Prazosin for psychiatric disorders
Before reading this article it would be worthwhile reading the Tree Model of Brain Disease
Prazosin is a cardiac drug which is now being used in Post-Traumatic Stress Disorder (PTSD). This article explains how it may work.
PTSD is a combination of fear (anxiety), self-pity (depression), resentment (hatred), dishonesty (criminality) and often obsessive-compulsive behavior (OCD) which tends to affect people who are genetically predisposed (5-HTT, DRD2, DAT and CNB1. Some genes are associated with particular symptoms of PTSD e.g. re-experiencing and the APOE2 allele).1
2. Protein Kinase (PKC) and Psychiatric disease
PKC is an enzyme which is often elevated in psychiatric disease resulting in dendritic spine loss and reduced firing. Inhibition of PKC rescued working memory impairments and reversed dendritic spine loss. 2
3. Effect of CRF on PKC
Stress hormones such as corticotrophin-releasing hormone stimulate PKC. 3
4. PKC and alpha-1 receptor stimulation
Alpha-1 receptor stimulation stimulates PKC activity. 4
5. Prazosin on brain morphology
Prazosin (an alpha-1 receptor blocker) treatment results in increased dendritic spine density. 5
6. Prazosin and PKC
Prazosin reduces PKC activity. 6
7. Anti-inflammatory action of Prazosin
As with other psychiatric drugs, Prazosin has anti-inflammatory actions. 7
Perhaps prazosin acts in the following manner in accordance with the tree model of brain disease
1. CRF causes an immunogenic response in the brain in genetically predisposed individuals mediated by stimulation of PKC.
2. Dendritic spine morphology changes occur, namely reduced density in the frontal lobes, hippocampus (memory centre) and amygdala (fear centre).
3. Clinical features of fear, self-pity, resentment and dishonesty and obsession-compulsion develop.
4. Prazosin reduces protein kinase levels activity.
5. The immunogenic response is reduced.
6. Dendritic spine density increases.
7. The clinical features improve resulting in gratitude, trust, acceptance and honesty with reduction in obsession-compulsion.
In practice night-time prazosin does reduce nightmares and daytime prazosin reduces psychological distress specifically to trauma cues in patients with PTSD. 8 It is anticipated that Prazosin will be trialled in other psychiatric diseases in which fear is prominent.
Tree Model of Brain Disease video