Clinical Review

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

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Study Design

Initial effectiveness of each agent was determined by reviewing subjects’ progress notes after the initial prescription of clonidine or prazosin for documentation of improvement in symptoms within 6 months of the prescription start date. A decrease in frequency or intensity of nighttime PTSD symptoms, nightmares, or insomnia, as documented in the patient chart, was interpreted as improvement of symptoms.

Long-term continuation was assessed by reviewing subjects’ prescription records, to determine whether prescription(s) for clonidine or prazosin continued for 2 years after the date of the initial prescription.

Any gap between medication fills that resulted in an anticipated period without medication of ≥ 6 months (eg, 9 months after receiving a 
90-day supply) was considered discontinuation of therapy. Prescription refill history was also reviewed, and medication possession ratio (MPR) was calculated to assess whether patients were adherent to the study drug as prescribed. Adherence was defined as an MPR of ≥ 80%. Patients who left the VAPHCS service area but continued to receive care at another VA were assessed for continuation of therapy, but refill data and/or MPR were not assessed.

Tolerability was assessed by reviewing subjects’ medical records to determine whether therapy with clonidine or prazosin was discontinued due to documented adverse effects (AEs). The occurrence of AEs was determined by reviewing progress notes and other chart documentation surrounding the date of discontinuation. If the drug was discontinued but the reason was not explicitly documented or if the prescription expired without a documented reason for nonrenewing, the reason for discontinuation was coded as “not specified.” Discontinuation due to treatment failure, change in symptoms, nonadherence, or other causes was also recorded. If multiple reasons for discontinuation were cited for a single patient, all were included in the data. This project was approved by the institutional review board at the VAPHCS.

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Statistical Considerations

Based on clinical experience, it was presumed that many of the patients who were prescribed clonidine would be receiving it as a second-line therapy after failing prazosin. Therefore, statistical analysis of the relative effectiveness and tolerability of clonidine and prazosin could not be performed. Neither power nor sample size needed to demonstrate any difference in effectiveness or tolerability between the groups was calculated. All results are expressed using descriptive statistics.


An initial database search for patients with PTSD who received a first prescription for clonidine between January 1, 2009, and December 31, 2011, from a VAPHCS provider yielded a list of 149 patients. The same search criteria applied for prazosin yielded 1,116 patients, 149 of whom were randomly selected for screening. After screening, 42 patients on clonidine and 60 patients on prazosin were included in this analysis (Figure).

Patient Demographics

The average age of the clonidine patients was 38.5 years (range 21-65 years) (Table 1). The clonidine group was primarily male (90%) and white (83%). Eighteen of the 42 patients in the clonidine group had a
baseline PTSD Checklist-Civilian version (PCL-C) score available within the 90 days before the first prescription of clonidine; the average baseline PCL-C score in this subgroup was 
62 ± 12.0 (median 65.5, range 
31-82). Most of the clonidine patients (71%) had a concomitant diagnosis of a depressive disorder. About one-quarter of the group (24%) had previously tried prazosin per prescription records. In 24 patients (57%), the first prescription for clonidine was written by a psychiatrist or psychiatric nurse practitioner; 18 patients (43%) were started on clonidine by PCPs.

The average age of the prazosin patients was 46.1 years (range 21-74 years). The prazosin group was also primarily male (93%) and white (88%). Twenty of the 60 patients in the prazosin group had a baseline PCL-C score available within the 
90 days before the first prescription of prazosin; the average baseline PCL-C score in this subgroup was 55 ± 16.1 (median 64, range 30-72). Most of the prazosin patients (63%) had a concomitant diagnosis of a depressive disorder. Four patients (7%) had previously tried clonidine per prescription records. In 35 patients (58%), the first prescription for prazosin was written by a psychiatrist or psychiatric nurse practitioner; 
25 patients (42%) were started on prazosin by PCPs.

Data pertaining to initial and long-term effectiveness, tolerability, and MPR for both clonidine and prazosin are presented in Table 2.


Of the 42 clonidine patients assessed, 24 (57%) had a positive response to the medication for nighttime PTSD symptoms documented in the Computerized Patient Record System (CPRS) within 6 months of starting therapy. Six months after starting clonidine, 23 patients (55%) continued to take clonidine. Two years after starting therapy, 8 of the original 
42 patients continued on clonidine for an overall 2-year continuation rate of 19%.

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