High-dose prazosin for the treatment of post-traumatic stress disorder

Koola, Maju Mathew; Varghese, Sajoy P.; Fawcett, Jan

doi:10.1177/2045125313500982

Cited by 47 publications

(31 citation statements)

References 16 publications

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“…This is a confounding result as higher prazosin doses have been reported to be more effective in cases when more moderate doses have produced partial responses [78,79]. The VAMC dose ranges were congruent with what was reported by Davidson et al [19], Raskind [44], Raskind [46], Van Liempt et al [20], Raskind [45], Taylor [80], Peskind [81], Aurora et al [21], Raskind [26], and Taylor 2008 [47].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

Detweiler

Pagadala

Candelario

et al. 2016

JCM

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The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0–6.0 mg), clonidine (63%, 0.1–2.0 mg), quetiapine (50%, 12.5–800.0 mg), mirtazapine (50%; 7.5–30.0 mg), and terazosin (64%, 50.0–300.0 mg). Notably, olanzapine (2.5–10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares.

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Section: Discussionmentioning

confidence: 99%

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

Detweiler

Pagadala

Candelario

et al. 2016

JCM

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“…The use of combination treatment is playing a major role in the treatment of several other complex pathological conditions such as depression in schizoaffective disorder, bipolar type, posttraumatic stress disorder (PTSD), unipolar and bipolar depression (Koola et al, 2011; Koola et al, 2014). There is evidence that naltrexone and prazosin combination may be effective for PTSD and alcohol use disorder (Qazi et al, in press).…”

Section: Discussionmentioning

confidence: 99%

Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia

Koola

Boyer

Pillai

et al. 2014

Schizophrenia Research

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The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia projects were designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia. The MATRICS project identified three drug mechanisms of particular interest: dopaminergic, cholinergic, and glutamatergic. As a group, while people with schizophrenia have moderate cognitive impairment, it is the best predictor of long-term outcome. Unfortunately, there are no approved medications for cognitive impairment in this population. Hence, the development of new pharmacological approaches is critical for reducing illness-related disability. The combination of an acetylcholinesterase inhibitor (AChEI) and memantine is more effective than either medication alone to improve cognition in Alzheimer’s dementia. Galantamine is not only an AChEI, but also a positive allosteric modulator of the α4β2 and α7 nicotinic receptors. Hypofunction of N-methyl-D-aspartate (NMDA) receptors has been implicated in the pathophysiology of cognitive symptoms in schizophrenia and hence memantine may positively impact cognition. Memantine decreases the tonic NMDA current and galantamine enhances the action potential mediated by a postsynaptic NMDA current. This results in an increased signal transmission; therefore, a greater signal-to-noise ratio occurs with the combination than memantine alone. Galantamine improves the α-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)-mediated signaling which could be neuroprotective and may improve memory coding. The combination of galantamine and memantine may be particularly effective in schizophrenia in order to increase the selective cognition enhancement produced by either medication alone. In the future, multitarget-directed ligands may play a role in the treatment of complex diseases like schizophrenia.

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“…Endogenous NE signaling is elevated in PTSD and drugs that block NE receptors are already being used with some success to either prevent or treat PTSD, including its symptoms of hyperarousal and nightmares (14)(15)(16)(17)(18). Clinically effective noradrenergic drugs include the α1-adrenoceptor antagonist, prazosin, and the β1/β2-adrenoceptor antagonist, propranolol (17,(19)(20)(21). The neural mechanisms underlying the efficacy of these drugs remain poorly understood.…”

mentioning

confidence: 99%

Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

Fitzgerald

Giustino

Seemann

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

117

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Stress-induced impairments in extinction learning are believed to sustain posttraumatic stress disorder (PTSD). Noradrenergic signaling may contribute to extinction impairments by modulating medial prefrontal cortex (mPFC) circuits involved in fear regulation. Here we demonstrate that aversive fear conditioning rapidly and persistently alters spontaneous single-unit activity in the prelimbic and infralimbic subdivisions of the mPFC in behaving rats. These conditioning-induced changes in mPFC firing were mitigated by systemic administration of propranolol (10 mg/kg, i.p.), a β-noradrenergic receptor antagonist. Moreover, propranolol administration dampened the stress-induced impairment in extinction observed when extinction training is delivered shortly after fear conditioning. These findings suggest that β-adrenoceptors mediate stress-induced changes in mPFC spike firing that contribute to extinction impairments. Propranolol may be a helpful adjunct to behavioral therapy for PTSD, particularly in patients who have recently experienced trauma.fear | extinction | propranolol | prefrontal cortex | rat

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High-dose prazosin for the treatment of post-traumatic stress disorder

Cited by 47 publications

References 16 publications

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia

Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

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