66. Psychopharmacology for Elderly Patients

8/12/2019 66. Psychopharmacology for Elderly Patients

1/6

74 Psychopharmacology for Elderly Patients5 . Fry PS: Depression, Stress, and Adaptations in the Elderly. Rockville, MD, Aspen, 1986,pp 323-347.6 Hackett TP: Sexual activity in the elderly. In Jenicke M A ed): Clinical Perspectives on Aging. Philadelphia,7. James JW, Cherry F: The Grief Recovery Handbook. New York, Harper Row, 1988.8. Meston CM: Aging and sexuality. West J Med 167:285-290, 1997.9. Nemiroff RA, Colarusso CA: The Race Against Time. New York, Plenum Press, 1985.

Wyeth-Ayerst Laboratories, 1985.

10. Pearlman CK: Frequency of intercoursein males at different ages. Med Aspects Hum Sex 6:92, 1972.11 PipherM: Another Country: Navigating the Emotional Terrain of Our Elders. Riverhead Books, 1999.12. WeismanA: On Dying and Denying. Behavioral Publications, 1972,pp 137-157.13. Zarit SH, Knight BG eds):A Guide to Psychotherapy and Aging: Effective Clinical Interventions in a LifeState Context. Washington, DC, American Psychological Association, Oct 1997.

66. PSYCHOPHARMACOLOGY FORELDERLY PATIENTS

RoGerta M. Richardson, M . D

1. How do changes in body composition that occur with aging affect your choice of psy-chotropic medication?

The aging body shows a significant decrease in lean body mass corresponding increase intotal body fat and decrease in total body water. Thus, water-soluble drugs have a greater concen-tration per unit dose because of the apparent decrease in the size of the reservoir. The blood alcohollevel per drink rises with age, and the usual two martinis a day cant be tolerated at age 70.

Fat-soluble drugs have a greater volume of distribution. They are stored in fat and released grad-ually, and therefore show a longer half-life in the elderly. The highly fat-soluble benzodiazepines,such as diazepam, have a greatly increased half-life in older individuals, and typical antipsychoticsare affected by this phenomenon as well. Remember, too, that the brain is a very fatty organ.2. Why is it essential to know the route of metabolism of any drug prescribed?

Most drugs are metabolized primarily in the liver. In general, hepatic blood flow and size decreasesignificantly with aging. However, individual variation in activity of liver enzymes is vast. For thisreason, there can be a 20-fold difference in appropriate dose of some antidepressants among patients ofthe same advanced age.

Ignorance of this fact leads to two common prescribing mistakes: overdosing and underdosing.Remember to start low, go slow-but dont stop too soon. Also take into account metabolic interac-tions with other medications. This is especially crucial for older patients who may be taking anumber of different medications, and who are more vulnerable to adverse effects of blood levels thatclimb too high, or drop too low.

Medications with renal metabolism are more predictable. Creatinine clearance decreasessteadily and predictably with age. Age and body weight are factors, such that the older and smaller aperson is, the lower his or her creatinine clearance will be. Lithium is the psychotropic medicationmost influenced by this phenomenon. Dosages must be drastically reduced in the elderly to avoidtoxicity. Some of the benzodiazepines also are metabolized renally and have a slower clearance inelderly patients.3. How are changes in receptor sensitivity and neurotransmitters relevant?

Aging brings reduced sensitivity to some pharmacologic agents and increased sensitivity toothers. The most important consideration in prescribing psychotropics, however, is the cholinergicneurotransmitter system. Several of the commonly used psychotropic agents have significant


2/6

Psychopharmacology for Elderly Patients 375anticholinergic properties. But in the aging brain, cholinergic binding sites are decreased; cholineacetyltransferase, vital for making acetylcholine, is decreased; and acetylcholine is even more de-creased in the brains of patients with Alzheimers disease. Therefore, the elderly are predisposed tocentral anticholinergic toxicity in the form of confusion, delirium, and psychosis.

