Posttraumatic stress disorder: An integrated overview of the neurobiological rationale for pharmacology.

Kelmendi, Benjamin; Adams, Thomas G.; Southwick, Steven M.; Abdallah, Chadi G.; Krystal, John H.

doi:10.1111/cpsp.12202

Cited by 16 publications

(31 citation statements)

References 104 publications

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“…We also will review why we are in strong agreement with Kelmendi et al. () that extinction‐based and cognitive‐behavioral therapy (CBT) combined with pharmacological agents should be given top priority in future research. In this discussion, we will highlight some specific issues in combined approaches that warrant attention given their relevance and ability to inform future research and clinical practice.…”

supporting

confidence: 57%

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Translating neurobiological findings into improved combined pharmacological and psychotherapeutic interventions for posttraumatic stress disorder.

Maples‐Keller¹,

Rauch²

2017

Clinical Psychology: Science and Practice

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Reaching as far back as the 17th century and Ren e Descartes' philosophy of dualism, the mind and body have historically been viewed as distinct entities, and consistent with this view, biology and psychotherapy have often been approached separately in the empirical literature. We propose that the exciting neurobiological findings about posttraumatic stress disorder (PTSD) reviewed by Kelmendi, Adams, Southwick, Abdallah, and Krystal (2017) illustrate the complementary nature of these disciplines. Consistent with this review's framework of using research on the neurobiology of PTSD as a foundation for hypotheses related to mechanisms of pharmacotherapy for this disorder, we would like to emphasize that this biological research can also be used as a foundation for hypotheses related to psychotherapy for PTSD, as well as combined psychotherapy and pharmacotherapy approaches. As noted recently (Arbuckle, Travis, & Ross, 2017), the distinctions between "biological" and "psychological" are diminishing, particularly given empirical findings that effective interventions, including psychotherapeutic or pharmacologic approaches, alter brain networks and thus can be conceptualized as biological in nature. As such, within our commentary we elaborate on translational fear conditioning models as an important framework for investigating and understanding specific biological and psychological mechanisms across pharmacological, psychotherapeutic, and combined PTSD treatment approaches. We also will review why we are in strong agreement with Kelmendi et al. (2017) that extinction-based and cognitive-behavioral therapy (CBT) combined with pharmacological agents should be given top priority in future research. In this discussion, we will highlight some specific issues in combined approaches that warrant attention given their relevance and ability to inform future research and clinical practice.Kelmendi et al. (2017) provide a thoughtful review of neurobiological findings with regard to PTSD, and how this literature informs our understanding of mechanisms underlying existing and novel pharmacological interventions for this disorder. Recent empirical literature has provided many notable findings regarding the pathophysiology of PTSD and has provided a richer illustration of the complexity surrounding this disorder. PTSD is a disorder that is heterogeneous, involves multiple neurobiological systems, and is frequently comorbid with other mental and physical illnesses. As noted in this review, there is a paucity of literature on combined pharmacological and psychotherapy approaches for PTSD. We believe that this is a crucial area to highlight, particularly as pharmacological interventions are frequently combined with psychotherapy in clinical practice. Thus, it is imperative that neurobiological findings are used to inform research investigating the effectiveness and optimal timing of combined approaches. THE RELEVANCE OF TRANSLATION AND FEAR CONDITIONING AND EXTINCTION MODELSMammals demonstrate a similar evolutionarily conserved neural...

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confidence: 57%

“…We are pleased that Kelmendi et al. () reviewed research investigating pharmacological early interventions. As noted above with reference to treatment optimization, fear conditioning and translational models can also be used to test novel pharmacological early interventions.…”

Section: Early Intervention Approachesmentioning

confidence: 99%

Translating neurobiological findings into improved combined pharmacological and psychotherapeutic interventions for posttraumatic stress disorder.

