145 replies to this topic

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PSSD (Post ssri Sexual Dysfunction)
J Clin Psychopharmacol. 2015 Jun;35(3):273-8. doi: 10.1097/JCP.0000000000000300.
Post-SSRI Sexual Dysfunction: Clinical Characterization and Preliminary Assessment of Contributory Factors and Dose-Response Relationship.
· Abstract
Emerging evidence suggests that sexual dysfunction emerging during treatment with selective serotonin reuptake inhibitors (SSRIs) and/or serotonin-norepinephrine reuptake inhibitors (SNRIs) persists in some patients beyond drug discontinuation (post-SSRI sexual dysfunction [PSSD]). We sought to identify and characterize a series of such cases and explore possible explanatory factors and exposure-response relationship. Subjects who responded to an invitation in a forum dedicated to PSSD filled out a survey via online software. Case probability was defined according to the following 3 categories of increasing presumed likelihood of PSSD. Noncases did not meet the criteria for possible cases. Possible cases were subjects with normal pretreatment sexual function who first experienced sexual disturbances while using a single SSRI/SNRI, which did not resolve upon drug discontinuation for 1 month or longer as indicated by Arizona Sexual Experience Scale scores. High-probability cases were also younger than 50-year-olds; did not have confounding medical conditions, medications, or drug use; and had normal scores on the Hospital Anxiety and Depression Scale. Five hundred thirty-two (532) subjects completed the survey, among which 183 possible cases were identified, including 23 high-probability cases. Female sex, genital anesthesia, and depression predicted current sexual dysfunction severity, but dose/defined daily dose ratio and anxiety did not. Genital anesthesia did not correlate with depression or anxiety, but pleasureless orgasm was an independent predictor of both depression and case probability. Limitations of the study include retrospective design and selection and report biases that do not allow generalization or estimation of incidence. However, our findings add to previous reports and support the existence of PSSD, which may not be fully explained by alternative nonpharmacological factors related to sexual dysfunction, including depression and anxiety.

Eur J Pharmacol. 2015 Apr 15;753:263-8. doi: 10.1016/j.ejphar.2014.11.031. Epub 2014 Dec 4.
Penile anesthesia in Post SSRI Sexual Dysfunction (PSSD) responds to low-power laser irradiation: a case study and hypothesis about the role of transient receptor potential (TRP) ion channels.
· Treatment of paroxetine-induced penile anesthesia in Post SSRI Sexual Dysfunction (PSSD) by Low-power Laser Irradiation (LPLI) is unknown in medical literature. The aim of the current article is to report partial efficacy of LPLI for paroxetine-induced persistent penile anesthesia. We report on a male patient who presented with a history of reversible loss of smell, taste and skin sensitivity occurring within a week after start of 20mg/day paroxetine-hemihydrate for a depressive period. Concurrently, patient suffered from penile anesthesia, scrotum hypesthesia, anejaculation and erectile difficulties with normal sexual desire. During 2.5 years of paroxetine treatment and throughout 2 years after paroxetine discontinuation, genital and sexual complaints persisted. Penile anesthesia was treated by LPLI with single and multi diode pulsed laser probes. After 20 LPLI-treatment sessions of 15min each, patient reported partial return of penile touch and temperature sensation. Clinical improvement of glans penis sensitivity was reported to 20% and 40%, compared to pre-paroxetine treatment penile sensitivity during erect and flaccid states, respectively. However, anejaculation and erectile difficulties remained unchanged. Briefly, in the current patient with early onset of PSSD, LPLI treatment reduced paroxetine-induced penile anesthesia. It is hypothesized that SSRI treatment induces disturbances of transient receptor potential (TRP) ion channels of mechano-, thermo- and chemosensitive nerve endings and receptors resulting in the penile anesthesia in PSSD. It is further hypothesized that there are two types of PSSD, one of which occurs soon after the start of SSRI treatment.

The Open Women' Health Journal, 2007, 1, 1-3
Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction Following Discontinuation of Citalopram and the Atypical Antidepressant Nefazodone
Robert P. Kauffman* and Amanda Murdock Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, School of Medicine, 1400 Coulter Drive, Amarillo, Texas 79106 USA

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PSSD (Post ssri Sexual Dysfunction) (cont)

The Open Psychology Journal, 2008, 1, 42-50
1874-3501/08 2008 Bentham Open
Open Access
Persistence of Sexual Dysfunction Side Effects after Discontinuation of
Antidepressant Medications: Emerging Evidence

http://pssd.nl/Persi... medication.pdf
Persistent Sexual Dysfunction after Discontinuation of Selective
Serotonin Reuptake Inhibitors

Introduction. Sexual dysfunctions such as low libido, anorgasmia, genital anesthesia, and erectile dysfunction are very common in patients taking selective serotonin reuptake inhibitors (SSRIs). It has been assumed that these side effects always resolve after discontinuing treatment, but recently, four cases were presented in which sexual function
did not return to baseline. Here, we describe three more cases.

Case #1: A 29-year-old with apparently permanent erectile dysfunction after taking fluoxetine 20 mg once daily for
a 4-month period in 1996.

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PSSD (Post ssri Sexual Dysfunction) (cont)

Case #2: A 44-year-old male with persistent loss of libido, genital anesthesia, ejaculatory anhedonia, and erectile
dysfunction after taking 20-mg once daily citalopram for 18 months.

Case #3: A 28-year-old male with persistent loss of libido, genital anesthesia, and ejaculatory anhedonia since
taking several different SSRIs over a 2-year period from 2003–2005.

Results. No psychological issues related to sexuality were found in any of the three cases, and all common causes of sexual dysfunction such as decreased testosterone, increased prolactin or diabetes were ruled out. Erectile capacity is temporarily restored for Case #1 with injectable alprostadil, and for Case #2 with oral sildenafil, but their other
symptoms remain. Case #3 has had some reversal of symptoms with extended-release methylphenidate, although it is not yet known if these prosexual effects will persist when the drug is discontinued.

Conclusion. SSRIs can cause long-term effects on all aspects of the sexual response cycle that may persist after they are discontinued. Mechanistic hypotheses including persistent endocrine and epigenetic gene expression alterations
were briefly discussed.

Csoka A, Bahrick A, and Mehtonen O-P. Persistent sexual dysfunction after discontinuation
of selective serotonin reuptake inhibitors. J Sex Med 2008;5:227–233.

http://psychrights.o...aetal(2007).pdf
OR
http://onlinelibrary...07.00630.x/full

One hundred and twenty cases of enduring
sexual dysfunction following treatment

BACKGROUND: There have been reports for over a decade linking serotonin reuptake inhibitors, finasteride and isotretinoin
with enduring sexual dysfunction after treatment stops.
OBJECTIVE: To explore the clinical pictures linked to all 3 drugs.
METHODS: We have selected 120 reports to RxISK.org reporting the problem and mined these for data on age, gender, drug
of use, and impact of the problem.

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PSSD (Post ssri Sexual Dysfunction) (cont)

RESULTS: The data make it clear that the three drugs show extensive overlap in symptom profile, regardless of sex or country
of origin.
CONCLUSIONS: The availability of 120 reports from over 20 countries add to the case for the validity of the syndrome. This is
severe and enduring condition can result in death. An understanding of its physiology and an approach to treatment are needed.
http://wp.rxisk.org/...Is-and-PSSD.pdf
The prescriber information for Prozac from Eli Lilly's website. Halfway through the 15th page is a clause which reads, “Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment."

Journal of Contemporary Psychotherapy June 2009, Volume 39, Issue 2, pp 135-143
Sexual Side Effects of Antidepressant Medications: An Informed Consent Accountability Gap
Abstract
Sexual side effects of antidepressant medications are far more common than initially reported, and their scope, quality, and duration remain poorly captured in the literature. Antidepressant treatment emergent sexual dysfunctions may decrease clients’ quality of life, complicate psychotherapy, and damage the treatment alliance. Potential damage to the treatment alliance is greatest when clients have not been adequately informed of risks related to sexual side effects. It had previously been assumed that sexual side effects always resolve shortly after medications are discontinued. Emerging evidence, however, suggests that in some individuals, sexual dysfunction side effects may persist indefinitely. The authors argue that all psychologists should be well-informed about sexual side effects risks of antidepressant medications, should routinely conduct a pre-medication baseline assessment of sexual functioning, and take an active role in the informed consent process.