Whenever prescribing psychotropic medications for the elderly, therefore, choose the least anti-cholinergic agent in each class and avoid combining two or more highly anticholinergic medica-tions. For example, among the tricyclic antidepressants TCAs), the secondary amines nortriptylineand desipramine are preferred. Amitriptyline is highly anticholinergic and should be avoided.Among the antipsychotics, the high-potency agents such as haloperidol are preferred over the moreanticholinergic thioridazine or chlorpromazine. Clozapine also is highly anticholinergic. Avoid over-the-counter sleep medications and antihistamines.Note: Central anticholinergic toxicity may occur without peripheral manifestations in older pa-tients.Summary o Changes in the Aging Body and Their ffect on Psychotropic Drugs

CHANG E EFFECT EXAM PLEIncreased body fat Fat-soluble drugs stored longer, releasing DiazepamDecreased body water Water-soluble dmgs show higher EthanolDecreased liver size and blood flowDecreased creatinine clearance Drugs metabolized renally cleared more Lithium, gabapentinDecreased acetylcholine in brain

slowlyconcentrationslowly, but individual variation is greatslowly; predictablecentral toxicity Chlorpromazine

Drugs metabolized in liver cleared more Antidepressants

Anticholinergic drugs more likely to cause Amitriptyline

4. What are the major considerations in choosing an antidepressant for older patients?All treatments for depression are potentially useful for elderly patients see Chapter 47). As inany patient, the many available agents carry various risks, side effects, and costs. Consider the indi-vidual patients health, other medications, tolerance of particular side effects, cognitive abilities,social resources, and financial means. Comorbid psychiatric conditions such as anxiety, psychosis,and substance abuse also may affect the choice. Most importantly, be thoroughly familiar with con-traindications to specific agents, major drug interactions and common side effects of agentsbeing prescribed.5. Why should I always check the electrocardiogram before prescribing a TCA in patientsover the age of 40?The TCAs have quinidine-like effects on cardiac conduction; they slow conduction across theatrioventricular node. Clinically relevant problems at therapeutic blood levels are limited to patientswith preexisting conduction disease. However, only severe disease absolutely contraindicates use ofTCAs. Stoudamire and Atkinson reported that asymptomatic patients with right bundle branchblock, isolated left anterior fascicular block, and left posterior fascicular block usually can be treatedsafely with TCAs if dosage is increased gradually and ECGs obtained following each dosage in-

crease. Note the word asymptomatic. Syncopal attacks suggest n intermittently higher degree ofblock, and TCAs should not be used unless a pacemaker is in place. The same applies to patientswith bifascicular or trifascicular block.TCAs also are contraindicated for at least 6 weeks after an acute myocardial infarction. In pa-tients who develop persistently long Q-Tc intervals, the risk for fatal ventricular fibrillation is in-creased. If TCAs must be used, they should be used cautiously, in association with ECG monitoringand consultation with a cardiologist about the acceptable upper limit of Q-Tc intervals for the partic-ular patient.


3/6

376 Psychopharmacology for Elderly Patients6. List other contraindications to the use of TCAs.Other contraindications to TCA s are due to their anticholinergic effects and include: (1) narrow-angle glaucoma, 2) significantly enlarged prostate, 3) marginally compensated congestive heartfailure (because tachycardia may precipitate f ailure) . Also consider the possibility of 4) orthostatic

hypotension, which increa ses the risk of falling.7. Is it safe to prescribe monoamine oxidase inhibitors MAOIs) to elderly patients?MA OIs can be tricky in elderly patients. T he biggest concern is the need for compliance with

dietary restrictions because ingestion of foods high in tyramine may cause a hypertensive crisis.MA OIs should not be prescribed for patients who can not be relied on to understand an d follow thisdiet. Certain concurrent medications also must be avoided. Most significant are the sympathomim et-ics, which include medications used to treat asthma; therefore, patients with asthma should not re-ceive MAOIs. The s am e applies to p atients with a history of anaphylaxis, because the epinephrinerequired for treatment m ay precipitate a hypertensiv e crisis in the presence of MAOIs. Orthostatichypotension also is a comm on side effect.8. Arent the newer antidepressants preferable?To date, the selective serotonin reuptake inhibitors SSRIs) appear to be the safest of the antidepres-sants. There are no data to suggest that nefazodone, venlafaxine, or mirtazapine are unsafe, but fewerdata have been collected about the use of these relatively newer agents in the g eriatric popu lation.

