POWER OVER PROZAC – The Use of Herbal Medicines to Withdraw from SSRIs

POWER OVER PROZAC –  The Use of Herbal Medicine to Withdraw from SSRIS
Jill E Stansbury ND

WEANING FROM PHARMACEUTICALS ANTIDEPRESSANTS

SSRI Withdrawal
Long-term use of SSRIs leads to down regulation of serotonergic activity, as the tissues adjust to the presence or elevated serotonin levels. Withdrawing from SSRIs too abruptly can lead to many unpleasant symptoms, and can even be potentially fatal. It is necessary to wean down gradually from these drugs and allow the brain to increase the number of serotonin receptors and readjust. The most commonly reported symptoms are depression, anxiety, panic, tachycardia, and insomnia. For most people, withdrawal symptoms are an aggravated presentation of what caused them to go on the drugs initially. Offering herbs that are specific for a person’s complaints may aid in withdrawal from SSRI drugs. The herbs may be started before a person starts the weaning process to reduce withdrawal symptoms. After a month on low doses of carefully selected botanical medicines or supplements, the dosage of the antidepressant may be cut by ¾ or ½ depending on how long a person has been on the medication, and how large the dose is. It is much easier and you can move more quickly in someone who has been on 10 mg Paxil for 3 months. It is much more difficult and you must wean down more slowly for someone who has been 40mg of Paxil for 3 or more years. If all is well after 2 to 4 weeks, the dosage may be cut in half again, and in another several weeks reduced again. Once a person is down to 5 mg, you may reduce to every other day or discontinue altogether. If at any time in the withdrawal process, a person experiences emotional difficulties, see if they might be remedied through botanical, nutritional, or cognitive therapies first, before increasing the does of the SSRI again. However, for severe emotional upset, or when a person does not quickly respond to other therapies, return to the pharmaceutical and trying weaning more slowly at some point in the future.

Serotonin Syndrome
Serotonin syndrome is a collection of symptoms caused by excessive levels of serotonin present in the neural synapse. This potentially serious syndrome can result from an overdose of pharmaceuticals that affect serotonin. Using botanicals that elevate serotonin levels, or taking large amounts of tryptophan that elevate serotonin levels, simultaneously with SSRI drugs could also induce this syndrome. The clinical challenge is therefore, providing serotonin enhancing therapies that can replace the pharmaceutical, but not over medicating and inducing serotonin syndrome. Distinguishing transient and minor withdrawal symptoms from the onset of serotonin syndrome may also prove challenging. To reduce the risk of inducing serotonin syndrome, natural therapies should be introduced cautiously, while staying in close contact with the patient and watching carefully for any difficulties. Keep the approach fairly simple at first, to make it easier to evaluate the effects of any substance given. Avoid combining multiple therapies that all affect serotonin. Consider exercise, meditation, and cognitive therapies for several months prior to weaning from pharmaceuticals, so that these benefits are in place to assist in the withdrawal process.

MAO-I Withdrawal
Withdrawing from MAO inhibitors can also cause worsening of the depression, anxiety, and palpitations, The most serious withdrawal symptoms are severe hypertension and tachyarrhythmias. Since the B adrenergic response becomes muted over time while using MAO inhibitors, sudden hypertension may result from increased adrenergic activity upon withdrawal. As norepinephrine is no longer suppressed, increasing binding at the B1 receptors leads to vasoconstriciton. Using Beta Blocking herbs such as Tilia europea or Leonurus cardiaca, may reduce cardiovascular symptoms. It is extremely dangerous to combine MAO I with amphetamines due to the risk of over stimulation. Likewise, botanical stimulants such as caffeine, theophylline, and Ephedra should be avoided.

BEYOND MONOAMINES
The botanical remedy may be fine-tuned by considering the entire state of health, not just a desired monoamine or CNS effect. Through a complete review of systems, understanding of a person’s constitution and through considering the myriad other clues, botanical and nutritional prescribing can be made much more accurate and specific.

 
For example, liver and alterative botanicals are often supportive to medication withdrawal, as they support absorption of nutrients, elimination of wastes, bile quality and flow, fat digestion, and hormonal metabolism and excretion. This digestive support may also lead to improved nutrition and amino acid metabolism and neurotransmitter synthesis. Insuring adequate intake of quality proteins may support the synthesis of neurotransmittors.

 
Adrenal support may also be indicated. Adrenal insufficiency may be an underlying cause of depression since abnormal levels of cortisol and catecholamines can contribute to anxiety, poor stress tolerance, fatigue, poor concentration, emotional difficulties. Furthermore, B adrenergic response becomes muted with long term use of antidepressants.