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PSSD (Post ssri Sexual Dysfunction) (cont)

Wikipedia article
http://www.thefullwi...ual_dysfunction

https://www.ncbi.nlm...pubmed/25483212
Eur J Pharmacol. 2015 Apr 15;753:263-8. doi: 10.1016/j.ejphar.2014.11.031. Epub 2014 Dec 4.
Penile anesthesia in Post SSRI Sexual Dysfunction (PSSD) responds to low-power laser irradiation: a case study and hypothesis about the role of transient receptor potential (TRP) ion channels.
Treatment of paroxetine-induced penile anesthesia in Post SSRI Sexual Dysfunction (PSSD) by Low-power Laser Irradiation (LPLI) is unknown in medical literature. The aim of the current article is to report partial efficacy of LPLI for paroxetine-induced persistent penile anesthesia. We report on a male patient who presented with a history of reversible loss of smell, taste and skin sensitivity occurring within a week after start of 20mg/day paroxetine-hemihydrate for a depressive period. Concurrently, patient suffered from penile anesthesia, scrotum hypesthesia, anejaculation and erectile difficulties with normal sexual desire. During 2.5 years of paroxetine treatment and throughout 2 years after paroxetine discontinuation, genital and sexual complaints persisted. Penile anesthesia was treated by LPLI with single and multi diode pulsed laser probes. After 20 LPLI-treatment sessions of 15min each, patient reported partial return of penile touch and temperature sensation. Clinical improvement of glans penis sensitivity was reported to 20% and 40%, compared to pre-paroxetine treatment penile sensitivity during erect and flaccid states, respectively. However, anejaculation and erectile difficulties remained unchanged. Briefly, in the current patient with early onset of PSSD, LPLI treatment reduced paroxetine-induced penile anesthesia. It is hypothesized that SSRI treatment induces disturbances of transient receptor potential (TRP) ion channels of mechano-, thermo- and chemosensitive nerve endings and receptors resulting in the penile anesthesia in PSSD. It is further hypothesized that there are two types of PSSD, one of which occurs soon after the start of SSRI treatment.

[fishinghat]

PSSD (Post ssri Sexual Dysfunction) (cont)

https://www.ncbi.nlm...pubmed/25815755
Post-SSRI Sexual Dysfunction: Clinical Characterization and Preliminary Assessment of Contributory Factors and Dose-Response Relationship.
Emerging evidence suggests that sexual dysfunction emerging during treatment with selective serotonin reuptake inhibitors (SSRIs) and/or serotonin-norepinephrine reuptake inhibitors (SNRIs) persists in some patients beyond drug discontinuation (post-SSRI sexual dysfunction [PSSD]). We sought to identify and characterize a series of such cases and explore possible explanatory factors and exposure-response relationship. Subjects who responded to an invitation in a forum dedicated to PSSD filled out a survey via online software. Case probability was defined according to the following 3 categories of increasing presumed likelihood of PSSD. Noncases did not meet the criteria for possible cases. Possible cases were subjects with normal pretreatment sexual function who first experienced sexual disturbances while using a single SSRI/SNRI, which did not resolve upon drug discontinuation for 1 month or longer as indicated by Arizona Sexual Experience Scale scores. High-probability cases were also younger than 50-year-olds; did not have confounding medical conditions, medications, or drug use; and had normal scores on the Hospital Anxiety and Depression Scale. Five hundred thirty-two (532) subjects completed the survey, among which 183 possible cases were identified, including 23 high-probability cases. Female sex, genital anesthesia, and depression predicted current sexual dysfunction severity, but dose/defined daily dose ratio and anxiety did not. Genital anesthesia did not correlate with depression or anxiety, but pleasureless orgasm was an independent predictor of both depression and case probability. Limitations of the study include retrospective design and selection and report biases that do not allow generalization or estimation of incidence. However, our findings add to previous reports and support the existence of PSSD, which may not be fully explained by alternative nonpharmacological factors related to sexual dysfunction, including depression and anxiety.

https://www.ncbi.nlm...pubmed/28778697
Post-SSRI Sexual Dysfunction: A Literature Review.

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PSSD (Post ssri Sexual Dysfunction) (cont)

https://www.ncbi.nlm...pubmed/28642048
Sex Med Rev. 2017 Oct;5(4):429-433. doi: 10.1016/j.sxmr.2017.05.002. Epub 2017 Jun 20.
Sexual Consequences of Post-SSRI Syndrome.
INTRODUCTION:
Sexual dysfunctions are well-known side effects of selective serotonin reuptake inhibitor (SSRI) use. Altered libido, erectile dysfunction, vaginal dryness, ejaculatory disorders, and orgasmic problems are frequently reported by patients treated with SSRIs. Moreover, these antidepressant-emergent sexual dysfunctions do not always resolve after discontinuation of the medication and can persist indefinitely. These complaints are termed post-SSRI sexual dysfunctions (PSSD).
AIM:
To examine the existence of this clinical entity, possible theoretical mechanisms, possible risk factors, and possible treatment modalities.
METHODS:
Through literature research and clinical experience, the available information about PSSD is reviewed.
MAIN OUTCOME MEASURES:
Summary of the current literature with insights into possible causes and management options.
RESULTS:
There are some indications that antidepressant-emergent sexual dysfunctions do not always resolve after discontinuation of the medication and can persist indefinitely in some individuals. Although some or all sexual side effects that start with the use of SSRIs might continue after stopping the medication, other sexual complaints can develop. Decreased capacity to experience sexual pleasure is the most frequent characteristic of this syndrome.
CONCLUSION:
The research and understanding of PSSD remain limited and not well understood; however, the data support the existence of PSSD, which can have a substantial effect on the quality of life of these patients. More research is warranted to show the cause and possible mechanisms of PSSD that could lead to the correct diagnosis and treatment. Reisman Y. Sexual Consequences of Post-SSRI Syndrome. Sex Med Rev 2017;5:429-433.

http://www.wikidoc.o...ual_dysfunction
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[fishinghat]

What is Anxiety?
Chronic Adrenergic State
(Anxiety)

Alternate Names

Irritable Heart
Soldier’s Heart
Da Costa’s Syndrome
Hyperdynamic Beta Adrenergic State
Effort Syndrome

Conditions Associated with a Chronic Adrenergic State

Addresses the breathing difficulties associated with an adrenergic state.
Hyperventilation Syndrome
Addresses the fatigue aspect of an adrenergic state.
One of the many causes of Chronic Fatigue Syndrome
Neurocirculatory Asthenia
Addresses the similarity of an adrenergic state to certain heart problems
Mitral Valve Prolapse Syndrome
Addresses symptoms with standing that are associated with an adrenergic state.
Orthostatic Hypotension.
Idiopathic Orthostatic Intolerance
Idiopathic Orthostatic Tachycardia Syndrome
Orthostatic Tachycardia Syndrome
Hyperadrenergic Postural Hypertension
Miscellaneous
Idiopathic Hypovolemia (Loss of blood plasma volume due to Na+ loss)

Symptoms

Palpitations, Arrhythmias, PVCs, Tachycardia
Chest pain, Thoracic Cramping, Spasms and Chest Wall Pain.
(Heart symptoms more apparent when lying on side.)
Fatigue, Exercise Intolerance
Dizziness, Lightheaded, Headaches, Presyncope or Syncope (fainting)
Hostility or Anger, Giddiness
Shortness of Breath, Sighing and Yawning, Dyspnea (difficult or labored breathing)
Hypocapnea (low CO2 in blood), Respiratory Alkalosis (shift to high pH in the
Blood due to increased respiration)
Anxiety, Depression, Mood Swings
Poor Memory, Poor Concentration, Disorientation (Due to decreased blood flow
to the brain)
Poor Sleep, Bloating, IBS (Irritable Bowel Syndrome), Belching, Flatulence,
Numbness, Paresthesias, Seizures

[fishinghat]

What is Anxiety? (cont)

Definitions

Hyperadrenergic State – A physical condition characterized by elevated levels of circulating adrenaline. It may or may not exist for an extended time.

Chronic Adrenergic State – A hyperadrenergic state of extended nature.

History

Jacob DaCosta was the first one to document this disorder among soldiers during the civil war. While called De Costa’s Syndrome after the founder it is generally referred to as a chronic adrenergic state or anxiety by modern medicine.

Aggravating Agents and Vulnerability

Symptoms become more severe during emotional stress, tired, or exertive physical stress, such as rushing around rapidly or extreme exercise. Those who “bottle up” their emotions are usually the most susceptible. Symptoms usually begin between the ages of 20 to 30. Patient usually seeks medical aide as heart symptoms worsen. Frequent ER visits usually exist in severe cases of a chronic adrenergic anxiety. Patients with obsessive personalities are more prone to a hyperadrenergic state and frequently exhibit anxiety, phobias, feelings of inadequacy or poor adjustment to many stages of life. Symptoms may be disabling to work and everyday life or even completely incapacitating.

