Top Banner
Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life altering psychiatric conditions that severely impair the quaiity of iife of those suffering from them. They are the most common psychiatric disorders in the United States,' and are characterized by numerous somatic symptoms, such as facial flushing, hyperhydrosis (excessive sweating), muscle tension, paresthesias (numbness and tingling), shallow breathing, syncope (fainting), and tachycardia (rapid heart rate). The emotional symptoms of anxiety disorders occur simultaneously with the somatic ones and include agitation, dereaiization (feelings of unreality), tearfulness, feelings of impending doom, irritability, nervousness, and shyness. Patients with anxiety disorders often report escape and avoidance behaviors that merely reinforce and perpetuate their ongoing anxiety. They also tend to engage in catastrophic thinking by over-predicting the negative consequences of events.^ Patients tend to misinterpret benign bodily sensations as warning signals for Table 1: Lifetime Consequences of Most sufferers of anxiety: commonly report their health as poor. have a higher risk of suicide. smoke cigarettes and abuse other substances- have an increased chance of developing chronic medical illnesses (e.g., chronic obstructive pulmonary disease, diabetes and hypertension) compared to the general population. have medical illnesses that are otten prolonged as a result of anxiety. will remain untreated and underdiagnosed many years after their initial diagnoses, leading to unremitting impairment in functional status and quality of life. by Jonathan E. Prousky, ND, FRSH more serious conditions. For example, heart palpitations are common among the anxiety sufferers, yet this symptom is often misinterpreted as being a heart attack. Anxiety sufferers desperately want their anxiety to go away, but they cannot control it. What these patients suffer from is a heightened autonomic nervous system (ANS) reaction to a perceived threat. There might even be some link between the anxiety of modern times and the lifesaving mechanism that was required of our prehistoric ancestors.^ For example, when the early hominids had to hunt and kill to feed themselves, they had to mobilize and react to real threats to their survival. By contrast, the anxiety sufferer of today manifests the same mobilization as if fleeing from a predator, but this mobilization is out of proportion to the actual threat. In some of us, anxiety might actually be built into our genes. Evolution might favor those who have anxiety because it makes sense to have a built-in system that ensures survival,^ Table 2: Questions To Ask The Anxious Patient^ Is the anxiety constant or intermittent? If intermittent, the work-up should focus on psychomotor epilepsy, pheochromocytoma, insulinoma, or intermittent cardiac arrhythmia, such as paroxysmal supraventricular tachycardia or atrial fibrillation. What is the patient's age? Young or middle-aged patients likely have an anxiety disorder. Older patients, by contrast, might be suffering from cerebral arteriosclerosis or other types of dementia. Is the tachycardia present during sleep? If present during sleep, causes such as cafteinism or other drug effects and hyperthyroidism need to be considered. Has there been any weight loss? If there is weight loss and tachycardia, hyperthyroidism is very likely. Is it better to have a system that gives more false positives then false negatives? The advantage might be survival, but at a tremendous cost to the sufferer due to a lifetime of discomfort (Table 1). Even with the unfortunate reality that anxiety might "live in" the genes of those susceptible to it, patients do not have to endure a lifetime of suffering. Anxiety sufferers want viable treatment options that can lessen their anxiety and improve their quality of life. An orthomolecular approach does just that—it is simple, effective, reduces the somatic and emotional symptoms of anxiety, and dramatically improves quality of life. The first part of this report will focus on the diagnosis of anxiety disorders. The second part will examine orthomolecular treatment strategies and will include case reports demonstrating the effectiveness of this approach. Diagnosing Anxiety Disorders To diagnose anxiety disorders it is necessary to first rule out organic causes before a psychiatric diagnosis can be made. Certain questions shouid be posed during the history when evaluating the anxious patient for organic causes (Table 2). Once a thorough history has been obtained the diagnostic work-up involves various tests depending on the nature of the anxiety.^ If the anxiety was found to be intermittent, it might be necessary to perform a wake-and-sleep electro- encephalogram (EEG) and possibly a computed tomography (CT) scan to rule out a cerebral tumor. In addition, the work- up might require a 24-hour urine collection forcatecholamines (to rule-out pheochromocytoma) or a 24-hour Holter monitor (to rule-out paroxysmal cardiac arrhythmia). If the anxiety is more constant than intermittent, the work-up involves other tests such as a thyroid panel (to rule-out hyperthyroidism), a drug screen, and an EEG. In cases of TOWNSEND LETTER for DOCTORS & PATIENTS - FEBRUARYA/IARCH 2005
7

Orthomolecular Treatment of Anxiety Disorders Treatment of Anxiety... · Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life

Apr 06, 2018

Download

Documents

buianh
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Page 1: Orthomolecular Treatment of Anxiety Disorders Treatment of Anxiety... · Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life

Best of NaturopathyOrthomolecular Treatment of

Anxiety Disorders

IntroductionA n x i e t y

disorders arelife alteringpsych ia t r ic

conditions thatseverely impair the quaiity of iife of thosesuffering from them. They are the mostcommon psychiatric disorders in theUnited States,' and are characterized bynumerous somatic symptoms, such asfacial flushing, hyperhydrosis (excessivesweating), muscle tension, paresthesias(numbness and tingling), shallowbreathing, syncope (fainting), andtachycardia (rapid heart rate). Theemotional symptoms of anxiety disordersoccur simultaneously with the somaticones and include agitation, dereaiization(feelings of unreality), tearfulness,feelings of impending doom, irritability,nervousness, and shyness. Patients withanxiety disorders often report escape andavoidance behaviors that merelyreinforce and perpetuate their ongoinganxiety. They also tend to engage incatastrophic thinking by over-predictingthe negative consequences of events.^Patients tend to misinterpret benignbodily sensations as warning signals for

Table 1:Lifetime Consequences ofMost sufferers of anxiety:• commonly report their health as poor.• have a higher risk of suicide.• smoke cigarettes and abuse other

substances-• have an increased chance of developing

chronic medical illnesses (e.g., chronicobstructive pulmonary disease, diabetesand hypertension) compared to thegeneral population.

