Psychotropic Drug Use in the Medically III Part II ALAN STOUDEMIRE. M.D MICHAEL

G.

MORAN. M.D.

BARRY S. FOGEL. M.D.

Underlying medical illness and drug interactions may make the use ofpsychotropic agents problematic in some physically ill patients. This overview. published in two parts. discusses six major classes ofpsychotropic medications (cyclic antidepressants. monoamine oxidase inhibitors. benzodiazepines. neuroleptics. lithium. psychostimulallts. and carbamazepine) and examines their use in the setting of specific types of medical illnesses (e.g .. cardiovascular. pulmonary. hepatic. and renal disease). Practical cm/siderations in using psychotropic medications in medical-surgical patients---particularly those who are elderly or medically debilitated-will receil'e special emphasis.

n Part I of this two-part series. special considerations in the use of cyclic antidepressants. monoamine oxidase inhibitors. benzodiazepines, and buspirone in the medically ill were considered. In part two, this series will conclude with a discussion of the neuroleptics (including c1ozapine).lithium, psychostimulants, and carbamazepine in medically compromised patients.

I

Part I ofthis series appeared in Psychosomatics, Volume 31 (FaIl1990).pp377-391.

Received August 8. 1989: revised May 21. 1990: accepted May 25. 1990. From the Medical Psychiatry Unit. Emory University Hospital and Emory University of Medicine. Atlanta: Ihe National Jewish Center for Immunology and Respiratory Medicine. Denver: and the Department of Psychiatry and Human Behavior. Brown University. Providence. Address reprint requests 10 Dr. Stoudemire. 5th Floor. Psychiatry Section. Emory Central Clinics. 1365 Clifton Road. N.E.. Atlanta. GA 30322. Copyright © 1991 The Academy of Psychosomatic Medicine.

34

NEUROLEPTICS

In addition to the treatment of psychotic disorders such as schizophrenia. neuroleptics have a special place in the setting of the medically ill patient. primarily in the adjunctive treatment of delirium. The choice of neuroleptic for the medically fragile patient should include considering the predominant side-effect profile of the individual drugs. As a general rule, the neuroleptics can be grouped into two categories based on side effects: I) the "high-potency" drugs (such as haloperidol. thiothixene. and fluphenazine). which are relatively less sedating, less anticholinergic. and which produce relatively more extrapyramidal side effects. and (2) the "low-potency" agents (such as chlorpromazine and thioridazine). which are more sedating and high in anticholinergic effects and which tend to have relatively fewer extrapyramidal side effects. Because of the already existent high potential for cerebral dysfunction in the medically ill patient (due to the confluence of such forces as other medications, electrolyte disturbances. unPSYCHOSOMATICS

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stable blood pressure. shifting volume status. and concurrent infection). neuroleptics from the "high-potency" category are usually the drugs of choice in the medical setting. Actual half-lives of the neuroleptics do not signiticantly change with aging. except perhaps in the case of chlorpromazine. which may achieve a higher blood level in the elderly for a given oral dose than it does in younger patients. As a rule. among the elderly. there is increased sensitivity. both to effects and to side effects of the neuroleptics. in almost every respect. Cardiac and Pulmonary Diseases The phenothiazines. particularly the "Iowpotency" agents (thioridazine and chlorpromazine). similar to tricyclic antidepressants. may have quinidine-like side effects. This effect may lead to PR- and QT-interval prolongation and some T-wave tlattening on the electrocardiogram (EKG). but these effects are usually of minor clinical consequence unless the patient is concurrently using Type I antiarrhythmics (in which case the side effects of the two drugs can theoretica

y have additive effects on cardiac conduction. as with the tricyclics) or unless there is preexisting significant heart block. Another exception to the generally benign effect of neuroleptics on the EKG occurs in patients with prolonged QT syndromes. This syndrome. in which the QTc interval is greater than 0.440 seconds. is usually caused by drugs with Type I (quinidine-like) antiarrhythmics effects (including the tricyclics) and may lead to fatal ventricular tachycardia. Thioridazine appears to be the phenothiazine most commonly associated with this syndrome.' Neuroleptics such as chlorpromazine and thioridazine are most likely to cause orthostatic hypotension because of their relatively higher propensity for alpha-adrenergic receptor blocking effects. For this reason. "high-potency" agents (for example. haloperidol and thiothixene) are preferable in patients with cerebrovascular and cardiovascular disease. unless effective symptom control can be obtained with relatively small dosages of low-potency agents (for examVOLUME