DEPRESSION AND LIVER FUNCTION
In traditional Chinese medicine the liver is thought to “smooth the chi”, and emotional lability, anger, and irritability may be attributed to the liver and its sphere of influence. In early European traditions, the liver was also associated with anxiety, anger, and irritability. Evidence of this philosophy is still present in some of the idioms of the English language. For example, the idiom where someone is referred to as being “bilious”, meaning that they are irritable or irascible. (Or referring to someone as being bitter, or something being a bitter pill to swallow.) Bitter personalities was associated with the liver in folkloric medicine, and botanical medicines promoting liver function are generally bitter.
Botanical agents that support liver and digestive function are appropriate in many cases of anxiety, depression, and hormonal difficulties, particularly when there is associated, constipation, skin disease, history of liver disease, and poor diet. Since the liver conjugates active hormones in circulation, serving to metabolize and excrete them from the body, liver stagnation, constipation, high fat diet, ingestion of hormones and hepatotoxins, will all impair the body’s ability to process estrogens and progesterones. The use of bitter herbs and alteratives will support liver function, promote bile flow and the emulsification of fats, improve hormone metabolism, and enhance digestive, absorptive, and eliminative functions. The use of liver herbs, bitters, and alterative agents is a whole discussion unto itself, and will not be covered in any detail here. Rather, this document will include a brief summary of hormonal balancing herbs that may be considered in addition to alteratives, or in cases where alteratives do not appear indicated. Besides, prescribing bitter alterative agents such as Dandelion root – Taraxicum, Burdock root – Arctium, Yellow Dock root – Rumex, or others, some women may benefit from specific hormonal and anti-anxiety botanicals as the situation and symptoms dictate. Following is a brief summary of a few botanicals useful for insomnia and anxiety states including several plants helpful in hormonal regulation and cyclical anxiety states.

DEPRESSION AND ADRENAL FUNCTION
Stress, anxiety, confusion, and fatigue are highly associated with adrenal insufficiency. There are many mechanisms and pathways whereby the adrenal glands may contribute to depression. Prolonged stress may lead to “down regulation” of the adrenal glands as the organs adjust to continuous stimulation by adrenotropins. The tissues may also down regulate as they adjust to perpetual stimulation by adrenaline and cortisol. An overall dampening, referred to as the General Adaptation Syndrome occurs where muted stress management, adrenal hormone stimulation and response develops.
Botanicals that support adrenal regulation and response may improve depression, anxiety, and hormonal disorders. Glycyrrhiza glabra, Panax ginseng, Eleutherococcus senticosis, and Opolopanax horridum are among those herbs thought to stimulate, nourish, or otherwise affect adrenal hormone activity.

BOTANICALS AFFECTING SEROTONIN ACTIVITY
Serotonin is a monoamine neurotransmitter that is synthesized from the amino acid tryptophan. Serotonin has a sedating and antidepressant effect and appears to affect the mood and disposition. Serotonin is also known to concentrate in blood platelets where it plays a role in inflammation. Hypericum perforatum is currently thought to act as a natural serotonin re-uptake inhibitor, as well as affect MAO and catechol methyl-transferase, the 2 enzymes that break down serotonin. Ginkgo biloba has been credited with preventing age- related decline in the number of serotonin receptors. Ginkgo may also increase the number of serotonin receptors in general.

BOTANICALS AFFECTING MONOAMINE OXIDASE
Monoamine oxidase is the primary enzyme responsible for degrading serotonin and other monoamines. If you inhibit MAO, serotonin will not be broken down and stimulation of serotonin receptors in the brain will be prolonged. Hypericum has also been investigated for MAO inhibition. Passiflora incarnata contains the indole alkaloids harmine, and telepathine thought to act as MAO inhibitors.

BOTANICALS AFFECTING GABA (Benzodiazepine) RECEPTORS
GABA is a neurotransmitter synthesized from glutamine that has a sedating effect. GABA or gamma amino butyric acid is one of the primary inhibitory neurotransmitters. Animal studies have shown that mice that are anxious tend to have less GABA receptors in their brains than mice that are not anxious. Melatonin has been reported to have an anti-anxiety effect in mice due to activity at GABA receptors.
Valeriana officianalis and Valeriana stichensis are known to bind to GABA receptors and produce mild to marked sedation. Such GABA agonists may be calming and tension relieving for anxiety states, but may occasionally worsen depression due mild sedation. Other herbs considered to be classic anxiolytics have been shown to be GABA agonists including Kava (Piper methysticum), Passion Flower (Passiflora incarnata), and the poppies Bleeding Heart (Corydalis cava) and the California Poppy (Eschscholzia californica). Isoquinoline alkaloids in the poppy family members Eschscholtzia californica and Corydalis cava are known to bind to GABA receptors as does chrysin, a flavonol in Passiflora species. Hypericine, a flavonol in Hypericum effects serotonin degradation weakly, as well as binds GABA. The strongly sedating herbs Valerian and Kava are known to act via GABA receptors in part.