Chemistry

Dopamine is associated with the sensation of pleasure and motivation as well as inhibiting pain. A decrease in dopamine is involved with restless leg syndrome, fibromyalgia and anxiety. This decrease in dopamine is because during stress dopamine is oxidized to norepinephrine by dopamine hydroxylase, which in turn is usually converted to adrenaline (epinephrine).

A chronic adrenergic state also increases the catecholamine enzyme PNMT that accelerates the conversion of norepinephrine to adrenaline there by continuing the hyperadrenergic state. This state can continue as a perpetual state just by the presence of every day stressors. The reason for this is that during long periods of stress the stress conditions the fear circuits in the amygdala and hippocampus. These areas in turn regulate the production of adrenaline. With time these fear circuits become conditioned (sensative) to negative stress. With each subsequent stress these areas in the brain call for more and more adrenaline from the adrenal gland. This perpetuation of abnormal cellular functions is termed cellular conditioning. In severe cases the stress of everyday life can be enough to perpetuate the chronic adrenergic state. It is also interesting to note that these two fear circuits in the amygdale and hippocampus are the same two circuits that have been shown to be damaged by Cymbalta.

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What is Anxiety? (cont)

Physiology

Stressors, especially emotional ones, stimulate the sympathetic nervous system which causes the release of catecholamines such as norepinephrine, serotonin, cortisol, and adrenaline from the medulla of the adrenal gland. The stress stimulation occurs in the locus coeruleus region of the brain where the noradrenergic nucleus regulates the brains production of noradrenaline which effects nearly all regions of the brain. Also involved is the ventral tegmental nucleus which helps regulate the adrenergic/noradrenergic system in the pons/medulla area of the brain. These sympathetic nerve signals result in excretions from the medulla of the adrenal gland (80% adrenaline, 20% noradrenaline and a trace of dopamine). In the short term these compounds activate alpha and beta adrenergic receptors located in the liver, heart, vascular, intestinal, kidneys and genital/urinary smooth muscle. Initially adrenaline and noradrenaline act on alpha adrenergic receptors to constrict arteries and veins in the skin and organs while they simultaneously act on beta adrenergic receptors to cause vasodilation in cardiac and skeletal muscles. Alpha adrenergic receptors in the liver are responsible for the release of glycogen that is converted to glucose and used to “fuel” the “adrenaline rush”. Alpha adrenergic receptors in the sweat glands act as vasoconstrictors and also stimulate sweat gland production. Beta adrenergic receptors in the cardiac muscles are stimulated by adrenaline or noradrenaline to increase the intracellular breakdown of triglycerides. The cortisol released from the adrenal gland is used to convert noncarbohydrates to glucose and to break down proteins. During chronic adrenergic conditions the excess cortisol acts as a general vasoconstrictor to reduce blood flow and therefore reduce oxygen availability. It is also responsible for the decrease in immune system function during stress. During long periods of high cortisol fat metabolism decreases and fat deposition increases. Melatonin is derived from serotonin and with reduction in light and noradrenaline levels it causes sleepiness. The elevated noradrenaline levels during a chronic adrenergic state inhibits this production of melatonin and causes sleep disturbances. In turn sleep deprivation leads to increase secretion of adrenaline.

Symptoms of an initial hyperadrenergic state is dilated pupils; increase in heart rate, force and frequency; pulmonary dilation, blood vessels constrict in nonessential areas such as the kidneys and gastrointestinal tract. This causes a decrease in activity in these two areas as long as the hyperadrenergic state continues.

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What is Anxiety? (cont)

Note – The parasympathetic nervous system decreases metabolic activity BUT it should be noted that there is NO parasympathetic nerves in the heart or the adrenal gland to slow the adrenal response.
Note – In times of stress, the sympathetic nervous system prepares the body for response by innervating a variety of tissues throughout the body, including increasing heart rate, dilating the pupils and raising blood pressure. This increase in blood pressure is accomplished by signaling the release of renin from the kidneys. During periods of stress the adrenergic receptors in the kidneys release renin, angiotension and aldosterone. Renin is an enzyme that mediates extraellulr volume (i.e., that of the blood plasma, lymph and interstitial fluid)and arterial vasoconstriction.Thus, it regulates the body's mean arterial blood pressure. Renin is often improperly referred to as a hormone although it has no peripheral receptors and rather has an enzymatic activity with which it hydrolyses angiotensinogen to angiotensin 1. The enzyme renin is secreted by the afferent arterioles of the kidney in response to sympathetic nervous system activity, which also controls blood pressure, acting through the beta adrenergic receptors.The renin circulates in the blood stream and breaks down angiotensinogen secreted from the liver into the peptide angiotensin I. Angiotensin I is further cleaved in the lungs by an angiotensin-converting enzyme into angiotensin_ I, the most vasoactive peptide in the body. Angiotensin II also acts on the adrenal glands and causes the release of aldosterone, which stimulates the epithelial cells in the distal tubule and collecting ducts of the kidneys to increase re-absorption of sodium, exchanging with potassium to maintain electrochemical neutrality, and water, leading to raised blood volume and raised blood pressure. Aldosterone is a steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. These compounds also acts on the CNS to increase water intake by stimulating thirst, as well as conserving blood volume and by reducing urinary loss through the secretion of vasopressin from the posterior pituitary gland. This can cause significant edema in body tissues.

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What is Anxiety? (cont)

Note – It has recently been shown that excessive exercise, especially in athetes, will cause the generation of extra adrenaline. If these high levels of exercise go on for an extended period then the athlete can and usually does develop a chronic adrenergic state.
Heart – The heart contains autorhythmic cells that generate a basal heart rate. The adrenaline and noradrenaline stimulation increases heart rate and output. A chronic adrenergic state depletes calcium reserves in the sarcoplasmic reticulum of the heart muscles. The catecholamines (adrenaline, noradrenaline and dopamine), are produced from phenylalanine and tyrosine. They elevate levels of cAMP (part of energy transport system for cellular activity) that stimulate and open the Ca2+ channels in the sarcoplasmic reticulum (a cellular structure that stores Ca+2 and is wrapped around the muscle fibers). The flow of Ca+2 into the heart muscle cytoplasm causes a change in the voltaic potential within the cell. This change in potential changes the shape of the tropin in the actin/myosin fibers and allows these muscle fibers to slide easier causing an increase in frequency and strength of the heart contraction; in other words an increase in heart rate and heart output. Simultaneously the Ca+2 is returning from the muscle cytoplasm to the sarcoplasmic reticulum by active transport pumps, BUT this process is slower. Once the Ca+2 is mostly depleted in the cardiac muscles the calcium channel from the sarcoplasmic reticulum closes, the fibers relaxe and the calcium builds back into the sarcoplasmic reticulum and the process prepares to repeat. Muscle fatigue is affected by this process as well as affected by the decrease in oxygen, depletion of glycogen/glucose, buildup of ADP and a decrease in ATP (the compounds that actually carries the energy within a cell). Eventually the chronic adrenergic state causes hypophosphoralation (low phosphorus concentrations) and the depletion of calcium from the cardiac cells into the extracellular fluid, which causes cardiac arrhythmias such as atrial fibrillation (16 - 57% of all atrial fibrillation patients have their atrial fibrillation caused by an adrenergic state) ventricular tachycardia and PVCs. Due to lack of oxygen in intercellular fluids and the constant presence of catecholamines, in the chronic adrenergic state the heart continues to try and increase its output by increasing heart rate and the force of constriction. During this Ca+2 depletion a decrease in blood K+ or Na+ decreases the pulse and strength of contraction. In addition, any excess Na+ blocks the inflow of calcium from the sarcoplasmic reticulum and decreases the force of the heart contraction. Due to the increase in heart constriction and strength during a chronic adrenergic state it can cause left atrial enlargement. This left atrial enlargement decreases the flow of blood from the left atrium and increases the risk of blood clots. The result is an increase risk of stoke by 5 to 6 fold. This condition is very similar to Mitral Valve Prolapse where the valve between the left ventricle and left atrium extends in to the left atrium that also reduces blood flow and increases the risk of stroke. Adrenaline in the initial acute adrenergic state acts as a vasodilator to the heart but during the chronic adrenergic state it acts as a vasoconstrictor to the heart, further reducing blood flow to the body. Therefore, the left atrial enlargement and vasoconstriction can cause ischemia (insufficient blood flow to the body). The presence of atrial fibrillation, decrease oxygen availability and/or decreased blood flow all contribute to a condition called exercise intolerance. Patients with severe anxiety often have to perform work in small periods allowing for rest in between.

