Prazosin hydrochloride is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Prazosin's efficacy in hypertensive patients appears to be similar to that of thiazide diuretics, β-adrenergic blocking agents, hydralazine, and centrally acting adrenergic inhibitors (e.g., clonidine, methyldopa). However, in one randomized, double-blind clinical study (the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]), doxazosin, an α1-blocker, was shown to be less effective in lowering mean systolic blood pressure (by about 2-3 mm Hg) than chlorthalidone, a thiazide-like diuretic. In order to achieve target blood pressure in hypertensive patients, use of doxazosin required additional hypotensive therapy more frequently than chlorthalidone. In addition, interim analysis (median follow-up: 3.3 years) of this study indicates that use of doxazosin in high-risk (at least 2 risk factors for coronary heart disease) hypertensive patients 55 years of age and older was associated with a higher risk of stroke and incidence of combined cardiovascular disease events (including twice the risk of congestive heart failure than use of chlorthalidone. Study investigators concluded that such increased risk of congestive heart failure could not have been caused by the relatively small difference in the mean target systolic blood pressure observed in patients receiving doxazosin compared with those receiving chlorthalidone. Therefore, based on these findings, the trial's Data Safety and Monitoring Board recommended that the α-blocker treatment arm be terminated prematurely. The remaining antihypertensive arms (e.g., calcium-channel blocking agents, angiotensin-converting enzyme [ACE] inhibitors, diuretics) and lipid-lowering (pravastatin vs usual care) components of the study subsequently were completed and reported.
Because of established clinical benefits (e.g., reductions in overall mortality and in adverse cardiovascular, cerebrovascular, and renal outcomes), ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics generally are considered the preferred drugs for the initial management of hypertension in adults. Although in the past α1-blockers such as prazosin were recommended as one of several classes of first-line antihypertensive therapy or as initial therapy in selected hypertensive patients (e.g., those with symptomatic prostatic hyperplasia), current antihypertensive and urology guidelines no longer recommend α1-blockers as preferred first-line therapy for any patients with hypertension, principally because of negative findings observed in ALLHAT. However, α1-blockers are effective antihypertensive drugs and many experts still consider their use appropriate for the management of resistant hypertension as a component of combination therapy. Although some experts state that an α1-blocker may be a useful component of antihypertensive treatment regimens in older men with coexisting benign prostatic hyperplasia (BPH), the American Urology Association (AUA) states that monotherapy with these drugs is not optimal in hypertensive patients with lower urinary tract symptoms (LUTS) or BPH and that such conditions should be managed separately .
The beneficial effects of α1-blockers on blood glucose and lipid concentrations may mitigate some of the adverse metabolic effects of diuretics, and α1-blockers may offer some advantage in patients with underlying lipoprotein disorders (e.g., hypercholesterolemia) or in those with lipoprotein abnormalities induced by other antihypertensive agents (e.g., thiazide diuretics). The possibility that geriatric patients may be more susceptible than younger patients to the postural hypotensive effects of α1-blockers should be considered in the selection of therapy. Blood pressure response to α1-blockers appears to be comparable in white and black patients.
Prazosin generally is most effective when used with a diuretic. The use of a diuretic may permit reduction of prazosin dosage. Prazosin has also been used with other hypotensive drugs, permitting a reduction in the dosage of each drug and, in some patients, minimizing adverse effects while maintaining blood pressure control.
(See Drug Interactions: Diuretics and Hypotensive Agents.)
For further information on overall principles and expert recommendations for treatment of hypertension,
Benign Prostatic Hyperplasia
Prazosin has been used to reduce urinary obstruction and relieve associated manifestations (e.g., urinary hesitancy and/or urgency, nocturia) in patients with symptomatic benign prostatic hyperplasia (BPH, benign prostatic hypertrophy) but efficacy relative to other α1-blockers remains to be established. For patients who can tolerate the potential cardiovascular and other effects of α1-adrenergic blockade, the drug can effectively relieve mild to moderate obstructive manifestations in a substantial proportion of patients, at least in the short term, and may be a useful alternative to surgery, particularly in those who are awaiting or are unwilling to undergo surgical correction of the hyperplasia (e.g., via transurethral resection of the prostate [TURP]) or who are not candidates for such surgery.
