Advances in Posttraumatic Stress Disorder (PTSD): A Primer

Advances in Posttraumatic Stress Disorder (PTSD): A Primer

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Advances in Posttraumatic Stress Disorder (PTSD): A Primer

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https://psychscenehub.com/psychinsights/advances-posttraumatic-stress-disorder-ptsd/
sani…

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These traumatic events trigger intense feelings of fear, helplessness, and horror, setting
the sta…

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A PTSD diagnosis was originally considered a normal response to an extreme situation;
however, the…

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Among Vietnam veterans, lifetime PTSD prevalence was 30.9% for men and 26.9%
for women; 15–18 year…

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Social Support
Lack of social support following trauma.
Additional Stressors
Experiencing furthe…

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Specific Gene Associations:
CRFR1 and PAC1R:
Variations in genes encoding CRFR1 and PAC1R are lin…

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Epigenetic Mechanisms in Psychiatric Disorders – Major Depression, Psychosis and
Addiction
Trauma…

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Disturbances to arousal and reactivity that began, or worsened, after the trauma are
characterised…

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The dissociative subtype of PTSD (PTSD-DT) and Complex PTSD (CPTSD), recently
included in the DSM-…

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The amygdala integrates sensory inform…

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NEUROTRANSMITTER SYSTEMS IN FEAR AND A…

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Glutamate, the principal excitatory neurotransmitter, facilitates rapid communication
between the …

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Dopamine (DA) serves as a central modulator of both fear extinction and aversive
learning, impacti…

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Noradrenaline (NA):
Noradrenaline, re…

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Increased noradrenergic arousal contributes to deficits in fear extinction, underscoring
mechanism…

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Such acute cortisol responses facilitate immediate adaptation and promote the
encoding of stressfu…

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increased heart rate and activation of the HPA axis.
In PTSD, amygdala hyperactivity persists due …

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volume, are evident in PTSD and may be due to cortisol-induced neurotoxicity,
impairing extinction…

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Regulate fear processing.
In PTSD, there is often an overactivation of Fear-On circuits and a conc…

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The HPA axis is the primary stress-response system, initiating in the hypothalamus
with the secret…

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The hippocampus and mPFC typically exert inhibitory control over the HPA axis. In
PTSD, structural…

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Genetic variants affecting these genes can predispose individuals to abnormal
glucocorticoid signa…

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impulsivity, and intrusive memories.
Chronic stress upregulates 5-HT2 and downregulates 5-HT1A rec…

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metabolism that governs whether an individual develops PTSD and what symptoms
they may display.
H…

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Others
Glutamate (excitatory) release via the NMDA receptors is involved in synaptic
plasticity, …

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facilitating NMDA receptor function, supporting neurocognitive resilience. [van
Zuiden et al., 201…

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PTSD AND NEUROINFLAMMATION
Posttrauma…

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They interact with microglia in a feedback loop, perpetuating the inflammatory response.
Astrocyti…

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For example, cytokines upregulate the kynurenine pathway, depleting serotonin
precursors and incre…

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Given the association between inflammation and poorer PTSD outcomes,
addressing inflammation throu…

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PTSD AND PAIN
Posttraumatic stress di…

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This comorbidity complicates treatment, as pain can act as a trigger for trauma-related
memories, …

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Noradrenergic dysregulation, particularly involving the locus coeruleus, amplifies
descending pain…

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pleasure and pain perception. [Fenton et al., 2015]
In the ventral striatum, this diminished dopam…

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reflecting broader dysregulation within corticolimbic networks. [Defrin et al., 2015]
This highlig…

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Hippocampal Dysfunction:
Disrupts contextual memory processing, contributing to the misinterpretat…

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Frequent nightmares often occur during REM sleep, as this phase is involved in fear
memory consoli…

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Deficits in the prefrontal cortex and hippocampal function hinder the extinction of
fear memories,…

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Emotional Undermodulation (PTSD + Hype…

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INTEGRATED NETWORK MODEL OF PTSD
Thre…

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Central Executive Network (CEN) or Executive Control Network (ECN):
Anchored in the dorsolateral p…

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STAGING MODEL OF PTSD
Recently, a sta…

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TREATMENT OF PTSD - GENERAL PRINCIPLES…

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Traditionally, PTSD treatments have ta…

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Key recommendations include: [Martin et al., 2021]
Pharmacological Treatment:
SSRIs are universal…

