TRD stages are the following: stage I: failure of at least one adequate trial of a major class of antidepressants; stage II: stage I resistance plus failure of an adequate trial of an antidepressant (or combination) in a distinctly different class from that used in stage I [Thase and Rush, 1997]. The following medications failed to provide benefit: paroxetine (dose unknown), venlafaxine

262.5 mg, duloxetine 60 mg daily, gabapentin 600 mg at bedtime, propranolol 10 mg three times a day, trazodone (dose unknown), prazosin 3 mg (which was discontinued because the patient was not able to tolerate it due to side Inhibitors,research,lifescience,medical effects), chlorpromazine 100 mg at bedtime, dextroamphetamine extended release 5 mg, risperidone 2 mg, aripiprazole 15 mg and lithium 900 mg. The patient came to us on clonazepam 2 mg twice a day, Inhibitors,research,lifescience,medical mirtazapine 45 mg at bedtime and zolpidem 20 mg at bedtime, all taken orally. The patient scored 27 on PHQ-9, which is suggestive of severe depression. The patient’s 1-year-old son had died and she was still grieving after 24 years. The patient’s PTSD was from adult physical and sexual abuse, including rape. PTSD symptoms were flashbacks, hypervigilance, reliving the experience, avoidance, nightmares, insomnia and concentration difficulties. PTSD symptoms were chronic and active for Inhibitors,research,lifescience,medical many years. Prazosin was started at 1 mg orally at bedtime and was gradually titrated over 4

weeks to 15 mg in the morning, 5 mg at noon and 10 mg at bedtime based on response. Morning and noon doses were specifically to target daytime symptoms and the bedtime dose to target nightmares. Each time prazosin was increased by 2 mg daily to target a specific daytime

Inhibitors,research,lifescience,medical or nighttime symptom. In this patient, daytime symptoms were more pronounced than the nightmares and hence required 20 mg during Inhibitors,research,lifescience,medical the daytime and 10 mg at bedtime. The patient tolerated prazosin without reporting any side effects. Her baseline sitting BP was 133/106 and standing BP was 132/104, sitting HR was 75 and standing HR was 78. On prazosin 30 mg, sitting BP was 124/85, standing BP was 121/95, sitting HR was 83 and standing HR was 86. For the management of comorbid TRD, mirtazapine, zolpidem and clonazepam were tapered and discontinued. The patient was started on clomipramine because of TRD stage II. The patient was asked to continue psychotherapy and was referred for bereavement counseling. The patient was asked to start walking for 5 min daily for behavioral these activation and gradually to increase the duration. The patient also attended the weekly depression/bipolar/psychosis group. Two months later, the patient’s PHQ-9 was 0 and her PTSD was asymptomatic on clomipramine 300 mg orally daily and prazosin 15 mg in the morning, 5 mg at noon and 10 mg at bedtime. It is unclear what specific side effects the patient had on prazosin 3 mg when it was tried for the first time. It is also ZD1839 ic50 unknown what the starting dose was then and how quickly it was titrated.