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pie. thioridazine and chlorpromazine). There is no categorical contraindication to the use of neuroleptics in patients with cardiac disease. even after acute myocardial infarction. However. because of possible effects on blood pressure anticholinergic-induced tachycardia. the high potency agents are again preferred. Antipsychotic medications have wellknown side effects that may involve other organ systems (including the liver. skin. hematologic. endocrine. and gastrointestinal tract). and use of these drugs in patients with organ system disease should be considered on an individual basis (e.g.• use of neuroleptics in a patient with a prolactinoma or hepatitis). Although chlorpromazine-induced jaundice was commonly described many years ago. this problem has apparently decreased markedly in frequency for unknown reasons. Preexistent or coexistent hepatic disease does not necessarily raise the risk for development of cholestatic jaundice or of hepatotoxicity. Transient elevations of liver function tests in patients on neuroleptics (especially chlorpromazine) usually do not require the cessation of the medication. nor do they usually herald the onset of severe toxicity. Traditional neuroleptics rarely have been reported to cause agranulocytosis. although the frequency with the novel antipsychotic c10zapine (Clozaril) may be as high as I %-2%. With traditional neuroleptics such as chlorpromazine. agranulocytosis usually occurs within the first 8 weeks of treatment. but is otherwise unpredictable. and routine complete blood counts have not been shown to be helpful. There may be. however. increased risk for agranulocytosis among patients with antecedent leukopenia. Thus. agranulocytosis may be one example of a preexistent medical illness precluding the use of neuroleptics because of the potential for side effects within the same organ system. As for the endocrine system. the common side effects of galactorrhea. amenorrhea. and gynecomastia are reversible and generally not contraindicated by preexistent diseases involving that system. Patients with asthma may show special sensitivity to parenteral preparations of neuroleptics such as chlorpromazine. Certain neuroleptics 35

Psychotropic Drug Use in the Medically III

TABLE l. Drug interactions with

neurolepticsu.\.,,~

Interactive Effect

Medication Type I-A anti-arrhythmics Tricyclics; beta blockers; 1~7.I~K chloramphenicol; disulfiram; MAO-I; acetaminophen; buspironel~9 Barbiturates; hypnotics; rifampin; griseofulvin; phenylbutazone; carbamazepine Gel-type antacids with AI+ and Mg+ Narcotics; epinephrine; enflurane; isoflurane Prazosin; ACE-inhibitors; (captopril. enalapriljl(,() Narcotics; tricyclics; barbiturates Iproniazid Guanethidine; c10nidine

Chlorpromazine/thioridazine may prolong cardiac conduction May increase neuroleptic levels Lower neuroleptic levels through induction of hepatic enzymes May interfere with neuroleptic absorption Potentiate hypotensive effects of neuroleptics Increase hypotensive effect May increase sedative effects of neuroleptics May cause encephalopathy and hepatotoxicity when used with neuroleptics Neuroleptics may decrease blood pressure control

Note: MAO-I=monoamine oxidase inhibitor; ACE=angiotensin-convening enzyme.