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Prazosin is considered a first-line treatment for nightmares by two guidelines, but
others either …

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1. Imaginal Exposure: Revisiting trauma memories with the processing of emotions.
2. In Vivo Expos…

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Encourages reliving sensory, emotional, and physiological trauma memories to
foster exposure and r…

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It increases awareness of personal narratives that sustain distress.
SIT is a flexible, tailored f…

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Key findings:
Trauma-focused CBT (TF-CBT) and EMDR are effective in reducing PTSD
symptoms, with …

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Exposure-based CBT can effectively reduce PTSD symptoms in early intervention
stages, especially a…

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SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
Venlafaxine is the most studied SNRI for PTSD…

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Risperidone: While it has shown some benefit in reducing re-experiencing, a large
RCT found no sig…

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Doxazosin
Doxazosin, an alternative to prazosin, offers a longer half-life and potentially fewer
…

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Despite mixed evidence and a lack of large-scale trials, clonidine may offer an
alternative for in…

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Ketamine and Esketamine in Depression – A Synopsis on Efficacy and Mechanism of
Action
Memantine:…

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Preliminary evidence suggests cannabis may reduce overall PTSD symptoms, but
high-quality data is …

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Prevent synthesis of ACE inhibitors or block ARB angiotensin II receptors, reducing
inflammation.
…

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Vagal Nerve Stimulation (VNS)
VNS aims to modulate the parasympathetic system to counteract the sy…

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There is no evidence that rTMS or ECT reduce PTSD symptoms; however, they may
be effective in pati…

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Propranolol:
In PTSD, reactivated memories become temporarily labile and require stabilisation,
w…

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This pharmacological algorithm has been modified from the original framework from [Bajor
et al.,20…

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The modifications incorporate recent s…

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If sleep disturbances or nightmares are present:
First-line: Prazosin or clonidine.
Clonidine is …

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Monitor response:
If no response, move to the next line of treatment.
If partial response without…

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Consider advanced interventions like stellate ganglion block, reconsolidation
therapy, or high-int…

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has the best evidence.
Augmentation of SSRI or quetiapine is recommended in the context of marked
…

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PTSD AND COMORBIDITIES

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PTSD and Depression: [Rosen et al., 2020]
Residual symptoms like insomnia and hyperarousal often p…

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et al., 2014]
Ongoing trials are examining the efficacy of topiramate combined with PE to
enhance…

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Naltrexone has demonstrated effectiveness in reducing alcohol use severity when
combined with trau…

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Pathophysiological Mechanisms Linking Sleep Dysfunction and PTSD:
Noradrenergic Hyperactivity: Hyp…

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PTSD and Psychosis:
Lifetime PTSD rates are higher in individuals with psychotic disorders (30%) t…

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Risperidone has shown modest efficacy, particularly in reducing psychotic symptoms
in PTSD-SP, but…

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This combination complicates treatment and often results in poorer outcomes. The familial
co-aggre…

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Studies indicate that the prevalence of PTSD among bipolar patients is approximately
16%, which is…

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The development of PTSD involves complex interactions between pre-trauma
vulnerabilities, acute pe…

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Benjet, C., Bromet, E., Karam, E. G., Kessler, R. C., McLaughlin, K. A., Ruscio, A. M.,
Shahly, V.…

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Uher, R., Caspi, A., Houts, R., Sugden, K., Williams, B., Poulton, R., & Moffitt, T. E. (2011).
Se…

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Crimmins, B. E., Lingawi, N. W., Chieng, B. C., Leung, B. K., Maren, S., & Laurent, V.
(2023). Bas…

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Sumner, J. A., Nishimi, K. M., Koenen, K. C., Roberts, A. L., & Kubzansky, L. D. (2020).
Posttraum…

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systematic review and meta-analysis of monotherapy, augmentation and head-to-head
approaches. Euro…

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Post-Traumatic Stress Disorder in Military Veterans. The New England journal of
medicine, 378(6), …

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of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. The
American journa…

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Blakey, S. M., Rae Olmsted, K. L., Hirsch, S., Asman, K., Wallace, D., Olmsted, M. G.,
Vandermaas-…

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Hien, D. A., Papini, S., Saavedra, L. M., Bauer, A. G., Ruglass, L. M., Ebrahimi, C. T.,
Fitzpatri…

