Selective serotonin re-uptake inhibitor (SSRI) discontinuation syndrome

 Article written on request of my twitter friend, UK Garden Designs ‏@UK_GD


Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor (SSRIs) are a types of  antidepressant medications to treat depression and certein neurological disorders, including  obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD), etc..

SSRI discontinuation syndrome is defined as a condition of a syndrome as a result of interruption, reduced doses or discontinuation of any anti depressant medication, including SSRI (selective serotonin re-uptake inhibitor) and serotonin–norepinephrine reuptake inhibitor (SNRI), researchers  showed that The SSRI discontinuation syndrome is a characteristic selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome appears to exist. It is usually mild, commences within 1 week of stopping treatment, resolves spontaneously within 3 weeks, and consists of diverse physical and psychological symptoms, the commonest being dizziness, nausea, lethargy and headache. SSRI reinstatement leads to resolution within 48 h(1).

I. Symptoms and signs 
The use of medication duration is usually 1 month with symptoms developing within a few days  after SSRI interruption, cessation, or reduction of dosage.
1. Dizziness
The abrupt withdrawal from an SSRI is likely to cause a sudden decrease in serotonin in the VNC, which will disrupt the function of VNC neurons bilaterally, causing dizziness without vertigo(2).

2. Sleep disturbance
The abrupt discontinuation of paroxetine seemed associated with sudden and impairing effects, some patients may experience sleep disturbances and dizziness(3)

3. AQgitation, irritability, vertigo, lightheadedness and fever
There are a report that a 30-year-old man with depression who was treated with paroxetine (Seroxat) developed severe withdrawal symptoms when the medication was gradually diminished and stopped: agitation, irritability, vertigo, lightheadedness and fever up to 40 degrees C. The symptoms disappeared after the medication was reintroduced but recurred after rediscontinuation(4).


4. Visual and auditory hallucinations, headache, insomnia, and nausea
Other report that Discontinuation symptoms can follow the stoppage of almost all classes of antidepressants can experience visual and auditory hallucinations in addition to dizziness, headache, insomnia, and nausea a couple of days after paroxetine discontinuation(5).

5.  Balance, sensory abnormalities, and possibly aggressive and impulsive behavior
Other researchers  found that the discontinuation of Selective serotonin re-uptake inhibitor (SSRI) also cause the symptoms of Selective serotonin re-uptake inhibitor (SSRI) such as nausea, lethargy, insomnia, and headache, are similar to those reported with tricyclic discontinuation. However, SSRI discontinuation is also associated with novel symptom clusters, including problems with balance, sensory abnormalities, and possibly aggressive and impulsive behavior(6).

6. Sexual dysfunction
Some patients may also experience Post-SSRI sexual dysfunction (PSSD) caused by the previous use of selective serotonin reuptake inhibitor (SSRI) antidepressants. While apparently uncommon, it can last for months, years, or sometimes indefinitely after the discontinuation of SSRIs(7).

II. Causes and risk factors
A. Causes
Dr. Blier P and Dr. Tremblay P. at the University of Ottawa suggested that in the development of animal models to explain the mechanisms of this clinical problem has proved challenging, because less than half of all patients experience any discontinuation symptoms, many of which are subjective in nature. One explanation is that SRI discontinuation symptoms may arise from the rapid decrease in serotonin (5-HT) availability when treatment ends abruptly. Yet, it would appear that discontinuation discomforts may not be mediated exclusively through 5-HT receptors, given the major regulatory role 5-HT exerts on a number of specific chemical receptor systems in the brain(8).
Others showed that one explanation is that antidepressant discontinuation symptoms may arise from the rapid decrease in serotonin availability when treatment ends abruptly. It would appear that discontinuation discomfort may not be mediated exclusively through serotonin receptors, given the major regulatory role serotonin exerts on a number of specific chemical receptor systems in the brain. As a result, attempts to explain the determinants of this phenomenon rely on a certain level of speculation. The article discusses the three systems most likely to account in the symptomatology--the serotonin, the norepinephrine, and the cholinergic systems--and the possible interactions among them(9).

B. Risk factors
Risks of Selective serotonin re-uptake inhibitor (SSRI) discontinuation syndrome are depending to the medication taken. there appears to be less risk with the abrupt interruption of fluoxetine. Paroxetine is the SSRI most often mentioned in the case reports and the reason for this may be as simple as the fact that it is most frequently prescribed. An alternative explanation may involve paroxetine s affinity for cholinergic (muscarinic) receptors, causing cholinergic rebound on discontinuation(10).

