Discussion
The existing literature reports few outcomes for older veterans prescribed prazosin for PTSD. One report included a 75-year-old otherwise-healthy veteran, who received 2-mg prazosin at bedtime. At this dose, he reported good tolerability and response, as indicated by a reduction in his CAPS nightmare severity score.11 An open-label trial assessed prazosin in 9 geriatric men with chronic PTSD and found low-dose prazosin (average [SD] maximum prazosin dose reported was 2.3 [0.7] mg, range 2-4 mg per day) greatly reduced nightmares and overall PTSD severity in 8 of 9 subjects.12 Despite the veterans in that study having multiple medical comorbid conditions and taking concomitant medications, prazosin was reported to be well tolerated, and changes in BP were determined to be clinically insignificant.12 A recent study of middle-aged veterans (average [SD] age 52 [14] years) reported prazosin did not significantly alleviate PTSD-related nightmares.13 However, we observed prazosin therapy significantly reduced nightmares and sleep disturbances, and significantly improved PTSD severity in our older veteran population.
To our knowledge, the current study is the largest retrospective study that evaluates prazosin therapy for the treatment of PTSD-related nightmares in older veterans. The findings of this study are similar to a previous study in older veterans as well as studies of prazosin in younger and middle-aged adult veterans, with the average age ranging from 30 to 56 years.6-12 Like the previously reported studies, prazosin also was well tolerated in our sample of veterans with multiple comorbidities and concomitant medications. Changes in BP were not clinically significant.
Studies have demonstrated increased noradrenergic activity as a component of the normal aging process.16,17 This may require utilizing caution during prazosin dose titration and frequent patient assessment, due to the concern for risk of hypotension in older patients and in particular those who may require increased doses to achieve efficacy. In our study, favorable outcomes were achieved at an average (SD) total daily dose of 5.1 (5.3) mg (median, 2.5 mg; range 0-17 mg). A previous report showed efficacy of prazosin around an average (SD) maximum dose of 2.3 (0.7) mg, which is lower than the doses reported in the current study.12 In addition, 13 veterans (40.6%) from our sample reached doses of ≥ 5 mg per day, and 8 veterans (25.0%) reached doses of ≥ 10 mg per day.
The doses reached in this study were reflective of a management approach using assessment of patient-reported symptoms at weekly to biweekly follow-up visits. The individualized management approach applied in the PTC by MH CPSs aids in uncovering the most efficacious and tolerated dose of prazosin for each veteran. Evaluation of symptom change during treatment in PTC was facilitated use of objective rating scales, which helped measure nightmare frequency and intensity, sleep satisfaction, and global PTSD severity. Given the variability in dosing of prazosin reported in the literature, further studies may be warranted to provide more definitive clinical guidance as far as dosing prazosin in older patients.
The study by Peskind and colleaguesrationalized that lower doses of prazosin may be used in older patients given pharmacokinetic effects of aging, age-associated changes in PTSD pathophysiology, and effects and interactions of concomitant medications.12 However, our study found that prazosin could be well tolerated at higher doses. The rate of discontinuation due to intolerable AEs was low. AEs reported were consistent with the established AE profile of prazosin, with dizziness, orthostasis, and headache most commonly reported. Similar to the Peskind and colleagues study, BP had a tendency to decrease in this current study; however, the change was not clinically significant.12 That study also reported transient dizziness with prazosin titration, which was shown to be tolerable in the majority of our veterans reporting dizziness.12 Other common AEs with prazosin, such as rash, priapism, sedation, syncope, other cardiac AEs, and sleep disturbance were not reported in our study population.
MH CPS-managed PTCs are one venue that may allow veterans to achieve favorable outcomes through frequent follow-up. As prazosin dosing is specific to each individual patient, frequent follow-up visits are helpful in determining optimal doses that maximize efficacy while minimizing intolerable AEs. The majority of veterans treated in our PTC continued use of prazosin 6 months postdischarge, while 3 veterans required a postdischarge dose change.
The 2017 VA/DoD PTSD guidelines recommend individual, trauma-focused psychotherapy over pharmacologic therapy for the primary treatment of PTSD.14 About half of the veterans in the current study participated in either group or individual psychotherapy during enrollment in the PTC. A systematic review of psychotherapy in older veterans reported mixed results, with 4 studies indicating positive effects of therapy, while the other 3 studies reported no benefit or mixed effects for PTSD symptoms. The review concluded that fewer older adults experience complete remission of symptoms with psychotherapy alone.18 A previous study of older veterans described improvement in PTSD-related symptoms with prazosin without concurrent psychotherapy.12