Prazosin in the pharmacological treatment of sleep disturbances in post traumatic stress disorder, a placebo-controlled study using polysomnography

Posttraumatic stress disorder (PTSD) is an often chronic and disabling
disorder. Nightmares have been acknowledged as the hallmark of PTSD. Overall,
sleep complaints affect about 70% of PTSD patients.
The majority of PTSD patients is treated with a selective serotonin reuptake
inhibitor (SSRI). Although SSRIs are effective for most PTSD symptoms, sleep
disturbances are generally therapy resistant to SSRIs.
Placebo controlled studies in PTSD have shown that prazosin, an alpha 1
adrenoceptor blocking agent, was effective in the treatment of nightmares and
insomnia after 8 weeks of treatment. Only subjective sleep quality was measured
to evaluate the effect of prazosin in this study.
In spite of the disturbed subjectieve sleep quality, a relatively normal
(macro)sleep architecture is seen with controlled studies using polysomnography
(PSG). However, PSG studies did identify disturbed sleep patterns such as a
higher number of (micro)awakenings.
Evaluating the efficacy of prazosin with both subjective and objective
parameters may provide more insights in the underlying mechnisms of sleep
complaints in PTSD.

The aim of this study is to evaluate the efficacy of prazosin for the treatment
of PTSD related sleep disturbances, and to evaluate response with objective and
subjective parameters.

This study is a double-blind, placebo-controlled randomized trial with prazosin
or placebo as add-on medication to standard treatment with a SSRI. This trial
will be conducted at the research centre of the MGGZ in collaboration with the
UMC Utrecht and Kempenhaghe, Centre for Sleep and Wake Disorders and Centrum
45. A patient information form will be provided and written informed consent
will be obtained from all subjects prior to entry to the trial.
After screening for psychiatric co-morbidity and other relevant medical
conditions, the subjects will be randomized into the prazosin or placebo group.
Clinician and patient are blind for the treatment status. Patients will be
treated for 8 weeks. Polysomnography will be performed at baseline and endpoint
of the treatment phase. Additional visits are planned at week 3, 5 and 7 for
evaluating side effects and blood pressure and, when needed, for adjusting the
dosage.

Treatment with prazosin or placebo for 8 weeks.

1. Side effects after administration of prazosin.
To reduce risks:
*Slow titration in first four weeks
*When orthostatic hypotension occurs as a side effect, patients will be advised
to avoid situations that can cause hypotension in the first weeks, like
suddenly rising from a chair or bed. When these symptoms occur patients are
advised to lie down until symptoms subside.
*Patients can call physician on call in case of side effects.

2. PSG recordings (Participants of MGGZ and UMC Utrecht).
Subjects will sleep with PSG equipment for a total of 4 nights.
To minimize the burden we will use ambulantory equipment (2 nights before and 2
nights at the end of the treatment phase), so the participants can sleep at
home. Electrodes will be applied at the MGGZ or, and removed after the second
night at the MGGZ. Or the researchers go to the homes of the participants to
apply, and remove, the electrodes.