Dopamine agonist

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Dopamine_agonist 

 

Dopamine agonist
Drug class
The skeletal structure of dopamine
Class identifiers
Use	Parkinson's disease, hyperprolactinemia, restless legs syndrome
ATC code	N04BC
Biological target	Dopamine receptors
External links
MeSH	D010300

A dopamine agonist (DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D₂-like and D₁-like, and they are all G protein-coupled receptors. D₁- and D₅-receptors belong to the D₁-like family and the D₂-like family includes D₂, D₃ and D₄ receptors. Dopamine agonists are primarily used in the treatment of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. The use of dopamine agonists is associated with impulse control disorders and dopamine agonist withdrawal syndrome (DAWS).

Medical uses

Parkinson's disease

Dopamine agonists are mainly used in the treatment of Parkinson's disease.  The cause of Parkinson's is not fully known but genetic factors, for example specific genetic mutations, and environmental triggers have been linked to the disease. In Parkinson's disease dopaminergic neurons that produce the neurotransmitter dopamine in the brain slowly break down and can eventually die. With decreasing levels of dopamine the brain can't function properly and causes abnormal brain activity, which ultimately leads to the symptoms of Parkinson's disease.

There are two fundamental ways of treating Parkinson's disease, either by replacing dopamine or mimicking its effect.

Dopamine agonists act directly on the dopamine receptors and mimic dopamine's effect. Dopamine agonists have two subclasses: ergoline and non-ergoline agonists. Both subclasses target dopamine D₂-type receptors. Types of ergoline agonists are cabergoline and bromocriptine and examples of non-ergoline agonists are pramipexole, ropinirole and rotigotine. Ergoline agonists are much less used nowadays because of the risk of cartilage formation in heart valves.

Treatment of depression in Parkinson's patients

Depressive symptoms and disorders are common in patients with Parkinson's disease and can affect their quality of life. Increased anxiety can accentuate the symptoms of Parkinson's and is therefore essential to treat. Instead of conventional antidepressant medication in treating depression, treatment with dopamine agonists has been suggested. It is mainly thought that dopamine agonists help with treating depressive symptoms and disorders by alleviating motor complications, which is one of the main symptoms of Parkinson's disease.  Although preliminary evidence of clinical trials has shown interesting results, further research is crucial to establish the anti-depressive effects of dopamine agonists in treating depressive symptoms and disorders in those with Parkinson's.

Hyperprolactinemia

Dopamine is a prolactin-inhibiting factor (PIFs) since it lowers the prolactin-releasing factors (PRFs) synthesis and secretion through D₂-like receptors. That is why dopamine agonists are the first-line treatment in hyperprolactinemia. Ergoline-derived agents, bromocriptine and cabergoline are mostly used in treatment. Research shows that these agents reduce the size of prolactinomas by suppressing the hypersecretion of prolactin resulting in normal gonadal function.

Restless leg syndrome

Numerous clinical trials have been performed to assess the use of dopamine agonists for the treatment of restless leg syndrome (RLS). RLS is identified by the strong urge to move and is a dopamine-dependent disorder. RLS symptoms decrease with the use of drugs that stimulate dopamine receptors and increase dopamine levels, such as dopamine agonists.

Adverse effects

Side effects

Dopamine agonists are mainly used to treat Parkinson’s disease but are also used to treat hyperprolactinemia and restless legs syndrome. The side effects are mainly recorded in treatment for Parkinson’s disease where dopamine agonists are commonly used, especially as first-line treatment with levodopa.

Dopamine agonists are divided into two subgroups or drug classes, first-generation and newer agents. Ergoline derived agonists are the first generation and are not used as much as the newer generation the non-ergoline derived agonists. Ergoline derived agonists are said to be "dirtier" drugs because of their interaction with other receptors than dopamine receptors, therefore they cause more side effects. Ergoline derived agonists are for example bromocriptine, cabergoline, pergolide and lisuride. Non-ergoline agonists are pramipexole, ropinirole, rotigotine, piribedil and apomorphine.

The most common adverse effects are constipation, nausea and headaches. Other serious side effects are hallucinations, peripheral edema, gastrointestinal ulcers, pulmonary fibrosis and psychosis.

Dopamine agonists have been linked to cardiac problems. Side effects such as hypotension, myocardial infarction, congestive heart failure, cardiac fibrosis, pericardial effusion and tachycardia. A high risk for valvular heart disease has been established in association with ergot-derived agonists especially in elderly patients with hypertension.

Somnolence and sleep attacks have been reported as an adverse effect that happen to almost 30% of patients using dopamine agonists. Daytime sleepiness, insomnia and other sleep disturbances have been reported as well.

Impulse control disorder that is described as gambling, hypersexuality, compulsive shopping and binge eating is one serious adverse effect of dopamine agonists.

After long-term use of dopamine agonist a withdrawal syndrome may occur when discontinuing or during dose reduction. The following side effects are possible: anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalised pain, and drug cravings. For some individuals, these withdrawal symptoms are short-lived and make a full recovery, for others a protracted withdrawal syndrome may occur with withdrawal symptoms persisting for months or years.

Interactions

Dopamine agonists interact with a number of drugs but there is little evidence that they interact with other Parkinson’s drugs. In most cases there is no reason not to co-administer Parkinson's drugs. Although there has been an indication that the use of dopamine agonists with L-DOPA can cause psychosis therefore it is recommended that either the use of dopamine agonists be discontinued or the dose of L-DOPA reduced. Since ergot-dopamine agonist have antihypertensive qualities it is wise to monitor blood pressure when using dopamine agonists with antihypertensive drugs to ensure that the patient does not get hypotension. That includes the drug sildenafil which is commonly used to treat erectile dysfunction but also used for pulmonary hypertension.

There is evidence that suggests that since ergot dopamine agonists are metabolized by CYP3A4 enzyme concentration rises with the use of CYP3A4 inhibitors. For example, in one study bromocriptine was given with a CYP3A4 inhibitor and the AUC (e. Area under the curve) increased 268%. Ropinirole is a non-ergot derived dopamine agonist and concomitant use with a CYP1A2 inhibitor can result in a higher concentration of ropinirole. When discontinuing the CYP1A2 inhibitor, if using both drugs, there is a change that a dose adjustment for ropinirole is needed. There is also evidence the dopamine agonists inhibit various CYP enzymes and therefore they may inhibit the metabolism of certain drugs.

Pharmacology

Ergoline class

Pharmacokinetics of Bromocriptine

The absorption of the oral dose is approximately 28% however, only 6% reaches the systemic circulation unchanged, due to a substantial first-pass effect. Bromocriptine reaches mean peak plasma levels in about 1–1.5 hours after a single oral dose. The drug has high protein binding, ranging from 90-96% bound to serum albumin. Bromocriptine is metabolized by CYP3A4 and excreted primarily in the feces via biliary secretion. Metabolites and parent drugs are mostly excreted via the liver, but also 6% via the kidney. It has a half-life of 2–8 hours.

Pharmacokinetics of Pergolide

Pergolide has a long half-life of about 27 hours and reaches a mean peak plasma level in about 2–3 hours after a single oral dose. The protein binding is 90% and the drug is mainly metabolized in the liver by CYP3A4 and CYP2D6. The major route of excretion is through the kidneys.

Drug	Maintenance	Half-life	Protein binding	Peak plasma	Metabolism	Excretion
Bromocriptine	Oral, 2.5–40 mg/day	2–8 hours	90-96%	1-1,5 hours	Hepatic, via CYP3A4, 93% first-pass metabolism	Bile, 94-98% Renal, 2-6%
Pergolide	Oral, 0.05 mg/day Usual response up to 0.1 mg per day	27 hours	90%	2–3 hours	Extensively hepatic	Renal, 50% Fecal 50%

Non-Ergoline class

Pharmacokinetics of Pramipexole

Pramipexole reaches maximum plasma concentration 1–3 hours post-dose. It is about 15% bound to plasma proteins and the metabolism is minimal. Pramipexole has a long half-life, around 27 hours. The drug is mostly excreted in the urine, around 90%, but also in feces.