III. Diagnosis
There are no specific diagnosis criteria, but researchers in the study of "Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria", suggested that the criteria are 2 or more of the following symptoms developing within 1 to 7 days of discontinuation or reduction in dosage of an SSRI after at least 1 month's use, when these symptoms cause clinically significant distress or impairment and are not due to a general medical condition or recurrence of a mental disorder: dizziness, light-headedness, vertigo or feeling faint; shock-like sensations or paresthesia; anxiety; diarrhea; fatigue; gait instability; headache; insomnia; irritability; nausea or emesis; tremor; and visual disturbances(11).

IV. Prevention
B. Diet to reduce the symptoms of Selective serotonin re-uptake inhibitor (SSRI) discontinuation syndrome
B.1. Foods to Increase Serotonin
Various fruits boost serotonin and other mood-improving chemicals in the brain, including
The following fruits had a high serotonin concentration (mean +/- SEM) expressed in micrograms/g weight: plantain 30.3 +/- 7.5; pineapple 17.0 +/- 5.1; banana 15.0 +/- 2.4; Kiwi fruit 5.8 +/- 0.9; plums 4.7 +/- 0.8; and tomatoes 3.2 +/- 0.6. Only nuts in the walnut or hickory family had a high serotonin concentration expressed in micrograms/g weight; butternuts 398 +/- 90; black walnuts 304 +/- 46; English walnuts 87 +/- 20; shagbark hickory nuts 143 +/- 23; mockernut hickory nuts 67 +/- 13; pecans 29 +/- 4; and sweet pignuts 25 +/- 8. Ingestion of these fruits and nuts resulted in an increase in urinary 5-hydroxyindoleacetic acid excretion with no change in platelet serotonin concentration(13).
B.2. Serotonin Boost from Protein Sources
Food contain high levels of tryptophan such asTurkey, Lean beef, Salmon, etc. can enhance the production of the levels of serotonin, as trytophan ia a precursor of the sorotonin. Some researchers showed  that tryptophan is an antidepressant in mild to moderate depression and a small body of data suggests that it can also decrease aggression. Preliminary data indicate that tryptophan also increases dominant behavior during social interactions. Overall, studies manipulating tryptophan levels support the idea that low serotonin can predispose subjects to mood and impulse control disorders. Higher levels of serotonin may help to promote more constructive social interactions by decreasing aggression and increasing dominance(14).

B.3. Carbohydrate-based Foods and carbohydrate snacking that Increase Serotonin
Carbohydrate-based Foods and carbohydrate snacking found abundantly in foods consists of glucose that can boost serotonin production. Evidence is presented that carbohydrate snacking seems to be related to a "need" to increase the level of brain serotonin; treatment with a drug, d-1 fenfluramine, that increases serotoninergic neurotransmission significantly decreases carbohydrate snack consumption(15).

B.4. Etc.

C. Phytochemicals and antioxidants to reduce the symptoms of Selective serotonin re-uptake inhibitor (SSRI) discontinuation syndrome
1. Tangeretin
Tangeretin, a citrus flavonoid in  the oral administration resulted in significant levels of tangeretin in the brain (hypothalamus, striatum and hippocampus). Treatment of the rats with the dopaminergic neurotoxin 6-hydroxydopamine resulted in reduced levels of dopamine, an effect which was reversed by the administration of tangeretin. This study concluded that tangeretin can cross the blood-brain barrier and has a potential use as a neuroprotective agent(16).


2. Epigallocatechin-3-gallate and Polyphenols
Green tea polyphenols (GTPs and epigallocatechin-3-gallate (EGCG) modulation could improve the cognitive impairments induced by psychological stress. The related mechanisms may be involved with the changes of catecholamines, 5-hydroxytryptamine, cytokines and expressions of metallothioneins(17).

3. Furanocoumarins 
furanocoumarins found abundantly in grapefruit with CYP2D6 inhibition achieved in the range of 190-900 nM and Anthocyanins and anthocyanidins were shown to be about 1,000-fold less potent, they are unlikely to interfere with drug metabolism by CYP2D6(18).

4.  N-acetyl-cysteine and curcumin
 N-acetyl-cysteine has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. Additionally, curcumin, the yellow pigment of curry, has been shown to strongly interfere with neuronal redox homeostasis in the CNS and to possess antidepressant activity in various animal models of depression, also thanks to its ability to inhibit monoamine oxidases(19)

 5. Etc.
 
V. Treatments
A. In conventional medicine perspective
A.1. Graduation of doses and later discontinued
There are suggestion that symptoms may occur even if the SSRI dose is tapered gradually. In half of 50 reported cases, an attempt was made to taper the SSRI, although details concerning the duration and rapidity of taper were not provided consistently. At this point, it is unclear whether tapering SSRIs will reduce the risk nor is it clear whether we should advocate the routine taper of SSRIs when stopping treatment. The only known effective treatment is the re-introduction of the SSRI which is associated with rapid resolution of symptoms. Unfortunately, the syndrome tends to recur in approximately 75% of patients when the same SSRI is later discontinued(12).