Maples‐Keller¹,

Rauch²

2017

Clinical Psychology: Science and Practice

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“…The statement by Kelmendi et al. (, p. 3) that “limited efficacy of SSRIs in the treatment of PTSD must be understood in terms of variable individual genetic profile” is appropriate, and we argue that genetic aspects in PTSD treatment deserve further elaboration. If we are to learn from our colleagues in medical subspecialties, an understanding of an individual's genotypes has the potential to significantly influence treatment selection and can therefore enhance the effectiveness of an intervention.…”

Section: Genetic Factors and Ptsd Treatmentmentioning

confidence: 77%

“…The review by Kelmendi et al. () provides an analysis of neurotransmitter systems and the alterations found in these systems in PTSD, which is essential for the development of effective pharmacological agents. In this commentary, we discuss three additional considerations that are likely to improve current treatment practices.…”

Section: Optimal Timing and Temporal Dynamics Of Ptsd Developmentmentioning

confidence: 99%

Enhancing efficacy of PTSD treatment: Role of circuits, genetics, and optimal timing.

Lokshina

Liberzon

2017

Clinical Psychology: Science and Practice

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Current treatment approaches for posttraumatic stress disorder (PTSD) include the use of medications, psychotherapy, or a combination of both, but they are limited in their effectiveness as only some have access to or are able to tolerate exposure therapy, and pharmacotherapy is largely nonspecific and only partially effective. As PTSD incurs substantial cost both to individuals (e.g., disruptions in daily life functioning, health status, and well-being) and to society (with elevated rates of substance use, hospitalization, and suicidal behavior), the development of more effective pharmacological treatments is critical and requires a better understanding of the neurobiological mechanisms implicated in the pathogenesis of PTSD. Kelmendi, Adams, Southwick, Abdallah, and Krystal (2017) provide a comprehensive review of neurotransmitter systems implicated in PTSD and highlight that the understanding of neurotransmitters and the modulatory systems involved is essential for sophisticated use of pharmacotherapy in PTSD. It is important, however, to take into consideration that neurotransmitter "abnormalities" occur within an anatomical/functional context, that is within specific neural circuits, which perform specific functions and thus lead to specific symptoms. For example, exaggerated norepinephrine (NE) in the amygdala might lead to one symptom, but exaggerated NE secretion in the hippocampus or prefrontal cortex might lead to a different set of symptoms. Thus, understanding the role of neural circuits involved in different intermediate phenotypes and disorder subtypes (Liberzon & Abelson, 2016) will be critical for designing more specific treatment approaches. Further, the fact that dysfunction in neurotransmitter systems can be affected by an individual's genetic factors has been gaining increased attention, and related concepts have led to the development of "personalized medicine" in other fields, such as cancer therapy. Certain genotypes, or epigenetic processes, such as DNA methylation, or histone acetylation, can not only constitute risk or resilience factors for PTSD development, but may also serve as the biomarkers of outcomes of specific treatments. Kelmendi et al. (2017) briefly mention the role of individual genetic profiles, in the context of limited efficacy and lack of specificity of available PTSD treatments, but we believe these important topics deserve further attention, as they have critical implications for clinical practice. We also mention another important factor that was not directly addressed in the review by Kelmendi et al., but we believe should be considered in developing effective treatment approaches, which is the timing of an intervention, within the dynamics of PTSD development. NEUROCIRCUITRY-BASED MODELS OF PTSD: REPRESENTING ALTERED BRAIN FUNCTIONS AND DIFFERENT INTERMEDIATE PHENOTYPES As noted by Kelmendi et al. (2017), dysregulations on an anatomical level lie within distinct neural systems.Advances in affective neuroscience in the last decade have unveiled specific neural system...

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“…Research is underway to investigate internet-based treatments (Sijbrandij, Kunovski, & Cuijpers, 2016), brief intensive psychological treatments (Ehlers et al, 2014), and medications and drugs to augment existing psychological treatments (Kelmendi, Adams, Southwick, Abdallah, & Krystal, 2017).…”

Section: New and Emerging Developmentsmentioning

confidence: 99%

A clinician’s quick guide of evidence‐based approaches: Post‐traumatic stress disorder

Wade

Lau

Nixon

2018

Clinical Psychologist

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Posttraumatic stress disorder: An integrated overview of the neurobiological rationale for pharmacology.

Cited by 16 publications

References 104 publications

Translating neurobiological findings into improved combined pharmacological and psychotherapeutic interventions for posttraumatic stress disorder.

Translating neurobiological findings into improved combined pharmacological and psychotherapeutic interventions for posttraumatic stress disorder.

Enhancing efficacy of PTSD treatment: Role of circuits, genetics, and optimal timing.

A clinician’s quick guide of evidence‐based approaches: Post‐traumatic stress disorder

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