Pharmacotherapy of Post-Traumatic Stress Disorder

ChapterinCurrent Topics in Behavioral Neurosciences 2(2):505-525 · November 2009with8 Reads
DOI: 10.1007/7854_2009_15
In book: Behavioral Neurobiology of Anxiety and Its Treatment, pp.505-525
Abstract
Post-traumatic stress disorder (PTSD) is a prevalent psychiatric disorder that may result in significant social and occupational debilitation unless symptoms are recognized and treated appropriately. Considerable research effort has been devoted over the last 20years to developing effective pharmacological treatments for this illness. At this time, the bulk of the agents investigated include antidepressants, anticonvulsants, atypical antipsychotics, benzodiazepines, and antiadrenergic agents. Herein, we review the existing evidence base for these different classes of psychotropics in PTSD. Emphasis is placed on discussion of evidence stemming from randomized placebo-controlled clinical trials wherever possible. A brief description of novel agents that have shown initial promise for PTSD treatment is also provided.
    • In this event, progressive psychotherapeutic approaches, such as progressive desensitization and/or stimulus immersion are less likely to succeed. Pharmacotherapy using benzodiazepines, while somewhat effective, is burdened by side effects (inclusive of sedation, tolerance, and withdrawal), and other pharmacological approaches (e.g., azapirones; betareceptor antagonists) have been shown to be only nominally effective (Ravindran and Stein, 2010). In these cases, DBS of the amygdala may be useful to suppress abnormal activity within amygdalar-prefrontocortical circuits, and " re-set " the inhibitory tone necessary for fear extinction and reduction of PTSD symptoms.
    [Show abstract] [Hide abstract] ABSTRACT: This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.
    Full-text · Article · Nov 2016
    • This proposition is also supported by twin studies, which indicate that approximately 30% of the variability in PTSD risk is attributable to genetic factors (heritability) [3], [4], [5], [6]. Many genetic studies of PTSD to date have focused on the serotonin system, as PTSD can be treated by targeting the serotonin transporter (SLC6A4) with selective-serotonin reuptake inhibitors (SSRIs) [7], [8]. The extensively studied 5-HTTLPR variant of the SLC6A4 gene is a repeat length polymorphism in the 5' flanking promoter region that regulates gene expression levels [9].
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To examine the association between the 5-HTTLPR polymorphism of the serotonin transporter (SLC6A4) gene, combat exposure, and posttraumatic stress disorder (PTSD) diagnosis and among two samples of combat-exposed veterans. Method: The first sample included 550 non-Hispanic Black (NHB) combat-exposed veterans. The second sample included 555 non-Hispanic White (NHW) combat-exposed veterans. Participants were genotyped for the 5-HTTLPR/rs25531 variants of the SLC6A4 gene. A structured clinical interview was used to diagnose PTSD. Combat and civilian trauma exposure were assessed with validated self-report instruments. Logistic regression was used to test for main effects of 5-HTTLPR on PTSD diagnosis as well as gene x environment (GxE) interactions after adjusting for sex, ancestry proportion scores, civilian trauma exposure, and combat exposure. Results: Within the NHB sample, a significant additive effect was observed for 5-HTTLPR (OR = 1.502, p = .0025), such that the odds of having a current diagnosis of PTSD increased by 1.502 for each additional S' allele. No evidence for an association between 5-HTTLPR and PTSD was observed in the NHW sample. In addition, no evidence for combat x 5-HTTLPR effects were observed in either sample. Conclusion: The present study suggests that there may be an association between 5-HTTLPR genotype and PTSD diagnosis among NHB veterans; however, no evidence for the hypothesized 5-HTTLPR x combat interaction was found.
    Full-text · Article · Mar 2015
    • At present, there is no effective treatment against chronic neuropsychiatric and neurological disorders caused by OP poisoning. Pharmacotherapy aimed at affecting individual symptoms or clusters of chronic neuropsychiatric and neurological disorders (De Wester 1996; Sink et al. 2005; Ravindran and Stein 2010) may help improve recovery from neurobehavioral malfunctions in victims of OP poi- soning.
    [Show abstract] [Hide abstract] ABSTRACT: Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.
    Full-text · Article · Sep 2014
    • The benzodiazepines were developed as a safer alternative to barbiturates, however, their beneficial effects are overshadowed by the emergence of physical and psychological dependence and withdrawal reactions [6,7]. Other drugs used for treatment of anxiety having unfavorable side-effect profiles include buspirone [8,9], antidepressants101112 and beta-blockers [5]. Due to adverse effects associated with the currently available drugs, patients on anxiolytic drugs usually terminate the treatment before full recovery [13].
