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Traditional and Herbal Medication Used in the Treatment of Depression and Anxiety Presented at DDAP Trainers Day: 6/11/14 Craig Strickland, PhD https://sites.google.com/site/bioedcon [email protected] Learning Objectives for Today • List herbal treatments for depression • List at least three of the most common herbal treatments used to reduce the symptoms of anxiety and depression • Summarize the effects of marijuana on the central nervous system (CNS) • And if time permits, list the benefits of vagal nerve stimulation (VNS) for depression Background Information on herbals: Natural does not necessarily mean “safe” • Side-effects and adverse reactions – Herbal medications are “drugs” although they are considered supplements by the FDA – These compounds do, for the most part, act on the CNS • Production of allergic reactions • Interactions with other herbs and with more traditional medications Background Information on herbals: Natural does not necessarily mean “safe” •Dosing is somewhat more difficult – % of active ingredients may differ across manufacturers – Herbs are not “pure” – Variety of administration formulas • Capsules (regular vs. SR vs. XR) • The dried herb itself • Liquid extract • Tincture • Transdermal application Background Information on herbals: Natural does not necessarily mean “safe” • Because herbals are “supplements”: – Labeling is not regulated – Herbal cannot be patented • Thus, rigorous testing may or may not be available • Data may be missing regarding: – long-term safety – dose-response curves – Drug interactions Some “safe” ways to go re: herbal products • Commission E: part of the German Regulatory Authority • The Herbal PDR • Nature’s Way & other companies • Vitacost.com • Naturopaths & pharmacists • Peer-reviewed journals • Cross-referencing of sources 6 Non-Pharmaceutical Approaches to Treating Depression: St. John’s Wort Saint John’s Wort 8 Herbal Treatment of Depression: Saint John’s Wort • Clinical effects: mild anti-depressant – Mechanism of action: like SSRI • Inhibits reuptake of 5-HT, NE, DA • May cause down regulation of 5-HT2 autoreceptors (increases amount of 5-HT release) 9 Herbal Treatment of Depression: Saint John’s Wort • Clinical effects/uses: –Anxiety –Depression –Insomnia –Menopausal mood changes/premenstrual syndrome –OCD –Social anxiety disorder • Thus like an SSRI 10 Herbal Treatment of Depression: Saint John’s Wort • Other Clinical effects/uses: – Inflammation of the skin – Blunt injuries, wounds, burns (has anti-bacterial properties) – Migraine headaches • Drug interactions: – Anti-depressants (especially serotonergic) – Protease inhibitors – Contraceptives 11 Herbal Treatment of Depression: Saint John’s Wort •Side effects: St. John’s Wort is fairly safe –Agitation, anxiety, irritability, restlessness –Dry mouth –Dizziness; headache –GI discomfort –Hypomania –Fatigue –Abnormal dreams 12 Herbal Treatment of Depression: Saint John’s Wort •Therapeutic dose: –450 mg (2x/day) – Take 4-6 weeks (trial period) •Cost: $ 4.99/90 capsules at 450 mg strength 13 Non-Pharmaceutical Approaches to Treating Depression: Ginkgo Biloba Herbal Treatment of Depression: Ginkgo Biloba (Ginkgo) • Not listed in the “herbal PDR” for use as an anti-depressant • Clinical effects: mild anti-depressant – Mechanism of action is not fully known – Increase in # of 5-HT receptors • Via increase in protein synthesis • Via antioxidant mechanism (decrease in free radical activity which damages cell membranes) 15 Herbal Treatment of Depression: Ginkgo Biloba (Ginkgo) •Increase in vascular flow (increases nutrients/O2 to the brain) • Works well in persons over 50 years old (5-HT receptors decrease with age) 16 Ginkgo Biloba (cont.) • Other indications (Commission E) – Symptomatic relief of organic brain syndrome/Alzheimer’s disease – Intermittent claudication – Vertigo (vascular origin) – Tinnitus (vascular origin) • Drug interactions – Can take with traditional antidepressants (unlike St. John’s Wort) – Anticoagulants/ASA (bleeding time) – May interfere with anti-convulsants 17 Ginkgo Biloba (cont.) •Side effects: generally a safe herb to use – Increased bleeding time – Mild GI complaints – BP problems (maybe related to reported dizziness/headaches) – Allergic skin reactions – Adverse effects on oocytes 18 Non-Pharmaceutical Approaches to Treating Depression: Amino Acid Treatment Depression: Amino Acid Treatment • Amino acids used to treat depression include phenylalanine, tyrosine, tryptophan, and methionine – Phenylalanine & tyrosine are precursors to DA (converts to NE) – Tryptophan (and 5-hydroxytrytophan) are precursors to serotonin (5-HT) 20 Depression: Amino Acid Treatment •Methionine gets converted to s-adenosyl-methionine (SAM) – The extract of this is SAMe (“sammy”) • SAM increases levels of the monoamines • Improves monoamine binding naturally – SAM levels-lower in depressed persons – Side effects include nausea/vomiting •Dose: 400 to 1600mg/day be reached gradually •Also used to treat osteoarthritis and fibromyalgia 21 Non-Pharmaceutical Approaches to Treating Depression: Nutritional supplements Depression: Nutritional Supplements • Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) : found in fish oils – Enhances levels of omega-3 fatty acids – Omega-3 levels have been shown to be reduced in people with depression – Amount to take unclear although 3 grams/day (3000mg) is of EPA/DHA not unusual – Side effects: high cholesterol and increased blood sugar (and fish breath…eeewwww!!!) Depression: Nutritional Supplements • Other supplements to consider: the “B” vitamins including folic acid, B6 & B12 • Iron supplements • Take note: – Deficiencies in the levels of these supplements can worsen mood – Thus, such supplements • can decrease depressive symptoms • but will have little effect on depressed people with normal levels of the B vitamins & iron Treating Anxiety The Biochemistry of Anxiety 26 The Biochemistry of Anxiety •Important neurotransmitters – Gamma aminobutyric acid (GABA: cortical and limbic areas (Hippocampus, etc.) – Norepinephrine (sympathetic nervous system) – Serotonin •Neurohormones: e.g. cortisol as the stress hormone 27 Anxiety •Traditional treatment of anxiety – Medications acting on the GABA complex • Alcohol • Barbiturates & non-barbiturate sedatives • Benzodiazepines 28 Non-Pharmaceutical Approaches to Treating Anxiety: Kava Kava Kava Kava 30 Herbal Treatment of Anxiety: Kava Kava • Clinical effects: – Muscle relaxant, anticonvulsive, anti-spasmodic – Hypnotic/sedative, analgesic, and anti-anxiety – Effects are mediated via GABA system – Compare these effects with benzodiazepines • Other clinical effects: – Antithrombitic, asthmatic, nervous tension, stress and agitation 31 Herbal Treatment of Anxiety: Kava Kava • Drug interactions: – Can potentiate effects of most CNS depressants – May potentiate St. John’s Wort, valerian & traditional anti-depressants – Antagonizes effects of meds. designed to increase dopamine (e.g. L-Dopa used to treat Parkinson’s Disease) 32 Herbal Treatment of Anxiety: Kava Kava (cont.) • Side Effects: dose dependent (occur primarily with higher dosages) – Yellowing of the skin, hair, nails – AM tiredness (early in tx. phase) – Minor movement inhibition/impaired motor reflexes; dyskinesia (involuntary movements) – Weight loss (only from high doses over an extended period – Increased risk of suicide in persons with an endogenous depression 33 Herbal Treatment of Anxiety: Kava Kava (cont.) • Side Effects (cont.): –Liver damage including: • Hepatitis • Liver failure • Cirrhosis –Some European countries have banned the sale of Kava ?????????????????????????? –Those at risk for or with known liver disease should not take Kava 34 Herbal Treatment of Anxiety: Kava Kava (cont.) •Therapeutic doses: – Anxiety: 50-70 mg kavalactones 3x/day – Insomnia: 150-210 mg kavalactones in a