SSRIs should be started at low d oses, and increased more gradually in the elderly. In rare in-stances, they can cause park inson ism and, less rarely, an akathisia-like syndrome. Therefore, usethem cautiously in those with Parkinsons disease. Older patients frequently experience postural in-stability early in the course of treatment with SSRls; although this resolves within a few weeks, itmay cause falls, with seriou s consequences for an olde r person. O ther significant and common sideeffects include nausea, anorexia, diarrhea, headache, tremor, insomnia, and sedation. B ecause of theextraordinarily long half-life of fluoxetine, the shorter acting ones might be preferable. Sertralineand citalopram also are less likely to interfere with the metabolism of com monly prescribed medica-tions such as coum adin, phenytoin, and cimetadine.9. How can the other newer antidepressants be used?Bupropion is a useful antidepressant in a class by itself. It can be u sed safely and effectively inthe elderly, always with a consideration toward seizure risk. It should not b e used in any one with ahistory of seizures, or significant brain lesions that m ight predispose to seizures. D osing guidelinesmust be strictly followed. An advantage over other antidepressants is its mildly stimulating effect,

rather than sedation which accompanies most of the others. A disadvantage is that two to three times aday dosing is necessary, increasing the likelihood of mistakes, missed dosages, and non compliance.Nefazodone and mirtazapine may be especially helpful for the person with high anxiety andorinsomnia. Vanlafaxine has many similarities to the SSRIs, but may be effective when an SS RI is not.It also has been approved recently fo r the treatment of generalized anxiety disorder, based on con-trolled studies of its effectiveness.10. What are the treatment options if none of the above antidepressants is safe toleratedand/or effective?

Psychostimulants such as methylphenidate, may b e helpful in very old, frail patients with a pa-thetic depression; for ex amp le, medically ill patients who are not participating in their care or reha-bilitation or not eating. In spite of their reputation for suppressing appetite, in this setting thestimu lants generally inc rease appetite, energy, an d interest. T he s timu lants are rarely contraindi-cated; even patients with heart disease usually tolerate them . A careful approac h, beginning with alow do se and mon itoring vital signs after each do se until stabilized, is recommended.

Electroconvulsive therapy is another possibility for frail elderly persons wh o are depressed.Despite its scary reputation, E CT is o ne of the safest treatments for certain older peop le. Intracranialmasses should be ru led out, and consultation with a cardiolog ist is necessary for patients with significant


4/6

Psychopharmacology for Elderly Patients 377heart disease. In addition, patients with a history of retinal detachment should have a consultation witha know ledgeable ophthalmologist, because the sudden increase in blood pressure m ay cause problems.11. How should I approach the treatment of anxiety in elderly patients?

First, make a careful diagnosis. In many older people who present with anxiety as their chiefcomp laint, the actual diagnosis is m ajor depression. Anxiolytics do not treat such p atients ade-quately. In fact, the sedative-hypnotics m ay worsen depression. Th e appropriate response is to pre-scribe an antidepressant which often provides sufficient treatment even in the short term whilewaiting for the antidepressant to take full effect. Venlafaxine may be a good choice, as it has recentlyobtained FDA approval for treatment of generalized anxiety disorder.If an anx iolytic medication is needed, consider low do ses of the benzodiazepines lorazepamand oxazepam both of which are m etabolized in the blood through oxidation. Because this processdoes not change appreciably with aging, lorazepam and oxazepam, unlike other anxiolytic agents,do not accum ulate in the aging body as a result of slowed metabolism. T his unique method of me-tabolism, however, does not mean that older people should receive the same dosages as youngerpeople. Older people are m uch m ore susceptible to postural instability and mem ory loss. In all cases,the lowest possible do sage should be used, and signs of toxicity should be m onitored carefully.Buspirone is not a substitute for benzodiazepines, because the patient will feel no immediaterelief. Buspirone may be helpful with generalized anxiety over time, and some evidence suggeststhat it may have an tidepressant effects. However, it is not very helpful as an early treatment of d e-pression nor as treatment for situational anxiety.Do not neglect nonpharmacologic means of anxiety control, such as relaxation exercises, deepbreathing, and manipulation of the environment.12. Which agents are preferred in the treatment of psychosis in elderly patients?As always, the first consideration is diagnosis. Elderly schizophrenics need and usually toleratehigher doses than demented o r delirious patients. Patients with affective illness show a wide range o fneed and tolerance.The high-potency agents are preferred for ge riatric patients because of their side-effec t profile.Th e minimal advantage of increased sedation w ith the low-potency medications, such as chlorpro -mazine and thioridazine, is far outweighed by the disadvantages of increased anticholinergic s ide ef-fects and h igher incidence of orthostatic hypotension. Th e second-generation antipsychoticsrisperid one , olanz apine , and perhaps qu etiapine are preferred because of their lower risk of ex-trapyramidal symptoms. Olanzapine, especially, combines the benefits of sedation with low risk ofEPS . The high cost of these agents should be considered, however.13. What is the main problem with high-potency antipsychotics?The main problem with haloperido l and other high-potency antipsychotics is the likely occurrenceof extrapyramidal symptoms.Acute dystonia is extremely uncomm on in the elderly. Parkinsonism,however, is quite com mon and con tributes significantly to the risk for falling. Its onset m ay be insidi-ous. On e month after hospital discharge, for example, the patient may be found t o be stooped, shuf-fling, stiff, and possibly tremulous. For these reasons, the physician must be very cautious, using thelowest effective dose and m onitoring the patient closely for a few months if he o r she is to stay on theantipsycho tic med ication. Prophylactic anticholinergic medications such as benztropine are no substi-tute; they increase the risk of mental confusion and other side effects of anticholinergics.