• have medical illnesses that are ottenprolonged as a result of anxiety.

• will remain untreated andunderdiagnosed many years after theirinitial diagnoses, leading to unremittingimpairment in functional status andquality of life.

by Jonathan E. Prousky, ND, FRSH

more serious conditions. For example,heart palpitations are common among theanxiety sufferers, yet this symptom isoften misinterpreted as being a heartattack.

Anxiety sufferers desperately wanttheir anxiety to go away, but they cannotcontrol it. What these patients suffer fromis a heightened autonomic nervoussystem (ANS) reaction to a perceivedthreat. There might even be some linkbetween the anxiety of modern times andthe lifesaving mechanism that wasrequired of our prehistoric ancestors.^ Forexample, when the early hominids hadto hunt and kill to feed themselves, theyhad to mobilize and react to real threatsto their survival. By contrast, the anxietysufferer of today manifests the samemobilization as if fleeing from a predator,but this mobilization is out of proportionto the actual threat. In some of us, anxietymight actually be built into our genes.Evolution might favor those who haveanxiety because it makes sense to havea built-in system that ensures survival,^

Table 2:Questions To Ask The Anxious

Patient^Is the anxiety constant or intermittent? Ifintermittent, the work-up should focus onpsychomotor epilepsy,pheochromocytoma, insulinoma, orintermittent cardiac arrhythmia, such asparoxysmal supraventricular tachycardiaor atrial fibrillation.What is the patient's age? Young ormiddle-aged patients likely have ananxiety disorder. Older patients, bycontrast, might be suffering fromcerebral arteriosclerosis or other types ofdementia.

Is the tachycardia present during sleep?If present during sleep, causes such ascafteinism or other drug effects andhyperthyroidism need to be considered.Has there been any weight loss? If thereis weight loss and tachycardia,hyperthyroidism is very likely.

Is it better to have a system that givesmore false positives then false negatives?The advantage might be survival, but ata tremendous cost to the sufferer due toa lifetime of discomfort (Table 1).

Even with the unfortunate reality thatanxiety might "live in" the genes of thosesusceptible to it, patients do not have toendure a lifetime of suffering. Anxietysufferers want viable treatment optionsthat can lessen their anxiety and improvetheir quality of life. An orthomolecularapproach does just that—it is simple,effective, reduces the somatic andemotional symptoms of anxiety, anddramatically improves quality of life. Thefirst part of this report will focus on thediagnosis of anxiety disorders. Thesecond part will examine orthomoleculartreatment strategies and will include casereports demonstrating the effectivenessof this approach.

Diagnosing Anxiety DisordersTo diagnose anxiety disorders it is

necessary to first rule out organic causesbefore a psychiatric diagnosis can bemade. Certain questions shouid be posedduring the history when evaluating theanxious patient for organic causes (Table2).

Once a thorough history has beenobtained the diagnostic work-up involvesvarious tests depending on the nature ofthe anxiety.^ If the anxiety was found tobe intermittent, it might be necessary toperform a wake-and-sleep electro-encephalogram (EEG) and possibly acomputed tomography (CT) scan to ruleout a cerebral tumor. In addition, the work-up might require a 24-hour urinecollection forcatecholamines (to rule-outpheochromocytoma) or a 24-hour Holtermonitor (to rule-out paroxysmal cardiacarrhythmia). If the anxiety is moreconstant than intermittent, the work-upinvolves other tests such as a thyroidpanel (to rule-out hyperthyroidism), adrug screen, and an EEG. In cases of

TOWNSEND LETTER for DOCTORS & PATIENTS - FEBRUARYA/IARCH 2005

Page 2: Orthomolecular Treatment of Anxiety Disorders Treatment of Anxiety... · Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life

chronic anxiety, a 24-hour Holter monitormight also be helpful.

When the work-up does not reveal anorganic cause, or when the historystrongly indicates a non-organic cause ofanxiety, a psychiatric diagnosis needs tobe considered. Anxiety disorders areclassified into various categories such asgeneralized anxiety disorder (GAD),obsessive-compulsive disorder (OCD),panic disorder (PD), posttraumatic stressdisorder (PTSD), and social phobia/socialanxiety disorder (SAD),^ See Table 3 fora brief description of the main types ofanxiety disorders. To make anappropriate psychiatric diagnosis, it isnecessary that certain criteria be met forthe anxiety disorder being considered,

Orthomolecular Treatment Strategy#1: Niacinamide (Nicotinamide)

The main treatment approach foranxiety disorders is to use a high enoughdose of certain nutrients to diminish theANS reaction, eliminate the fear of anxietysymptoms, decrease the cycle ofavoidance and anxiety, and improvequality of life. One of the most effectiveways to accomplish this is through the useof the amide of niacin (nicotinic acid)known as niacinamide (nicotinamide).This B-vitamin has remarkabletherapeutic benefits for those sufferingfrom anxiety. In a recent report, a reviewof the literature was undertaken todetermine the biological mechanism forniacinamide's anxiolytic effects.'" Itappears that niacinamide has therapeutic

Table 3:Categories of Anxiety Disorders^^

• Generalized Anxiety Disorder: Patientsworry constantly, have great difficultywith trying to control their worry, andhave simiiar symptoms to those seen indepressive disorders.

