_nhmrc/publications/attachments/mh13.pdf  [Accessed 14 May 2015].
  12. Wallace D, Cooper J. Update on the management of posttraumatic stress disorder. Aust Prescr 2015;38:55–59.
  13. Raskind MA, Peskind ER, Hoff DJ, et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry 2007;61:928–34.
  14. Byers MG, Allison KM, Wendel CS, et al. Prazosin versus quetiapine for nighttime post-traumatic stress disorder symptoms in veterans: an assessment of long term comparative effectiveness and safety. J Clin Psychopharmacol 2010;30:225–29.
  15. Germain A, Richardson R, Moul DE, et al. Placebo controlled comparison of prazosin and cognitive behavioural therapy for sleep disturbances in U.S. Military Veterans. J Psychosom Res 2012;72:89–96.
  16. Taylor FB, Martin P, Thompson C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma post-traumatic stress disorder: a placebo controlled study. Biol Psychiatry 2008;63:629–32.
  17. Koola MM, Varghese SP, Fawcett JA. High-dose prazosin for the treatment of post-traumatic stress disorder. Ther Adv Psychopharmacol 2014;4:43–47.
  18. Department of Health, Therapeutic Goods Administration. Product information prazosin. Canberra: Commonwealth of Australia, 2014. Available at www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=prazosin [Accessed 21 May 2015].

Correspondence afp@racgp.org.au

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Type

Clinical

2015