Pharmacotherapy as Prophylactic Treatment of Post-Traumatic Stress Disorder: A Review of the Literature

Roque, Autumn

doi:10.3109/01612840.2015.1057785

Cited by 15 publications

(15 citation statements)

References 21 publications

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“…As prazosin acts by putatively blocking α1 receptors, antagonism of alpha-1 receptors could possibly prevent further stress or trauma from triggering the norepinephrine-mediated stimulation of stress axis reactivity (Ma & Morilak, 2005). Thus, prazosin may work better as a prophylactic in treating stress-related conditions, as has been observed for other medications (Roque, 2015), although much more clinical work would be necessary to establish this as a potential option for therapy.…”

Section: Discussionmentioning

confidence: 99%

Effects of chronic prazosin, an alpha-1 adrenergic antagonist, on anxiety-like behavior and cortisol levels in a chronic unpredictable stress model in zebrafish (Danio rerio)

O’Daniel

Petrunich-Rutherford

2020

PeerJ

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Post-traumatic stress disorder (PTSD) is often associated with significant neuroendocrine dysfunction and a variety of other symptoms. Today, there are limited efficacious treatment options for PTSD, none of which directly target the dysfunction observed with the hypothalamic-pituitary-adrenal (HPA) axis. The development of new pharmacological treatments is expensive and time consuming; thus, there is utility in repurposing compounds already approved for use in other conditions. One medication in particular that has shown promise for the alleviation of PTSD symptoms is prazosin, an alpha-1 adrenergic receptor antagonist used to treat hypertension. While there have been many studies indicating the efficacy of prazosin in the treatment of PTSD symptoms, no studies fully elucidate mechanisms elicited by this treatment, nor is it clear if prazosin normalizes neuroendocrine dysfunction associated with trauma exposure. The use of zebrafish (Danio rerio) has been growing in popularity, in part, due to the homology of the stress response system with mammals. In this study, the zebrafish model was utilized to determine behavioral and biological changes induced by chronic unpredictable stress (CUS) and how these effects could be modulated by chronic prazosin treatment. The results indicated that 7d of CUS increased anxiety-like behavior in the novel tank test and decreased basal levels of cortisol. Chronic (7d) prazosin treatment decreased anxiety-like behaviors overall but did not appear to affect CUS-induced changes in behavior and basal cortisol levels. This suggests that the clinical effectiveness of prazosin may not normalize dysregulated stress responses prevalent in many patients with PTSD, but that prazosin-induced relief from anxiety in stress-related conditions may involve an alternative mechanism other than by normalizing neuroendocrine dysfunction.

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Section: Discussionmentioning

confidence: 99%

Effects of chronic prazosin, an alpha-1 adrenergic antagonist, on anxiety-like behavior and cortisol levels in a chronic unpredictable stress model in zebrafish (Danio rerio)

O’Daniel

Petrunich-Rutherford

2020

PeerJ

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“…Major Depressive Disorder (MDD) and Posttraumatic Stress Disorder (PTSD) place great burdens on individuals, families, and society (e.g., Kessler, 2000 ; Greenberg et al, 2015 ). Although considerable advances have been made in the treatment of these disorders, many patients do not benefit from current therapeutic interventions (e.g., Turner et al, 2008 ; Cuijpers et al, 2009 ; Kar, 2011 ; Roque, 2015 ), resulting in a growing interest in the translation of findings from basic cognitive-neuroscience to the treatment of mental health issues such as MDD and PTSD (Cuthbert and Insel, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Memory Specificity Training for Depression and Posttraumatic Stress Disorder: A Promising Therapeutic Intervention

Erten

2018

Front. Psychol.

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“…These use cases could include partially remitted or treatment discontinuing MDD or BPD patients that are at high risk for relapse (Judd, 1997;Mueller et al, 1999;Nierenberg et al, 2010;Iovieno et al, 2011) or individuals exposed to acute trauma that are at high risk for developing PTSD (Roque, 2015).…”

Section: Introductionmentioning

confidence: 99%

Prophylactic efficacy of riluzole against anxiety- and depressive-like behaviors in two rodent stress models

Fee

Misquitta

Sibille

et al. 2020

Preprint

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BackgroundChronic stress-related illnesses, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), share symptomatology, including anxiety, anhedonia, and helplessness. Across disorders, neurotoxic dysregulated glutamate (Glu) signaling may underlie symptom emergence. Current first-line antidepressant drugs (ADs), which do not directly target Glu signaling, fail to provide adequate benefit for many patients and are associated with high relapse rates. Riluzole modulates glutamatergic neurotransmission by increasing metabolic cycling and modulating signal transduction. Clinical studies exploring riluzole’s efficacy in stress-related disorders have provided varied results. However, the utility of riluzole for treating specific symptom dimensions or as a prophylactic treatment has not been comprehensively assessed.MethodsWe investigated whether chronic prophylactic riluzole (∼12-15/kg/day p.o.) could prevent the emergence of behavioral deficits induced by unpredictable chronic mild stress (UCMS) in mice. We assessed i) anxiety-like behavior using the elevated-plus maze, open field test, and novelty-suppressed feeding, ii) mixed anxiety/anhedonia-like behavior in the novelty-induced hypophagia test and, iii) anhedonia-like behavior using the sucrose consumption test. Z-scoring summarized changes across tests measuring similar outcomes. In a separate learned helplessness (LH) cohort, we investigated whether chronic preventative riluzole treatment could block the development of helplessness-like behavior.ResultsUCMS induced an elevation in anxiety-, anhedonia-like behavior, and overall behavioral emotionality that was blocked by prophylactic riluzole. In the LH cohort, preventative riluzole blocked the development of helplessness-like behavior.ConclusionThis study supports the utility of riluzole as a prophylactic medication, and potential relapse-preventing treatment targeting anhedonia, anxiety, and helplessness symptoms associated with stress-related disorders.Significance StatementRiluzole is a glutamate-modulating drug with mixed evidence of efficacy in clinical studies of patients with stress-related disorders. Based on evidence suggesting that glutamatergic dysfunction contributes to the pathogenesis of stress-related disorders, we investigated whether prophylactic treatment with riluzole could prevent the onset of behavioral deficits induced by unpredictable chronic mild stress or learned helplessness in mice. Riluzole effectively prevented the emergence of anxiety-, anhedonia-like behavior, and overall behavioral emotionality in mice exposed to unpredictable chronic mild stress. In a separate cohort, riluzole blocked the emergence of helplessness-like behavior as measured in an active avoidance paradigm. These results support testing riluzole as a prophylactic treatment strategy in stress-related illnesses such as major depressive disorder or post-traumatic stress disorder.

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Pharmacotherapy as Prophylactic Treatment of Post-Traumatic Stress Disorder: A Review of the Literature

Cited by 15 publications

References 21 publications

Effects of chronic prazosin, an alpha-1 adrenergic antagonist, on anxiety-like behavior and cortisol levels in a chronic unpredictable stress model in zebrafish (Danio rerio)

Effects of chronic prazosin, an alpha-1 adrenergic antagonist, on anxiety-like behavior and cortisol levels in a chronic unpredictable stress model in zebrafish (Danio rerio)

Memory Specificity Training for Depression and Posttraumatic Stress Disorder: A Promising Therapeutic Intervention

Prophylactic efficacy of riluzole against anxiety- and depressive-like behaviors in two rodent stress models

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