available for parenteral use are packaged in vials that contain sodium bisulfate and sodium sulfite. which may cause allergic and anaphylactic reactions in susceptible individuals-particularly asthmatics. Neuroleptics and Other Medical Disorders In patients with narrow angle glaucoma who are untreated. the "lower-potency" agents with relatively high anticholinergic effect (e.g.• thioridazine and chlorpromazine) should be avoided. Elderly patients and patients with organic brain disease are more likely to become delirious from anticholinergic effects. Prostatism can be exacerbated by the antimuscarinic effect of the low-potency neuroleptics. Sexual dysfunction in men is also more frequent with low-potency neuroleptics. Thioridazine. in particular. is frequently associated with impotence and retrograde ejaculation. I04 Other Side Effects Parkinsonian side effects can occur with all neuroleptics (with the exception of clozapine) and are seen much more frequently with high-potency drugs. The elderly are most vulnerable to parkinsonian effects. while young males have a high susceptibility to dystonias. Thioridazine and mesoridazine apparently have the lowest frequency of parkinsonian effects of the standard 36

neuroleptics: c10zapine is superior in this regard. but hematologic side effects may limit its generalized use. although patients with Parkinson's disease with psychotic symptoms may be ideal candidates (see below). Patients with chronic pulmonary disease who take neuroleptics may develop abnormal involuntary movements in the respiratory musculature. and experience them as dyspnea. Head-injury patients may suffer significant respiratory depression when given antipsychotic medications. 1Il5 All neuroleptics lower seizure threshold: seizures in nonepileptic patients have been most frequently reported with chlorpromazine and clozapine. In vitro work suggests that molindone and fluphenazine may have the least effect on seizure threshold: 106 among low-potency agents. thioridazine and mesoridazine appear less proconvulsant than chlorpromazine. 107 Combinations of two different neuroleptics may have a synergistic effect. As with antidepressants. neuroleptics may affect anticonvulsant levels. so these should be monitored frequently during initiation of neuroleptic therapy. 40 Drug interactions with neuroleptics are summarized in Table I. Two potentially catastrophic reactions. neuroleptic-induced catatonia and neuroleptic malignant syndrome. may occur with neuroleptics: medically debilitated. dehydrated. and neurologically impaired patients may be at somewhat higher risk for such syndromes. 10K These synPSYCHOSOMATICS

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dromes are more commonly associated with high-potency neuroleptics such as haloperidol and tluphenazine. One should consider dehydrated patients to be at a potentially greater risk for the development of neuroleptic malignant syndrome. Close monitoring of the vital signs and tluid intake of delirious patients placed on neuroleptics is thus of great importance. The diagnosis and treatment of these syndromes has been reviewed elsewhere. lllx . Hl'l Clozapine Clozapine is a novel neuroleptic recently introduced for the treatment of refractory schizophrenia and psychotic syndromes in patients with Parkinson's disease. The major liabilities of this drug with respect to its use in patients with medical and neurological illness would be its high anticholinergic profile, its propensity to cause orthostatic hypertension, and its potential to lower the seizure threshold. Nevertheless, c10zapine may have definite advantages in patients who are prone to extrapyramidal reactions since it has minimal extrapyramidal effects. Specifically, the drug has been safely used in patients with psychosis in Parkinson's disease and has actually been found to improve symptoms of Parkinson's disease. 11ll The reported problems with agranulocytosis (I % to 2% of patients) now requires weekly blood monitoring. Of those patients at low doses (below 300 mg/day), 1%-2% are at risk of seizure: this risk increases to 3%-4% for those patients on intermediate doses and appears to reach a prevalence of 5% at higher doses (600-900 mg/day). LITHIUM Renal Disease Patients with impaired renal function present potential problems in prescribing lithium since the kidney is the route of excretion. Lithium essentially occupies the "sodium space," and any condition or medication that affects the movement of sodium is likely to affect the disposition of lithium and, hence, its serum concentration. VOLUME