Therapy with α1-blockers appears to be less effective in relieving irritative than obstructive symptomatology. In addition, therapy with the drugs generally can be expected to produce less subjective and objective improvement than prostatectomy, and periodic monitoring (e.g., performance of digital rectal examination, serum creatinine determinations, serum prostate specific antigen [PSA] assays) is indicated in these patients to detect and manage other potential complications of or conditions associated with BPH (e.g., obstructive uropathy, prostatic carcinoma). While symptomatic improvement has been observed in the short term in some patients receiving prazosin therapy, the long-term effects of α1-blockers on the need for surgery and on the frequency of developing BPH-associated complications such as acute urinary obstruction remain to be established. Currently available α1-adrenergic blockers (with the exception of prazosin, for which there are insufficient data to compare) are considered comparably effective.
Current evidence from principally uncontrolled, short-term studies suggests that the α1-selective adrenergic blocker prazosin produces beneficial effects in approximately 60-70% of treated patients without the degree of adverse effects associated with nonselective adrenergic blockers; alleviation of both obstructive and irritative manifestations of the hyperplasia has been reported in some patients with prazosin therapy. In a few placebo-controlled or comparative studies, therapy with prazosin in dosages of 1-9 mg daily (generally 2 mg twice daily) has improved urinary flow rates and reduced urinary frequency and nocturia in patients with BPH.
Combination therapy with an α1-blocker and 5α-reductase inhibitor (e.g., finasteride) has been more effective than therapy with either drug alone in preventing long-term BPH symptom progression; combined therapy also can reduce the risks of long-term acute urinary retention and the need for invasive therapy compared with α1-blocker monotherapy.
For additional information on the use of α1-blockers in the management of BPH,
Posttraumatic Stress Disorder
Prazosin has been used in the management of posttraumatic stress disorder (PTSD), particularly in combat veterans and in patients experiencing nighttime PTSD symptoms (e.g., nightmares, sleep disturbances). Nightmares and other sleep disturbances reportedly occur in about 70-87% of patients with PTSD; such patients often have decreased sleep efficiency because of more frequent nocturnal awakenings, as well as a higher incidence of other parasomnias and sleep-related breathing disorders compared with patients who have idiopathic nightmares.
Although selective serotonin-reuptake inhibitors (SSRIs; e.g., paroxetine, sertraline) generally have been considered the drugs of choice for the pharmacologic treatment of PTSD, they usually have not been effective in treating nighttime PTSD symptoms, which can be very disturbing and substantially interfere with the patient's quality of life. Atypical antipsychotic agents also have been studied in the treatment of PTSD and have been shown to reduce nighttime PTSD symptoms and may help reduce accompanying psychotic and other symptoms (e.g., agitation, irritability) in some patients; however, routine and long-term use of these drugs is discouraged by some clinicians because of the risk of clinically important adverse effects, such as weight gain and diabetes mellitus.
Clinical experience with prazosin in PTSD to date, which is mainly from small case series, case reports, retrospective or open-label studies, and several small randomized placebo-controlled studies, indicates that the drug is effective in suppressing or eliminating the nighttime sleep-related symptoms associated with PTSD. In several open-label and retrospective studies, prazosin therapy substantially improved trauma-related nightmares and reduced the severity of PTSD (as assessed by the recurrent distressing dreams item of the Clinician-Administered PTSD Scale [CAPS] and/or the Clinical Global Impression of Change [CGI-C] Scale, a 7-point clinician-rated assessment measuring overall PTSD severity and function).