Pharmacokinetics of Ropinirole

Ropinirole is rapidly absorbed after a single oral dose, reaching plasma concentration in approximately 1–2 hours. The half-life is around 5–6 hours. Ropinirole is heavily metabolized by the liver and in vitro studies show that the enzyme involved in the metabolism of ropinirole is CYP1A2.

Pharmacokinetics of Rotigotine

Since rotigotine is a transdermal patch it provides continuous drug delivery over 24 hours. It has a half-life of 3 hours and the protein binding is around 92% in vitro and 89.5% in vivo. Rotigotine is extensively and rapidly metabolized in the liver and by the CYP enzymes. The drug is mostly excreted in urine (71%), but also in feces (23%).

Drug	Maintenance	Half-life	Protein binding	Peak plasma	Metabolism	Excretion
Pramipexole	Oral, 0.125 mg 3x/day (IR) Oral, 0.375 mg/day (ER)	8–12 hours	15%	1–3 hours	Minimal < 10%	Urine 90% Fecal 2%
Ropinirole	Oral, 0.25 mg 3x/day (IR) Oral, 2 mg/day (ER)	5–6 hours	10-40%	1–2 hours	Hepatic, via P450 CYP1A2 — can increase ↑ INR	Renal > 88%
Rotigotine	Transdermal, 2 – 4 mg/day	3 hours	92%	24 hours	Hepatic (CYP-mediated).	Urine 71% Fecal 23%

Mechanism of action

The dopamine receptors are 7-transmembrane domains and are members of the G protein-coupled receptors (GPCR) superfamily. Dopamine receptors have five subtypes, D₁ through D₅, the subtypes can be divided into two subclasses due to their mechanism of action on adenylate cyclase enzyme, D₁-like receptors (D₁ and D₅) and D₂-like receptors (D₂, D₃ and D₄). D₁-like receptors are primarily coupled to Gα_s/olf proteins and activates adenylate cyclase which increases intracellular levels of cAMP, they also activate the G_βγ complex and the N-type Ca²⁺ channel. D₂-like receptors decrease intracellular levels of the second messenger cAMP by inhibiting adenylate cyclase.

Bromocriptine

Bromocriptine is an ergot derivative, semi-synthetic. Bromocriptine is a D₂ receptor agonist and D₁ receptor antagonist with a binding affinity to D₂ receptors of anterior pituitary cells, exclusively on lactotrophs. Bromocriptine stimulates Na⁺, K⁺-ATPase activity and/or cytosolic Ca²⁺ elevation and therefore reduction of prolactin which leads to no production of cAMP.

Pramipexole

Pramipexole is a highly active non-ergot D₂-like receptor agonist with a higher binding affinity to D₃ receptors rather than D₂ or D₄ receptors. The mechanism of action of pramipexole is mostly unknown, it is thought to be involved in the activation of dopamine receptors in the area of the brain where the striatum and the substantia nigra is located. This stimulation of dopamine receptors in the striatum may lead to the better movement performance.

Structure–activity relationship

Further information: Structure–activity relationship

When dealing with agonists it can be extremely complex to confirm relationships between structure and biological activity. Agonists generate responses from living tissues. Therefore, their activity depends both on their efficacy to activate receptors and their affinity to bind to receptors.

Crossing the blood brain barrier

Many molecules are unable to cross the blood brain barrier (BBB). Molecules must be small, non-polar and lipophilic to cross over. If compounds do not possess these qualities they must have a specific transporter that can transport them over the BBB. Dopamine cannot diffuse across the BBB because of the catechol group, it is too polar and therefore unable to enter the brain. The catechol group is a dihydroxy benzene ring.

The synthesis of dopamine consists of three stages. The synthesis process starts with an amino acid, called L-Tyrosine. In the second stage Levodopa (L-dopa) is formed by adding a phenol group to the benzene ring of L-Tyrosine. The formation of L-dopa from L-tyrosine is catalyzed by the enzyme tyrosine hydroxylase. The third stage is the formation of dopamine by removing the carboxylic acid group from L-dopa, catalysed by the enzyme dopa decarboxylase.

Levodopa is also too polar to cross the blood brain barrier but it happens to be an amino acid so it has a specialized transporter called L-type amino acid transporter or LAT-1 that helps it diffuse through the barrier.

Dopamine

When dopamine interacts with ATP, which is a component of some dopamine receptors, it has a significant preference for a trans-conformation of the dopamine molecule. The dopamine-ATP complex is stabilised by hydrogen bonding between catechol hydroxyls and purine nitrogens and by electrostatic interactions between the protonated ammonium group of dopamine and a negative phosphate group. Two conformers of dopamine have been identified as alpha- and beta-conformers in which the catechol ring is coplanar with the plane of the ethylamine side chain. They are substantial in agonist-receptor interactions.

Ergoline derivatives

Central dopaminergic agonist properties of semisynthetic ergoline derivatives lergotrile, pergolide, bromocriptine and lisuride have been established. Some studies suggest that ergot alkaloids have the properties of mixed agonist-antagonist with regards to certain presynaptic and postsynaptic receptors. N-n-Propyl groups (chemical formula: –CH₂CH₂CH₃) frequently enhance dopamine agonist effects in the ergoline derivatives.

Bromocriptine

The (+)-enantiomer displays notably diminished activity whereas the (-)-enantiomer possess potent dopamine agonist properties.

Bromocriptine

Bromocriptine has an ergot alkaloid structure. Ergot alkaloids are divided into 2 groups; amino acid ergot alkaloids and amine ergot alkaloids, bromocriptine is part of the former group. It contains a bromine halogen on the ergot structure which increases the affinity for the D₂-receptor but often reduces the efficacy. The similarity between the dopamine structure and the ergoline ring in bromocriptine is likely the cause for its action on the dopamine receptors. It has shown to have equal affinity for D₂- and D₃-receptor and much lower affinity for D₁-receptor.

Apomorphine

Non-ergoline derivatives

Non-ergoline dopamine receptor agonists have higher binding affinity to dopamine D₃-receptors than dopamine D₂-receptors. This binding affinity is related to D₂ and D₃ receptor homology, the homology between them has a high degree of sequence and is closest in their transmembrane domains, were they share around 75% of the amino acid.

Rotigotine

Apomorphine

Apomorphine has a catechol element and belongs to a class called β-phenylethylamines and its main components are similar to the dopamine structure. The effect that apomorphine has on the dopamine receptors can also be linked to the similarities between its structure and dopamine. It is a chiral molecule and thus can be acquired in both the R and S form, the R form is the one that is used in therapy. When apomorphine interacts with the dopamine receptor, or the ATP on the receptor, the catechol and nitrogen are important to stabilize the structure with hydrogen bonding. The position of the hydroxyl groups is also important and monohydroxy derivatives have been found to be less potent than the dihydroxy groups. There are a number of stability concerns with apomorphine such as oxidation and racemization.

Rotigotine

Rotigotine is a phenolic amine and thus has poor oral bioavailability and fast clearance from the body. Therefore, it has been formulated as a transdermal patch, first and foremost to prevent first pass metabolism in the liver.

Members

Examples of dopamine agonists include:

Partial agonist

• Aripiprazole (Partial agonist of the D₂ family receptors - Trade name "Abilify" in the United States; atypical antipsychotic)
• Phencyclidine (a.k.a. PCP; partial agonist. Psychoactivity mainly due to NMDA antagonism)
• Quinpirole (Partial agonist of the D₂ and D₃ family of receptors)
• Salvinorin A (chief active constituent of the psychedelic herb salvia divinorum, the psychoactivity of which is mainly due to Kappa-opioid receptor agonism; partial agonist at the D₂ with an Intrinsic activity of 40-60%, binding affinity of K_i=5-10nM and EC₅₀=50-90nM)

Agonists of full/unknown efficacy

• Apomorphine (Apokyn – used to treat Parkinson's disease & Restless leg syndrome ) – biased at the D1 receptor.
• Bromocriptine (Parlodel – used to treat PD/RLS)
• Cabergoline (Dostinex – used to treat PD/RLS)
• Ciladopa (used to treat PD/RLS)
• Dihydrexidine (used to treat PD/RLS)
• Dinapsoline (used to treat PD/RLS)
• Doxanthrine (used to treat PD/RLS)
• Epicriptine (used to treat PD/RLS)
• Lisuride (used to treat PD/RLS)
• Pergolide (used to treat PD/RLS) – previously available as Permax, but removed from the market in the USA on March 29, 2007.
• Piribedil (Pronoran and Trivastal – used to treat PD/RLS)
• Pramipexole (Mirapex and Sifrol – used to treat PD/RLS)
• Propylnorapomorphine (used to treat PD/RLS)
• Quinagolide (Norprolac – used to treat PD/RLS)
• Ropinirole (Requip – used to treat PD/RLS)
• Rotigotine (Neupro – used to treat PD/RLS)
• Roxindole (used to treat PD/RLS)
• Sumanirole (used to treat PD/RLS)

Some, such as fenoldopam, are selective for dopamine receptor D1.

