TRENDS in Molecular Medicine Vol.7 No.8 August 2001unlikely that neuronal loss in neurodegenerative How do neurons die diseases is solely accomplished by apoptosis. Anyproposed mechanisms of neuronal death shouldexplain this extraordinarily slow time course. in neurodegenerative Morphological and molecular hallmarks of individual neurodegenerative diseases diseases? Each disease has
Pastoral pharmacology, part iiPastoral Psychopharmacology
Historical Evolution of Behavioral Disorders and Psychopharmacology
Beginning in the late nineteenth century a systematic study of disorders of the mind (thought processes and emotions) began to evolve out of themedical discipline of neurology. The nomenclature was empirical anddescriptive, usually with little relation to cause, since causes of the diseaseswere not known. Two broad categories were described at the turn of thecentury—neurosis and psychosis—largely due to the work of SigmundFreud, an Austrian physician who began as a neurologist, studying underthe great French neurologist Charcot, but who founded his own school(psychoanalysis). Freud sought to diagnose and treat by delving into thepatient’s past and by trying to explore the subconscious mind through freeassociation interviews and analysis of dreams. Psychosis was seen as asevere deterioration of intellectual and social functioning in which thepatient would withdraw partially or completely from reality. Psychoticpatients were characterized by aberrations of perception in the form ofhallucinations and delusions, and oft times lived in their own world com-pletely or in a world that was a distortion of the real world around them.
Neurosis was a functional disorder of much less incapacitation, involvingbehavior patterns such as anxiety, phobias, etc. Such persons occasionallyacted bizarre, or had peculiar habit patterns, but usually were functionalcitizens. Classically, neither of these general categories was associated withorganic disease such as stroke, tumor, or direct injury to the brain; neurosisand psychosis thus represented functional rather than structural aberrationsof the nervous system.
But things were far from simple. It was noted that “mental illness” really represented a tremendous spectrum of behavioral abnormalities. Some ofthese were seeming exaggerations of normal responses, others were causedby specific diseases, and still others had no perceptible cause. Forexample, death of a spouse was apt to produce a depression in an other- 1979, The Christian Counseling and Educational Foundation All rights reserved. No portion of this publication should be reproduced, copied or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from The Christian Counseling and Educational Foundation. Inquiries should be made in writing, addressed to CCEF, 1803 East Willow Grove Ave, Glenside, PA 19038.
wise normal individual; depression could also result from serious medicaldisease or be the result of drug therapy. The various states might be in-distinguishable although the apparent causes were different. Or a personcould become raving mad (psychotic and paranoid) as a result of a medicaldisease (syphilis), a brain tumor, a reaction to a drug, or for no apparentreason at all. Treatment of mental illness which seemed related to a specificorganic cause was naturally directed toward relieving the cause. But for so-called idiopathic mental illness (that for which no specific cause wasevident) all sorts of empirical treatments arose, including insulin orelectroshock therapy for severe depression: treated patients seemed toimprove more rapidly than patients not so treated. But exactly what insulinshock or electroshock did to the brain was unknown.