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Common examples of such conditions are volume depletion and thiazide diuretic use. Volume depletion, in the medically ill patient, can result from diarrhea, vomiting, polyuria, and excessive sweat loss. Decreased replenishment of salt and water, due to a patient's physical disabilities or to decreased sensation of thirst, can also result in volume depletion. All the conditions mentioned would result in a contraction of the sodium space; the result is increased proximal renal tubular sodium and increased lithium reabsorption. This leads to a higher lithium blood level for a given daily dose of lithium. Diuretics vary in their effect on sodium and lithium clearance. Thiazide diuretics probably cause more proximal reabsorption than furosemide and more than the potassium-sparing agents spironolactone and triamterene. Furosemide does not appear to have clinically significant effects on lithium excretion. I II Amiloride, a potassiumsparing diuretic, decreases lithium transport into collecting duct cells and inhibits lithium-induced resistance to vasopressin (an antidiuretic hormone [ADH]). Amiloride does not have an effect on lithium excretion and appears to be helpful in decreasing lithium-induced diabetes insipidUS.!·II!.II.'

Some drugs with diuretic effects, such as acetazolamide and the methylxanthines, actually increase lithium excretion. The nonsteroidal antiintlammatory drugs (NSAIDs) reduce the clearance of lithium and, like thiazide diuretics, result in increased lithium levels for a given oral dose of Iithium."~ Aspirin has no effect on lithium clearance. Patients on hemodialysis do not eliminate lithium between dialyses. Since lithium dialyzes easily, it should be replaced after each dialysis, and need not be given between dialyses. To determine the appropriate dosage, a lithium level should be checked 2-3 hours after the dose. The usual dose is 300-600 mg/day, but it may be higher or lower according to the patient's body weight and the target lithium level."~ Elderly patients are more susceptible to tremor and lithium-induced delirium. Renal function can decrease 30%-40% with advancing age, thus generally dictating lower dosages in the J7

Psychotropic Drug Use in the Medically III

elderly to maintain a given serum level. I 16 Carbamazepine and possibly sodium valproate are alternative considerations for bipolar patients in whom the use of lithium is problematic because of renal disease or the concurrent use of diuretics. Drug interactions with lithium are summarized in Table 2. Other Side Effects Lithium has been reported to cause hypothyroidism in 2%-15% of patients taking the drug. Another 3%-4% may develop goiter without clinical or chemical hypothyroidism. Those at greatest risk for hypothyroidism may be those who demonstrate marked elevations of thyroidTABLE 2.

stimulating hormone (TSH). The occurrence of hypothyroidism during treatment with lithium need not mandate the cessation of the lithium. Thyroid function tests (TSH and T4). however. should be monitored at 3- to 6-month intervals. Should the TSH become elevated or the T4 decreased. exogenous thyroid hormone should be administered. followed by continuation of monitoring. Cardiac effects are generally insignificant. although the EKG may be altered nonspecifically. Reversible nonspecific T-wave changes occur but are of little clinical significance. although these changes may reflect a shift of intracellular lithium in exchange for potassium. possibly reflecting intracelIular hypokalemia and

Drug interactions with lithium (Li+)'·~.\·I1~

Medication

Interactive Effect

Thiazide diuretics: spironolactone: triamterene: enalapril: 161 non-steroidal anti-inflamrnatants (e.g.. indomethacin. ibuprofen. phenylbutazone. pirox icam) \(.1

Raise Li+ levels

Acetazolamide: theophylline: aminophylline Calcium channel blockers 10.1. If>.l

Lower Li' levels May either raise or lower Li+ levels. effects not clear: verapamil may cause brddycardia when used with Li' May increase lithium levels: may increase chances of nephrotox ic ity Minor elevation of Li+ levels

Metronidazole

lM

Tetracycline

TABLE 3.

Drug interactions with benzodiazepines, psychostimutants. and carbamazepinel.~

Medication Benzodiazepines Cimetidine: disulfiram: ethanol; isoniazid Estrogens; cigarettes; methylxanthine derivatives; rifampin Psychostimutants Guanethidine Vasopressors Oral Anticoagulants Anticonvulsants Tricyclics MAO-I"s Carbamazepine lM Erythromycin Anti-arrhythmics Diltiazem: 107 venlpamil; lOll danazol l &!