Related class of drugs: Indirect agonists

There are two classes of drugs that act as indirect agonists of dopamine receptors: dopamine reuptake inhibitors and dopamine releasing agents. These are not considered dopamine agonists, since they have no specific agonist activity at dopamine receptors, but they are nonetheless related. Indirect agonists are prescribed for a wider range of conditions than standard dopamine agonists.

The most commonly prescribed indirect agonists of dopamine receptors include:

• Amphetamine and/or dextroamphetamine (used to treat ADHD, narcolepsy, and obesity)
• Bupropion (used to facilitate smoking cessation and treat nicotine addiction and clinical depression)
• Lisdexamfetamine (used to treat ADHD and binge eating disorder)
• Methylphenidate or dexmethylphenidate (used to treat ADHD and narcolepsy)

Other examples include:

• Cathinone
• Cocaine (anesthetic with no medical uses as a central nervous system stimulant)
• Methamphetamine (used in rare circumstances to treat ADHD and obesity)
• Phenethylamine (endogenous trace amine)
• p-Tyramine (endogenous trace amine)

History

Since the late 1960 Levodopa (L-DOPA) has been used to treat Parkinson’s disease but there has always been a debate whether the treatment is worth the side effects. Around 1970 clinicians started using the dopamine agonist apomorphine alongside L-DOPA to minimize the side effects caused by L-DOPA, the dopamine agonists bind to the dopamine receptor in the absence of dopamine. Apomorphine had limited use since it had considerable side effects and difficulty with administration. In 1974 bromocriptine was use widely after clinicians discovered its benefits in treating Parkinsons. When using the two drug classes together there is a possibility to reduce the amount of L-DOPA by 20-30% and thus keeping the fluctuating motor responses to a minimum. Dopamine agonists are often used in younger people as monotherapy and as initial therapy instead of L-DOPA. Although it is important to know that there is a correlation between the two drugs, if l-DOPA doesn't work dopamine agonists are also ineffective.

The early dopamine agonists, such as bromocriptine, were ergot derived and activated the D₂-receptor. They induced major side effects such as fibrosis of cardiac valves. It is considered that the reason they induced such side effects is that they activate many types of receptors.

Because of the major adverse effects of ergot derived dopamine agonists they are generally not used anymore and were mostly abandoned in favor of non-ergot agonists such as pramipexole, ropinirole and rotigotine. They do not induce as serious side effects although common side effects are nausea, edema and hypotension. Patients have also shown impaired impulse control such as overspending, hypersexuality and gambling.

Eye movement desensitization and reprocessing

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Eye_movement_desensitization_and_reprocessing

Eye movement desensitization and reprocessing (EMDR) is a form of psychotherapy devised by Francine Shapiro in the 1980s that was originally designed to alleviate the distress associated with traumatic memories such as post-traumatic stress disorder (PTSD). EMDR involves focusing on traumatic memories in a manner similar to exposure therapy while engaging in side-to-side eye movements or other forms of bilateral stimulation. There is some evidence that it may also be beneficial for other psychological conditions. There is debate about how the therapy works and whether it is more effective than other established treatments. The eye movements have been criticized as having no scientific basis. The founder promoted the therapy for the treatment of PTSD and proponents employed untestable hypotheses to explain negative results in controlled studies. EMDR has been characterized as a pseudoscientific purple hat therapy (i.e. only as effective as its underlying therapeutic methods without any contribution from its distinctive add-ons).

EMDR is recommended for the treatment of PTSD by various government and medical bodies citing varying levels of evidence, including the World Health Organization, the UK National Institute for Health and Care Excellence, the Australian National Health and Medical Research Council, and the US Departments of Veteran Affairs and Defense. The US National Institute of Medicine found insufficient evidence to recommend it as of 2008. Treatment guidelines note EMDR effectiveness is statistically the same as trauma-focused behavioral therapy, and the Australian National Health and Medical Research Council notes that this may be due to including most of the core elements of CBT.

Classification and technique

EMDR adds a number of non-scientific practices to exposure therapy. EMDR is classified as one of the "power therapies" alongside thought field therapy, Emotional Freedom Techniques and others – so called because these therapies are marketed as being superior to established therapies which preceded them.

EMDR is typically undertaken in a series of sessions with a trained therapist. The number of sessions can vary depending on the progress made. A typical EMDR therapy session lasts from 60 to 90 minutes.

Trauma and PTSD

The person being treated is asked to recall an image, phrase, and emotions that represent a level of distress related to a trigger while generating one of several types of bilateral sensory input, such as side-to-side eye movements or hand tapping. The 2013 World Health Organization practice guideline says that "Like cognitive behavioral therapy (CBT) with a trauma focus, EMDR aims to reduce subjective distress and strengthen adaptive beliefs related to the traumatic event. Unlike CBT with a trauma focus, EMDR does not involve (a) detailed descriptions of the event, (b) direct challenging of beliefs, (c) extended exposure or (d) homework."

Training

Shapiro was criticized for repeatedly increasing the length and expense of training and certification, allegedly in response to the results of controlled trials that cast doubt on EMDR's efficacy. This included requiring the completion of an EMDR training program in order to be qualified to administer EMDR properly after researchers using the initial written instructions found no difference between no-eye-movement control groups and EMDR-as-written experimental groups. Further changes in training requirements and/or the definition of EMDR included requiring level II training when researchers with level I training still found no difference between eye-movement experimental groups and no-eye-movement controls and deeming "alternate forms of bilateral stimulation" (such as finger-tapping) as variants of EMDR by the time a study found no difference between EMDR and a finger-tapping control group. Such changes in definition and training for EMDR have been described as "ad hoc moves [made] when confronted by embarrassing data".

Medical uses

EMDR is controversial within the psychological community. It is used by some practitioners for trauma therapy and in the treatment of complex post-traumatic stress disorder.

Post-traumatic stress disorder

Effectiveness

• A Cochrane systematic review comparing EMDR with other psychotherapies in the treatment of Chronic PTSD found EMDR to be just as effective as TF-CBT and more effective than the other non-TF-CBT psychotherapies. Caution was urged interpreting the results due to low numbers in included studies, risk of researcher bias, high drop-out rates, and overall "very low" quality of evidence for the comparisons with other psychotherapies.
• A 2016 systematic review and meta-analysis found that the effect size of EMDR for PTSD is comparable to other evidence-based treatments, but that the strength of evidence was of a low quality, indicating that the effect sizes achieved are associated with substantial uncertainty.

Many randomized trials of EMDR have been criticized for poor control groups, small sample sizes, and other methodological flaws. It has been called a purple hat therapy because any effectiveness is provided by the underlying therapy (or the standard treatment), not from EMDR's distinctive features.

There is some evidence that EMDR can be as effective as trauma focused cognitive behavioral therapy (TF-CBT) for treating PTSD, though concerns have been raised about the poor quality of the underlying studies. In a 2021 systematic review of 13 studies, clients had mixed perceptions of the effectiveness of EMDR therapy.