Evaluate elderly patients for sym ptoms of parkinsonism efore starting an antipsychotic.Patients with Parkinsons disease or similar syndromes may deteriorate clinically, and antipsychoticsshould be avoided in such patients if at all possible. The only currently available antipsychotic thathas definitely been proven not to worsen Parkinsons disease sym ptoms is clozapine, w hich is quiteuseful in treating psychosis associated with P arkinsons disease. The required d osag es are muchlower than those used to treat schizophrenia-25-50 mg/day is often sufficient. Weekly blood countsare needed because of the risk of agranulocytosis. Quetiapine, the newest antipsychotic at this writ-ing, also looks quite p romising for use in Parkinsons patients.


5/6

378 Psychopharmacology for Elderly Patients14. What is the risk of tardive dyskinesia in antipsychotic treatment?The risk of tardive dyskinesia increases with age. A recent study showed that am ong those overage 65 treated w ith a typical antipsy chotic, one- third developed tardive dyskinesia at 12 months:one-half at 2 years: and two-thirds at 3 years. The incidence is higher in women and in patients withmood disorders. Thus elderly w omen with psychotic depression are at particular risk for developingtardive dyskinesia; antipsychotic medications should be prescribed only with informed con sent andclose follow-up. U se newer ag ents if at all possible. With frequent and careful examination for earlysigns, tardive dyskinesia can be detected and the offending agent stopped before a debilitating con-dition develops.15. Name one of the most common and serious yet overlooked complications of psychotropicmedication in elderly patients.Most of the psychotropics in current use increase the risk of falling in older patients.Osteoporosis is endemic among elderly wom en; thus, it doe s not take much to cause serious frac-tures. A fractured hip may lead to all of the morbidity and mortality associated with prolonged im -mobility a nd possible surgery, including pulmonary em bolus, pn eum onia, urosepsis, decubitusulcers, and lengthy and expensive rehabilitation efforts after the bone has healed. Subduralhematomas may result from relatively minor b lows to the head in older people. The elder who livesalone and cannot get up after a fall may develop muscular necrosis and even dehydration if not foundfor som e time.For many elderly people the prospect of falling is so frightening that, especially after one fallhas occurred, activity may b e significantly limited. Su ch limitation may lead to increasing dep res-sion and declining health.Psychotropic medications can contribute to falling through various mechanisms, a nd the physi-cian must be alert for symp tom s in several areas. TC As, MA OIs, and so m e of the antipsychoticscomm only cau se orthostatic hypo tension. Patients m ust be warned and then asked abou t a feeling offaintness upon rising fro m a lying or sitting position. If the reply is positive, blood pressure shouldbe measured in recumbent and standing positions. A drop of 20 points or more in systolic pressureusually is considered significant. Asymptomatic findings may be tolerated; symptomatic findingsshould not. Fainting is one of the m ost dangerous reasons for a fall, because the victim has no con-trol over the landing.16. True or false: The SSRIs do not cause risk of falling.False. Unfortunately, the SSRIs are not foolproof in this regard. SSRIs can c ause significantpostural instability in m any older p eople early in the course of treatment. Fortunately, this symptomseems to resolve within a few weeks, an d the risk may b e minimized by more gradual titration of thedose. Dizziness is a relatively common side effect of the new antidepressant venlafaxine at all ages.Elderly patients taking these m edications should be asked if they feel dizzy or unsteady on their feet.If so, the dosage should be lowered o r special precautions taken to increase safety, depend ing on thefrailty and dependability of the patient as well as the seventy of the depression and dizziness.17. Discuss the effects of benzodiazepineson fall risk in the elderly.Benzodiazepines also cause postural instability. The effect may b e subtle, but the risks are not.When geriatric patients are prescribed doses that are too high or a long-acting agent that accumu-lates over time, frank intoxication may lead to a fall as long as 2 weeks after the dru g is started. Theclassic example is the patient wh o is prescribed flurazepam in the hospital and discharged with in-structions to continue the d rug at hom e. Two weeks later, when this particularly long-acting m edica-tion reaches peak blood level, the patient falls-or falls asleep at the wheel of a car Nystagm us is asign of excessive levels of benzodiazepine and ind icates cerebellar dysfunction .18. How might antipsychotics cause falls?Antipsychotics also are commonly associated with falls among elderly persons because of theinduction of parkinsonism. O ne of the cardinal features of this synd rom e is postural instability. If the