Interactive Effect May elevate serum levels of benzodiazepines metabolized predominantly by oxidation Tend to lower benzodiazepine levels

Decreased anti-hypenensive effect Increased pressor effect Increased prothrombin time Increased levels of phenobarbital. primidone. phenytoin Increased blood levels of CyAD Hypenension May raise carbamazepine levels and precipilate hean block May have additive effects on cardiac conduction time May raise carbamazepine levels 10 toxic levels

Note: MAO-I=monoamine oxidase inhibitor: CyAD=cyclic antidepressant.

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thereby enhancing sensitivity to digitalis toxicity.117.1IK The most common cardiac abnormality associated with lithium in therapeutic doses is sinoatrial node dysfunction; aggravation of ventricular arrhythmias and heart block have been very rarely reported.119-122 On the other hand. antiarrhythmic effects of lithium have been described.'2.~.'24

Practical Considerations The major adjustment required for lithium treatment in the medically ill involves adjusting dosage in the face of renal disease. dialysis. advanced age. and concurrent use of thiazide diuretics and certain other medications. such as methylxanthine derivatives and nonsteroidal anti-intlammatants (Table 2). Since patients who are elderly are more sensitive to the side effects of lithium (e.g.. tremor and cognitive dysfunction). serum levels should be adjusted to the lower end of the therapeutic range. if possible. although clinical efficacy could possibly be effected at lower serum levels. If elderly bipolar patients show special sensitivity to the side effects of lithium. carbamazepine or possibly sodium valproate may be considered as alternative drugs. PSYCHOSTIMULANTS The use of psychostimulants in the treatment of depressed. medically debilitated patients periodically receives attention.12~-m and several recent reports have indicated their usefulness in treating depression and cognitive dysfunction in patients with AIDS. 12K Most of the recommendations for use of psychostimulants are based on uncontrolled short-term use ofthe drugs in medical-surgical patients. The dose ranges suggested for methylphenidate vary from 10-40 mg/day and 10-20 mg/day for dextroamphetamine given in divided doses early in the day. The half-life for methylphenidate is much shorter than dextroamphetamine (2 vs. 12 hours). Despite the reports of the use of psychostimulants in the treatment of dysphoric and VOLUME.n· NUMBER I • WINTER )'1'11

depressive reactions in the medically ill. caution should be exerted for a number of reasons: I) there is a paucity of controlled outcome studies; 2) these drugs do not have formal FDA approval for the treatment of depression. and. thus. careful documentation as to the rationale for their use is required; 3) there may be rebound depression. agitation. and psychotic reactions; and 4) dependency may result (primarily from the use of amphetamines).129 A less controversial indication for their use is in the treatment of pain in cancer patients to counteract the oversedation of narcotics.I.~() In this setting. problems with dependency are moot. since most of these patients will have limited life expectancies. Drug interactions are summarized in Table 3. CARBAMAZEPINE Over the past few years. carbamazepine has emerged as an alternative agent for bipolar disorder in patients refractory to lithium therapy or intolerant of it for medical reasons. It has also been successfully employed in the treatment of explosive behavior. some forms of dysthymia. atypical psychoses. and organic mental syndromes following frontal lobe injury. Its dose-related toxicities include ataxia. diplopia. and sedation. Several additional toxicities are particularly relevant when carbamazepine is used in patients with concurrent medical illness. These include: I) hematologic toxicity. 2) hepatic toxicity. 3) hyponatremia. 4) quinidine-like cardiac effects. and 5) effects on the pituitary-thyroid axis. Carbamazepine produces a transient reduction in white blood count in approximately 10% of patients during the first 4 months of treatment.I.~1 Much more rarely. it produces the potentially fatal side effects of agranulocytosis and aplastic anemia. The incidence of the latter complication has been estimated at 0.5 cases per 100.000 treatment-years. 1.~2 Neitherthe age of the patient nor the duration of treatment predicts the development of aplastic anemia. which may have a mortality rate as great at 50%. n.~ Because of the risk of early neutropenia. weekly or biweekly monitoring of white blood