Medical guidelines

• The World Health Organization's 2013 report on stress-related conditions found "insufficient evidence" to support EMDR for acute symptoms, but recommended it with moderate evidence for adults and low evidence for children in treating chronic symptoms.
• The 2018 International Society for Traumatic Stress Studies practice guidelines "strongly recommend" EMDR as an effective treatment for post-traumatic stress symptoms.
• As of 2023, the American Psychological Association "conditionally recommends" EMDR for the treatment of PTSD.
• The UK National Institute for Health and Care Excellence's 2018 report on the treatment of PTSD found low-to-very-low evidence of efficacy for EMDR in treating PTSD.
• A 2017 joint report from the US Departments of Veterans Affairs and Defense describes the evidence for EMDR in the treatment of PTSD as "strong."
• The Australian National Health and Medical Research Council recommends EMDR for the treatment of PTSD in adults with its highest grade of evidence, noting that "EMDR now includes most of the core elements of standard trauma-focussed CBT (TF-CBT)" and "the two variants of trauma-focussed therapy are not statistically different."
• The Institute of Medicine's 2008 report on the treatment of PTSD found insufficient evidence to recommend EMDR, and criticized many of the available studies for methodological flaws including allegiance bias and insufficient controls.
• The Dutch National Steering Committee on Mental Health Care has released multidisciplinary guidelines which describe "insufficient scientific evidence" to support EMDR in the acute period following a stressful event (2008), but recommend EMDR's use in chronic PTSD (2003).

Other conditions

EMDR has been tested on a variety of other mental health conditions with mixed results. A 2021 systematic review and meta-analysis found EMDR to have a moderate benefit in treating depression, but the number and quality of the studies were low. Positive effects have also been shown for certain anxiety disorders, but the number of studies was low and the risk of bias high. The American Psychological Asssociation describes EMDR as "ineffective" for the treatment of panic disorder. EMDR has been found to cause strong effects on dissociative identity disorder patients, leading to recommendations for adjusted use.

Possible mechanisms

Incomplete processing of experiences in trauma

Many proposals of EMDR efficacy share an assumption that, as Shapiro posited, when a traumatic or very negative event occurs, information processing of the experience in memory may be incomplete. The trauma causes a disruption of normal adaptive information processing, which results in unprocessed information being dysfunctionally held in memory networks. According to the 2013 World Health Organization practice guideline: "This therapy [EMDR] is based on the idea that negative thoughts, feelings and behaviours are the result of unprocessed memories." This proposed mechanism has no known scientific basis.

Other mechanisms

Several other possible mechanisms have been proposed:

• EMDR may impact working memory. If a patient performs bilateral stimulation task while remembering the trauma, the amount of information they can recall is thought to be reduced, making the resulting negative emotions less intense and more bearable. This is seen by some as a 'distancing effect'. The client is then believed to re-evaluate the trauma and process it in a less-harmful environment. This explanation is plausible, given research showing that memories are more modifiable once recalled.
• Horizontal eye movement is thought to trigger an 'orienting response' in the brain, used in scanning the environment for threats and opportunities.
• The idea that eye movement prompts communication between the two sides of the brain. This idea is not grounded in accepted neuroscience.

Bilateral stimulation, including eye movement

Bilateral stimulation is a generalization of the left and right repetitive eye movement technique first used by Shapiro. Alternative stimuli include auditory stimuli that alternate between left and right speakers or headphones and physical stimuli such as tapping of the therapist's hands or tapping devices.

Most meta-analyses have found that the inclusion of bilateral eye-movements within EMDR makes little or no difference to its effect. Meta-analyses have also described a high risk of allegiance bias in EMDR studies. One 2013 meta-analysis with fewer exclusion criteria found a moderate effect.

Pseudoscience

EMDR has been characterized as pseudoscience, because the underlying theory and primary therapeutic mechanism are unfalsifiable and non-scientific. EMDR's founder and other practitioners have used untestable hypotheses to explain studies which show no effect. The results of the therapy are non-specific, especially if directed eye movements are irrelevant to the results. When these movements are removed, what remains is a broadly therapeutic interaction and deceptive marketing. According to Yale neurologist Steven Novella:

[T]he false specificity of these treatments is a massive clinical distraction. Time and effort are wasted clinically in studying, perfecting, and using these methods, rather than focusing on the components of the interaction that actually work.

EMDR has been characterised as a modern-day mesmerism, as the therapies have striking resemblances, from the sole inventor who devises the system while out walking, to the large business empire built on exaggerated claims. In the case of EMDR, these have included the suggestions that EMDR could drain violence from society and be useful in treating cancer and HIV/AIDS. Psychology historian Luis Cordón has compared the popularity of EMDR to that of other cult-like pseudosciences, facilitated communication and thought field therapy.

A parody website advertising "sudotherapy" created by a fictional "Fatima Shekel" appeared on the internet in the 1990s. Proponents of EMDR described the website as libelous, since the website contained an image of a pair of shifting eyes following a cat named "Sudo", and "Fatima Shekel" has the same initials as EMDR's founder, Francine Shapiro. However, no legal action took place against the website or its founders, who are likely protected by American First Amendment protections.

History

EMDR was invented by Francine Shapiro (1948 – 2019) in the late 1980s.

In a workshop, Shapiro related how the idea of the therapy came to her while she was taking a walk in the woods, and discerned she had been able to cope better with disturbing thoughts when also experiencing saccadic eye movements. Psychologist Gerald Rosen has expressed doubt about this description, saying that people are normally not aware of this type of eye movement.

Fuelled by marketing hype, EMDR was taken up enthusiastically by therapists even while scientists remained skeptical; by the mid-2000s as many as 40,000 therapists had been trained.

Society and culture

Prince Harry took a course of EMDR and filmed a session for Oprah Winfrey during a mental health television documentary in 2021. Producer and actress Sandra Bullock used EMDR following a home invasion by a stalker in 2014.

Combat stress reaction

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Combat_stress_reaction 

 

Combat stress reaction
A U.S. Marine, Pvt. Theodore J. Miller, exhibits a "thousand-yard stare", an unfocused, despondent and weary gaze which is a frequent manifestation of "combat fatigue"
Specialty	Psychiatry

Combat stress reaction (CSR) is acute behavioral disorganization as a direct result of the trauma of war. Also known as "combat fatigue", "battle fatigue", or "battle neurosis", it has some overlap with the diagnosis of acute stress reaction used in civilian psychiatry. It is historically linked to shell shock and can sometimes precurse post-traumatic stress disorder.

Combat stress reaction is an acute reaction that includes a range of behaviors resulting from the stress of battle that decrease the combatant's fighting efficiency. The most common symptoms are fatigue, slower reaction times, indecision, disconnection from one's surroundings, and the inability to prioritize. Combat stress reaction is generally short-term and should not be confused with acute stress disorder, post-traumatic stress disorder, or other long-term disorders attributable to combat stress, although any of these may commence as a combat stress reaction. The US Army uses the term/initialism COSR (Combat Stress Reaction) in official medical reports. This term can be applied to any stress reaction in the military unit environment. Many reactions look like symptoms of mental illness (such as panic, extreme anxiety, depression, and hallucinations), but they are only transient reactions to the traumatic stress of combat and the cumulative stresses of military operations.

In World War I, shell shock was considered a psychiatric illness resulting from injury to the nerves during combat. The nature of trench warfare meant that about 10% of the fighting soldiers were killed (compared to 4.5% during World War II) and the total proportion of troops who became casualties (killed or wounded) was about 57%. Whether a person with shell-shock was considered "wounded" or "sick" depended on the circumstances. Soldiers were personally faulted for their mental breakdown rather than their war experience. The large proportion of World War I veterans in the European population meant that the symptoms were common to the culture.

Signs and symptoms

Combat stress reaction symptoms align with the symptoms also found in psychological trauma, which is closely related to post-traumatic stress disorder (PTSD). CSR differs from PTSD (among other things) in that a PTSD diagnosis requires a duration of symptoms over one month, which CSR does not.