• Obsessive-Compulsive Disorder:Characterized by recurrent or persistentmental images, thoughts or ideas withcompulsive behaviours that arerepetitive, rigid, and self-prescribed(sometimes ritualistic) in order to preventthe associated obsession.

• Panic Disorder: Characterized byperiodic attacks of anxiety or terror thatmay occur with or without agoraphobia.

• Posttraumatic Stress Disorder: A re-experiencing ot symptoms, avoidance,and hyperarousal after exposure to atraumatic event.

" Sociai Anxiety Disorder: Patients have afear of being negatively evaluated byothers; being pubiicly scrutinized andhumiliated; and demonstrate extremeshyness and discomfort in socialsettings.

effects comparable to thebenzodiazepines. a class of medicationscommonly used for GAD, PD, and SAD."Benzodiazepine medications bind to amacromolecular complex that is foundwithin the central nervous system (CNS).referred to as the GABA ("gamma-aminobutyric acid) benzodiazepinereceptor-chloride ion channel complex,'^When benzodiazepines bind onto or nearthis macromolecular complex theypotentiate GABA-ergic synaptic inhibitionthrough membrane hyperpolarization,thus enhancing the conductance of thechloride lon by increasing the frequencyof channel-opening events,'^ The netresult is the reduction of anxiety andrelated symptoms via the diminution ofneurotransmission (e.g., neuronal firing)among many brain regions such as thespinal cord, hypothalamus, hippocampus,substantia nigra, cerebellar cortex, andcerebral cortex.'^

Niacinamide's therapeutic effects arelikely not related to it acting as a ligandfor the benzodiazepine receptor, eventhough it acts centrally and might have aweak binding affinity for thebenzodiazepine receptor. Both thebenzodiazepines and niacinamide exertsimilar anxiolytic effects through themodulation of neurotransmitterscommonly unbalanced in anxiety. Table4 summarizes niacinamide's benzo-diazepine-like effects. The three followingcase reports demonstrate niacinamide'ssuperb anxiolytic properties.

Case #1An 11 year-old girl first presented to

my office on November 10, 2003, withchief complaints of nervousness, anxiety,and excessive worrying. The onset of hersymptoms occurred when her father

tragically died in September 2003, Thepatient reported anxiety when she had tosit for examinations and when she wasaround her classmates. The mostconcerning symptom was her fear ofbeing kidnapped, which was instigated bya well-publicized kidnapping of a youngAsian girl In the city where she lives. Shealso reported having approximately twopanic attacks each month sinceSeptember for which she had learned todeal with them by "leaving the situationto get air." Other symptoms she reportedincluded some facial acne, frequentblushing, stomachaches, andsweatiness. She was diagnosed with PD,with some elements of SAD. A completephysical examination was performed andall findings were within normal limits. Shewas prescribed a daily multiple vitamin/mineral preparation, 25 mg of zinc, 100mg of pyridoxine, 400 of magnesium, and500 mg of niacinamide twice daily. Afollow-up appointment occurred onDecember 13,2003. The patient reporteda slight improvement with her anxiety.She was only taking the multiple vitamin/mineral preparation, zinc, andniacinamide. She agreed to increase thedose of niacinamide to 1000 mg twicedaily. No side effects were reported. Asecond follow-up occurred on February7, 2004, The patient reported a strikingimprovement with her anxiety. Her panicattacks completely stopped and her acnewas much improved as well. In a recentemail from the patient, she reported tobe taking only the 1000 mg of nlacinamldetwice daily. Her anxiety remained muchimproved and was no longer interferingwith her ability to engage in a regular life.

Table 4: Summary of Niacinamide's Benzodiazepine-Like EffectsNiacinamide modulated spinal cord activity, and had anticonflict, anticonvulsant, musclerelaxing, and hypnotic effects. The potency of niacinamide was found to be equivalent to ahighly potent benzodiazepine. Niacinamide had a low affinity for the benzodiazepine-binding site in the mammalian brain,'^Niacinamide antagonized the effects of diazepam, therefore interacting with thebenzodiazepine receptor in vivo. Niacinamide probably does have benzodiazepine-likeproperties at different benzodiazepine receptor sites in the CNS, but its effects areunrelated to the actions of GABA,'"'Niacinamide had a qualitatively similar effect to that of diazepam, it was concluded thatniacinamide exerted its effects by influencing the turnover of serotonin, noradrenaline(norepinephrine), dopamine and GABA in those areas of the brain thought to beunbalanced in anxiety.^^Niacinamide could possibly be a competitive antagonist for the benzodiazepine receptorsince it prevented the binding of kynurenine to the benzodiazepine receptor, tt was furtherpostulated that this action was more likely of central origin than peripheral origin.'^Niacinamide did not act as a specific ligand for the benzodiazepine receptor, but insteadhad a weak binding affinity for the receptor."Niacinamide and its analogs possessed properties simiiar to benzodiazepines at variouszones of the cerebral cortex by influencing the GABA-ergic system.'®

TOWNSEND LETTER tor DOCTOBS & PATIENTS - FEBRUARY/MARCH 2005 S3

Page 3: Orthomolecular Treatment of Anxiety Disorders Treatment of Anxiety... · Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life