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What is Anxiety? (cont)

Respiratory – The hyperadrenergic state usually produces hyperventilation (an increase in frequency and depth of respiration) in order to supply oxygen for the increase in metabolism. In the chronic adrenergic state the increase in respiration eventually causes hypocapnea (decreased CO2 in the blood stream). This decrease in CO2 levels cause alkalosis (elevated pH) of the blood and respiratory system. At an elevated pH the hemoglobin increases its affinity for oxygen (the Bohr Effect). This causes an increase in the hyperventilation if physical activity continues, thereby continuing or worsening the hypocapnea. Once severe hypocapnea occurs it can be maintained by even normal breathing. Those with a chronic adrenergic state often show this breathing pattern. The increase in hemoglobin affinity to oxygen decreases the amount of oxygen available to the cells and increases muscle fatigue and cerebral perfusion. This helps account for the diagnosis of chronic fatigue syndrome and exercise intolerance in the chronic adrenergic state. The hypocapnea rapidly causes the development of hypophosphotemia (low phosphate in the blood) that further reduces oxygen availability to tissues. Once a hypocapnia state is generated the stresses of everyday life may create the potential for a self-perpetuating cycle.

Brain – This decrease in oxygen availability from the blood due to hypocapnea and vasoconstriction causes cerebral perfusion (decreased oxygen to the brain). This accounts for dizziness, lightheaded, headaches, presyncope or syncope (fainting). The initial drop in cerebral diffusion is offset by vasodilation but this is very short lived. The decrease in oxygen to the brain frequently causes orthostatic hypertension also known as orthostatic intolerance (a drop in blood pressure upon standing). This condition may also be pronounced in patients taking alpha or beta blockers due to the resultant drop in blood pressure and heart rate (bradycardia) they cause. Patients suffering from an orthostatic condition known as POTS (postural tachycardia syndrome) usually are suffering from the worst cases of chronic adrenergic state and typically exhibit exercise intolerance, cognitive difficulties, sleep problems, palpitations, cardiac arrhythmias, tremors, labored breathing and even syncope. The “dizziness” upon standing is not only associated with fluids simply flowing away from the brain upon standing but the patient actually suffers from an increase in heart rate (tachycardia) due to the hyperadrenergic state. The subsequent drop in blood pressure is due to the lack of oxygen from blood alkalosis (Bohr’s effect), vasoconstriction and reduced blood output from the enlarged atrium.

Digestive system – The decrease in the digestive activity during a chronic adrenergic state often results in digestive hyperactivity at night when adrenaline levels are lower. This may result in eating at night, weight gain and disturbances in sleep. People suffering from this condition frequently diet. Hypoglycemia from skipping meals, dieting, fasting and other conditions increase vagal tone and cause an increase in production of adrenaline and noradrenaline thereby increasing the chronic adrenergic state.

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What is Anxiety? (cont)

Genetics

Individuals have been identified which have a dopamine hydroxylase deficiency, a congenital disorder. These individuals suffer from orthostatic hypotension and retrograde ejaculation. The patients also have more dopamine in their system, a precursor to adrenaline. Therefore these individuals are more likely to suffer from a chronic hyperadrenergic state. In addition, there have been 9 genetic variations of adrenergic receptors (6 alpha and 3 beta) that have been isolated so far. Each has its own unique structures and catecholamine affinities.

Treatments
Short-term treatment is for the patient to get away from stressors. Even with removal from stressors the symptoms may persist for long periods of time. Long-term treatment includes relaxation therapy and breathing with the diaphragm. Relaxation techniques often include activities designed to increase the amount of endorphins produced by the body. Endorphins are endogenous opioid inhibitory neuropeptides. They are produced by the central nervous system and pituitary gland. The class of endorphin compounds includes alpha-endorphin, beta-endorphin (80 times stronger pain killer than morphine, released during exercise), pi-endorphin, alpha-neo-endorphin and beta-neoendorphin. There is little agreement by researchers concerning the impact of endorphins. Tests have shown that given the same stimuli one person may produce a large amount of endorphins and the next may have little reaction. Generally speaking, endorphins are thought to act as a blocker of the transmission of pain signals and also can produce a euphoria feeling exactly like opiates.
Things that can cause a release of endorphins include;
Exercise
Eating Chocolate (although this has caffeine, a stimulant).
Eating hot peppers
Sex
Eating pleasure food
Drink Ginseng
Smell vanilla extract
Laughing and smiling
Breathing Exercises
Yoga
Meditation

Endorphins are associated with euphoria, help block pain, and block the uptake of adrenaline. Most specific types of endorphins have been discovered in the 70s and 80s.

Nitroglycerin does not relieve the chest pain associated with an adrenergic state.

Patients in a hyperadrenergic state are successfully treated using beta blockers (e.g. atenolol) and also clonidine (alpha agonist). Beta blockers block adrenaline uptake by the beta adrenergic receptors and therefore reduce heart muscle contractions and vasoconstriction. Beta blockers also reduce cardiac arrhythmias. Clonidine has specificity towards the presynaptic α2-receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, thus inhibiting the release of noradrenaline. The net effect is a decrease in sympathetic tone.

[fishinghat]

What is Anxiety? (cont)

Benzodiazepines have been shown to decrease activity of alpha 2 adrenergic receptors and therefore decrease the symptoms of anxiety. It should be noted that while very functional as an anxolytic agent the human body quickly adapts and builds up resistance to the benzodiazepines. This requires the use of higher and higher doses to achieve the same results. Most manufacturers suggest that benzodiazepines should not be used for over a 4 month period. These compounds are also very addictive.

Due to the left atrial enlargement the patient is usually treated with asa (aspirin) or warfarin (blood thinner) in order to reduce the risk of stroke.

Clonidine is also used to treat a chronic adrenergic state. Studies indicate that clonidine actually decreases output of renin from the kidneys as well as the excretion of aldosterone and catecholamines from the adrenal gland. Clonidine stimulates the presynaptic alpha-2 receptor in the brain, leading to inhibition of norepinephrine release, and it also stimulates the imidazoline receptor; both of these actions decrease sympathetic outflow. Clonidine is an agonist to alpha adrenergic receptors in the brain which reduces sympathetic nervous system output to the adrenal gland. It stimulates alpha adrenergic receptors in the hypothalmus which decreases sympathetic nerve signals to the adrenal gland and causing a decrease in adrenaline production.
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[brzghoff]

awesome aggregation of resources Dr Hat!

 

if i can add anything it is to suggest that due to the preponderance of great info it might take awhile to scroll through to find what you are looking for. use your ctrl f function to search.

 

for those who don't know about the "ctrl f" function on windows - or "command f" on a mac - when you press the ctrl (control) or command key and the letter f at the same time you'll get a search bar in the upper right hand corner. type in the word you are searching for and it will highlight it every time that word appears on that page. to the right on the scroll bar you'll see little yellow marks to show you where to scroll to see where that word appears through out the page. repeat the process for every page you're searching for a word. 

 

by the way, that works on any page of most any application on your computer, not just your web browser. its a feature of your computer's operating system.

 

Dr hat, anyway you can copy and paste my ctrl f instructions and edit them into your first post so its at the top of this thread? 

 

This document is an effort to summarize everything that members have tried in order to reduce their withdrawal symptoms. It includes, where available, what worked and what didn't work, medical research, health warnings, compatibilities, and much more.

 

It would be appreciated if ANY errors in typing or content be pointed out so that this document can be corrected.

 

Any suggestions for improvement would be appreciated.

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In addition this site has an excellent search function at the top right hand side of the page.