That things should have evolved in this way was not surprising: most of medicine had done so, with descriptions of abnormalities preceding de-termination of specific causes by many years. Pneumonia, for example,was described by the ancients, but its cause had to await the germ theory ofPasteur and Lister in the last century, and its specific cure the discovery ofantibiotics by Fleming in this century. And as with medical disease,serendipitous observations played a role which helped elucidate behavioraldisorders. Just as Fleming had noted inhibition of bacterial growth by abread mold which had contaminated his culture (leading him to discoverpenicillin), three fortuitous observations led to investigations of therapy for“mental illness.” First was the observation during the nineteenth centurythat the “alkaline waters” of certain medicinal spas had a calming effect onbehavior. (The significance of this was not apparent until the discovery oflithium, and even then the association was not made until specific studieswere done.) Second was the observation that a small number of patientstaking the antihypertensive drug Reserpine developed a severe depressionwhich was clinically indistinguishable from severe depression of unknowncause (idiopathic depression). The third observation made at this time (the1950s) was that certain TB hospital patients being given the drugiproniazid developed curious elevations of mood beyond what would beexpected from just physical improvement. This information began to fitwith data being generated by biochemists concerning the chemicalworkings of the human body. Early in the twentieth century Adrenalin hadbeen discovered, a hormone which stimulates the body, causing elevationof pulse, respiration and blood pressure, and often anxiety. Its chemicalisomer, Nor-Adrenalin, was found to be involved in the transmission ofnerve impulses. (At first it had been thought that nerve impulsetransmission was electrical—because nerves could be stimulated byelectric current—but further research showed chemical forces were in-volved, with certain hormones playing an important part in nerve functionand transmission.) Chemical derivatives of Nor-Adrenalin, collectively called biogenic amines, were present in brain tissue and, significantly,drugs such as Reserpine were found to deplete the brain of thesesubstances. A class of drugs called monoamine oxydase (MAO)inhibitors—which turned out to include iproniazid—were shown toproduce an increase in these biogenic amines. It was a logical jump topostulate that depletion of amines was associated with states of depression,whereas an increase led to euphoric states. The stage was set for advancesin psychopharmacology, as drugs which seemed to affect human behaviorwere developed and tested in clinical situations.
The above is a vastly simplified account of how drug therapy for be- havioral disorders has evolved. Let us now deal with current medicaltreatment of the so-called affective disorders, characterized byabnormalities of mood, including mania, hypomania, manic depressivestates and depression.
Patterns of Behavior in Affective Disorders
The manic individual is hyperactive, gregarious, and euphoric. He’s turned on, “on top of the world,” constantly moving, sleeps little, andusually is emotionally labile and flighty. His ideas may be grandiose, andwith impaired judgment he may spend lavishly and invest foolishly. Be-cause he soon physically and emotionally exhausts his friends and family,he is discovered and treated early.
Hypomania (less than mania) is an attenuated form of mania, less evi- dent and more insidious. The patient’s aberrations are not so blatant as toarouse great concern—his or those around him. His behavior often re-sembles an exaggeration of the normal but still easily depletes the emo-tional and financial resources of his family.
Depression also resembles an exaggeration of normal behavior in some respects (for example, fatigue or grief). But when prolonged or inap-propriate, it is associated with feelings of hopelessness, helplessness, guilt,and shame. It can take the form of great passivity and withdrawal fromsocial intercourse, or less often may be manifest as agitation. Usuallyslowness and lack of energy predominate, associated with constipation, de-creased appetite, reduced sexual desire, and sleep disturbances, most oftenearly morning awakening.
Manic-Depressive is a term which describes a state characterized by mania and depression to variable degrees. Classically the patient alternatesbetween mania and depression, with interspersed periods of relative nor-malcy, but any combination may occur.
Lithium Therapy for Manic-Depressive Problems
Lithium is one of the most effective psychotrophic drugs, one of the oldest, and yet the least understood. It is the lightest solid, a metal, third in the periodic table of the elements, having three neutrons, protons, andelectrons, and is chemically similar to sodium and potassium. (Sodium andpotassium are the two major positive ions in the body: salt water forms thegreat bulk of our blood and tissue fluid, while potassium-rich solutions arethe major fluid components within our cells. The ionic balance between theintracellular compartment and the extracellular fluid is critical formaintenance of life.) In the l950s excessive dietary salt (sodium chloride)was suspected as a cause for heart disease and hypertension. Therapeuticefforts were therefore directed toward dietary salt restriction and treatmentwith diuretics (drugs which promote excretion of sodium in the urine).
Because of its chemical similarity to sodium, lithium was tried as asubstitute for salt in patients’ diets. Hypertension was not ameliorated,although much was learned about lithium toxicity: lithium salts fell intodisrepute and were removed from the American market in 1950. But duringthe previous year an Australian researcher had noted a beneficial effect oflithium on mania. And in Denmark lithium continued to be used to treatbehavioral disorders; its effectiveness was confirmed during the nextdecade.