Case #2A 28 year-old woman came to my

private practice with a chief complaint ofGAD on May 10, 2004. She had beenstruggling with this anxiety disorder forthe past twelve years. She is a highschool teacher and noted that her anxietywas more pronounced during theacademic year. Her anxiety was worsein the morning with symptoms of frequentmuscular tension, the passing of flatus,and chest pain. She reported a fear ofsmelling when she needed to expel gas.The anxiety also made it difficulf for herto concentrate and focus on things. Whenshe experienced anxiety symptoms shewould feel the need to isolate herself fromothers. The same isolating need occurredwhen she simply thought about feelingnervous and expelling gas. She alsoreported fears of embarrassment, andworried about being criticized by others.She had been on paroxetine for one yearbut had not noticed any improvement.She reported feeling depressed due tothe anxiety, and would get apathetic whenher anxiety was at its worst. Physicalexamination revealed a well-nourishedwoman with normal vital signs. All hersystems were within normal limits. Shewas subsequently diagnosed with GADwith some SAD. Niacinamide wasprescribed at an initial dose of 500 mgfhree times daily for three days, afterwhich she was instructed to increase itto 1000 mg every morning, 500 mg atlunch, and 1000 mg at dinner. She wasalso prescribed 5-hydroxytryptophan (5-HTP) at a dose of 100 mg twice daily forher mild depression, and 2000 mg ofvitamin C to be taken daily for herthrombocytopenia (a previous diagnosis).The patient had a follow-up appointmenton May 31, 2004. She had difficultyswallowing the niacinamide pills due totheir bitter taste. Despite this, she wastaking the recommended dose of 2500mg per day. Her anxiefy significantlyimproved and she experienced only threeminor panic attacks since the initial visit.The patient continued to complain ofdepression, which she felt was morepronounced prior to menses. The patientwas unsure if the treatments wereworking due to her time away fromteaching. We agreed that she woulddiscontinue all prescribed treatmentsexcept for the vitamin C until June 14,2004. After this date, the patient wouldresume the 5-HTP, the niacinamide, and

take 250 mg of vitamin B-6, and 400 mgof magnesium. The vitamin B-6 andmagnesium were prescribed for thepremenstrual symptoms of depression.On June 4, 2004, I received an urgenttelephone call from fhe patient. Sincediscontinuing the prescribed treatmentson June 1, her anxiety symptomsreturned promptly and she had difficultyfunctioning. She agreed fo resume onlythe niacinamide tablets. On July 2,2004,the patient emailed me with an update.She discontinued all the prescribedtreatments except for the niacinamide.She found her anxiety and depression tobe much relieved because she was athome and not teaching during thesummer months. When she felt anxiety,she would take niacinamide and it wouldhelp. In her words: "I take the niacinamideand I'm fine afterwards."

Case #3A 42 year-old woman first presented

to my private practice on May 16, 2004,for chief complaints of constipation andanxiety. About three weeks earlier, herfather was diagnosed with advancedcarcinoma of fhe stomach. Since herfather's diagnosis, she had been feelingvery anxious with symptoms ofshakiness, light-headedness, numbnessof the extremities, and balance problems.Her medical doctor had her do a 24-hourHolter monitor and the results werenormal. She was unable to correlate heranxiety with feelings of hunger. In thepast, she would have the same kind ofanxiety symptoms when stressful eventsoccurred. Her medical doctor felt that thepatient's anxiefy was related tohyperventilation. On physicalexamination, the patient was well-nourished, slightly overweight, wifhnormal blood pressure and normal heartsounds. All other systems were withinnormal limits. She was diagnosed withpanic attacks, dyspepsia (possiblyirritable bowel syndrome), and mildobesity. She was advised to continue withher liquid multiple vitamin/mineralpreparation, take 500 mg of niacinamidethree times each day for two days, andwas told to increase the dose to 1000 mgtwice daily. In addition, two capsules oflactobacillus acidophilus were prescribedevery morning upon rising, A follow-upvisit occurred on May 26, 2004. Thepatient felt a little better during the firsfweek on niacinamide; however, she feltjittery and related this to her father's grimprognosis. Her sleep was unaffected,even though she did wake up once eachnight to go to the bathroom. Overall, she

felt much more under control. She wasadvised to increase the niacinamide to1000 mg three times each day. On July12, 2004, she came in for another visit.She cut back on the niacinamide to 2000mg per day since she felt that it causedher to have feelings of unreality. Heranxiety was much improved on this dose,and the previous shakiness hadcompletely resolved. In fact, she had notexperienced any episodes of shakinesssince fhe last visit. She was told tocontinue the prescribed treatments andto add a B-complex vitamin preparationand 1 mg of folic acid to her current plan.Her most recent follow-up appointmentwas on September 15, 2004. Shereported no anxiety symptoms or panicattacks since the last visit despite herfather's declining health. She hascontinued fo take 1000 mg of niacinamidetwice daily.