Fatigue-related symptoms

The most common stress reactions include:

• The slowing of reaction time
• Slowness of thought
• Difficulty prioritizing tasks
• Difficulty initiating routine tasks
• Preoccupation with minor issues and familiar tasks
• Indecision and lack of concentration
• Loss of initiative with fatigue
• Exhaustion

Autonomic nervous system – Autonomic arousal

• Headaches
• Back pains
• Inability to relax
• Shaking and tremors
• Sweating
• Nausea and vomiting
• Loss of appetite
• Abdominal distress
• Frequency of urination
• Urinary incontinence
• Heart palpitations
• Hyperventilation
• Dizziness
• Insomnia
• Nightmares
• Restless sleep
• Excessive sleep
• Excessive startle
• Hypervigilance
• Heightened sense of threat
• Anxiety
• Irritability
• Depression
• Substance abuse
• Loss of adaptability
• Attempted suicides
• Disruptive behavior
• Mistrust of others
• Confusion
• Extreme feeling of losing control

Battle casualty rates

The ratio of stress casualties to battle casualties varies with the intensity of the fighting. With intense fighting, it can be as high as 1:1. In low-level conflicts, it can drop to 1:10 (or less). Modern warfare embodies the principles of continuous operations with an expectation of higher combat stress casualties.

The World War II European Army rate of stress casualties of 1 in 10 (101:1,000) troops per annum is skewed downward from both its norm and peak by data by low rates during the last years of the war.

Diagnosis

The following PIE principles were in place for the "not yet diagnosed nervous" (NYDN) cases:

• Proximity – treat the casualties close to the front and within sound of the fighting.
• Immediacy – treat them without delay and not wait until the wounded were all dealt with.
• Expectancy – ensure that everyone had the expectation of their return to the front after a rest and replenishment.

United States medical officer Thomas W. Salmon is often quoted as the originator of these PIE principles. However, his real strength came from going to Europe and learning from the Allies and then instituting the lessons. By the end of the war, Salmon had set up a complete system of units and procedures that was then the "world's best practice". After the war, he maintained his efforts in educating society and the military. He was awarded the Distinguished Service Medal for his contributions.

Effectiveness of the PIE approach has not been confirmed by studies of CSR, and there is some evidence that it is not effective in preventing PTSD.

US services now use the more recently developed BICEPS principles:

• Brevity
• Immediacy
• Centrality or contact
• Expectancy
• Proximity
• Simplicity

Between the wars

The British government produced a Report of the War Office Committee of Inquiry into "Shell-Shock", which was published in 1922. Recommendations from this included:

In forward areas

No soldier should be allowed to think that loss of nervous or mental control provides an honorable avenue of escape from the battlefield, and every endeavor should be made to prevent slight cases leaving the battalion or divisional area, where treatment should be confined to provision of rest and comfort for those who need it and to heartening them for return to the front line.

In neurological centers

When cases are sufficiently severe to necessitate more scientific and elaborate treatment they should be sent to special Neurological Centers as near the front as possible, to be under the care of an expert in nervous disorders. No such case should, however, be so labelled on evacuation as to fix the idea of nervous breakdown in the patient's mind.

In base hospitals

When evacuation to the base hospital is necessary, cases should be treated in a separate hospital or separate sections of a hospital, and not with the ordinary sick and wounded patients. Only in exceptional circumstances should cases be sent to the United Kingdom, as, for instance, men likely to be unfit for further service of any kind with the forces in the field. This policy should be widely known throughout the Force.

Forms of treatment

The establishment of an atmosphere of cure is the basis of all successful treatment, the personality of the physician is, therefore, of the greatest importance. While recognizing that each individual case of war neurosis must be treated on its merits, the Committee are of opinion that good results will be obtained in the majority by the simplest forms of psycho-therapy, i.e., explanation, persuasion and suggestion, aided by such physical methods as baths, electricity and massage. Rest of mind and body is essential in all cases.

The committee are of opinion that the production of deep hypnotic sleep, while beneficial as a means of conveying suggestions or eliciting forgotten experiences are useful in selected cases, but in the majority they are unnecessary and may even aggravate the symptoms for a time.

They do not recommend psycho-analysis in the Freudian sense.

In the state of convalescence, re-education and suitable occupation of an interesting nature are of great importance. If the patient is unfit for further military service, it is considered that every endeavor should be made to obtain for him suitable employment on his return to active life.

Return to the fighting line

Soldiers should not be returned to the fighting line under the following conditions:

(1) If the symptoms of neurosis are of such a character that the soldier cannot be treated overseas with a view to subsequent useful employment.

(2) If the breakdown is of such severity as to necessitate a long period of rest and treatment in the United Kingdom.

(3) If the disability is anxiety neurosis of a severe type.

(4) If the disability is a mental breakdown or psychosis requiring treatment in a mental hospital.

It is, however, considered that many of such cases could, after recovery, be usefully employed in some form of auxiliary military duty.

Part of the concern was that many British veterans were receiving pensions and had long-term disabilities.

By 1939, some 120,000 British ex-servicemen had received final awards for primary psychiatric disability or were still drawing pensions – about 15% of all pensioned disabilities – and another 44,000 or so were getting pensions for 'soldier's heart' or Effort Syndrome. There is, though, much that statistics do not show, because in terms of psychiatric effects, pensioners were just the tip of a huge iceberg."

War correspondent Philip Gibbs wrote:

Something was wrong. They put on civilian clothes again and looked to their mothers and wives very much like the young men who had gone to business in the peaceful days before August 1914. But they had not come back the same men. Something had altered in them. They were subject to sudden moods, and queer tempers, fits of profound depression alternating with a restless desire for pleasure. Many were easily moved to passion where they lost control of themselves, many were bitter in their speech, violent in opinion, frightening.

One British writer between the wars wrote:

There should be no excuse given for the establishment of a belief that a functional nervous disability constitutes a right to compensation. This is hard saying. It may seem cruel that those whose sufferings are real, whose illness has been brought on by enemy action and very likely in the course of patriotic service, should be treated with such apparent callousness. But there can be no doubt that in an overwhelming proportion of cases, these patients succumb to 'shock' because they get something out of it. To give them this reward is not ultimately a benefit to them because it encourages the weaker tendencies in their character. The nation cannot call on its citizens for courage and sacrifice and, at the same time, state by implication that an unconscious cowardice or an unconscious dishonesty will be rewarded.

World War II

American

At the outbreak of World War II, most in the United States military had forgotten the treatment lessons of World War I. Screening of applicants was initially rigorous, but experience eventually showed it to lack great predictive power.

The US entered the war in December 1941. Only in November 1943 was a psychiatrist added to the table of organization of each division, and this policy was not implemented in the Mediterranean Theater of Operations until March 1944. By 1943, the US Army was using the term "exhaustion" as the initial diagnosis of psychiatric cases, and the general principles of military psychiatry were being used. General Patton's slapping incident was in part the spur to institute forward treatment for the Italian invasion of September 1943. The importance of unit cohesion and membership of a group as a protective factor emerged.

John Appel found that the average American infantryman in Italy was "worn out" in 200 to 240 days and concluded that the American soldier "fights for his buddies or because his self respect won't let him quit". After several months in combat, the soldier lacked reasons to continue to fight because he had proven his bravery in battle and was no longer with most of the fellow soldiers he trained with. Appel helped implement a 180-day limit for soldiers in active combat and suggested that the war be made more meaningful, emphasizing their enemies' plans to conquer the United States, encouraging soldiers to fight to prevent what they had seen happen in other countries happen to their families. Other psychiatrists believed that letters from home discouraged soldiers by increasing nostalgia and needlessly mentioning problems soldiers could not solve. William Menninger said after the war, "It might have been wise to have had a nation-wide educational course in letter writing to soldiers", and Edward Strecker criticized "moms" (as opposed to mothers) who, after failing to "wean" their sons, damaged morale through letters.

Airmen flew far more often in the Southwest Pacific than in Europe, and although rest time in Australia was scheduled, there was no fixed number of missions that would produce transfer out of combat, as was the case in Europe. Coupled with the monotonous, hot, sickly environment, the result was bad morale that jaded veterans quickly passed along to newcomers. After a few months, epidemics of combat fatigue would drastically reduce the efficiency of units. Flight surgeons reported that the men who had been at jungle airfields longest were in bad shape:

Many have chronic dysentery or other disease, and almost all show chronic fatigue states. … They appear listless, unkempt, careless, and apathetic with almost mask-like facial expression. Speech is slow, thought content is poor, they complain of chronic headaches, insomnia, memory defect, feel forgotten, worry about themselves, are afraid of new assignments, have no sense of responsibility, and are hopeless about the future.