Good to see you again brz

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Methods of Getting off Cymbalta

OPTIONS
There are three ways to do it. Cold Turkey, swapping meds (Cross taper) and bead counting.
I don’t recommend cold turkey unless there is no choice. The cold turkey withdrawal can be quite severe and usually lasts longer. The FDA and the nanufacturers have issued warnings against going cold turkey. It can cause seizures, suicidal thoughts, fear, panic and much more. With swapping meds you lower your dose of cymbalta over a 4 or 5 week level to zero and at the same time go on a different ssri with a lot less severe withdrawal, say zoloft, lexapro or prozac. Once you make the switch you slowly come off the new ssri. Very slowly. The third choice, bead counting, is where you open the cymbalta capsule each day and remove a few beads, usually 2 or 3 (1%). So the first day you remove 3 beads, the next day 6 beads, the next 9 beads etc. This provides for a slow steady withdrawal. If symptoms get to bad you just hold at that dosage for a while until you stabilize. Then start dropping again. Be aware that for most the last few beads give the worse withdrawal. Be prepared to slow down when you get to the very end. Now this is just an example. Some can only remove 1 bead a day and others 7 or 8 beads a day. You will have to play with it a little bit to find what works for you. This doesn't mean you won't have withdrawal but it will be lighter and you will have some control over it.

DURATION OF WITHDRAWAL

The first 4 to 8 weeks of withdrawal symptoms after coming totally off the Cymbalta are the worse. By the 8th to 12th week usually see signs of good days followed by bad days but at least there is light at the end of the tunnel. Now that is the average. I have known people who actually quit cold turkey without a symptom. And others where the withdrawal last 6 months to over a year but these are rare. Research says between 30 to 80% of people do not experience withdrawal while other research shows that around 7% - 15% experience withdrawal of 6 months or more.

http://neuro.psychia...ticleid=1828814
http://www.jad-journ...0286-7/abstract
44.3% have withdrawal

http://www.ncbi.nlm....pubmed/19337457
30% have withdrawal

http://www.ncbi.nlm....ubmed/15912562/
0% serious(?) withdrawal events

http://www.aafp.org/.../0801/p449.html
20% have withdrawal.

http://www.aafp.org/.../0801/p449.html
20%

Duloxetine Induced Discontinuation Syndrome:
http://www.jcdr.net/...1619_6_4_11.pdf
http://www.fda.gov/d..../UCM172866.pdf

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Methods of Getting off Cymbalta (cont)

Misc.
http://www.fsijourna...0495-7/abstract

SSRI Discontinuation syndrome.
http://www.ncbi.nlm....ith agoraphobia
45%
https://www.ncbi.nlm...pubmed/20478876
Paroxetine (Paxil) and venlafaxine (Effexor) seem to be particularly difficult to discontinue and prolonged withdrawal syndrome lasting over 18 months have been reported with paroxetine. (See the following 3 references)
https://www.ncbi.nlm...pubmed/11347722
https://www.ncbi.nlm...pubmed/12008858
Gartlehner G, Hansen RA, Morgan LC, et al. (December 2011). Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression: An Update of the 2007 Comparative Effectiveness Review (Report). Comparative Effectiveness Reviews. Rockville, MD: Agency for Healthcare Research and Quality – via NCBI Bookshelf.

http://www.fda.gov/d...e/UCM172866.pdf

The following document was issued by the FDA warning of the severity of Cymbalta Discontinuation Syndrome.

Page 1
Cymbalta (Duloxetine) Discontinuation Syndrome
Issues of Scope, Severity, Duration & Management
June 9, 2009

Page 3
⦁ The effects of discontinuation can be severe and extend for weeks or even months Extreme mood swings (anger, irritability)
Debilitating “Brain Zaps”
Physical and neurological problems

⦁ Page 4
⦁ Claims

⦁ Cymbalta discontinuation syndrome is more severe and much more widespread than acknowledged by Eli-Lilly

⦁ Lilly sales representatives and marketing materials do not adequately inform physicians about the likelihood and severity of discontinuation syndrome

⦁ Lilly Direct to Consumer (DTC) advertizing is misleading related to the probability, severity and complexity of Cymbalta discontinuation

⦁ Lilly has not developed and fielded a clinically proven protocol for safely discontinuing Cymbalta

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Methods of Getting off Cymbalta (cont)

Page 8

⦁ 2) Lilly sales representatives and marketing materials do not adequately inform physicians about the likelihood and severity of Cymbalta discontinuation syndrome

⦁ Unaware physicians unable to discuss Cymbalta benefit-risk profile (including discontinuation) with their patients
⦁ Physicians can not make an accurate comparative assessment of Cymbalta vs. alternatives
⦁ Patients can not make an fully informed choice to take the drug
⦁ Practical effects (common in anecdotal reports):Patient becomes totally distrustful of the physician who did not advise/warn them in the first place
⦁ Doctor /patient relationship is wrecked
⦁ Patient in distress refuses to ingest Cymbalta under any pretext
⦁ Tapering is taken off the table
⦁ Patient fires the doctor or the doctor disengages from the patient
⦁ Syndrome mood swings militate anger directed at the physician
⦁ Physician may deny syndrome even exists
⦁ Physician may jettison a newly “difficult” patient
⦁ Physician seeks to avoid malpractice implications
⦁ Patient becomes deeply suspicious of any psychotropic medication
⦁ Underlying problem may go untreated
⦁ This is a process flaw – there is no excuse for it

Page 9

⦁ Lilly Direct to Consumer (DTC) advertizing is misleading related to the probability, severity and complexity of Cymbalta discontinuation

Also states that “opening the capsule is required to taper”

Page 14

⦁ Lilly does not offer small dose Cymbalta formulations to facilitate tapering. Patient required to open capsules and count drug beads
⦁ Patient may require compounding pharmacy services at his/her expense

⦁ Tapering may take weeks or months



https://dailymed.nlm...f2-c185fbad64ba

Cymbalta Drug Insert

2.7 Discontinuing CYMBALTA
Adverse reactions after discontinuation of CYMBALTA, after abrupt or tapered discontinuation, include: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [see Warnings and Precautions .


Section 5.7
Patients should be monitored for these symptoms when discontinuing treatment with CYMBALTA. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate [see Dosage and Administration (2.7)].

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Methods of Getting off Cymbalta (cont)

Section - Dosage and Administration
Discontinuing CYMBALTA: Gradually reduce dosage to avoid discontinuation symptoms (2.7, 5.7)

Section - Warnings and Precautions
Discontinuation: May result in symptoms, including dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue (5.7)

6.12 Postmarketing Spontaneous Reports
The following adverse reactions have been identified during post approval use of CYMBALTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Adverse reactions reported since market introduction that were temporally related to CYMBALTA therapy and not mentioned elsewhere in labeling include: acute pancreatitis, anaphylactic reaction, aggression and anger (particularly early in treatment or after treatment discontinuation), angioneurotic edema, angle-closure glaucoma, colitis (microscopic or unspecified), cutaneous vasculitis (sometimes associated with systemic involvement), extrapyramidal disorder, galactorrhea, gynecological bleeding, hallucinations, hyperglycemia, hyperprolactinemia, hypersensitivity, hypertensive crisis, muscle spasm, rash, restless legs syndrome, seizures upon treatment discontinuation, supraventricular arrhythmia, tinnitus (upon treatment discontinuation), trismus, and urticaria.
6. discontinuation symptoms: Do not stop Cymbalta without first talking to your healthcare provider. Stopping Cymbalta too quickly or changing from another antidepressant too quickly may result in serious symptoms including:

SUPPORT

And don't worry about support here. Great group of people. Don't be afraid to let out all your worries and fears here. We know how you feel. We are here anytime for you.
Just be there for your spouse and realize that the emotion swings are just from the medicine. My wife was tremendous help to me during my withdrawal. She always would pass by and smile at me, or reach over and just hold my hand for a second. Little things like that are VERY reassuring. One of the main withdrawal symptoms is that it really makes you feel unsure of yourself, hard to make a decision and real insecure. Just be there. Your heart will tell you what to do. I strongly suggest you keep a journal of your experiences. Your short term memory is very unreliable during withdrawal. This will help you keep things in perspective.

I would also recommend that your family read some of the posts on here and get a feeling what you are going through. It will give them a better sense of what you are feeling and what is coming in the future.


Every other day Withdrawal

Cymbalta has a half life of 12 hours. If you skip a day by the second day your blood Cymbalta levels have dropped around 90%!! So what do they have you do? Take another pill, jack your Cymbalta levels back up and go through the same withdrawal all over again. Dumb. Most drs don't take this withdrawal seriously because when they are trained by the pharm company they are told it is no be deal. I know that none of the drs I have had was against bead counting. And if they are, so what, it is your health. You have to make the final decision.

Cross Tapering Details
https://www.ncbi.nlm...les/PMC4919171/
Describes how to switch antidepressants.

https://www.ncbi.nlm...cles/PMC181142/
Has section on switching antiDs.

https://www.ncbi.nlm...pubmed/18494539
http://www.gpnoteboo...m?ID=1637482568
Guidelines from various sources.