Prescribing InstructionsMost pafients require 2000-4500 mg

of niacinamide per day fo achievetherapeutic results. These dosages werederived from the work of Hoffer, whorecommended 1500-6000 mg ofniacinamide per day for all patients wifhpsychiatric syndromes.'^ Patients usuallyexperience relief of their symptoms withinone month of taking the medication{personal observation). The fhreepatients tolerated the largepharmacological doses of niacinamidevery well. One pafient needed to reduceher dose from 3000 mg per day to 2000mg per day due to feelings of unreality.The 28 year-old patient had problemsswallowing the niacinamide tablets. Forthis reason, it might be necessary toswitch some patients to capsules orpowder forms of niacinamide. Largepharmacological doses of niacinamide(1500-6000 mg per day) have been safelyused in children and adolescents forextended periods of fime without anyadverse side effects or complicationssuch as clinical hepatitis.^-^' The mostcommon side effect with niacinamide issedation,^^ but dry mouth and nauseahave been the most common side effectsthat I have observed among some of mypatients. There has been one case reporflinking large pharmacological doses ofniacinamide (9 grams per day) to hepatictoxicity.^^ The patient in the cited reporthad no evidence of clinical hepatitis whentaking 2000-3000 mg per day ofniacinamide, but did develop clinicalhepatitis when the dose was increasedto 9000 mg daily. All ctinical abnormalitiesdid revert to normal once fhe niacinamide

84 TOWNSEND LETTER for DOCTORS & PATIENTS - FEBRUARY/MARCH 2005

Page 4: Orthomolecular Treatment of Anxiety Disorders Treatment of Anxiety... · Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life

was discontinued. I never prescribe morethan 6000 mg per day of niacinamidesince most patients will develop nauseaand sometimes vomiting on a dose higherthan this.'^ There is hardly any need togo above 4500 mg per day when treatinganxiety. If nausea does occur, decreasingfhe dose by 1000 mg usually corrects theproblem.

Orthomolecular Treatment Strategy#2: L-Glycine

Glycine is a nonessential (or neutral)amino acid that has profound anxiolyticproperties. If is considered to be aninhibitory amino acid since it increasesmembrane permeability to chloride ions,producing an inhibitory postsynapticpotential (IPSP), and preventing actionpotential generation.^'' In other words,glycine works similarly fo fhebenzodiazepines. Receptors for glycineare found in fhe vertebrate CNS, spinalcord and brain stem areas, and areequally distributed throughoutmammalian tissues.^^ The highestconcentrations of glycine are found in thethalamus, amygdala, substantia nigra,putamen, and globus palidus.^^The mostunique aspect of glycine's mechanism ofaction has to do with its presumedantagonism of norepinephrine (NE).^ Theneurons for NE are located in a part ofthe brain stem called the locus coeruleus,from which the NE neurons branch out totouch as many as half of all the cells inthe brain (probably several billion) in thecerebral cortex." When an individualexperiences anxiety or panic, NE isreieased from the locus coeruleus andaffects a parf of the brain known as thenucleus accumbens, leading to feelingsof anxiety and panic.^^ Glycineantagonizes fhe release of NE from thelocus coeruleus and the ensuing signalsto the nucleus accumbens, thusmitigating anxiety and panic, and feelingsof over-arousal.^^

Prescribing InstructionsThe best way to administer glycine is

sublingually so that the gastrointestinalroute is bypassed. This allows for quickerabsorption, a faster onset of action, andswift entry to the CNS. At least 2-10grams are required in order to stop apanic attack. It is very palatable andsweet fasting making it easy to administersublingually, I have my patients place 2grams under their tongue at the onset ofan acute panic attack. They can takeanother 2 grams every few minutes untilthe panic attack subsides. It usually workswithin a matter of a few minutes. Side

effects are very rare with high doses ofglycine. There is one report that 14 gramsgiven to a 70 Kg adulf male producednausea,^^ However, 15-30 grams havebeen given to two manic patientsproducing no side effects except forcessation of fhe manic episode andcalmness within one hour ofsupplementation." I have never foundglycine to work better than niacinamidefor daily use. It is best reserved for acutepanic attacks or acute periods of anxiefy,

Orthomoiecuiar Treatment Strategy#3: intramuscuiar (iM) injections ofVitamin B12 (cobaiamin)

Vitamin B12 (cobaiamin) is involvedin numerous biochemical reactions as acofactor and coenzyme. Its mainfunctions involve DNA synthesis,mefhionine synthesis from homocysteine,and conversion of propionyl into succinylcoenzyme A from mefhylmalonate,^"

The psychiatric manifestations ofvitamin B12 deficiency include irritability,personality change, mild memoryimpairment, dementia, depression, andpsychosis.^^ Patients most likely todevelop vitamin B12 deficiency haveclinical conditions such as atrophicgastritis, bacterial overgrovirth of the smallintestine, and pernicious anemia.

It is clear that vitamin B12 helps thosewho are deficient; yet, fhere are manypatients who seem to benefitpsychologically from regular vitamin B12injections despite fhe absence ofdiseases and serologic evidence ofvitamin B12 deficiency, in a sfudyinvolving two subjects, each wasrandomized to receive weekly injectionsof hydroxocobalamin or placebo(phenolsulfonphfhalein) for 25 weeks.^Prior to the study and after the sfudy,gastric analysis was performed and thesubjects were found to have noabsorption problems. Each week duringthe study, the subjects were given aquestionnaire ranking various items suchas the helpfulness of fhe injection, theduration of benefit, and if the injectionimproved energy, pep, strength,depression, nerves, appetite, tremor,fatigue, and outlook. Even though fherewere no differences found between thehydroxocobalamin or placebo, thesubjects did report a benefit in terms ofnervousness and fatigue from thehydroxocobalamin.

In another sfudy, a double-blind cross-over trial involving 28 subjectscomplaining of tiredness, injections ofhydroxocobalamin or matching placebowere administered.^^ The subjects were

given 5 mg of hydroxocobalamin twiceweekly for two weeks followed by a restperiod of two weeks, and then a similarcourse of matching placebo injections.Symptoms were assessed by a daily self-rafing method fhat included appetite,mood, energy, sleep, and general feelingof well-being. Those subjecfs whoreceived fhe placebo in the first two-weekperiod showed a favorable response tohydroxocobalamin in the second periodin all measurements made. Specifically,statistical significance (p=0.006) wasachieved with respect to general well-being, while "happiness" also showedstatistical significance (p=0.032).