The exact mechanism of action of lithium is unknown. It probably facilitates the destruction of biogenic amines at the nerve endings in thebrain and has a stabilizing effect on enzymes responsible for degradation ofthese amines. It is effective to treat and abort episodes of acute mania, andis most effective to prevent episodes of mania or depression in predisposedindividuals given maintenance therapy. It smoothes out the wide swings ofbehavior in such patients. Although toxicity is always a hazard in chroniclithium therapy (see below), lithium concentrations in the blood are easilymeasured, and metabolism and excretion of the ion remains constant inmost patients. But a low sodium diet, diuretics, excessive sweating, and ill-nesses characterized by nausea and vomiting all can upset the body’ssodium balance and lead to lithium toxicity. Patients should be warnedabout this risk.
The most common side effects of lithium treatment are fine tremor, mild nausea, and light headedness. Early signs of toxicity include weakness,ataxia, drowsiness or excitement, diarrhea, vomiting, and lack of coordi-nation. If the patient has more severe intoxication due to misdosage or lossof salt from the body, more severe signs may be manifest, includingirritability, slurred speech, confusion, blackout spells, lethargy, and evenconvulsions. Patients taking lithium chronically need to have frequentblood tests done early in the course of their treatment until the dose isstabilized. If the toxic signs are present, a lithium blood level test should bedone to confirm the diagnosis; such signs and symptoms may be due tosome other illness and not the drug itself, and if so the drug should not bestopped.
Whether a patient on lithium therapy for manic depressive problems should be maintained on the drug indefinitely is a moot point. My ownpreference is to have such patients begin counseling to determine theirrelationship with God and their fellow man. In most behavioral disorderssinful life patterns are very evident. Transforming the person through theSpirit of God—salvation sanctification—should be the goal of the coun-seling, and if evidence of such change comes forth, then the drugs shouldbe withdrawn. I would urge that in cases of this type the counselor workclosely with the physician; such association, born out of mutual respect,can also provide a very effective witness for the individual physician.
Drug Therapy for Depression
Depression is probably best thought of as a constellation of symptoms rather than a disease. A certain amount of depression is a normal and an-ticipated response to losses that occur during life, especially those asso-ciated with bereavement. Depression is abnormal if it is excessively pro-longed or inappropriate. It is an extremely common symptom complex andis also the accompaniment of many bona fide diseases, as manifested byweight loss, fatigue, and anorexia.
Drug therapy of depression is extremely common in the medical com- munity for two reasons. First, most if not all depressions are associatedwith symptoms which resemble somatic disease, which lead the person toseek medical attention: physicians often see patients who are depressed.
although depression can be a concomitant of true medical illness, moreoften medical illness is mimicked by depression. The wise physician care-fully interviews and examines such patients to rule out significant organicdisease such as anemia, tumors, metabolic disorders, endocrine disorders,and nutritional deficiencies, all of which can cause symptoms ofdepression.
The second reason depression is often treated by physicians with drugs is that the physician lacks the time or inclination (or orientation or training)to engage in counseling. The press of time and his own busy schedule, with30 to 40 patients each day, make him inclined to use drugs; indeed, he isone of few persons specifically licensed to do so in our society. When hebelieves there is a valid physiological and biochemical reason to prescribeantidepressant drugs, and is convinced that they are more effective than aplacebo, the prevalence of drug treatment is understandable. The statisticsshow that more than half (some studies show as high as 75 percent) ofpatients with serious behavioral disorders are being treated by general andfamily physicians.
Most physicians try to be objective in their approach to diagnoses— indeed, to be otherwise can be hazardous, as when an intoxicated and de-lirious motor vehicle accident victim is thought to be just drunk, but ac-tually has a blood clot developing in his brain or inadequate ventilation from broken ribs, etc. But the objective amoral approach (not immoral,please!) can be a liability in other situations, such as treatment of de-pression. If the physician does not believe in sin, or takes no stand as re-gards sinful behavior (as opposed to illegal behavior), then he usuallycannot help the patient to break out of the downward spiral of reaction andresponse which so effectively feeds depression: the person feels depressed,and so does something (sinful) to make himself feel better; but this makeshim guilty, and therefore he feels more depressed, etc. Sin is the root factorin non-organic depression. When one considers what has taken place in oursociety over the last half-century, including the emergence of situationethics, the God-is-dead movement, and the progressive loosening of themoral code of our society, it is no surprise that many persons feel guiltyand depressed but are puzzled as to the cause. It is the job of the Christiancounselor to ferret out and determine these sinful root patterns in patients’lives and start them living righteously, effecting a reconciliation betweenthe individual and God.