A.2. Treatment depends on symptom severity
If symptoms of SSRI discontinuation are so severe, or do not respond to symptom management, patients may be necessary to reinstate the antidepressants and withdrawn the medication slowly as mention above. Others suggested to switch to a long half-life medication at a relatively low dose and then stop taking  SSRI altogether(20).

A.3. Treating the symptoms
Certain medication may be prescribed to treat the symptoms of Selective serotonin re-uptake inhibitor (SSRI) discontinuation syndrome. Please consult with your doctor.

B. In herbal medicine perspective
A. Herbs to treat depresiion
Treatments of Selective serotonin re-uptake inhibitor (SSRI) discontinuation syndrome can try herbs as reinstated medicine and withdrawn them slowly with little or no side effect. Please consult with your doctor before applying.
1. St John Wort
n the analyzing the effects of a chronic hyperforin of of the medicinal plant Hypericum perforatum (St. John's wort).treatment on brain cell, found that Hyperforin stimulated the expression of TRPC6 channels and TrkB via SKF-96365-sensitive channels controlling a downstream signalling cascade involving Ca2+, protein kinase A, CREB and p-CREB. In vivo, hyperforin augmented the expression of TrkB in the cortex but not in the hippocampus where hippocampal neurogenesis remained unchanged. In conclusion, this plant extract acts on the cortical BDNF/TrkB pathway leaving adult hippocampal neurogenesis unaffected. This study provides new insights on the neuronal responses controlled by hyperforin, according to "The antidepressant hyperforin increases the phosphorylation of CREB and the expression of TrkB in a tissue-specific manner" by Gibon J, Deloulme JC, Chevallier T, Ladevèze E, Abrous DN, Bouron A.(21)

2. Rhodiola Rosea
In the evaluation of herbal medicines, other than St. John's wort, in the treatment of depression
found that the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo, according to "Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review" by Dwyer AV, Whitten DL, Hawrelak JA.(22) 

3. Etc.

B. Herbs to treat symptoms of  Selective serotonin re-uptake inhibitor (SSRI) discontinuation syndrome
1. Lemon Balm
a. Anxiety-like reactivity
In the determination of the effects of chronic (15 consecutive days of treatment) per os administration of Melissa officinalis L. extract (Cyracos, Naturex) on anxiety-like reactivity in mice, found that the Cyracosdose at which it exerted anxiolytic-like effects in the elevated plus maze did not alter exploratory or circadian activities. Therefore, our results demonstrate that Cyracos has anxiolytic-like effects under moderate stress conditions and does not alter activity levels, according to "Effects of chronic administration of Melissa officinalis L. extract on anxiety-like reactivity and on circadian and exploratory activities in mice" by

Ibarra A, Feuillere N, Roller M, Lesburgere E, Beracochea D.(23)

b. Anxiety disorders and insomnia
In the assessment of Cyracos(®), a standardized Melissa officinalis L. extract and it anti-stress and anxiolytic effects found that Cyracos(®) reduced anxiety manifestations by 18% (p < 0.01), ameliorated anxiety-associated symptoms by 15% (p < 0.01) and lowered insomnia by 42% (p < 0.01). As much as 95% of subjects (19/20) responded to treatment, of which 70% (14/20) achieved full remission for anxiety, 85% (17/20) for insomnia, and 70% (14/20) for both, according to "Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances" by Cases J, Ibarra A, Feuillère N, Roller M, Sukkar SG.(24)

2 Ginseng Asia
a. Antipsychotic effect
In the investigation of Panax quinquefolium (PQ) and its significant neuroactive properties for its antipsychotic potential found that PQ blocked ketamine induced memory impairment in the passive avoidance paradigm. In the chronic studies, PQ reduced the ketamine induced enhanced immobility in the forced swim test and did not show extra-pyramidal side effects in bar test and wood block test of catalepsy. These behavioural effects were compared with standard drugs haloperidol and clozapine. Further PQ reduced DA and 5-HT content after chronic treatment, but not after acute administration, according to "Evaluation of the Antipsychotic Potential of Panax quinquefolium in Ketamine Induced Experimental Psychosis Model in Mice" by Chatterjee M, Singh S, Kumari R, Verma AK, Palit G.(25)


b. Neuroprotective effect
In the analyzing Panax ginseng C.A. Meyer and its beneficial effects in cerebral ischemia and inhibition of the inflammatory cascade in sepsis found that Ginsenoside Rb1 (GRb1) partially inhibited the activation of nuclear factor-κB (NF-κB) pathway from 6 h to 72 h after ischemia and reperfusion onset, as determined by the expression of total and phosphorylated NF-κB/p65, inhibitor protein of κB (IκB)-α, and IκB-kinase complex (IKK)-α. All these results indicate that suppression of local inflammation after cerebral ischemia might be one mechanism that contributes to the neuroprotection of GRb1, according to "Suppression of local inflammation contributes to the neuroprotective effect of ginsenoside Rb1 in rats with cerebral ischemia" by Zhu J, Jiang Y, Wu L, Lu T, Xu G, Liu X.(26)

