Prazosin and Other Medications for PTSD and mTBI

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Prazosin (and Other Medications) for PTSD and mTBI Murray A. Raskind, MD Director, VISN-20 Mental Illness Research, Education, and Clinical Center Professor and Vice-Chair Dept. of Psychiatry & Behavioral Sciences University of Washington School of Medicine

Prazosin A non specific lipid-dissolvable alpha-1 adrenoreceptor (AR) adversary presented in 1973 as "Minipress" for treatment of hypertension Short length of activity (6-10 hours) Costs pennies every day

Neurobiologic Model of PTSD Brain "adrenaline surge" that spares lives in battle gets to be distinctly diligent and maladaptive. Durable upregulation of mind postsynaptic adrenoreceptor (AR) reaction to norepinephrine at the alpha 1 AR (in prefrontal cortex, amygdala?) adds to reexperiencing and hyperarousal indications.

Two Prazosin RCTs in Vietnam Veterans with PTSD: CAPS Recurrent Distressing Dreams ("Nightmares")

Two Prazosin RCTs in Vietnam Veterans with PTSD: Clinical Global Impression of Change (CGIC)

Individual PTSD Symptoms Responsive to Prazosin in Crossover Study p esteem < 0.001 < 0.01 <0.01 < 0.05 < 0.05 < 0.05 < 0.05 < 0.1 CAPS Item Recurrent troubling dreams Difficulty falling/staying unconscious Physiological reactivity to injury updates Irritability or outrage upheavals Intrusive injury memories Diminished intrigue/cooperation in exercises Restricted effect… desensitizing Hypervigilance

Sleep Physiology of Trauma Nightmares and PTSD Trauma bad dreams emerge from upset REM rest and light rest (stages 1 and 2). In creatures, alpha-1 incitement with methoxamine upsets REM rest and stretches light rest. These impacts are turned around by prazosin. Taylor FB, et al., Biol Psychiatry 63:629-32, 2008.

Prazosin and Sleep Physiology: A Placebo-Controlled Crossover Study REMview® gadget recorded rest versus wake and REM versus non-REM. 10 of 13 members gave an entire three evenings of REMview information in both support prazosin condition (3.1 ± 1.3 mg hs) and fake treatment condition.

Effects of Prazosin versus Fake treatment on Sleep Measures in PTSD Subjects with Nocturnal Symptoms 500 Placebo ** Prazosin 400 300 Mean Sleep time (Minutes ± SD) ** 200 100 ** * 0 Total Sleep Time REM Sleep Time Sleep Latency REM Latency Mean REM Period Duration *Significant distinction amongst prazosin and fake treatment gather by rehashed measures ANOVA *p < 0.05, **p < 0.01

Placebo-Controlled Trial of Prazosin in Alcohol Dependent Persons Seeking Abstinence: Subjects and Methods 17 liquor subordinate men without PTSD (46 ± 7 years). Two week titration to target dosage of prazosin (or fake treatment) 4 mg BID, 8 mg HS. Kept up at target measurement for 4 weeks. Simpson, TL et al., Alcohol Clin Exp Res 31:60A, 2007.

Mean Drinking Days Per Week by Condition (Male Completers Only) Controlling for drinking days every week at gauge and week number, the prazosin gather revealed less drinking days every week than the fake treatment bunch amid the last 3 weeks of the review (β = - 1.84; 95% CI = - 2.74, - .93; p < 0.001).