Indication

• Distress/functional impairment in patients with post-traumatic stress disorder (PTSD)-related nightmares.
• May be used as monotherapy for PTSD nightmares, or as an adjuvant to other medications used for global PTSD symptoms as a specific addition to reduce nightmares.
• There is no evidence that prazosin is effective as monotherapy for global PTSD symptoms and there is conflicting evidence for its efficacy on overall sleep quality. 

Off-label prescribing

• Patients should be made aware that this is not a licensed indication for prazosin. 

Cautions 

• May add to the antihypertensive affect of other medications e.g. phosphodiesterase type 5 inhibitors and other antihypertensives (eg, beta blockers, calcium channel blockers).

Contraindications

• Hypersensitivity to the active substance, prazosin, other quinazolines or to any of the excipients (listed in section 6.1 of the SPC).

For initiation by or on the advice of a hospital specialist only

• It is important that patients being considered for treatment with prazosin for PTSD nightmares are also assessed within the Community Mental Health Team to identify psychiatric co-morbidities and to consider referral for appropriate trauma-focused psychological therapies.
• NICE guidelines emphasise that all patients with PTSD should have access to trauma-focused psychological therapies, and that drug treatments for PTSD should not be used as a routine first-line treatment for adults (in general use or by specialist mental health professionals) in preference to a trauma-focused psychological therapy. (NICE NG116)

Prescribing agreement 

• It may be worth considering a prescribing agreement in collaboration with the patient, which sets out treatment goals, plans for monitoring response and an agreement to stop the medication if it is not effective.
• A suggested form is available within the ICP | Nhsh Pds Education (nhshdbtservice.wixsite.com)

Suggested dose schedule

• Start doses at 1mg at night to prevent initial dose syncope (reported by 1% at doses 2mg and up).
• Titrate dose upwards to 2mg after a 2 to 3 days, and then upwards in steps of 1mg every 2 to 7 days depending on benefit and side-effects (dizziness 10%, headache 8%, drowsiness 8%, lack of energy 7%, weakness 7%, palpitations 5%, nausea 5%).
• US Veterans PTSD guidelines state the target dose as being 6mg to 10mg/day, but studies suggest that veterans may require higher doses than civilians.
• Patients with severe complex dissociative PTSD resulting from childhood abuse may also require higher doses.
• Response is described at doses from 1mg to 16mg+.
• Use the minimum effective dose.

Common adverse effects

• Dizziness 10%, headache 8%, drowsiness 8%, lack of energy 7%, weakness 7%, palpitations 5% and nausea 5%.

Effects on ability to drive and operate machinery

• Patients should be advised on how to avoid symptoms resulting from postural hypotension and what measures to take should they develop.
• Patients should be cautioned to avoid situations where injury could result should dizziness or weakness occur during the initiation of prazosin treatment

Duration of treatment

• The optimum duration of treatment is not established, so, in discussion with the individual patient it would be appropriate to try withdrawing this medication after a period of stability, particularly if psychological therapy has also been effective in reducing other PTSD symptoms.

Toxicity in overdose (Toxbase entry Aug 2020)

• Coma and severe hypotension have been reported in adults following ingestion of between 80mg to 200mg of prazosin. All patients made a full recovery within 36 to 48 hours with symptomatic and supportive care alone (Lenz et al, 1985: Rygnestad & Dale, 1983; McClean, 1976).
• Co-ingestion of other drugs with blood pressure lowering effects may potentiate the hypotensive effects of prazosin.
• Following therapeutic doses, peak activity occurs between 1 to 2 hours and the plasma half-life is 2 to 3 hours (Hypovase SPC, 2021).