British

Unlike the Americans, the British leaders firmly held the lessons of World War I. It was estimated that aerial bombardment would kill up to 35,000 a day, but the Blitz killed only 40,000 in total. The expected torrent of civilian mental breakdown did not occur. The Government turned to World War I doctors for advice on those who did have problems. The PIE principles were generally used. However, in the British Army, since most of the World War I doctors were too old for the job, young, analytically trained psychiatrists were employed. Army doctors "appeared to have no conception of breakdown in war and its treatment, though many of them had served in the 1914–1918 war." The first Middle East Force psychiatric hospital was set up in 1942. With D-Day for the first month there was a policy of holding casualties for only 48 hours before they were sent back over the Channel. This went firmly against the expectancy principle of PIE.

Appel believed that British soldiers were able to continue to fight almost twice as long as their American counterparts because the British had better rotation schedules and because they, unlike the Americans, "fight for survival" – for the British soldiers, the threat from the Axis powers was much more real, given Britain's proximity to mainland Europe, and the fact that Germany was concurrently conducting air raids and bombarding British industrial cities. Like the Americans, British doctors believed that letters from home often needlessly damaged soldiers' morale.

Canadian

The Canadian Army recognized combat stress reaction as "Battle Exhaustion" during the Second World War and classified it as a separate type of combat wound. Historian Terry Copp has written extensively on the subject. In Normandy, "The infantry units engaged in the battle also experienced a rapid rise in the number of battle exhaustion cases with several hundred men evacuated due to the stress of combat. Regimental Medical Officers were learning that neither elaborate selection methods nor extensive training could prevent a considerable number of combat soldiers from breaking down."

Germans

In his history of the pre-Nazi Freikorps paramilitary organizations, Vanguard of Nazism, historian Robert G. L. Waite describes some of the emotional effects of World War I on German troops, and refers to a phrase he attributes to Göring: men who could not become "de-brutalized".

In an interview, Dr Rudolf Brickenstein stated that:

... he believed that there were no important problems due to stress breakdown since it was prevented by the high quality of leadership. But, he added, that if a soldier did break down and could not continue fighting, it was a leadership problem, not one for medical personnel or psychiatrists. Breakdown (he said) usually took the form of unwillingness to fight or cowardice.

However, as World War II progressed there was a profound rise in stress casualties from 1% of hospitalizations in 1935 to 6% in 1942. Another German psychiatrist reported after the war that during the last two years, about a third of all hospitalizations at Ensen were due to war neurosis. It is probable that there was both less of a true problem and less perception of a problem.

Finns

The Finnish attitudes to "war neurosis" were especially tough. Psychiatrist Harry Federley, who was the head of the Military Medicine, considered shell shock as a sign of weak character and lack of moral fibre. His treatment for war neurosis was simple: the patients were to be bullied and harassed until they returned to front line service.

Earlier, during the Winter War, several Finnish machine gun operators on the Karelian Isthmus theatre became mentally unstable after repelling several unsuccessful Soviet human wave assaults on fortified Finnish positions.

Post-World War II developments

Simplicity was added to the PIE principles by the Israelis: in their view, treatment should be brief, supportive, and could be provided by those without sophisticated training.

Peacekeeping stresses

Peacekeeping provides its own stresses because its emphasis on rules of engagement contains the roles for which soldiers are trained. Causes include witnessing or experiencing the following:

• Constant tension and threat of conflict.
• Threat of land mines and booby traps.
• Close contact with severely injured and dead people.
• Deliberate maltreatment and atrocities, possibly involving civilians.
• Cultural issues.
• Separation and home issues.
• Risk of disease including HIV.
• Threat of exposure to toxic agents.
• Mission problems.
• Return to service.

Pathophysiology

SNS activation

A U.S. Long Range Reconnaissance Patrol leader in Vietnam, 1968.

Many of the symptoms initially experienced by people with CSR are effects of an extended activation of the human body's fight-or-flight response. The fight-or-flight response involves a general sympathetic nervous system discharge in reaction to a perceived stressor and prepares the body to fight or run from the threat causing the stress. Catecholamine hormones, such as adrenaline or noradrenaline, facilitate immediate physical reactions associated with a preparation for violent muscular action. Although the flight-or-fight-response normally ends with the removal of the threat, the constant mortal danger in combat zones likewise constantly and acutely stresses soldiers.

General adaptation syndrome

The process whereby the human body responds to extended stress is known as general adaptation syndrome (GAS). After the initial fight-or-flight response, the body becomes more resistant to stress in an attempt to dampen the sympathetic nervous response and return to homeostasis. During this period of resistance, physical and mental symptoms of CSR may be drastically reduced as the body attempts to cope with the stress. Long combat involvement, however, may keep the body from homeostasis and thereby deplete its resources and render it unable to normally function, sending it into the third stage of GAS: exhaustion. Sympathetic nervous activation remains in the exhaustion phase and reactions to stress are markedly sensitized as fight-or-flight symptoms return. If the body remains in a state of stress, then such more severe symptoms of CSR as cardiovascular and digestive involvement may present themselves. Extended exhaustion can permanently damage the body.

Treatment

7 Rs

The British Army treated Operational Stress Reaction according to the 7 R's:

• Recognition – identify that the individual has an Operational Stress Reaction
• Respite – provide a short period of relief from the front line
• Rest – allow rest and recovery
• Recall – give the individual the chance to recall and discuss the experiences that have led to the reaction
• Reassurance – inform them that their reaction is normal and they will recover
• Rehabilitation – improve the physical and mental health of the patient until they no longer show symptoms
• Return – allow the soldier to return to their unit

BICEPS

Modern front-line combat stress treatment techniques are designed to mimic the historically used PIE techniques with some modification. BICEPS is the current treatment route employed by the U.S. military and stresses differential treatment by the severity of CSR symptoms present in the service member. BICEPS is employed as a means to treat CSR symptoms and return soldiers quickly to combat.

The following subsections on the BICEPS program are adapted from the USMC combat stress handbook:

Brevity

Critical Event Debriefing should take 2 to 3 hours. Initial rest and replenishment at medical CSC (Combat Stress Control) facilities should last no more than 3 or 4 days. Those requiring further treatment are moved to the next level of care. Since many require no further treatment, military commanders expect their service members to return to duty rapidly.

Immediacy

CSC should be done as soon as possible when operations permit. Intervention is provided as soon as symptoms appear.

Centrality/Contact

Service members requiring observation or care beyond the unit level are evacuated to facilities in close proximity to, but separate from the medical or surgical patients at the BAS, surgical support company in a central location (Marines) or forward support/division support or area support medical companies (Army) nearest the service members' unit. It is best to send service members who cannot continue their mission and require more extensive respite to a central facility other than a hospital, unless no other alternative is possible. The service member must be encouraged to continue to think of themselves as a war fighter, rather than a patient or a sick person. The chain of command remains directly involved in the service member's recovery and return to duty. The CSC team coordinates with the unit's leaders to learn whether the over-stressed individual was a good performer prior to the combat stress reaction, or whether they were always a marginal or problem performer whom the team would rather see replaced than returned. Whenever possible, representatives of the unit, or messages from the unit, tell the casualty that they are needed and wanted back. The CSC team coordinates with the unit leaders, through unit medical personnel or chaplains, any special advice on how to assure quick reintegration when the service member returns to their unit.

Expectancy

The individual is explicitly told that he is reacting normally to extreme stress and is expected to recover and return to full duty in a few hours or days. A military leader is extremely effective in this area of treatment. Of all the things said to a service member experiencing combat stress, the words of his small-unit leader have the greatest impact due to the positive bonding process that occurs during combat. Simple statements from the small-unit leader to the service member that he is reacting normally to combat stress and is expected back soon have positive impact. Small-unit leaders should tell service members that their comrades need and expect them to return. When they do return, the unit treats them as every other service member and expects them to perform well. Service members experiencing and recovering from combat stress disorder are no more likely to become overloaded again than are those who have not yet been overloaded. In fact, they are less likely to become overloaded than inexperienced replacements.