The data presented does indicate apotential anxiotytic benefit from regular IMinjections of hydroxocobalamin. The casedescribed below is an example of theclinical response that is possible withvitamin B12.

Case #4A 25 year-old presented to my private

practice on August 7, 2004, with chiefcomplaints of anxiety and depression.The onsef of the patient s anxiety begantwo years ago when she started her newjob as a graphic designer. She describedsymptoms of heart racing, sweating,dizziness, stomach pain, nausea,vomiting, light-headedness, and diarrhea.She also reported difficulties fallingasleep, and would even wake-up wifh herheart beating very fast. She was currentlyon 25 mg of paroxetine daily, and hadtaken it for the pasf two years. The anxiefyattacks mainly occurred at work, whichoften forced her to leave early. She alsodescribed a history of depression thatbegan when she was only 12 years ofage. The depression improved initiallywhen she first started the paroxetine, butnow it seemed to have worsened again.Physical examination revealed a slightlyoverweight female, with normal vital signsand normal findings of all other systems.She was diagnosed with GAD, and wasprescribed a program of 120 mg/day ofGinkgo biloba extract to help with hersexual dysfunction, 1 teaspoon of fish oil,and niacinamide at increasing doses until1000 mg three times daily was reached.At a follow-up appointmenf on September9,2004, the patient complained of feelingsick and nauseous with the niacinamide.She also reported feeling paranoid andpanicky. The pafient had anxiety for theprevious two weeks and was crying all

TOWNSEND LETTER for DOCTORS & PATIENTS - FEBRUARY/MARCH 2005 85

Page 5: Orthomolecular Treatment of Anxiety Disorders Treatment of Anxiety... · Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life

the time. She was fold to reduce theniacinamide to 500 mg three times daily,to add 50 mg of 5-HTP three times daily,and was given 1000 micrograms (meg)of hydroxocobalamin by IM injection. Forfhe next five weeks, the patient receivedinjections of hydroxocobalamin twiceweekly and discontinued all the otherprescribed supplements on her own. OnOctober 16, 2004, the patient describedherself as being free of any anxiety andpanic. She had nof had a panic attacksince September 9. About one-monthlater, on November 13, 2004, the patientreturned for another vitamin B12 injection.She described a slight worsening of heranxiety and panic since stopping fhetwice-weekly injections. Forthe previoustwo weeks, the patient had spells ofnausea and hot flushes; however, shehad not needed to leave work early asshe did in the past. Another 1000 meg ofhydroxocobalamin was administered IM,and she was instructed to return moreregularly for the injections. In a follow-upemail on November 17, the patientreported the following: "I've been panicfree since the weekend, which is nice. Ihaven't had hot flashes or heart beatingfast in the morning either. I'm starting tothink it has a lot to do with how well I havebeen feeling!"

Prescribing instructionsWhen trying to contro! symptoms of

anxiety, it might be necessary for patientsto receive regular injections ofhydroxocobalamin. The dose shouldalways be 1000 meg and can be givenonce or twice every week until symptomsimprove. The best form is injectablehydroxocobalamin as can be seen fromTable 5.^

The only rare side effect fromhydroxocobalamin is an acneiformexanthema, particularly in women.*^

These lesions have been reporfed foresult from oral supplementation, but Ihave seen the same eruption occur fromhydroxocobalamin injections. The lesionsconsist of loosely disseminated smallpapules or papulopustules on fhe face,the upper parts of the back and chest,and can spread to the upper arm. Theygo away within a week once the regularinjections have been discontinued.

What is the mechanism that canaccount for the benefits of injectablehydroxocobalamin? In a study involving49 patients with organic mental disorders,deficient CSF levels of vitamin B-12 (<5pg/ml) were found in 30 patients,^ Whenthe serum levels of vitamin B-12 weretested, normal values (200-800 pg/ml)were found in 45 of them, indicating amarked difference between bothcompartments. A group of ten patientswere also given injectablehydroxocobalamin at a dose of 1000 megtwice weekly for six weeks. This groupwas compared against a group of fwopatients given 0.1 mg of oralcyanoeobalamin three times daily for sixweeks. As ean be seen from Table 6, thegroup given the injeetions achieved amueh greafer inerease in their CSF levelsof vitamin B12. Given fhat serum levelsof vitamin B-12 can be normal yetdeficient in the CSF, pafients respondingfo regular IM injections ofhydroxocobalamin might have animprovement in their anxiety due tomarked (supraphysiological) increases intheir CSF vitamin B12 levels, or from thecorrection of defieienf CSF levels ofvitamin Bl 2. The best way to aehieve highCSF levels of vitamin Bl 2 is through twiceweekly injections.