In 2 randomized, double-blind, placebo-controlled trials conducted in combat veterans with PTSD, prazosin was found to be superior to placebo in reducing trauma-related nightmares and sleep disturbances. In the first study, 10 Vietnam combat veterans (mean age: 53 years) with chronic PTSD and severe trauma-related nightmares were randomized to receive prazosin or placebo with crossover to the opposite treatment arm occurring midway through the 20-week study. Prazosin was found to be more effective than placebo in reducing nightmares and sleep disturbances (assessed by CAPS) as well as improving overall PTSD severity and functional status (assessed by the CGI-C Scale). The second study, which was 8 weeks in duration, was conducted in a larger group of patients (40 US combat veterans; mean age: 56 years) with chronic PTSD, distressing trauma nightmares, and sleep disturbances. Compared with placebo, patients receiving prazosin in this study experienced substantially greater improvements in each of the 3 primary outcome measures addressing frequency and intensity of trauma-related nightmares and sleep quality used in this study (the CAPS recurrent distressing dreams item, the Pittsburgh Sleep Quality Index, and the CGI-C).
In a double-blind, placebo-controlled study in 13 patients with civilian trauma-related PTSD, prazosin reduced trauma-related nightmares, distressed awakenings, and total PTSD Checklist-Civilian scores; improved Clinical Global Impression of Improvement scores; and changed the PTSD Dream Rating Scale toward normal dreaming compared with placebo; the drug also improved objective measures of sleep (total sleep time, total REM sleep time, mean REM period duration) without changing sleep onset latency. In a historical prospective cohort study using retrospective chart review, the short-term effectiveness of prazosin (62 patients) and quetiapine (175 patients) in treating nighttime PTSD symptoms in combat veterans was found to be similar. However, long-term effectiveness (3-6 years) of prazosin was better compared with quetiapine; the quetiapine-treated patients were found to be more likely to discontinue therapy because of adverse effects than the prazosin-treated patients (approximately 35 and 18%, respectively). Prazosin therapy was generally found to be well tolerated when used in the treatment of PTSD-associated nightmares and other symptoms.
Some clinicians recommend prazosin as either first-line or alternative therapy when treating PTSD patients with prominent nighttime symptoms (e.g., nightmares, insomnia, sleep disturbances), particularly in combat veterans. Prazosin therapy could potentially be beneficial in some older PTSD patients who have hypertension and/or benign prostatic hyperplasia, since these conditions also may respond to therapy with the drug. Although preliminary findings have been very encouraging, larger, well controlled studies are needed to more fully define the role and optimum dosing of prazosin in the pharmacologic management of PTSD. In addition, further studies are needed to determine the safety and efficacy of prazosin in civilians with noncombat trauma-related PTSD and in the treatment of daytime symptoms associated with PTSD. Several controlled studies, including comparative and augmentation trials, are planned or currently underway to further evaluate prazosin in patients with this disorder.
For additional information on management of PTSD,
Prazosin has been effective in conjunction with cardiac glycosides and diuretics for the management of severe congestive heart failure, often producing improvements in cardiac function indexes and exercise tolerance. Although partial or complete tolerance to the hemodynamic effects of prazosin has reportedly developed rapidly in some patients, the attenuated response may be transient and/or corrected by dosage adjustment, by temporarily withdrawing the drug, and/or by the addition of an aldosterone antagonist (e.g., spironolactone) to the treatment regimen; acute hemodynamic attenuation does not preclude a beneficial hemodynamic response, especially during exercise. Most studies evaluating the long-term effects of prazosin have suggested that beneficial clinical and hemodynamic effects are sustained; however, conflicting results have been reported. Further studies are needed to determine the efficacy and role of prazosin for the long-term treatment of severe congestive heart failure.
Prazosin has been used with good results alone or in combination with a β-blocker for the preoperative management of the signs and symptoms of pheochromocytoma in a limited number of patients; however, these patients may be particularly susceptible to a marked hypotensive response to the initial dose of prazosin. Limited data also suggest that prazosin may be useful for the treatment of Raynaud's disease or phenomenon and ergotamine-induced peripheral ischemia.