3. Ginkgo  
a. Brain-cognition effects
Ginkgo Biloba extract (GBE) have exhibited the function of alleviating symptoms of cognitive impairment in aging populationby increasing the SSVEP(state visually evoked potentia) amplitude at occipital and frontal sites and SSVEP latency at left temporal and left frontal sites, according to the study of "Examining brain-cognition effects of ginkgo biloba extract: brain activation in the left temporal and left prefrontal cortex in an object working memory task" by Silberstein RB, Pipingas A, Song J, Camfield DA, Nathan PJ, Stough C., posted in PubMed(27)

b. Acute cognitive effects
Administration of GBE complexed with phosphatidylserine have exerted the results of improingsecondary memory performance and speed of memory task performance, according to the study of "Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine" by Kennedy DO, Haskell CF, Mauri PL, Scholey AB., posted in PubMed(28) 

4. Etc.


C. In traditional Chinese medicine perspective
According to APPENDIX 1: Guipi Tang and SSRI Withdrawal Syndrome, Western interpretation of the symptoms as relative deficiency in serotonin availability or an imbalance of neurotransmitters after the drugs are removed. In TCM the withdrawal syndrome may be caused qi and blood deficiency, as a result of the spleen (for qi) and liver (for blood). Treatment of SSRI withdrawal syndrome is depending to the differentiation of the symptom. Herbs used include
Atractylodes (white atractylodes): tonifies qi, resolves damp
Peony (white peony): nourishes blood, vitalizes blood circulation
Tang-kuei: nourishes blood, vitalizes blood circulation
Zizyphus: nourishes liver and heart blood and clams shen
Saussurea: circulates qi, calms shen
Ginseng: tonifies qi, calms shen
Astragalus: tonifies qi, raises yang qi
Polygala: resolves phlegm, calms shen
Fu-shen or Hoelen: resolves damp, calms shen
Pinellia: resolves damp, lowers stomach qi
Citrus: resolves damp, circulates qi

Natural Remedies for Dementia Memory Loss Reversal
Guarantee to Stop Progression and Reverse Memory Loss in Alzheimer and  Dementia  with step by step instructions through Scientific Studies  within 2 Months or your Money back

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/10958258
(2) http://www.ncbi.nlm.nih.gov/pubmed/20144124
(3) http://www.ncbi.nlm.nih.gov/pubmed/8602387
(4) http://www.ncbi.nlm.nih.gov/pubmed/10422558
(5) http://www.ncbi.nlm.nih.gov/pubmed/21489048 
(6) http://www.ncbi.nlm.nih.gov/pubmed/9219489
(7) http://en.wikipedia.org/wiki/Post-SSRI_sexual_dysfunction 
(8) http://www.ncbi.nlm.nih.gov/pubmed/16683857
(9) http://www.ncbi.nlm.nih.gov/pubmed/20214096 
(10) http://www.circlemedhealthcare.com/ssri.pdf
(11) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1407715/
(12) http://www.circlemedhealthcare.com/ssri.pdf
(13) http://www.ncbi.nlm.nih.gov/pubmed/2413754
(14) http://www.ncbi.nlm.nih.gov/pubmed/11888576
(15) http://www.ncbi.nlm.nih.gov/pubmed/6381575
(16) http://www.ncbi.nlm.nih.gov/pubmed/11726811
(17) http://www.ncbi.nlm.nih.gov/pubmed/20463297
(18) http://www.ncbi.nlm.nih.gov/pubmed/19357792
(19) http://www.ncbi.nlm.nih.gov/pubmed/22668245
(20) http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291099-1166%28199806%2913:6%3C421::AID-GPS774%3E3.0.CO;2-Y/abstract;jsessionid=3C78BDD20E857C086A4C305B9880784E.d02t02
(21) http://www.ncbi.nlm.nih.gov/pubmed/22226089
(22) http://www.ncbi.nlm.nih.gov/pubmed/21438645

(23) http://www.ncbi.nlm.nih.gov/pubmed/20171069
(24) http://www.ncbi.nlm.nih.gov/pubmed/22207903
(25) http://www.ncbi.nlm.nih.gov/pubmed/22189635
(26) http://www.ncbi.nlm.nih.gov/pubmed/22173011
(27) http://www.ncbi.nlm.nih.gov/pubmed/21941584
(28) http://www.ncbi.nlm.nih.gov/pubmed/17457961 
(29) http://www.dr-bob.org/babble/alter/20100516/msgs/947782.html