    [Show abstract] [Hide abstract] ABSTRACT: Background Foeniculum vulgare locally known as ensilal, is an aromatic plant widely cultivated in temperate and tropical regions. The anti-anxiety activity of the crude extract of F. vulgare has been reported. However, the fraction responsible for anxiolytic activity is not known and there is no any report on the anti-anxiety activity of the essential oil of F. vulgare. The objective of study was to evaluate the anxiolytic activity of the essential oil of Foeniculum vulgare Miller. Methods Adult Swiss albino male mice were randomly divided into six groups (n = 6). Groups I and II received Tween 80 (5%, v/v) and diazepam (0.5 mg/kg, ip), respectively, while groups III to V received orally 50, 100, and 200 and 400 mg/kg doses of the essential oil of F. vulgare, respectively. The mice were then individually placed in animal anxiety models: elevated plus maze (EPM), staircase test (SCT) and open field test (OFT) and evaluated for various parameters. Results In EPM test, 100 and 200 mg/kg doses of the essential oil significantly increased percent number of entries and time spent in open arms compared to control. In SCT these doses also reduced rearing significantly compared to controls, while only the 200 mg/kg dose significantly increased number of squares crossed at the center in the OFT test. Conclusion The essential oil of F. vulgare was found to exhibit a promising anxiolytic activity.
    Full-text · Article · Aug 2014
    • Considerable research efforts have been devoted over the last 20 years to developing effective pharmacological treatments for this illness. Currently, the bulk of the agents investigated include antidepressants, anticonvulsants, atypical antipsychotics, benzodiazepines, and antiadrenergic agents120121122123. With regard to pharmacological treatment, SSRIs are the treatment of choice.
    [Show abstract] [Hide abstract] ABSTRACT: The aim of this paper was to critically review the current treatment of anxiety disorders including general anxiety disorder, panic disorder, social anxiety disorder and post-traumatic stress disorder. For all these disorders, this paper will suggest treatment guidelines based on literature data as well as personal experience. Obsessive compulsive disorder (OCD) even considered in DSM IV as an anxiety disorder is somewhere different from the other anxiety disorder (almost lack of placebo response, efficacy of cognitive-behavioural therapy and deep brain stimulation).
    Full-text · Article · Feb 2013
    • Perhaps the best grounds for proposing that a 5-HT dysfunction exists in PTSD resides in the beneficial treatment effects of SSRIs, which, to date, have already been established as the firstline pharmacotherapeutic agents for treating acute and chronic PTSD. However, SSRIs largely have disadvantages including delayed onset of action, partial response with residual symptoms or non-response, and severe side effects (e.g., loss of sexual drive, gastrointestinal effects, changes in body weight), which limit their utility and indicate a major unmet medical need to explore more promising treatment approaches in PTSD11121314151617. Traditional Chinese medicine (TCM), because of its better compliance and lower side effects [18], draws more and more attentions and provides a prospective alternative to the treatment of several mental disorders [18– 22].
    [Show abstract] [Hide abstract] ABSTRACT: The dysregulation of the serotonergic system has long been recognized as an important factor underlying the pathophysiology of PTSD. To date, SSRIs have already been established as the firstline pharmacotherapeutic agents for treating acute and chronic PTSD. However, SSRIs largely have several disadvantages which limit their utility. Our previous study has also shown that administration of the total flavonoids, isolated from the extract of Xiaobuxin-Tang (XBXT, mild mind-easing decoction), comprising four Chinese medicines including Haematitum, Flos Inulae, Folium Phyllostachydis Henonis, and Semen Sojae Preparatum, exerted significant antidepressant-like effect in chronically mildly stressed rats, possibly mediated by serotonergic activation. Since the central serotonergic dysfunction is an important and well-known cause mediating the pathophysiology of trauma-related symptoms in PTSD, it is reasonable to predict that flavonoids may exert therapeutic effects on PTSD in animal models. Therefore, the present study aims to examine the effect of flavonoids in alleviating the enhanced anxiety and fear response induced in two PTSD animal models. Ser, an SSRI, was administered as a positive control. Furthermore, the changes of brain monoaminergic neurotransmitters after chronic flavonoids administration have also been assessed in SPS-treated rats.
    Full-text · Article · Dec 2012
Show more