Haddad, Peter M.; Anderson, Ian M. (October 2007). "Recognising and managing antidepressant discontinuation symptoms". Advances in Psychiatric Treatment. 13 (6): 447–57. doi:10.1192/apt.bp.105.001966  .
Discontinuation syndrome is often prevented by taking medication as directed, and when discontinuing, doing so gradually. When discontinuing an antidepressant with a short half-life, switching to a drug with a longer half-life (e.g. fluoxetine or citalopram) and then discontinuing from that drug can decrease the likelihood and severity of symptoms.

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Methods of Getting off Cymbalta (cont)

https://www2.gov.bc....epress_appd.pdf
Gov guidelines

https://bpac.org.nz/...pages_34-35.pdf
New Zealand Guidelines

https://www.nps.org....antidepressants
Australian Guidelines
FH - Due to a longer half life I would recommend the ssri group that includes Prozac, Zoloft and Lexapro for cross tapering.
Jessica P
Honestly, I think it is because I went EXTREMELY slow at the end. It took me 10 weeks to go from 10 beads to none. If I had pushed that, it probably wouldn't have taken longer and been worse. It was worth it to go slow!
Bead counting data
Lupin - 7 -12 large beads Yes*
Solco - 146 - 157 beads Yes
Prasco - "Large number of beads" Yes
Teva - Approximately 315 beads Yes
Breckenridge - Unknown Yes
Citron - Small beads, approximately 300+ Yes
Devo - 150 beads Europe
Apotex - various size beads in each capsule as well as various number of beads. Yes
Cymbalta - 250 to 350 beads Yes

* Yes indicates that this brand is available in the USA.

https://dailymed.nlm...f2-c185fbad64ba
Excerts from the drug insert for Cymbalta.
"Do not open the capsule and sprinkle its contents on food or mix with liquids. All of these might affect the enteric coating."
Note - This would be due to the enteric coating dissolving/softening with contact with moisture in the food.
"Each capsule contains enteric-coated pellets of 22.4, 33.7, or 67.3 mg of duloxetine hydrochloride equivalent to 20, 30, or 60 mg of duloxetine, respectively. These enteric-coated pellets are designed to prevent degradation of the drug in the acidic environment of the stomach. Inactive ingredients include FD&C Blue No. 2, gelatin, hypromellose, hydroxypropyl methylcellulose acetate succinate, sodium lauryl sulfate, sucrose, sugar spheres, talc, titanium dioxide, and triethyl citrate. The 20 and 60 mg capsules also contain iron oxide yellow. "
Note - There is no indication of different enteric coatings on the beads.

https://www.fda.gov/...e/UCM172866.pdf
From the FDA quidance on Cymbalta.
"Lilly does not offer small dose Cymbalta formulations to facilitate tapering"
"Patient required to open capsules and count drug beads
Patient may require compounding pharmacy services
At his/her expense
Tapering may take weeks or months"

http://www.cymbaltaw...g-beadspellets/
An interesting account of bead sizes that took place on this site a number of years ago. While bead size may vary some what these folks found was rather consistant.

The following information is from...
The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979).
Spoke to Michelle S.
May 3rd, 2017 at 8:50 AM

'Filled by weight. '
'Unknown variation in size.'

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Methods of Getting off Cymbalta (cont)

Opening Capsules

https://www.ncbi.nlm...pubmed/25325120
Prescrire Int. 2014 Sep;23(152):209-11, 213-4.
Crushing tablets or opening capsules: many uncertainties, some established dangers.
Abstract
For patients who have difficulty swallowing, a common solution is to crush tablets or open capsules. What are the consequences of this practice? We reviewed the main evidence available using the standard Prescrire methodology. The clinical consequences for the patient of crushing tablets or opening capsules can be serious: alteration of the drug's absorption can result in sometimes fatal overdose, or conversely underdosing, rendering the treatment ineffective. When it disrupts a drug's sustained-release properties, the active ingredient is no longer released and absorbed gradually, resulting in overdose. When a gastro-resistant layer is destroyed by crushing, underdosing is likely. The active ingredient released may degrade on contact with light, moisture or the food with which it is mixed for administration. The person who crushes the tablets or opens the capsules is exposed to drug particles, which may be carcinogenic, teratogenic or fetotoxic. They are sometimes allergenic. In practice, there are many drugs that should never be crushed or opened. Before crushing a tablet or opening a capsule, it is better to consider and research the impact it will have on the drug's effects. It is sometimes preferable to use a different dosage form, or a different active ingredient

"The active ingredient released may degrade on contact with light, moisture or the food with which it is mixed for administration. The person who crushes the tablets or opens the capsules is exposed to drug particles, which may be carcinogenic, teratogenic or fetotoxic. They are sometimes allergenic."
Comment -These statements seems invalid as any carcinogenic, tetragenic, fetotoxic or allergenic components would be consumed whether the tablet where opened or not. Now I will admit it is logical that when opening a capsule or crushing one, the added surface area will increase the rate of absorbtion and go into the blood stream faster. However, the exposure of medicine to the acidic environment in the stomach could alter the composition of the medicine and its absorbtion, especially if the medicine is water soluble.
https://www.ncbi.nlm.../pubmed/2595104
Respiration. 1989;55(4):210-3.
Theophylline serum levels in children with bronchial asthma after administration of slow release theophylline as open or closed capsules.
Naspitz CK1, Solé D.
⦁ Abstract
Theophylline serum levels were studied after oral administration of slow release theophylline (Talofilina) in children with bronchial asthma. The children received the drug as closed capsules or as granules, obtained by opening the capsules, for 1 week in each form. The mean dose used was 8.6 mg/kg every 12 h. The theophylline blood levels at 4, 8 and 12 h after drug ingestion were significantly lower when granules from open capsules were used. Our recommended dose of Talofilina for Brazilian children is 16 mg/kg/day, if administered as closed capsules, every 12 h. On open capsule administration every 12 h, the total daily recommended dose is 20 mg/kg/day.
Comment - Interesting. The use of an open capsule with beads resulted in slower drug absorbtion.

http://www.nature.co...jg2000744a.html
The American Journal of Gastroenterology 95, 2448 (September 2000) | doi:10.1111/j.1572-0241.2000.02487.x
Esomeprazole open capsule mixed with applesauce is bioequivalent to the intact capsule when administered to healthy volunteers
Tommy Andersson, David J Magner, Jay B Patel, Paul Rogers and Jeffrey G Levine
Abstract
Purpose: To determine whether an open capsule of esomeprazole (NEXIUM™) 40 mg (OC) in applesauce is bioequivalent to an intact capsule (IC).Methods: In a randomized, single-center, open-label crossover, pharmacokinetic study consisting of 2 study days separated by a minimum 7-day washout period, 45 healthy volunteers (21 males) aged 18 to 45 years received a single dose of OC or IC in a randomized sequence.

Comment - No noticable effect on efficacy of medicine by opening capsule. This medicine is designed to be released in the stomach.

http://www.ismp.org/.../DoNotCrush.pdf
Oral Dosage Forms That Should Not Be Crushed
"Cymbalta (DULoxetine), Capsule Slow‐release, (a) (Note: may add contents of capsule
to apple juice or applesauce but NOT chocolate)"

Comment - This would suggest opening the capsules is acceptable. Cymbalta is fat soluble and vertually insoluble in water so exposure to the medicine in the acidic contents of the stomach is less likely to have an impact.

http://www.fda.gov/d...s/ucm103473.pdf
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Compounding Pharmacies
I found about 20 or so references to members that used compounding pharmacists. Most did not repost information on their final outcome but those that did often made comments like the ones below.
Member - Vanilla - "I have been compounding the drug from 15 mgs to 10 and now at 10, am at home away from work, suicidal at times,and the withdrawal symptoms are there."
Poppylvr - "This time I had a compounding pharmacy make me up 10 mg capsules. I was able to go to 50 for several days, then 40, then 30, then 20, then 10. Last week I started trying to drop off the 10 mg/day. Holy Cow! SIGNIFICANT dizziness - driving is nearly impossible. Nausea, lack of appetite, and yet all I want to eat is crap - pure carbs (oh by the way I have diabetes too :x ). Napping brings me out of it for awhile."

