Treatment of PTSD-related nightmares with Prazosin

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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. 

Cautions: May add to the antihypertensive affect of other medications e.g. phosphodiesterase type 5 inhibitors and other antihypertensives (e.g. 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 only by or on the advice of a hospital specialist: 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)

Off-label prescribing
Patients should be made aware that this is not a licensed indication for prazosin. 

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 PD-ICP: Personality Disorder Integrated Care Pathway (PD-ICP)

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 May 2016)
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, 2009).