BOTANICALS AFFECTING THE LIMBIC SYSTEM
Recent investigations into some sedating plants have proposed activity via the Limbic system. While some botanicals have been noted to act as serotonin reuptake inhibitors, serotonin agonists, MAO inhibitors, or GABA agonists, these limbic botanicals are thought to somehow affect the activity around the limbic receptors without binding to the receptors themselves. Botanicals thought to affect the limbic system include Hops – Humulus lupulus, Kava – Piper methysticum, and Lemon Balm – Melissa citronelle

NERVOUS SYSTEM MATERIA MEDICA

CORYDALIS CAVA Bleeding Heart Papaveracea (Poppy) Family
Like many opium family plants, Corydalis contains sedating alkaloids. Corydalis extracts have been shown to bind to opiate receptors in the brain and promote sedation, pain relief, and sleep. Corydalis has also been shown to promote degradation of adrenaline and the synthesis of melanin from DOPA (dihydroxyphenylalanine).

ELEUTHROCOCCUS SENTICOSIS Siberian Ginseng Araliacae Family
Siberian Ginseng is considered to be an adaptogenic botanical useful for stress, exhaustion, and weakness. Eleutherococcus is reported to decrease stress induced activation of the adrenal cortex and stress induced involution of the thymus and lymphatic tissues. Eleutherococcus has been shown to increase the ability of the body to withstand physically adverse conditions.

ESCHSCHOLZIA CALIFORNICA California Poppy Papaveracea (Poppy) Family
The California poppy was used for pain and as a mild sedative by the Pacific coastal Native American people. The stems and roots of the bright orange poppy contain opiate-like isoquinoline alkaloids. Isoquinoline alkaloids such as morphine, and sanguinarine, are synthesized by poppies from the amino acid tyrosine. Benzylisoquinolines in poppies are believed to affect our endogenous enkephalins and endorphins, and have a sedative quality due to binding activity at opiate receptors. Eschscholtzia has been noted to inhibit the breakdown of catecholamines and adrenaline, through inhibition of the enzymes dopamine beta-hydroxylase and MAO-B. Diamine oxidase enzymes are inhibited by both Eschscholzia and Corydalis. The numerous alkaloids have collectively been found to affect vasopressin and reduce blood pressure. Chylerythrine and sanguinarine have both been found to inhibit binding of vasopressin, and have been investigated as an idea for the synthesis of non-peptidal vasopressin inhibitors.

HUMULUS LUPULUS Hops Canabinacea Family
Hops are a member of a very small but interesting family. The Canabinacea family includes just two genera, Hops and Marijuana. Both plants produce a resin that has been credited with strong physiologic activities. Marijuana contains the resin THC (tetrahydrocannabinol), and Hops contains the resinous Lupulin. Hops plants are huge climbing vines that produce plain little flowers, technically known as strobiles. Lupulin is known to affect receptor binding and neurotransmission in the limbic, though it not thought to bind directly to neural synapses itself. The ripe strobiles are harvested during the summer where hops are grown commercially in the Pacific Northwest.
HYPERICUM PERFORATUM SAINT JOHNSWORT Hyperiaceae Family
The term “wort” implies the longstanding use of this herb medicinally. The genus name Hypericum is from hyper- meaning above, and icon meaning spirit, as this herb was often hung above doorways to ward off evil spirits or burned to protect and sanctify an area. Modern studies on the central nervous system actions of Hypericum began in the 1980’s with a series of animal studies and in vitro nervous tissue suggesting possible MAO inhibition. Later studies could not confirm a strong in vivo inhibition of MAO , but some researchers still report possible MAO antagonism with Hypericum. Catechol-o-methyl transferase is another enzyme that may metabolize serotonin. Hypericum has been noted to suppress catechol-o-methyltransferase, though the mechanism is unknown. The most recent research on this valuable medicine has investigated inhibition of serotonin re-uptake like the popular anti-depressant drugs.