Psychotropic Drug Use in the Medically III

count is a reasonable precaution during the first few months of therapy. During this time. carbamazepine should in most cases be discontinued if the white blood count drops below 3500. However. exceptions may need to be made when the psychiatric indications for carbamazepine are very strong or when the patient has a concurrent medical problem or drug treatment that might also be contributing to the decreased blood count. In this situation. hematologic consultation is advisable to determine the appropriate frequency of monitoring and cut-off point for drug discontinuation. Concurrent administration of lithium and carbamazepine lowers the risk for neutropenia because lithium stimulates white blood cell production. The lithium-carbamazepine combination thus might be considered in a patient who has concurrent or preexisting medical or hematologic problems that depress the white count and who has bipolar disorder unresponsive to lithium alone. I34 .1.15 Hepatic toxicity from carbamazepine. like hematologic toxicity. comes in a benign and frequently occurring form. as well as in a rare and malignant form. Benign carbamazepine toxicity consists of mild asymptomatic elevations in serum glutamic oxaloacetic transaminase (SGOT). serum glutamic pyruvic transaminase (SGPT). and gamma glutamyl transpeptidase (GGTP). which occur in 5%-10% of patients treated with the drug. DH17 Life-threatening acute hepatitis with liver failure occurs on an allergic basis in less than I in 10.000 treated patients. 1.17 This toxicity most often occurs during the first month of therapy. While the hepatic toxicity of carbamazepine may be additive to other liver disease or hepatotoxic drugs. synergy has not been conclusively demonstrated. Therefore. in a patient with preexisting liver disease. carbamazepine would be relatively. but not absolutely. contraindicated. Frequent monitoring of liver enzymes and prothrombin time. however. would be a reasonable precaution. While in patients without liver disease. elevations of SGOT and SGPT to twice normal would usually be acceptable. the upper bounds of transaminase elevation might need to be greater in patients with preexisting liver disease who required car40

bamazepine therapy. Consultation with a gastroenterologist would be indicated to choose both an appropriate schedule for monitoring and a criteria for drug discontinuation. Hyponatremia is a frequently occurring side effect of carbamazepine. for which advanced age and higher serum levels are risk factors. 1.1K-1411 The effect may be due to a combination of renal and hypothalamic actions '41 and may be aggravated by other conditions predisposing to hyponatremia. including diuretic use. congestive heart failure. and occult malignancy. Patients with risk factors for hyponatremia should receive weekly electrolyte determinations during the first month of carbamazepine therapy. with additional determinations if there is any significant change in physical or mental status. carbamazepine dosage. or other medications known to affect carbamazepine levels or serum sodium itself. Should hyponatremia occur. the c1inician's response should depend upon its severity. Sodium levels of less than 125 mEqIL would usually be a reason to discontinue carbamazepine. Lesser degrees of hyponatremia should be considered relative to the strength of the indication for the drug; in some cases other drugs aggravating hyponatremia. such as diuretics. could be discontinued instead. Persistent hyponatremia. despite discontinuation of carbamazepine. would indicate a full work-up for inappropriate ADH secretion. Carbamazepine shares a tricyclic structure with the tricyclic antidepressants. and. like them. it has quinidine-like cardiac effects. Clinically significant aggravation of heart block has been reported. 14~.IH Thus. patients over 40 or with known cardiac risk factors should have a pretreatment EKG before receiving carbamazepine. Precautions and relative contraindications for carbamazepine are identical with those for tricyclic antidepressants. Carbamazepine has been implicated in a large number of drug interactions. Two are particularly deserving of emphasis in the context of psychiatric treatment of the medically ill. The first is carbamazepine's potent effect on inducing drug metabolism by the hepatic microsomal system. l44 The effect of microsomal enzyme inducPSYCHOSOMATICS