single dose before bed 35 Non-Pharmaceutical Approaches to Treating Anxiety: Valerian Herbal Treatment of Anxiety: Valerian • Clinical effects: – CNS depressant, hypnotic/sedative, anti-anxiety and muscle relaxant – Humans: reduces sleep induction time – Similar to Kava Kava and/or benzodiazepines – Increase GABA activity by binding to GABA receptors – Valerian also contain glutamine (which the brain converts into GABA) 37 Herbal Treatment of Anxiety: Valerian •Other effects: anti-spasmodic & anti-ulcerogenic – Re: the latter reduces stress related hormone production – Perhaps through the hypothalamicpituitary-adrenal axis (HPA) • Drug interactions: – Can potentiate the effects of the CNS depressants (like Kava Kava) – No hard evidence regarding potentiation of alcohol, however 38 Herbal Treatment of Anxiety: Valerian (cont.) • Side effects: – Long term use: headaches, restless states, sleeplessness, disorders of cardiac function – Not recommended during pregnancy nor in nursing mothers • Therapeutic doses – Restlessness: 220mg extract 3x/day (dosage for anxiety would be similar) – Sleep aid: 300mg to 900mg extract 30-45 minutes before bed – Cost: $5.89 (180 capsules, 3 capsules HS) 39 Other Herbal Products for Reducing Anxiety (recommended by Commission E) • • • • • • • Bugleweed Camphor Tree English Lavender Hops Lemon Balm Lily of the Valley Passion Flower (taken in combination with Valerian) Passion Flower Treating Anxiety by Reducing Lactic Acid 41 Anxiety and Lactic Acid • Normal metabolic processes (involved with producing energy) are as follows: 1. Glucose Pyruvic acid + energy 2. Pyruvic acid + 02 H20 + C02 If no 02 is available (which occurs during strenuous exercise) then: 3. Pyruvic acid H20 +C02 + lactic acid • In people who suffer from panic attacks: – High lactic acid/pyruvic acid ratio – Lactate (soluble lactic acid) sensitivity 42 Anxiety and Lactic Acid • Methods of reducing anxiety by reducing lactic acid levels: – Reduce caffeine, alcohol and sugar intake – Increase intake of B-vitamins, niacin, pyridoxine, thiamin, calcium and magnesium 43 OK, What is this? 44 Marijuana • A unique sedative-euphoriant-psychedelic drug • Major psychoactive ingredient: delta-9-tetrahyrdocannabinol (delta-9-THC or just THC) • Effects include: – Motor (movement disruption) – Cognitive – Psychedelic – Analgesic 45 Pharmacologic Effects of THC • • • • • • • Disruption in attention Impairment in short-term memory Altered sensory awareness Analgesia Altered control of motor movements Immunosuppressive actions Appetite increases (the munchies!) 46 How does THC work? • THC binds to the cannabinoid receptor • Two main types of receptors: CB1 and CB2 – CB1 • Found in the brain – Substantia nigra – Cerebellum – Cortex – Limbic system e.g. hippocampus, amygdala – Hypothalamus – Other 47 Cannabinoid receptors • CB1 (cont.) – Substantia nigra: – Cerebellum: – Cortex: – Limbic system: – Hypothalamus: movement coordination cognitive functioning memory, emotion munchies 48 Cannabinoid Receptors • CB2 receptors – Found mostly within the immune system including T-cells • Accounts for immunosuppressive effects – Also found in the peripheral nervous system which is most probably associated with relief from pain 49 Pharmacological Effects in Humans • Central Nervous System (CNS) – Effects vary based on dose, route of administration, experience of the user, vulnerability to psychoactive effects and setting of use • Senses may be enhanced • Perception of time is altered • Increased sense of well-being • Mild euphoria; relaxation • Relief from anxiety 50 Pharmacological Effects in Humans • Why do some experience anxiety? – Occurs mostly at higher doses (and can also produce acute depressive reactions) – 50 to 60 percent of users experienced at least 1 episode of anxiety • Naïve versus experienced users • Loss of mental control • THC concentration and/or impurities • Personality characteristics &/or genetics • Social/drug