In addition, I found that compounding pharmacists that members used performed different methods to make their preperations. About 2/3 of them dissolved the cymbalta in something like PEG. The other one third made up new capsules by counting beads. Many also commented that their compounding facility would not make doses smaller than 5% or 2.5%. These final drops were very traumatic and many used bead counting at the very end of the weaning process.
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Post Acute Withdrawal Syndrome: Causes, Symptoms, Treatment
(Also Called Protracted Withdrawal)
Individuals that have used any potent drug, particularly for a long-term and/or at high doses are known to experience significant short-term withdrawal symptoms. These symptoms may include things like dizziness, headaches, nausea, and vomiting. Over time, they usually lessen in severity as the nervous system and physiology adjusts to function without the presence of the drug.
Unfortunately, for many people the withdrawal period is not limited to a short-term. After the first couple weeks of discontinuation, individuals may find that their symptoms fail to lessen in severity for weeks, months, or in rare cases – years beyond when they were told they should be fully recovered from withdrawal. To add to their frustration, many medical professionals either fail to inform their patients or completely dismiss the possibility of protracted withdrawals.
This adds to the patient’s anxiety and often leads them to perceive that something more serious is wrong (e.g. a brain tumor) when their dizziness persists for months. Although it is important to always get a medical and neurological screening to rule out the possibility of something more serious, if symptoms emerge upon discontinuation from a drug – they are usually a result of withdrawal.
What is post-acute withdrawal syndrome (PAWS)?
Post-acute withdrawal syndrome (PAWS) refers to withdrawal symptoms that persist for an extended duration following drug discontinuation. Post-acute withdrawals are most commonly referenced among individuals discontinuing opioids. This is due to the fact that during opiate withdrawal, individuals often endure intense short-term symptoms and think that their withdrawals will be over after they “weather the storm.”
In many cases, the short-term symptoms lessen, but never seem to go away. In some cases, new symptoms may emerge and a person experiences long-term functional impairment. This long-term impairment may last for weeks, but often persists for months – and in some cases years – beyond the expected date of recovery.
The condition is not limited to those discontinuing opioids, it commonly occurs among those discontinuing alcohol, benzodiazepines, antidepressants, antipsychotics, and other psychoactive drugs. Although “post-acute withdrawal syndrome” is not recognized by the Diagnostic Statistical Manual of Mental Disorders (DSM) or by any medical associations, to deny or dismiss its existence is short-sighted.
⦁ https://www.ncbi.nlm.../pubmed/8097618
⦁ http://addictionsand...-withdrawal.htm
⦁ http://addictions.ab...ndrome-Paws.htm
⦁ http://www.arctreatm...rawal-symptoms/
⦁ And many many more.

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Post-acute-withdrawal syndrome (cont)


From Wikipedia, the free encyclopedia
Post-acute-withdrawal syndrome (PAWS), or the terms post-withdrawal syndrome, protracted withdrawal syndrome, prolonged withdrawal syndromes describe a set of persistent impairments that occur after withdrawal from alcohol, opiaes, benzodiazepines, antidepressants and other substances. Infants born to mothers who used substances of dependence during pregnancy may also experience a post-acute withdrawal syndrome. While post-acute withdrawal syndrome has been reported by those in the recovery community, there have been few scientific studies supporting its existence.[7] Because of this, the disorder is not recognized by the Diagnostic and Statistical Manual of Mental Disorders or major medical associations.
Drug abuse, including alcohol and prescription drugs, can induce symptomatology which resembles mental illness. This can occur both in the intoxicated state and during the withdrawal state. In some cases these substance-induced psychiatric disorders can persist long after detoxification, such as prolonged psychosis or depression after amphetamine or cocaine abuse. A protracted withdrawal syndrome can also occur with symptoms persisting for months after cessation of use. Benzodiazepines are the most notable drug for inducing prolonged withdrawal effects with symptoms sometimes persisting for years after cessation of use. Severe anxiety and depression are commonly induced by sustained alcohol abuse which in most cases abates with prolonged abstinence. Even moderate alcohol sustained use may increase anxiety and depression levels in some individuals. In most cases these drug-induced psychiatric disorders fade away with prolonged abstinence.
There is a theory called protracted withdrawal by the drs and post acute withdrawal syndrome by the Detox Centers that treat benzo, alcohol and opium withdrawal.
I will use the term protracted withdrawal (PW)
Scientifically there are a fair number (2 dozen or so) medical research articles that have shown that protracted withdrawal offers. The science shows that, depending on the substance involved, the standard withdrawal lasts 2 weeks to 4 months for the great majority of people and if it is bad enough it is treated with drugs BUT in around 1-4% of the people (depending on the study) the patients will develop PW. This withdrawal typically lasts from 4 to 7 months of acute symptoms and then slowly fades away by the end of two years.
Now the detox Centers claim that It lasts up to 2 years, is drug resistant (therefore you need to check into one of their facilities during that time) and about 10% of the people using these drugs have the PW. well I can understand why they have a higher percentage. who is going to a detox center but the very worse of the withdrawal cases.
I spent a couple hours this afternoon looking at various forums and I would have to say the subjective evidence would be like 2 to 5% experience this. I can think of several members who easily took 1 to 2 years to get over the withdrawal.

Last note: Protracted withdrawal is a highly debated subject it is not recognized by the DSMO or ANY medical association. The few researchers that have documented it are often ridiculed. Most physicians believe it is just a return of symptoms.
http://www.cymbaltaw...mend#entry66238
PAWS is a term for protracted withdrawal
FH - I just found an article which studied the long lasting effect of ssri withdrawal symptoms. They noted that some of the psychological effects from the withdrawal lasted up to a year. Based on this research the Wiki site states that "Most cases of discontinuation syndrome last between one and four weeks, but a substantial minority, perhaps up to 15% of users, have persistant withdrawal symptoms evident one year post withdrawal." UP TO A YEAR? FOR REAL? 15% is a lot of people.
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Probiotics
Introduction
"Commonly claimed benefits of probiotics include the decrease of potentially pathogenic gastrointestinal microorganisms, the reduction of gastrointestinal discomfort, the strengthening of the immune system, the improvement of the skin's function, the improvement of bowel regularity, the strengthening of the resistance to cedar pollen allergens, the decrease in body pathogens, the reduction of flatulence and bloating, the protection of DNA, the protection of proteins and lipids from oxidative stress damage, and the maintaining of individual intestinal microbiota in subjects receiving antibiotic treatment."
Research
Probiotics are under considerable research, as the concept holds promise for human health and well-being, and corresponding commercial opportunities. Protection of consumers requires health claims to be confirmed with sufficient scientific evidence. Overall scientific demonstration of probiotic effects requires defining a healthy microbiota and interactions between microbiota and host, and the difficulty to characterize probiotic effectiveness in health and disease. Recent developments of high-throughput sequencing technology and the consequent progresses of metagenomics represent a new approach for the future of probiotics research.
Studies are examining whether probiotics affect mechanisms of intestinal inflammation, diarrhea,or urogenital infections. Through 2012, however, in all cases proposed as health claims to the European Food Safety Authority, the scientific evidence remains insufficient to prove a cause and effect relationship between consumption of probiotic products and any health benefit.
Research into the potential health effects of supplemental probiotics has included the molecular biology and genomics of Lactobaccillus in immune function, cancer, and antibiotic-associated diarrhea, travellers' diarrhea, pediatric diarrhea, inflammatory bowel disease, and irritable bowel syndrome. Testing of a probiotic applies to a specific strain under study. The scientific community cautions against extrapolating an effect from a tested strain to an untested strain.
Although research does suggests that the relationship between gut flora and humans is a mutualistic relationship, very little evidence supports claims that probiotic dietary supplements have any health benefits. Improved health through gut flora modulation appears to be directly related to long-term dietary changes.
In a 2009 blog post, one expert reasoned that preliminary clinical results exist for some applications, such as treating diarrhea, but wider health benefits claimed by probiotic proponents lack plausibility since the body's "ecosystem" is sufficiently complex that adding a few bacteria is unlikely to have the claimed effect. Accordingly, he reasoned, "the alleged health benefits of probiotics are often an example of spin". Since then, there has been an increase in the body of scientific evidence supporting the use of specific probiotics to improve health. Although the body's complex microbial community is incompletely understood at present, there is strong scientific consensus on the benefits of using of probiotics to address certain medical states or conditions.
Claims that some lactobacilli may contribute to weight gain in some humans remain controversial.
Allergies
Probiotics are ineffective in preventing allergies in children, with the possible exception of eczema.
Diarrhea
Some probiotics are suggested as a possible treatment for various forms of gastroenteritis, and a Cochrane Collaboration meta-analysis on the use of probiotics to treat acute infectious diarrhea based on a comprehensive review of medical literature through 2010 (35 relevant studies, >4500 participants) reported that use of any of the various tested probiotic formulations appeared to reduce the duration of diarrhea by a mean of 25 hours, also noting, however, that "the differences between the studies may be related to other unmeasured and unexplored environmental and host factors" and that further research was needed to confirm reported benefits.