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It provides a comprehensive overview of the disorder’s pathophysiology, diagnostic
complexities, a…

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Negative Alterations in Cognitions and Mood associated with the traumatic event
(s) – difficulty r…

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combination of a greater propensity to lifetime violence exposure and genetic vulnerability
(varia…

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Race: In the U.S., African Americans, Latino Americans, and Native Americans
exhibit the highest r…

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Heightened amygdala activation in response to ambiguous facial expressions (e.g.,
surprised or neu…

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In PTSD, epigenetic modifications adjust gene promoter activity, altering gene
expression without …

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and reactivity that began, or worsened, after the trauma are characterised by aggression,
self-des…

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higher rates of suicidal ideation, anxiety, depression, and comorbid BPD. [Burback et al.,
2024] W…

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The amygdala integrates sensory information to generate rapid, often reflexive responses,
mediated…

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impacting fear processing and emotional memory encoding. [Vitalis & Verney, 2018] In the
amygdala,…

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Noradrenaline (NA): Noradrenaline, released from the locus coeruleus, is integral to the
arousal c…

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PHYSIOLOGICAL RESPONSES IN FEAR AND ANXIETY
content The physiological responses to stress exhibit …

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plasticity (e.g., long-term potentiation and depression), and maintain neural
excitability beyond …

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The amygdala plays a central role in acquiring fear responses and mediating both
overconsolidation…

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The PFC, in conjunction with the hippocampus, manages emotion regulation by
assessing and updating…

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Dysregulated connectivity between these networks and the default mode network
(DMN) impedes the ab…

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observation supports the hypothesis that early intervention with high-dose
hydrocortisone post-tra…

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The persistent adrenergic hyperactivation drives chronic symptoms like
hypervigilance, heightened …

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Neurotransmitter Roles in PTSD: [Yehuda et al., 2015], [Sherin and Nemeroff, 2011]
Serotonin:
Alt…

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Noradrenaline:
In PTSD, there is increased noradrenaline transmission in networks that connect the…

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Increased striatal dopamine transporter (DAT) density observed in PTSD suggests
an aberrant DA-dep…

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memory recall, enhancing extinction, dampening inflammation, and improving sleep
by decreasing REM…

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symptoms, with increased kappa-opioid receptor activation in areas like the BNST
contributing to e…

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(CNS), play a critical role in synaptic pruning, chemotaxis, and neurogenesis under
normal conditi…

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2022] Additionally, cytokines affect dopamine synthesis by depleting tetrahydrobiopterin
(BH4), a …

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reduce PTSD-like symptoms in preclinical models. [Katrinli et al., 2022]
Additionally, adjunctive …

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PTSD AND PAIN
content
Posttraumatic stress disorder (PTSD) and chronic pain are intertwined throu…

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responses. [Scioli-Salter et al., 2015] The parabrachial nucleus routes pain signals directly
to t…

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Dopaminergic dysfunction in PTSD plays a critical role in both reward processing and pain
modulati…

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interventions by improving amygdala regulation, as suggested by functional neuroimaging
studies of…

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referential processing, emotion recognition, and autobiographical memory. This
contributes to symp…

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Physiological Correlates:
Elevated heart rate, increased skin conductance, and dysregulated HPA ax…

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PTSD PHENOTYPES
content The dynamic interaction between the mPFC and the amygdala creates two
dis…

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Diminished vmPFC inhibition of the amygdala and BNST leading to increased threat
expression and re…

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Anchored in the anterior cingulate cortex and ventral anterior insula and involves the
amygdala an…

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Impaired connectivity between the SN and DMN limits transitions between selfreferential states and…

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3. Address treatment resistance by matching interventions to the neurobiological state
at each sta…

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Traditionally, PTSD treatments have targeted abnormal fear circuits and trauma-related
cognitions,…

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TCAs are suggested as an alternative first-line option by the WHO, mainly when
SSRIs or venlafaxin…

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has a more extensive evidence base yet appears less frequently in guidelines
compared to prazosin.…

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It also addresses shame, guilt or feelings of mistrust.
Present-Centered Therapy (PCT) effectively…

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Key elements include stabilization, memory processing, and skills training for social
interactions…

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SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
Venlafaxine is the most studied SNRI for PTSD…

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though secondary analyses suggested mild improvements in sleep. [Krystal et al.,
2016]
Quetiapine…