Tabie 5: Vitamin B12: Effectiveness and Route of Administration

Route Maximum increase from baselineOralSublingualParenteral (hydroxocobalamin)Parenteral (cyanocobaiamin)

43%34%106%78%

24-hour urinary excretion0.009%0.004%2.7%4,2%

Tabie 6: Cerebrai Spinai Fiuid (CSF) and Serum Differences Betweeninjectabie & Orai Vitamin B12

Group Pre-TreatmentSerum B12

(pg/ml)

Injectable (10 patients) 310Oral (Patient #1) 430Oral (Patient #2) 450

Pre-TreatmentCSF B12(p9/mi)

<514<S

Post-TreatmentSerum B12

(pg/ml)

>24002400>2400

Post-TreatmentCSF B12(pg/ml)

70219.6

Orthomoiecuiar Treatment Strategy#4: Eiiminate Caffeine & Aicohoi

Although the case reports did nofspeeifieally identify eaffeine and aleoholas anxiety-triggers, these items should beeliminated in all patients with anxietydisorders. Caffeine is a stimulant and cansomefimes be the underlying cause of apafient's anxiety. Caffeine foxicity is notuncommon and has been shown fo causesymptoms such as lightheadedness,tremulousness, breathlessness,headache, and premature ventricularcontractions in one patient.^^ In the samepatient, these symptoms went away oneethe caffeine was discontinued, andrecurred on two separate occasions whencaffeine was re-challenged after periodsof abstinence.

Alcohol has been demonstrated toincrease the lactate-to-pyruvate ratio,which can precipitate anxiety.^^Numerous studies to date have confirmedthat lacfate sensitivity or an increasedresponsiveness to lactate is a factor inprovoking anxiety symptoms.^'"" Alcoholhas also been shown under double-blindconditions to increase anxiety.*'

ConciusionMore case reports, research, and

rigorous controlled trials are needed toproperly evaluate the fherapeuticeffectiveness, safety, and mechanisms ofaction of niacinamide, glycine, andvitamin B12. In light of the positive resultsaccomplished from using fhese nutrienfs,perhaps these orthomolecularsubstances are indicated for fhemanagement of anxiety. In fact, theseagents might be more effective thancurrent contemporary medications forthetreatment of anxiety disorders. Theirsafety profile is unmatched by mostconventional agents due to the relativeabsence of negative side effects whenlarge pharmacological doses are used,

AcknowiedgementsWritten consent was obtained from thesepatients or their guardians for publication ofthis report. A special thanks goes to Mrs, ErynnMarcus for tier editing and review of this report.

Correspondence:Jonathan E. Prousky, ND, FRSHChief Naturopathic Medical Officer andAssociate Dean, Clinical EducationThe Canadian College of NaturopathicMedicine1255 SheppardAve. E.Toronto, Ontario, M2K 1E2 [email protected]

as TOWNSEND LETTER for DOCTORS ft PATIENTS - FEBRUARY/MARCH 2005

Page 6: Orthomolecular Treatment of Anxiety Disorders Treatment of Anxiety... · Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life

References1. Kessler RC. UcGonagle KA, Zhao S, et al, Lifetime and

12-month prevalence of OSM-ill-R psychiatric disordersin the United Stales. Results from the NationalComofbidity Survey. >^rc')GenPs)'cf)/afry1994;51:8-19.

2. Shear MK, Optimal treatment of anxiety disorders.Patient Care 2003;May: 18-32.

3. Beck AT, Emery G, Greenberg RL, Anxiety DisordersandPhot>ias. Basic Books, NY, 1985, p.4.

4. Katon WJ, Von Kortt M, Lin E, Panic disorder:relationship to high medical utilization. ATD J Med1992,92:7S-11S.

5. Shader Rl, Greenblatt DJ. Use of benzodiazepine inanxiety disorders. New EngI J Med 1993;32e:1398-1405.

6. WellsKB, GoldingJM,BumamMA, Psychiatric disorderin a sample of the genera! population with and withoutchronic medical conditions. Am J Psychiatry1988:145:976-981,

7. Colman SS. Brod M, Potter LP, Buesching DP, RowlandCR, Cross-sectional 7-year lollow-up of anxiety inprimary care patients. Depress Anxiety 2004:19:105-111.

8. Collins, R. Douglas, Anxiety. In Algorithmic Diagnosisof Symptoms and Signs: A Cost-Eftective Approach,Lippincott Williams & Wiikins, PA, 2003, pp.35-36.

9. Diagnostic and Statislical Manual ol Mental Disorders.Fourth Edition. Text Reuision, American PsychiatricAssociation, DC, 2000.

10. Prousky JE, Niacinamide's potent role in aileviatinganxiety with its benzodiazepine-like properties: a casereport. JOrthofTJo/Med2004:19:104-110,

11. Zamorski MA, Whal to do when SSRIs tail: eightstrategies for optimizing treatment of panic disorder, AtnFam Physician 2002;66:1477-1488,

12. Trevor AJ, Way WL, Sedative-hypnotic drugs, Eds,Katzung BG. In Basic S Clinical Pharmacology. 6th ed.Applelon & Lange, CT, 1995, pp.338-339.

13. M6h)er H, Pole C, Cumin Fl, Pieri L, Kettler R,Nicotinamide is a brain constituent with benzodiazepine-like actions. Nature 1979:278:563 565.

U , Slater P, Longman DA, Effects of diazepam andmuscimol on GABA-mediated neurotransmission:interactions with inosine arid nicotinamide. Life Sci1979:25:1963-1967.

15, Kennedy B, Leonard BE, Similarity between the actionof nicotinamide and diazepam on neurotransmittermetabolism in the rat, Biochem Soc Trans 1980:8:59-60.

16, Lapin IP, Nicotinamide, inosine and hypoxanthine,putative endogenous ligands of the benzodiazepinereceptor, opposite to diazepam are much more effectiveagainst kynurenine-mduced seizures than againstpentylenetetfazol-induced seizures. PharmacolBiochem So/iav 1981:14:589-593,

17, Markin RS, Murray WJ, Searching for the endogenousbenzodiazepine using the graph theoretical approach,Pham Res 1988:5:408-412.