Is there a place for medical therapy? Yes, I believe there is, in two general circumstances. First is severe depression, where the patient may besuicidal and where there is real danger of self-destruction. Such patientscan benefit from drug therapy but also must be kept in a sheltered situation—not necessarily a mental hospital, but adequate supervision is imperative.
The role of small, familial, caring communities within the church has notbeen well defined, but I think this can be appropriate for severely depressedpersons. The problem I have seen with treatment on mental health units ingeneral hospitals is that they follow the “medical model” and make noattempt to ferret out sin: they are using band-aids and poultices whereradical surgery is needed. The second circumstance where drug therapy ispertinent relates to the way depressed persons present themselves for care.
Given the present structure of our society, many patients will continue tobe seen by physicians because of symptoms of depression and will doubt-less be started on medication by these physicians. But I would urge amongthe medical community that patients with nonorganic depression should bereferred for counseling. The real key to prevention of recurrent depressionin the life of the individual is transformation of that life by the Spirit ofGod, allowing the fruit of the Spirit to be manifest in his behavior. In oursociety this means a radical approach to the problem of living which needscareful management by someone who is deeply immersed in the Scriptures.
There are two major classes of antidepressant drugs currently being prescribed—the tricyclic antidepressants and monoamine oxydase (MAO)inhibitors. Both seem to work in a similar fashion, namely by increasing the availability of biologic amine neurotransmitters in the brain. (This ties indirectly with the theory of the metabolic hypothesis for depression asdescribed above.) The tricyclics are used more commonly and are the saferof the two types, hence are more apt to be encountered in pastoralcounseling situations. The major ones today (I am listing the brand names)are Sinequan, Elavil, Tofranil, Aventyl, and Norpramin. It is postulated thatthe administration of these drugs will effectively increase the level ofbiogenic amines in the nervous system, producing an elevation of mood andan amelioration of the depressive symptoms. The tricyclic antidepressantsalso have three other major effects which are important. First, they have asedative effect, more pronounced in some of the drugs than others, butpresent in all. Because of this they are usually prescribed at bedtime. Sec-ondly, they have a sleep-regularizing effect, separate from their sedativeeffect, which helps one of the major symptoms of depression—early morn-ing awakening. Finally, they have an anticholinergic effect which is re-sponsible for many of the side effects of the drug. (Acetylcholine is anothermajor neurotransmitter; the blocking effect of the tricyclic antidepressantscan result in symptoms such as constipation, urinary retention, blurredvision, confusion, and dry mouth.) Since there seems to be some variabilityin anticholinergic effects among the different drugs, physicians may switchdrugs to diminish these side effects. Tricyclic antidepressant drugs canpredispose to abnormalities of heart rate and rhythm. And patients on certainantihypertensive medications will have their drug effect neutralized by thetricyclics, which can lead to dangerous hypertension. The tricyclics shouldnot be taken with alcohol or with other sedative drugs, but they are generallysafe drugs and widely prescribed.
