The maximum dose recommended in the prazosin package insert (PI) is 40 mg daily. The most important adverse effect is the ‘first dose effect’ syncope with sudden loss of consciousness (1%) with an initial dose of at least 2 mg. Hence, prazosin should always be started at 1 mg. Some of the common side effects of prazosin are the following: dizziness (10%), headache (8%), drowsiness (8%), lack of energy (7%), weakness (7%), palpitations (5%) and nausea (5%). In 1–4% of patients taking prazosin the following side effects have been reported: vomiting,

diarrhea, constipation, edema, orthostatic hypotension, dyspnea, syncope, vertigo, depression, nervousness, rash, urinary frequency and nasal Inhibitors,research,lifescience,medical congestion. In less than 1% of patients taking prazosin, abdominal discomfort/pain, tachycardia, paresthesias, hallucinations, pruritus, incontinence, impotence and priapism have been reported (PI). We illustrate two case reports using high-dose (up Inhibitors,research,lifescience,medical to 30 and 45 mg) prazosin for PTSD with comorbid treatment-resistant mood disorders. In patients with partial response to currently available medications for PTSD,

greater utilization of high-dose prazosin for the management of PTSD may lead to better outcomes. Case Inhibitors,research,lifescience,medical 1 A 50-year-old Hispanic woman with major depressive disorder (MDD), recurrent, severe with a history of seasonal component and PTSD was referred to the treatment-resistant affective disorders (TRAD) clinic. She was on mirtazapine 45 mg daily, sertraline 200 mg daily and diazepam 5 mg four times daily, all taken orally. The psychotropic drug history showed that lorazepam, hydroxyzine 75 mg and

duloxetine (dose Inhibitors,research,lifescience,medical unknown) were not effective in the past. Considering the patient’s past hypomanic episodes (approximately 30 hypomanic episodes in the past 30 years, each lasting 2 days to 2 weeks), coupled with depressive episodes, the patient’s diagnosis was changed to bipolar II. At the time of presentation, the patient completed the Patient Health Questionnaire 9 (PHQ-9), a nine-item scale used to screen for depression [Kroenke et al. 2001]. The patient scored 23 on the PHQ-9 and reported her functioning Inhibitors,research,lifescience,medical as ‘extremely difficult’. The patient was physically and sexually abused as a child and as an adult. The patient endorsed nightmares and daytime symptoms such as hyperarousal, flashbacks and check details re-experiencing the trauma. PTSD symptoms were chronic and active for many years. Mirtazapine and sertraline were tapered Megestrol Acetate and discontinued because of the new bipolar II diagnosis [Sachs et al. 2007; Salvi et al. 2008; Alda and Yatham, 2009] and diazepam was tapered and discontinued as the patient had PTSD which was symptomatic [Asnis et al. 2004; Lund et al. 2012]. For PTSD, she was started on an oral dose of 1 mg prazosin at bedtime [Peskind et al. 2003]. Prazosin was gradually titrated based on response over 20 weeks to 15 mg in the morning, 10 mg at noon and 20 mg at night. The patient did not report any side effects from this high dose of prazosin.