18, Akhundov RA, Dzhafarova SA, Aliev AN, The searchfor new anticonvulsant agents based on nicotinamide.Eksp Klin Farma*(o/1992:55:27-29,

19, Hoffer A, Vitamin B-3: niacin and its amide, TLID&P1995:147:30-39.

20, Hofier A, Vitamin B3 dependent child. Schizophrenia1971:3:107-113,

21, Hoffer A, Dr. Hoffer's ABC of Natural Nutrition forChildren, Quarry Press Inc, ON, 1999.

22, Werbach MR, Adverse effects of nutritionalsupplements. In Foundations of Nutritional Medicine,Third Line Press, Inc, CA, 1997, pp,133-160.

23, Winter SL, Boyer JL, Hepatic toxicity from large dosesof vitamin B3 (nicotinamide), N Engi J Med1973;289:1180-1182.

24, Nicoll RA, Introduction to the pharmacology of CNSdrugs. Eds, Katzung BG, In Basic & CiinicaiPharmacology. 6th ed, Appleton 4 Lange, CT, 1995,p,33O.

25, Braverman ER, Pfeiffer CC, Blum K, Smayda R, TheHealing Nutrients Within, 2nd ed. Keats PubJIshing, CT,1997, pp,290-291,

26, Mitchell, WA, Jr., Foundations of Natural Therapeutics:Biochemicai Apologetics of Naturopathic Medicine,Southwest College Press, AZ, 1997, pp,105-iO8,

27, Daigle RD, Clark HW, Landry MIM, A primer onneurotransmitters and cocaine, J Psychoactive Drugs1988:20:283-295,

28, Andres E, Loukiii NH, Noel E, et al. Vitamin B12(cobaiamin) deficiency in elderly patients, CMAJ2004:171:251-259.

29, OH RC, Brown DL, Vitamin B12 deficiency. Am FamPhysician 2003:67:979-986, 993-994.

MESOTHERAPYTRAINING

21 Category 1 CMEs

Mesotlierapy - A Revolutionary Approachto Fain, rat Heduction, and Beauty

The OrSLY continuing education training in the United Statesendorsed by the International Society of Mesotherapy. Afaculty with more experience and than any group, anywherein the world, and delivers superior training in Mesotherapy.Join us for an intensive, hands-on course in Mesotherapytechniques and procedures for general medicine, sports Scpain, and aesthetic use.

(877) 243-8745WWW. RXMAN AG EM ENT.COM

Endorsed by the International Sociein cooperation with Rxnanagement Oe College Pharma;

UDD Thl i .-•< Hvlly luw >>rc-n pUinni-il and lMi|ih'ii><-r<lr<l In iu i i irdniiri ' w«h t)ir. r.a-uiiUM Aif.ia luid ftilli lt~. ct Ilii- lllJrtJf ci( Oi*ilhiilmol<iqy and Onj|nryn9i>Uiciy and IHc liili^inatlonal SIM Irty of Mcmxhtimpy. IHi! llUnol.-i SIM Irly c.f (iplUhHImoKmy anllTiiiliin miMllijil i-'lurall»n rnr pnyshrlan,-!

30, Schilling RF, Is vitamin B12 a tonic? Wis Med J1971:70:143-144,

31, Ellis FR, Nasser S, A pilot study of vitamin B12 in thetreatment of tiredness, Br J Nutr 1973:30:277-283,

32, SoNer A, Pfeifler CC, Kowalski T, Effectiveness androuteof administration of vitamin Bl 2, Int Clin Nut Rev1989:9:64-65.

33, Werbach MR, Moss J, Acne vulgaris. In Textbook ofNutritional Medicine. Third Line Press, Inc., CA,1999,pp.67-70.

34, van Tiggelen CJM, Peperkamp JPC, Tertoolen JFW,Vitamin B12 levels of cerebrospmal Muid in patients withorganic mentai disorders, J Orthomolec Psych1983:12:305-311.

35, Greden JF, Anxiety or caffeinism: a diagnostic dilemma.Am JPsych/afO'1974:131:1089-1092,

36, Alberti KG, Nattress M, Lactic acidosis. Lancet1977:ii:25-29.

37, Den Boer JA, Westenberg HG, Klompmakers AA, vanLint LE, Behavioral biochemicai and neuroendocrineconcomitants of lactate-induced panic anxiety, BiolPsychiatry 1989:26:612-622,

38, Leibowit; MR, Gorman JM, Fyer A, et al. Possiblemechanisms for lactate's induction of panic. Am JPsychiatry 1986:143:495-502.

39, Leibowitz MR, Gorman JM, Fyer AJ, et al. Lactateprovocation of panic attacks. II, Biochemical andphysiologicai fmdings. Arch Gen Psychiatry1985:42:709-719,

40, Shaichar A, Sajdyk TJ, Gehlert DR, Rainnie DG, Theamygdala, panic disorder, and cardiovascular reponses.Ann N Y Acad Sci 2003:985:308-325.

41, Monteiro MG, et al. Subjective feelings of anxiety inyoung men after ethanol ana diazepam infus'ons, J ClinPsychiatfy A 930:5: :12-I6.

of MesottierapyiCducatlonal Services

tlull nE-/%H<- illon^l adlvily

TOWNSENO LETTER for DOCTORS & PATIENTS - FEBRUARY/MARCH 2005

Page 7: Orthomolecular Treatment of Anxiety Disorders Treatment of Anxiety... · Best of Naturopathy Orthomolecular Treatment of Anxiety Disorders Introduction Anxiety disorders are life