Clinical Review

Evaluation of Clonidine and Prazosin for the Treatment of Nighttime Posttraumatic Stress Disorder Symptoms

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Tolerability

Of the 34 patients who discontinued clonidine within 2 years, 13 patients (38%) cited ineffectiveness of therapy as a reason for discontinuation. Another 13 patients (38%) reported discontinuing therapy due to AEs. Sedation (4 patients, 12%), dizziness/hypotension (3 patients, 9%), and paradoxical worsening of PTSD symptoms (4 patients, 12%) were the most common AEs leading to discontinuation. Other AEs cited as reasons for discontinuation were syncope 
(2 patients), erectile dysfunction 
(1 patient), rash (1 patient), myoclonus (1 patient), increased depression (1 patient), and fatigue (1 patient). One patient reported that he had discontinued clonidine due to symptom resolution/lack of need for treatment. In 8 of the 34 patients, no reason for discontinuation was found in chart documentation.

Medication Possession Ratio

Among the 21 evaluable patients who continued to receive clonidine 6 months after initiation, 10 (48%) were determined to be highly adherent to therapy, with an MPR of ≥ 80%. Six of the 21 patients (29%) had an MPR between 50% and 79%, and 
5 patients (24%) had an MPR < 50%.

Of the 8 patients who continued on clonidine at the 2-year mark, 
3 (38%) were adherent to therapy, with an MPR of ≥ 80%. Three more patients (38%) had a 2-year MPR between 50% and 80%, and 2 patients (25%) had an MPR < 50%.

Prazosin

Of the 60 prazosin patients assessed, 32 (53%) had a positive response to the medication for nighttime PTSD symptoms documented in the CPRS within 6 months of starting therapy. Six months after starting prazosin, 36 patients (60%) continued to take prazosin. Two years after starting therapy, 18 of the original 60 patients continued on prazosin for an overall 2-year continuation rate of 30%.

Tolerability

Of the 42 patients who discontinued prazosin within 2 years, six patients (14%) cited ineffectiveness of therapy as a reason for discontinuation. Thirteen patients (31%) reported discontinuing therapy due to AEs. Sedation (3 patients, 7%), dizziness/hypotension (3 patients, 7%), and paradoxical worsening of PTSD symptoms (6 patients, 14%) were the most common AEs leading to discontinuation. Other AEs cited as reasons for discontinuation were headache 
(2 patients), altered mental status (1 patient), and fatigue (1 patient). Three patients reported that they had discontinued clonidine due 
to symptom resolution/lack of need for treatment. Other reasons for discontinuation not related to 
AEs included flight rules (1 patient), changes to antihypertensive regimen (1 patient), refill issues (1 patient), and cost (1 patient). In 15 of 
the 42 patients, no reason for 
discontinuation was found in chart documentation.

Medication Possession Ratio

Among the 31 evaluable patients who continued to receive prazosin 
6 months after initiation, 20 (65%) were determined to be highly adherent to therapy, with an MPR of ≥ 80%. Five of the 31 patients (16%) had an MPR between 50% and 80%, and 6 patients (19%) had an MPR < 50%.

Of the 15 evaluable patients who continued on prazosin at the 2-year mark, 9 (60%) were adherent to therapy, with an MPR of ≥ 80%. Three patients (20%) had a 2-year MPR 
between 50% and 80%, and 3 patients 
(20%) had an MPR < 50%.

Discussion

Although prazosin has been shown to be effective for nighttime PTSD symptoms in both prospective and retrospective evaluations in veterans, this study provides the first evidence to support the use of clonidine in a veteran population.10-12,15

Interestingly, 42% of the patients assessed received their first prescription of an α2-adrenergic agent for nighttime PTSD symptoms from a PCP. Even with the recent increased focus on integrating mental health into primary care within the VA, this was a surprising finding. Primary care providers at VAPHCS may have a greater role in the outpatient management of PTSD than previously suspected. The information presented here may prove useful and applicable in both psychiatric and primary care treatment settings.

The study results indicated that a majority of subjects initially reported effectiveness with either clonidine or prazosin (53% and 57%, respectively). The initial effectiveness rate for prazosin is similar to those described in previous studies.10-13,15 The data also support a viable role for clonidine in the treatment of nighttime PTSD symptoms.

Regardless of initial improvement, the study results also suggest that the therapeutic benefit may not persist in the long term, as evidenced by a significant percentage of discontinuations attributed to ineffectiveness (38% for clonidine and 14% for prazosin) and a very low rate of long-term continuation (19% for clonidine and 30% for prazosin at 2 years). This latter observation contrasts with findings from previous studies; Byers and colleagues reported a 2-year prazosin continuation rate of 48.4% in a similar analysis, and Boehnlein and colleagues reported a sustained benefit of clonidine in responders over a 10-year period.14,15 The wide variety of reasons for discontinuation reported here may help providers who are considering clonidine or prazosin for their patients to anticipate barriers to long-term success.

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PTSD in Women and Men

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