6/6

Psychopharmacology for Elderly Patients 9more obvious s igns of parkinsonism are presen t ( i .e . , p i l l- ro l ling t remor , co gwh eel r ig id ity , shuf f l inggai t , masked fac ies , inhib i t ed a r m swing) , pos tura l ins tabil i ty i s present too . S te ps sho uld be t akene i t h e r to d e c r e a s e , d i s c o n t i n u e , or c h a n g e t h e m e d i c a t io n o r t o t r e a t t h e p a r k in s o n i sm w i t h a n ti -chol inerg ic age nts (wi th a t t en t ion to poss ib le a t t endant compl ica t ions) .

1

2.3.4.5 .6.7 .8.

9.10

I

12.13.

BIBLIOGRAPHYBlazer DG: Generalized anxiety disorder and panic disorder in the elderly: A review. Harv Rev PsychiatryFinkel SI: Efficacy and tolerability of antidepressant therapy in the old-old. J Clin Psychiatry 57:23-28,Friedman JH : A role for clozapine in Parkinsons disease. Neurol For 3:3-15, 1992.Jenike MA : G eriatric Psychiatry and P sychopharmacology: A Clinical Approach. C hicago, Year Book,Jeste DV, Rockwell E, Harris MJ, e t al: Conventional vs. newer antipsychotics in elderly patients. Am

Liu B , Anderson G, et al: Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and riskNakra BRS, G rossberg G T Lithium use in the elderly. J Geriatr Drug Ther 2:47-63, 1987.Salzman C : Recent advances in geriatric psychopharmacology. In Tasman A, Goldfinger SM , Kaufmann CA(eds): American P sychiatric Press Review of Psychiatry, vol 9. Washington, DC, A merican Psy chiatricPress, 1990, pp 279-293.Schneider L Clues to Psychotropic Prescribing Practices in Geriatric Med icine. Primary Psychiatry 5 2 326, 1998.Stanislav SW, Fabre T, Crismon ML, et al: Buspirones efficacy in organic-induced aggression. J ClinPsychopharmacol 14:126-130, 1994.Stoudem ire A, F ogel BS , Gulley LR, et al: Psychoph armacology in the medical patient. In Stoudem ire A,Fogel BS (eds): Psychiatric Care of the Medical Patient. New York, Oxford University Press, 1993, pp

155-206.Tune LE, Steele C, Co oper T: Neuroleptic drugs in the management of behavioral symptoms of Alzheimersdisease. Psychiatr Clin North Am 14:353-373, 1991.Yudofsky SC, Silver JM , Hales RE: Pharmac ologic managem ent of aggression in the elderly. ClinPsychiatry 5 1:22-32, 1990.

5:18-27, 1997.1996.

1989.Ge riat Psychiatry 7:70-76, 1999.of hip fractures in elderly people. Lancet 351:1303-1307, 1998.

66. Psychopharmacology for Elderly Patients

Documents

Transcript of 66. Psychopharmacology for Elderly Patients