Evidence-Based Reviews

How to treat PTSD in patients with comorbid mood disorders

Current Psychiatry. 2010 April;9(4):48-61

References

1. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity-Replication (NCS-R). JAMA. 2003;289:3095-3105.

2. Kessler RC, Sonnega A, Bromet E, et al. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048-1060.

3. Franklin CL, Zimmerman M. Posttraumatic stress disorder and major depressive disorder: investigating the role of overlapping symptoms in diagnostic comorbidity. J Nerv Ment Dis. 2001;189:548-551.

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6. Akiskal HS, Benazzi F. Optimizing the detection of bipolar II in outpatient private practice: toward a systematization of clinical diagnostic wisdom. J Clin Psychiatry. 2005;66:914-921.

7. Akiskal HS, Akiskal KK, Lancrenon S, et al. Validating the soft bipolar spectrum in the French National EPIDEP study: the prominence of BP-II. J Affect Disord. 2006;96:207-213.

8. Rabakowski JK, Suwalska D, Lojko D, et al. Bipolar disorders among Polish psychiatric outpatients treated for major depression. J Affect Disord. 2005;84:141-147.

9. Benazzi F. Bipolar disorder—focus on bipolar II disorder and mixed depression. Lancet. 2007;369:935-945.

10. Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.

11. Maj M, Pirozzi R, Magliano, et al. Agitated ‘unipolar’ major depression: prevalence, phenomenology, and outcome. J Clin Psychiatry. 2006;67:712-719.

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13. Dilsaver SC, Benazzi F, Akiskal KK, et al. Differential patterns of lifetime multiple anxiety disorder comorbidity between Latino adults with bipolar I and major depressive disorders. Bull Menninger Clinic. 2008;72:130-148.

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17. Schnurr PP, Friedman MJ, Engel CC, et al. Cognitive behavioral therapy for posttraumatic stress disorder in women: a randomized-controlled trial. JAMA. 2007;297:820-830.

18. Bisson J, Andrew M. Psychological treatment for posttraumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2005;CD003388.-

19. Cukor J, Spitalnick J, Difede J, et al. Emerging treatments for PTSD. Clin Psychol Rev. 2009;29(8):715-726.

20. Hogberg G, Pagani M, Sundin O, et al. Treatment of posttraumatic stress disorder with eye movement desensitization and reprocessing: outcome is stable in 35-month follow-up. Psychiatry Res. 2008;159(1-2):101-108.

21. Brady K, Pearlstein T, Asnis GM, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA. 2000;283:1837-1844.

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31. Braun P, Greenberg D, Dasberg H, et al. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. J Clin Psychiatry. 1990;51:236-238.

32. Taylor FB, Martin P, Thompson C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008;63:629-632.

33. Raskind MA, Perskind ER, Hoff DJ, et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with posttraumatic stress disorder. Biol Psychiatry. 2007;61:928-934.

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Prazosin can help diminish nightmares, dreams, and other painful recollections of trauma.^32,33 The drug does not affect time to sleep onset. It also has been reported to reduce avoidance behavior and hyperarousal, such as irritability and anger.³⁴ This has been my experience.

Box

Psychotherapies for PTSD with comorbid affective illness

Cognitive-behavioral therapy (CBT) involving prolonged exposure (PE) to trauma-related stimuli has been shown to be effective for posttraumatic stress disorder (PTSD) in controlled studies.^17,18 PE is an individual CBT designed to help patients process traumatic events and reduce psychological distress. It involves education about reactions to trauma, relaxation techniques, imaginal reliving of the trauma, exposure to cues associated with the trauma, and cognitive restructuring.

Administering D-cycloserine before behavioral treatment sessions facilitates fear extinction, and its use to enhance prolonged PE constitutes state-of-the-art treatment.¹⁹ Eye movement desensitization and reprocessing also may be effective.^18,20

PE is a reasonable first-line treatment for PTSD patients with comorbid bipolar spectrum disorders when PTSD symptoms persist after pharmacologic treatment for the bipolar spectrum disorder. PE also is a first-line treatment for PTSD in patients with comorbid major depressive disorder. Barriers to PE treatment include its cost and finding professionals who are expert in its use.

Prazosin to treat PTSD-related symptoms in children or adolescents has not been studied, but it can be useful in adults over a wide range of doses. As little as 1 mg at bedtime may confer benefit, although the mean prazosin dose in an 8-week, placebo-controlled study of 40 combat veterans was 13.3 mg in the evening.³³

I often initiate prazosin treatment as follows:

1 mg on the first night of treatment
2 mg on the second night
3 mg on the third night
then, if tolerated, 1 mg upon waking, 1 mg 8 hours later, and 3 mg at bedtime. I then slowly adjust the dose schedule based on the patient’s needs, such as minimizing painful re-experiencing of the trauma. Reducing avoidance and hyperarousal also are reasonable targets. For example, when using prazosin to treat extremely angry men with PTSD stemming from exposure to violent crimes, I have observed that even “murderous” rage ceases with prazosin treatment, only to reappear when prazosin is discontinued.

In treating approximately 100 patients with prazosin, I have not exceeded 16 mg/d. Dosages used for treating hypertension usually are 5 to 20 mg/d. When using prazosin, I always:

warn patients that faintness or fainting is a side effect and record this caveat in their chart
obtain sitting and standing blood pressure and pulse before starting treatment and subsequently
ask patients if they feel dizzy when changing posture before and after initiating treatment.

Most of my PTSD patients are suffering so much that they are willing to accept the risk of fainting associated with prazosin use. For PTSD comorbid with severe panic disorder,^12,13 I find that a benzodiazepine with antipanic properties such as alprazolam or clonazepam often works well in conjunction with prazosin.

Some patients with bipolar spectrum disorders might benefit from the addition of an SSRI after mood stabilizer treatment proves effective. However, I have never managed a patient in this manner, and like my own treatment strategy, this has not been subjected to rigorous empiric inquiry. In my view, psychological treatment is much preferred to antidepressant therapy.

Related resource

Benazzi F. Bipolar disorder—focus on bipolar II disorder and mixed depression. Lancet. 2007;369:935-945.

Drug brand names

Alprazolam • Xanax
Bupropion • Wellbutrin
Clonazepam • Klonopin
D-cycloserine • Seromycin
Fluoxetine • Prozac
Paroxetine • Paxil
Phenelzine • Nardil
Prazosin • Minipress
Sertraline • Zoloft
Venlafaxine • Effexor

Disclosure

Dr. Dilsaver reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.