The Mono Amine Oxydase (MAO) Inhibitors are not as safe to use as the tricyclics. The three major MAO inhibitor drugs presently marketed areNarplan, Nardil, and Parnate. They are second line drugs, prescribed if thetricyclics fail to work, or if the depression is characterized by markedsluggishness or sleepiness, or by excessive eating and weight gain. Certainmedications are contraindicated during the period when MAO inhibitors arebeing used, including amphetamines in all forms, L-Dopa (a drug used forParkisonism) and cold or sinus medications containing vasoconstrictors suchas Neo-Synephrine. More significant, however, is the importance ofeliminating from the person’s diet any food or beverage which containstyramine or dopa, two chemicals that precipitate an acute hypertensive crisisif combined with an MAO inhibitor. Unfortunately, such substances arepresent in many foods including eggs, cheese, sour cream, yogurt, pickles,chopped liver, bananas, raisins, citrus fruits, soy sauce, beer and wine, andany product made with yeast or by bacterial action. Such proscriptionscertainly could make life more miserable for the depressed patienttaking an MAO inhibitor! Hence most physicians treating depressed pa- tients with drugs will begin tricyclic antidepressants and reserve the MAOinhibitors for patients in the hospital or patients who have not responded tothe other drugs.
In summary, antidepressant drug therapy is widely used by physicians.
The rationale is that it helps to replete neurotransmitter amine substances inthe brain, attacking depression at a biochemical level. The drugs are oftenused as a substitute for counseling by busy physicians in an attempt to breakthe feeling-behavior cycle by elevating mood. I believe that these drugsshould not be used in the absence of counseling and that in many casescounseling alone will suffice if it is biblical and nouthetic. However,because a great proportion of depressed patients present themselves tophysicians for somatic complaints, they will continue to be treated withdrugs even if organic disease is not present. I would urge that pastors andcounselors try to establish relationships with physicians in their geographicarea to take on some of the burden of counseling for depressed patients whocome to doctors’ offices. Formation of physician-pastoral committees for thecare of the sick (in and out of the hospital) might be one way to approachthis subject, and I believe would bear rich fruit in areas besides counseling.
There is a definite need for improved relations between pastors andphysicians in all areas of practice, and this would be a good first step.
Adrenalin: A stimulatory hormone released by the adrenal glands which
causes increase in cardiac output and often symptoms of anxiety.
Affective Disorders: Behavioral disorders characterized by abnormalities of
mood, including mania, hypomania, manic depressive problems, anddepression.
Biogenic Amines: Chemical substances present in the brain and in the body
which act as hormones or neurotransmitters.
Delusions: A false concept or idea such as a patient believing he is Na-
Electroshock Therapy: An empirical therapy based on the induction of a
grand mal convulsion through an electroshock delivered to the brain.
Patients with psychotic depression were thought to improve after a seriesof such treatments.
Empirical: Based on observation or experience, not theory.
Hallucination: A sense perception that has no basis in reality—i.e., hearing
or seeing something that is not there.
Idiopathic Disease: Disease for which no specific abnormality or cause is
Insulin Shock Therapy: A treatment which induces hypoglycemic shock
through the use of insulin. Patients frequently experience convulsions.
Empirically, it was believed that this therapy sped recovery from de-pression.
Neurosis:An abnormal pattern of behavior characterized by anxiety, pho-
bia, etc., which does not incapacitate the patient greatly, but whichnevertheless is not normal.
Neurotransmitter Substances: Hormone-like substances which effect
transmission of nerves at the nerve endings.
Nomenclature: System of naming diseases.
Nor-Adrenalin:A hormone chemically identical to adrenalin which is re-
leased at certain nerve endings; a neurotransmitter substance.
Organic Disease: A disease caused by a structural or chemical abnormality.
Paranoid: Suffering from delusions of persecution; abnormal
Parkinsonism:An organic disease of the nervous system, also called the
shaking palsy, first described by James Parkinson in the nineteenthcentury.
Psychosis:A severe deterioration of intellectual and social functioning; the
patient withdraws partially or completely from reality and usually hasaberrations of perception in the form of hallucinations or delusions.
Serendipitous Observation: An observation of value not being sought for
PERPICH CENTER OF ARTS EDUCATION SELF-ADMINISTRATION OF OVER-THE-COUNTER MEDICATION Effective Monday, March 22, 2010 AHS students will be allowed to carry and self-administer acetaminophens oribuprofens on campus. This is typically Tylenol or Advil; other brands are listed below. These medications maybe brought to campus only in the labeled container in which they were purchased and must be