Proximity

In mobile war requiring rapid and frequent movement, treatment of many combat stress cases takes place at various battalion or regimental headquarters or logistical units, on light duty, rather than in medical units, whenever possible. This is a key factor and another area where the small-unit leader helps in the treatment. CSC and follow-up care for combat stress casualties are held as close as possible to and maintain close association with the member's unit, and are an integral part of the entire healing process. A visit from a member of the individual's unit during restoration is effective in keeping a bond with the organization. A service member experiencing combat stress reaction is having a crisis, and there are two basic elements to that crisis working in opposite directions. On the one hand, the service member is driven by a strong desire to seek safety and to get out of an intolerable environment. On the other hand, the service member does not want to let their comrades down. They want to return to their unit. If a service member starts to lose contact with their unit when he enters treatment, the impulse to get out of the war and return to safety takes over. They feel that they've failed their comrades who have already rejected them as unworthy. The potential is for the service member to become more and more emotionally invested in keeping their symptoms so they can stay in a safe environment. Much of this is done outside the service member's conscious awareness, but the result is the same. The more out of touch the service member is with their unit, the less likely they will recover. They are more likely to develop a chronic psychiatric illness and get evacuated from the war.

Simplicity

Treatment is kept simple. CSC is not therapy. Psychotherapy is not done. The goal is to rapidly restore the service member's coping skills so that he functions and returns to duty again. Sleep, food, water, hygiene, encouragement, work details, and confidence-restoring talk are often all that is needed to restore a service member to full operational readiness. This can be done in units in reserve positions, logistical units or at medical companies. Every effort is made to reinforce service members' identity. They are required to wear their uniforms and to keep their helmets, equipment, chemical protective gear, and flak jackets with them. When possible, they are allowed to keep their weapons after the weapons have been cleared. They may serve on guard duty or as members of a standby quick reaction force.

Predeployment preparation

Screening

Historically, screening programs that have attempted to preclude soldiers exhibiting personality traits thought to predispose them to CSR have been a total failure. Part of this failure stems from the inability to base CSR morbidity on one or two personality traits. Full psychological work-ups are expensive and inconclusive, while pen and paper tests are ineffective and easily faked. In addition, studies conducted following WWII screening programs showed that psychological disorders present during military training did not accurately predict stress disorders during combat.

Cohesion

While it is difficult to measure the effectiveness of such a subjective term, soldiers who reported in a WWII study that they had a "higher than average" sense of camaraderie and pride in their unit were more likely to report themselves ready for combat and less likely to develop CSR or other stress disorders. Soldiers with a "lower than average" sense of cohesion with their unit were more susceptible to stress illness.

Training

Stress exposure training or SET is a common component of most modern military training. There are three steps to an effective stress exposure program.

• Providing knowledge of the stress environment

Soldiers with a knowledge of both the emotional and physical signs and symptoms of CSR are much less likely to have a critical event that reduces them below fighting capability. Instrumental information, such as breathing exercises that can reduce stress and suggestions not to look at the faces of enemy dead, is also effective at reducing the chance of a breakdown.

• Skills acquisition

Cognitive control strategies can be taught to soldiers to help them recognize stressful and situationally detrimental thoughts and repress those thoughts in combat situations. Such skills have been shown to reduce anxiety and improve task performance.

• Confidence building through application and practice

Soldiers who feel confident in their own abilities and those of their squad are far less likely to develop combat stress reaction. Training in stressful conditions that mimic those of an actual combat situation builds confidence in the abilities of themselves and the squad. As this training can actually induce some of the stress symptoms it seeks to prevent, stress levels should be increased incrementally as to allow the soldiers time to adapt.

Prognosis

Figures from the 1982 Lebanon war showed that with proximal treatment, 90% of CSR casualties returned to their unit, usually within 72 hours. With rearward treatment, only 40% returned to their unit. It was also found that treatment efficacy went up with the application of a variety of front line treatment principles versus just one treatment. In Korea, similar statistics were seen, with 85% of US battle fatigue casualties returned to duty within three days and 10% returned to limited duties after several weeks.

Though these numbers seem to promote the claims that proximal PIE or BICEPS treatment is generally effective at reducing the effects of combat stress reaction, other data suggests that long term PTSD effects may result from the hasty return of affected individuals to combat. Both PIE and BICEPS are meant to return as many soldiers as possible to combat, and may actually have adverse effects on the long-term health of service members who are rapidly returned to the front-line after combat stress control treatment. Although the PIE principles were used extensively in the Vietnam War, the post traumatic stress disorder lifetime rate for Vietnam veterans was 30% in a 1989 US study and 21% in a 1996 Australian study. In a study of Israeli Veterans of the 1973 Yom Kippur War, 37% of veterans diagnosed with CSR during combat were later diagnosed with PTSD, compared with 14% of control veterans.

Controversy

There is significant controversy with the PIE and BICEPS principles. Throughout a number of wars, but notably during the Vietnam War, there has been a conflict among doctors about sending distressed soldiers back to combat. During the Vietnam War this reached a peak with much discussion about the ethics of this process. Proponents of the PIE and BICEPS principles argue that it leads to a reduction of long-term disability but opponents argue that combat stress reactions lead to long-term problems such as post-traumatic stress disorder.

The use of psychiatric drugs to treat people with CSR has also attracted criticism, as some military psychiatrists have come to question the efficacy of such drugs on the long-term health of veterans. Concerns have been expressed as to the effect of pharmaceutical treatment on an already elevated substance abuse rate among former people with CSR.

Recent research has caused an increasing number of scientists to believe that there may be a physical (i.e., neurocerebral damage) rather than psychological basis for blast trauma. As traumatic brain injury and combat stress reaction have very different causes yet result in similar neurologic symptoms, researchers emphasize the need for greater diagnostic care.

Acute stress disorder

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Acute_stress_disorder

Acute stress reaction
Specialty	Psychiatry
Causes	Exposure to a traumatic event

Acute stress disorder (ASD, also known as acute stress reaction, psychological shock, mental shock, or simply shock) is a psychological response to a terrifying, traumatic or surprising experience. It may bring about delayed stress reactions (better known as post-traumatic stress disorder, or PTSD) if not correctly addressed. Acute stress may present in reactions which include but are not limited to: intrusive or dissociative symptoms, and reactivity symptoms such as avoidance or arousal. Reactions may be exhibited for days or weeks post the traumatic event.

Diagnostic Criteria

According to the DSM-V, acute stress disorder requires the exposure to actual or threatened death, serious injury, or sexual violation by either directly experiencing it, witnessing it in person, learning it occurred to a close family or friend, or experiencing repeated exposure to aversive details of a traumatic event. In addition to the initial exposure, individuals may also present with a variety of different symptoms that fall within several clusters including intrusion, negative mood, dissociation, avoidance of distressing memories and emotional arousal. Intrusion symptoms include recurring and distressing dreams, flashbacks, or memories related to the traumatic event and related somatic symptoms. Negative mood refers to ones inability to experience positive emotions such as happiness or satisfaction. Dissociative symptoms include a sense of numbing or detachment from emotional reactions, a sense of physical detachment, decreased awareness of one's surroundings, the perception that one's environment is unreal or dreamlike, and the inability to recall critical aspects of the traumatic event (dissociative amnesia). Emotional arousal symptoms include sleep disturbances, hypervigilance, difficulties with concentration, more common startle response, and irritability. Symptom presentation must last for at least three consecutive days after trauma exposure to be classified as acute stress disorder. If symptoms persist past one month, the diagnosis of PTSD should be assessed for. The presenting symptoms must also cause significant impairment in multiple domains of one's life to be diagnosed.

Additional diagnoses that may develop from acute stress disorder include depression, anxiety, mood disorders, and substance abuse problems. Untreated acute stress disorder can also lead to the development of post-traumatic stress disorder.

Diagnostic Assessment

Evaluation of patients is done through close examination of emotional response. Using self-report from patients is a large part of diagnosing acute stress disorder, as acute stress is the result of reactions to stressful situations.

Development and Course

There are several theoretical perspectives on trauma response, including cognitive, biological, and psycho-biological. While PTSD-specific, these theories are still useful in understanding acute stress disorder, as the two disorders share many symptoms. A recent study found that even a single stressful event may have long-term consequences on cognitive function. This result calls the traditional distinction between the effects of acute and chronic stress into question.