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Probiotics (cont)

Antibiotic-associated diarrhea
Some of the best evidence in support of probiotic health benefits is in the treatment of antibiotic-associated diarrhea (AAD). Antibiotics are a common treatment for children, and 20% of antibiotic-treated children develop diarrhea. AAD results from an imbalance in the colonic microbiota caused by antibiotic therapy. Microbiota alteration changes in carbohydrate metabolism, with decreased short-chain fatty acid absorption and osmotic diarrhea as a result. The preventive role of some probiotics has been correctly assessed in randomized, controlled clinical trials. A review assessing the work of 16 different studies representing the evaluation of more than 3,400 patients concluded that the evidence gathered suggested a protective effect of some probiotics in this condition. In adults, some probiotics showed a beneficial role in reducing the occurrence of AAD. Another consequence of antibiotic therapy leading to diarrhea is the overgrowth of potentially pathogenic organisms such as Clostridium difficile.
Probiotic treatment might reduce the incidence and severity of AAD as indicated in several meta-analyses, For example, treatment with probiotic formulations including L. rhamnosus may reduce the risk of AAD, improve stool consistency during antibiotic therapy, and enhance the immune response after vaccination. However, further documentation of these findings through trials is required to confirm specific effects and obtain regulatory approval, which currently does not exist.
The potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage. A Cochrane Collaboration systematic review, in which 16 randomized clinical trials were analyzed, concluded that treatments with less than 5000 million CFUs/day did not show a significant decrease of AAD. However, patients treated with ≥5000 million CFUs/day (including L. rhamnosus and Saccharomyces boulardii) had 60% lower relative risk (95%CI: 44–71%) of experiencing AAD than untreated patients.
FH - I do recommend that after anyone has a bad case of diarrhea that they take probiotics every day for at least 7 days to reestablish the good bacteria in the intestines.
A caution - DO NOT take probiotics while on an antibiotic as the antibiotic will spend its energy killing the probiotics instead of your infection.
Lactose intolerance
Ingestion of certain active strains may help lactose-intolerant individuals tolerate more lactose than they would otherwise have tolerated.
Cholesterol
Preliminary human and animal studies have demonstrated the efficacy of some strains of lactic acid bacteria (LAB) for reducing serum cholesterol levels, presumably by breaking down bile in the gut, thus inhibiting its reabsorption (where it enters the blood as cholesterol).
A meta-analysis that included five double-blind trials examining the short-term (2–8 weeks) effects of a yogurt with probiotic strains on serum cholesterol levels found a minor change of 8.5 mg/dL (0.22 mmol/L) (4% decrease) in total cholesterol concentration, and a decrease of 7.7 mg/dL (0.2 mmol/L) (5% decrease) in serum LDL concentration.
A slightly longer study evaluating the effect of a yogurt with probiotic strains on 29 subjects over six months found no statistically significant differences in total serum cholesterol or LDL values. However, the study did note a significant increase in serum HDL from, 50 to 62 mg/dL (1.28 to 1.6 mmol/L) following treatment. This corresponds to a possible improvement of LDL/HDL ratio.
Studies specifically on hyperlipidemic subjects are still needed.

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Probiotics (cont)

Blood pressure
The consumption of probiotics may effect a modest benefit in helping to control high blood pressure.
Immune function and infections
Some strains of LAB may affect pathogens by means of competative inhibition (i.e., by competing for growth) and some evidence suggests they may improve immune function by increasing the number of IgA-producing plasma cells and increasing or improving phagocytosis, as well as increasing the proportion of T lymphocytes and natural killer cells. Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory-tract infections and dental caries in children. LAB products might aid in the treatment of acute diarrhea, and possibly affect rotavirus infections in children and travelers' diarrhea in adults, but no products are approved for such indications.
Helicobacter pylori
Some strains of LAB may affect Helicobacter pylori infections (which may cause peptic ulcers) in adults when used in combination with standard medical treatments, but no standard in medical practice or regulatory approval exists for such treatment.
Inflammation
Some strains of LAB may modulate inflammatory and hypersensitivity responses, an observation thought to be at least in part due to the regulation of cytokine function. Clinical studies suggest they can prevent reoccurrences of inflammatory bowel disease in adults, as well as improve milk allergies. How probiotics may influence the immune system remains unclear, but a potential mechanism under research concerns the response of T lymphocyts to proinflammatory stimuli.
Irritable bowel syndrome and colitis
Probiotics may help people with irritable bowel syndrome, although uncertainty remains around which type of probiotic works best, and around the size of the effect.
No good evidence indicates taking probiotics helps maintain remission from ulcerative colitis.
Necrotizing enterocolitis
Several clinical studies provide evidence for the potential of probiotics to lower the risk of necrotizing enterocolitis (NEC) and mortality in premature infants. One meta-analysis indicated that probiotics reduce all-cause mortality and risk of having NEC by more than 50% compared with controls.
Vitamin production
Probiotic treatment has been studied as a means of addressing maladies associated with vitamin deficiency, e.g., of Vit K, folic acid, and Vit B 12.
Eczema
Probiotics are commonly given to breast-feeding mothers and their young children to prevent eczema, but some doubt exists over the strength of evidence supporting this practice.

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Probiotics (cont)

Bacterial Vaginosis
Probiotic treatment of bacterial vaginosis is the application or ingestion of bacterial species found in the healthy vagina to cure the infection of bacteria causing bacterial vaginosis. This treatment is based on the observation that 70% of healthy females have a group of bacteria in the genus Lactobacillus that dominate the population of organisms in the vagina. Currently, the success of such treatment has been mixed since the use of probiotics to restore healthy populations of Lactobacillus has not been standardized. Often, standard antibiotic treatment is used at the same time that probiotics are being tested. In addition, some groups of women respond to treatment based upon ethnicity, age, number of sexual partners, pregnancy, and the pathogens causing bacterial vaginosis. In 2013, researchers found that administration of hydrogen peroxide producing strains, such as L. acidophilus and L. rhamnosus, were able to normalize vaginal pH and rebalance vaginal flora, preventing and alleviating bacterial vaginosis.
Side effects
In some situations, such as where the person consuming probiotics is critically ill, probiotics could be harmful. In a therapeutic clinical trial conducted by the Dutch Pancreatitis Study Group, the consumption of a mixture of six probiotic bacteria increased the death rate of patients with predicted severe acute pancreatitis.
In a clinical trial aimed at showing the effectiveness of probiotics in reducing childhood allergies, researchers gave 178 children either a probiotic or a placebo for the first six months of their lives. Those given the probiotic were more likely to develop a sensitivity to allergens.
Some hospitals have reported treating Lactobacillus septicemia, which is a potentially fatal disease caused by the consumption of probiotics by people with lowered immune systems or who are already very ill.
Probiotics taken orally can be destroyed by the acidic conditions of the stomach. A number of microencapsulation techniques are being developed to address this problem.
One 2009 paper cited a 2007 study in chickens as a support for causally linked probiotic products such as yogurts with obesity trends. However, this is contested as the link to obesity, and other health-related issues with yogurt may link to its dairy and calorie attributes.
Some experts are skeptical on the efficacy of many strains and believe not all subjects will benefit from the use of probiotics.
Member Discussions
http://www.cymbaltaw...rove#entry45197
It begins on post #68 and continues to post #73.
Info and discussion on probiotics.

http://www.cymbaltaw...ics/?hl=improve
Great Details on benefits of probiotics.

probiotic and serotonin,
https://www.ncbi.nlm...pubmed/28607543
After probiotic supplementation, we observed a significant increase in concentration of serum serotonin (P = .008) and a decreased level of tryptophan in plasma.
https://www.ncbi.nlm...les/PMC5102282/
Summary of the effects of pro and prebiotics on psychiatric functions.
https://www.huffingt...4b064e1b4b3a842
A layman's summary of the effects of pro and prebiotics on psychiatric functions.
https://www.ncbi.nlm...pubmed/25470391
https://www.ncbi.nlm...pubmed/24554471
https://www.ncbi.nlm...pubmed/20974015
https://www.ncbi.nlm...pubmed/21983070
https://www.ncbi.nlm...pubmed/25879690
https://www.ncbi.nlm...pubmed/23384445
and many more
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