PASSIFLORA INCARNATA PASSION FLOWER Passifloraceae Family
Passionflower contains several chemical groups thought to have a general sedating and relaxing effect. Interestingly, both the indole alkaloids and the flavinoids must present to yield sedative activities. When used in isolation, neither fraction has noteworthy anti-anxiety effects. The edulis species is reported to be the highest in the indole harmala alkaloids. These alkaloids are known to be hallucinogenic when taken in appreciable amounts in other botanicals. You won’t be likely to induce hallucinations with passion flower preparations, however, because of the quantity of these substances is too scant. Harmala alkaloids may inhibit MAO. The flavinoid constituents listed below are also thought to be tranquilizing, depressing motor activity without affecting respiratory rate. Passiflora depresses motor activity and blood pressure transiently, and the alkaloids are thought to be rapidly cleared from the body. Passiflora acts as a general central nervous system depressant. Small doses of Passiflora preparations tend to have a calming, relaxing and anti-anxiety effect. Large doses may stimulate some individuals rather than sedate, while others can become overly sedated and depressed from large dosages of Passiflora. Very large amounts and overdose can promote restlessness, and rarely hallucinations.

SCUTELLARIA LATERIFLORA SKULLCAP, MAD DOG Labiatae (Mint) Family
The common name of Mad Dog refers to Skullcap’s historical use for the hydrophobia of inflicted by the bite of a mad or rabid dog. The actions of Scutellaria are as a sedative nervine, as well as a mild antispasmodic and anti-hypertensive. Scutellaria is generally very well tolerated, has few side affects, and acts as a gentle relaxing and calming agent. In cases of insomnia, Scutellaria induces normal sleep without being a strong sedating or stupefying. Skullcap is used primarily for nervousness, anxiety, restlessness, insomnia, and muscular pain and tension. Folkloric uses of Scutellaria include hydrophobia that occurs with rabies, and St.Vitus’s dance.

PIPER METHYSTICUM KAVA KAVA Piperaceae (Pepper) Family
The actions of Kava are a curious combination of muscular relaxation combined with both CNS stimulation and sedation. Kava is relaxing to muscles and reduces emotional tension and anxiety, while simultaneously increasing flow of thoughts. Kava is most helpful in cases of anxiety accompanied by muscular tension overly sedating in those suffering from a type of lethargic depression. Studies have shown Kava to bind weakly to GABA A receptors and act as agonists. Some researchers feel this contributes to the sedative action of Kava, but many do not feel this to powerful enough to exert the sedative effects of Kava alone. Other studies and investigators have suggested that Kava affects the binding of other ligands to the GABA receptors without binding themselves. Kava appears to affect the brain most strongly in the regions of the hippocampus, amygdala, and the medulla oblongata. These brain regions are considered part of the limbic system.

VALERIANA OFFICINALIS, STICHENSIS Valerian Valerianaceae Family
The actions of Valerian include sedative nervine, hypotensive, anodyne, and antispasmodic. Valeriana contains valerenic acid and valeranone which are thought to be antispasmodic due to influence on intracellular calcium. , As an antispasmodic, Valerian is helpful to allay skeletal muscle cramps, muscle tension due to nervousness, uterine and bowel cramps. Valerian is useful in simple cases of stress, anxiety, and nervous tension as well as the more arduous cases of hysteria, nervous twitching, hyperactivity, chorea, heart palpitations and tension headaches. Valerian is also an herbal classic in the treatment of insomnia. Valerian is believed to shorten the length of time needed to fall asleep as well as improve quality of sleep. , Valerian is probably more helpful in anxiety states than it is for depression. Due to its action as a GABA agonist, Valerian may worsen depression in some individuals promoting undesirable sedation. Valerian may be indicated for depression only when due to prolonged stress and nervous tension.

WITHANIA SOMNIFERUM Indian Ginseng, Ashwaghanda Araliacea Family
A traditional ayruvedic botanical used as sedative and nervous tonic. As the species name implies, the plant has been used as a sleep inducer. Traditional uses include the plant as a chi tonic, especially to women. Sometimes referred to “Indian Ginseng”, Withania is noted to improve endurance and muscle mass like other adaptogens. Modern studies have shown Withania to enhance binding at GABA A receptors. Anti-tumor effects of Withania have also been investigated. , Withanolides, steroidal compounds including Withaferin A noted in the roots are reported to have a radio sensitizing effect that has been noted in animal studies to reduce the toxicity of irradiation therapy, while improving the effects.



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