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Once daily dosing. Dose: 8 to 16 mg/day. (Higher doses of up to 48 mg /day have
been used. Smith a…

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Trazodone is widely used to manage PTSD-related insomnia, with efficacy attributed
to its effects …

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In an open-label trial among civilian female PTSD patients, memantine significantly
improved PTSD …

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In a small study (n=10), 5 mg of THC twice daily as an add-on improved sleep,
reduced nightmares, …

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Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (e.g Celecoxib, Ibuprofen,
Naproxen):
Inhibit COX-…

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Since the stellate ganglion is connected to the amygdala, it has been explored as a
potential alte…

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MDMA (3,4-Methylenedioxymethamphetamine):
MDMA-assisted psychotherapy is currently considered an e…

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[Yehuda et al., 2015]
According to a systematic review and meta-analysis [Astill Wright et al., 20…

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The modifications incorporate recent scientific insights and practical considerations. Key
updates…

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markers (e.g., C-reactive protein), neuroendocrine changes (e.g., cortisol levels), and
biomarkers…

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Hydroxyzine: 25 -100 mg.
Monitor Sleep Response
If sleep improves, proceed to assess overall PTSD…

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Third-Line Medications
Include options like daytime prazosin or clonidine for persistent hyperarou…

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Reinforce psychoeducation to enhance resilience and coping.
Given its investigational status, MDMA…

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PTSD AND COMORBIDITIES
content PTSD and Depression: [Rosen et al., 2020]

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Residual symptoms like insomnia and hyperarousal often persist in PTSD,
overlapping with depressio…

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Adrenergic Modulators (e.g., Prazosin, Doxazosin):
Clinical trials in veterans with PTSD and AUD h…

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The "Project Harmony" study found that PE combined with naltrexone produced the
best long-term alc…

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Reciprocal Effects: Trauma-related hyperarousal can worsen OSA by promoting
disordered breathing, …

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Pathophysiology: The link between trauma, PTSD, and psychosis involves multiple
pathways [Hardy & …

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deficit/hyperactivity disorder: a systematic review and meta-analysis. J Clin Psychiatry.
2016 Jan…

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hospitalisations compared to those with BD alone.
Individuals with both disorders often receive se…

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symptoms solely to trauma, which could lead to misdiagnosis and inadequate care. The
development o…

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Comorbidity Survey Replication. Archives of general psychiatry, 62(6), 617–627.
Marmar, C. R., Sch…

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Bishop, J. R., Lee, A. M., Mills, L. J., Thuras, P. D., Eum, S., Clancy, D., Erbes, C. R.,
Polusny…

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Van Rooij, S. J. H., Kennis, M., Sjouwerman, R., Van Den Heuvel, M. P., Kahn, R. S., &
Geuze, E. (…

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Bonomi, R., Hillmer, A. T., Woodcock, E., Bhatt, S., Rusowicz, A., Angarita, G. A., Carson,
R. E.,…

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Dissociation and Its Relation to Cannabinoid- and Opioid-Mediated Stress Response: a
Transdiagnost…

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extended release: a 6-month randomized controlled trial. Archives of general
psychiatry, 63(10), 1…

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Rodgman, C., Verrico, C. D., Holst, M., Thompson-Lake, D., Haile, C. N., De La Garza,
R., 2nd, Ras…

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memantine in a social defeat stress paradigm. Molecular brain, 12(1), 68.
Ramaswamy, S., Madabushi…

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Astill Wright, L., Sijbrandij, M., Sinnerton, R., Lewis, C., Roberts, N. P., & Bisson, J. I.
(2019…

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Wendt FR, Garcia-Argibay M, Cabrera-Mendoza B, Valdimarsdóttir UA, Gelernter J, Stein
MB, Nivard M…

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MBBS, MRCPsych, FRANZCP
Dr. Sanil Rege is a Consultant Psychiatrist and founder of Psych Scene and…

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As a Pro user you can download this article in a PDF format.
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Advances in Posttraumatic Stress Disorder (PTSD): A Primer

@powderhownd1492

This presentation reviews recent advances in the understanding of Posttraumatic Stress Disorder (PTSD), discussing its pathophysiology, diagnosis, and evidence-based management. Highlights include the exploration of neurobiological underpinnings, symptomatology, and effective personalized and phase-specific interventions essential for improving patient outcomes.

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