use environmental context 51 Tolerance/Withdrawal • Tolerance – Occurs at the level of the brain – Occur rapidly, dissipates rapidly • Withdrawal – Includes restlessness, irritability, mild agitation, insomnia, sleep disturbances, nausea, cramping and drug craving – Withdrawal is considered mild – Lasts four to six days 52 Dependence • Animals do not self-administer THC…hmmm… • And THC does not substitute for drugs with strong reinforcing properties – Suggests limited potential for development of physical dependence – Limited psychological dependence given weak reinforcing properties of THC 53 Therapeutic Uses • Dronabinol: used as appetite stimulant in people with AIDS • Treat nausea/vomiting for those undergoing chemotherapy • Reduce muscle spasms/pain for those with MS • Reduce intraocular pressure associated with glaucoma 54 Vagal Nerve Stimulation (VNS) The Vagus Nerve Picture provided by Peter Jurek, MA, MS http://www.peterjurek.com What is vagal nerve stimulation (VNS)? • Note: this is an FDA approved technique (2005) for refractory depression; also approved (1997) as adjunctive therapy for partial-onset epilepsy • A pulse generator is surgically implanted in the left chest area under the clavicle • The leads from the generator are “wrapped” around the left vagus nerve branch; the right branch is avoided since it controls some aspects of cardiac function • Intermittent pulses are delivered to the nerve How does VNS work? • Exact anti-depressant mechanism unknown – Stimulation does affect blood flow in various regions of the brain – As a result, neurotransmitter activity increases, including 5-HT and NE which would have an anti-depressant affect • Side-effects: alteration of voice quality & loudness (during pulses only), hoarseness, throat pain, dyspnea (shortness of breath) & paresthesia Other uses for VNS? • • • • Various anxiety disorders Alzheimer’s disease Migraines Fibromyalgia OK, so all is said and done…or is it? What questions should you and the client be asking? What information do you and your client need regarding neutraceuticals? Decision making • Why am I taking this medication? • What symptoms do I wish to decrease? Will the alternative treatment do this? What symptoms can I live with? Are the symptoms more of an issue for me or for those around me? • Am I wanting to try something new because my medication is not working the way I want it to? • Have I given my current medication enough time to work? Would another pharmaceutical be a better choice? Decision making (cont.) • What are my beliefs about herbal medications? – Do I think they are safer? – Do I think natural is better? – Do I want to take an herbal medication because I do not trust big pharmaceutical companies? Decision making (cont.) • Will the herbs interact (either positively or negatively) with my current medications? • Will I need to stop/decrease/increase my current meds if I start taking herbal meds.? • What about non-prescription substances? – Over the counter (OTC)? – Nicotine? – Caffeine? Needed Information • What are the side effects of the herbals? Where can I get herbal medications? Which companies are trust worthy? • What do these herbal products cost? Does my insurance cover the cost of these substances? • How much is known about the herbal medication? Are there any head-to-head studies between herbal medications and pharmaceuticals? • Where can I get reliable information? • How long will the herbs take before they start working? Needed Information (cont.) • Will the herbs interfere with any medical conditions I have? – Cardiovascular – Liver – Gastrointestinal (GI) – Endocrine (diabetes, other endocrine disorders) • Does my doctor/pharmacist have the proper training to help me? If not, where can I get access to properly trained individuals? • Are there non-medicine alternatives? http://www.nlm.nih.gov/medlineplus/druginformation.ht ml Whooo hooo!!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!