Risk Factors

Risk factors for developing acute stress disorder include a previously existing mental health diagnosis, avoidant coping mechanisms, and exaggerated appraisals of events. Additional factors also include prior trauma history and heightened emotional reactivity. The DSM-V specifies that there is a higher prevalence rate of acute stress disorder among females compared to males due to higher risk of experiencing traumatic events and neurobiological gender differences in stress response.

Types

Sympathetic

See also: Fight-or-flight response

Sympathetic acute stress disorder is caused by the release of excessive adrenaline and norepinephrine into the nervous system. These hormones may speed up a person's pulse and respiratory rate, dilate pupils, or temporarily mask pain. This type of ASD developed as an evolutionary advantage to help humans survive dangerous situations. The "fight or flight" response may allow for temporarily-enhanced physical output, even in the face of severe injury. However, other physical illnesses become more difficult to diagnose, as ASD masks the pain and other vital signs that would otherwise be symptomatic.

Parasympathetic

Parasympathetic acute stress disorder is characterised by feeling faint and nauseated. This response is fairly often triggered by the sight of blood. In this stress response, the body releases acetylcholine. In many ways, this reaction is the opposite of the sympathetic response, in that it slows the heart rate and can cause the patient to either regurgitate or temporarily lose consciousness. The evolutionary value of this is unclear, although it may have allowed for prey to appear dead to avoid being eaten.

Pathophysiology

Stress is characterised by specific physiological responses to adverse or noxious stimuli.

Hans Selye was the first to coin the term "general adaptation syndrome" to suggest that stress-induced physiological responses proceed through the stages of alarm, resistance, and exhaustion.

The sympathetic branch of the autonomic nervous system gives rise to a specific set of physiological responses to physical or psychological stress. The body's response to stress is also termed a "fight or flight" response, and it is characterised by an increase in blood flow to the skeletal muscles, heart, and brain, a rise in heart rate and blood pressure, dilation of pupils, and an increase in the amount of glucose released by the liver.

The onset of an acute stress response is associated with specific physiological actions in the sympathetic nervous system, both directly and indirectly through the release of adrenaline and, to a lesser extent, noradrenaline from the medulla of the adrenal glands. These catecholamine hormones facilitate immediate physical reactions by triggering increases in heart rate and breathing, constricting blood vessels. An abundance of catecholamines at neuroreceptor sites facilitates reliance on spontaneous or intuitive behaviours often related to combat or escape.

Normally, when a person is in a serene, non-stimulated state, the firing of neurons in the locus ceruleus is minimal. A novel stimulus, once perceived, is relayed from the sensory cortex of the brain through the thalamus to the brain stem. That route of signalling increases the rate of noradrenergic activity in the locus ceruleus, and the person becomes more alert and attentive to their environment.

If a stimulus is perceived as a threat, a more intense and prolonged discharge of the locus ceruleus activates the sympathetic division of the autonomic nervous system. The activation of the sympathetic nervous system leads to the release of norepinephrine from nerve endings acting on the heart, blood vessels, respiratory centres, and other sites. The ensuing physiological changes constitute a major part of the acute stress response. The other major player in the acute stress response is the hypothalamic-pituitary-adrenal axis. Stress activates this axis and produces neuro-biological changes. These chemical changes increase the chances of survival by bringing the physiological system back to homeostasis.

The autonomic nervous system controls all automatic functions in the body and contains two subsections within it that aid the response to an acute stress reaction. These two subunits are the sympathetic nervous system and the parasympathetic nervous system. The sympathetic response is colloquially known as the "fight or flight" response, indicated by accelerated pulse and respiration rates, pupil dilation, and a general feeling of anxiety and hyper-awareness. This is caused by the release of epinephrine and norepinephrine from the adrenal glands. The epinephrine and norepinephrine strike the beta receptors of the heart, which feeds the heart's sympathetic nerve fibres to increase the strength of heart muscle contraction; as a result, more blood gets circulated, increasing the heart rate and respiratory rate. The sympathetic nervous system also stimulates the skeletal system and muscular system to pump more blood to those areas to handle the acute stress. Simultaneously, the sympathetic nervous system inhibits the digestive system and the urinary system to optimise blood flow to the heart, lungs, and skeletal muscles. This plays a role in the alarm reaction stage. The parasympathetic response is colloquially known as the "rest and digest" response, indicated by reduced heart and respiration rates, and, more obviously, by a temporary loss of consciousness if the system is fired at a rapid rate. The parasympathetic nervous system stimulates the digestive system and urinary system to send more blood to those systems to increase the process of digestion. To do this, it must inhibit the cardiovascular system and respiratory system to optimise blood flow to the digestive tract, causing low heart and respiratory rates. The parasympathetic nervous system plays no role in acute stress response.

Studies have shown that patients with acute stress disorder have overactive right amygdalae and prefrontal cortices; both structures are involved in the fear-processing pathway.

Treatment

This disorder may resolve itself with time or may develop into a more severe disorder, such as PTSD. However, results of Creamer, O'Donnell, and Pattison's (2004) study of 363 patients suggests that a diagnosis of acute stress disorder had only limited predictive validity for PTSD. Creamer et al. found that re-experiences of the traumatic event and arousal were better predictors of PTSD. Early pharmacotherapy may prevent the development of post-traumatic symptoms. Additionally, early trauma-focused cognitive behavioural therapy (TF-CBT) for those with a diagnosis of ASD can protect an individual from developing chronic PTSD.

Studies have been conducted to assess the efficacy of counselling and psychotherapy for people with acute stress disorder. Cognitive behavioural therapy, which includes exposure and cognitive restructuring, was found to be effective in preventing PTSD in patients diagnosed with acute stress disorder with clinically significant results at six-month follow-up appointments. A combination of relaxation, cognitive restructuring, imaginal exposure, and in-vivo exposure was superior to supportive counselling. Mindfulness-based stress reduction programmes also appear to be effective for stress management.

The pharmacological approach has made some progress in lessening the effects of ASD. To relax patients and allow for better sleep, Prazosin can be given to patients, which regulates their sympathetic response. Hydrocortisone has shown some success as an early preventative measure following a traumatic event, typically in the treatment of PTSD.

In a wilderness context where counselling, psychotherapy, and cognitive behavioural therapy is unlikely to be available, the treatment for acute stress reaction is very similar to the treatment of cardiogenic shock, vascular shock, and hypovolemic shock; that is, allowing the patient to lie down, providing reassurance, and removing the stimulus that prompted the reaction. In traditional shock cases, this generally means relieving injury pain or stopping blood loss. In an acute stress reaction, this may mean pulling a rescuer away from the emergency to calm down or blocking the sight of an injured friend from a patient.

History

The term "acute stress disorder" was first used to describe the symptoms of soldiers during World War I and II, and it was therefore also termed "combat stress reaction" (CSR). Approximately 20% of U.S. troops displayed symptoms of CSR during WWII. It was assumed to be a temporary response of healthy individuals to witnessing or experiencing traumatic events. Symptoms include depression, anxiety, withdrawal, confusion, paranoia, and sympathetic hyperactivity.

The APA officially included the term ASD in the DSM-IV in 1994. Before that, symptomatic individuals within the first month of trauma were diagnosed with adjustment disorder. According to the DSM-IV, acute stress reaction refers to the symptoms experienced immediately to 48 hours after exposure to a traumatic event. In contrast, acute stress disorder is defined by symptoms experienced 48 hours to one month following the event. Symptoms experienced for longer than one month are consistent with a diagnosis of PTSD.

Initially, being able to describe different ASRs was one of the goals of introducing ASD. Some criticisms surrounding ASD's focal point include issues with ASD recognising other distressing emotional reactions, like depression and shame. Emotional reactions similar to these may then be diagnosed as adjustment disorder under the current system of trying to diagnose ASD.

Since its addition to the DSM-IV, questions about the efficacy and purpose of the ASD diagnosis have been raised. The diagnosis of ASD was criticized as an unnecessary addition to the progress of diagnosing PTSD, as some considered it more akin to a sign of PTSD than an independent issue requiring diagnosis. Also, the terms ASD and ASR have been criticized for not fully covering the range of stress reactions.