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tion is to lower serum levels of other drugs metabolized by the liver. including (among many others) tricyclic antidepressants. neuroleptics. propranolol. quinidine. phenytoin. valproic acid. and warfarin. There is considerable inter-individual variation in the clinical significance of these effects. Levels of drugs metabolized by the hepatic microsomal system should probably be obtained more often in patients taking carbamazepine; repeat levels of the other medications may be needed if carbamazepine doses are changed significantly. Since carbamazepine is metabolized by the liver. drugs that inhibit the hepatic metabolic enzymes may raise carbamazepine levels. Such interactions may be clinically significant. leading to acute carbamazepine toxicity after a new drug is added. These types of clinically significant interactions have been reported for verapamiI.'4~.14h di ltiazem. '47 danazol. '4x propoxyphene.14~ and the antibiotic erythromycin.l~o Carbamazepine has two antithyroid effects: it increases the peripheral metabolism of thyroid hormone.'~' and it decreases TSH secretion by a direct effect on the pituitary .I~~ On occasion. these effects lead to the development of hypothyroidism'~1 or to an increase in the thyroxine requirement for patients already receiving thyroid replacement therapy.'~4 Patients receiving concurrent treatment with lithium and carbamazepine may experience additive antithyroid effects. The subtlety in considering thyroid effects of carbamazepine is that TSH levels may not necessarily be elevated even when the patient is hypothyroid because of the effect of carbamazepine on the pituitary. Patients with thyroid disease should have a complete thyroid function panel after carbamazepine therapy is instituted. and thyroid replacement-or an increase in thyroxine dosage-should be considered if the patient appears hypothyroid. even when the TSH is not elevated.'~~

Carbamazepine's direct or indirect effects on a number of neurotransmitter systems. including the dopaminergic. serotonergic. and cholinergic. imply its potential for pharmacodynamic interaction with conventional psychotropics. Numerous reports describe toxicity from combinaVOLUME 32· NUMBER I· WINTER 1'1'11

tions of carbamazepine with lithium or neuroleptics. even though the dosage of none of the drugs was excessive. Since such combinations may be potent and effective treatments for refractory mood disorders. the practical recommendation is for close monitoring. conservative dosage. and slow dosage increments when carbamazepine is combined with lithium or neuroleptics. 41 SUMMARY Although psychotropic agents must be used with a greater degree of caution in patients with underlying medical disease. there are relatively few absolute medical contraindications to their use. In each clinical situation. an assessment must be made of potential negative interactions with medical drugs. physiological factors that may affect drug half-life. clearance and end-organ sensitivity. and physiological/disease-related vulnerabilities of the patient. Even when the clinical situation may prevent the use of some psychotropics (such as the use of tricyclic antidepressants in patients with heart block). alternative agents are usually available. Finally. electroconvulsive therapy should be considered as a potential primary treatment for severely depressed medical patients. In medically debilitated depressed patients and those with advanced cardiovascular disease. appropriate pharmacologic management prior to and during anesthesia can usually attenuate the autonomic responses. such as hypertension and tachycardia. that pose the primary risks for elderly patients with cerebrovascular or cardiovascular disease. Advanced technical reviews of the use of electroconvulsive therapy and special anesthetic considerations in the medically ill may be found elsewhere.'~~·'~h

References

The reference section that follows provides a complete listing ofthe sources cited in hoth Part I and Part /I ofthis study. I. Sargenli CJ. Rizos AL. Jesle DV: Psycholropic drug interactions in the patient wilh lale-onset psychosis and

41

Psychotropic Drug Use in the Medically III

mood disorder. I. Psychiatr Clin North Am 11:235-252. 1988 2. Rizos AL. Sargenti CJ. Jeste OV: Psychotropic drug interactions in the patient with late-onset depression or psychosis. II. Psychiatr Clin North Am 11:253-277. 1988 3. Stoudemire A. Fogel BS: Psychopharmacology in the medically ill. in Principles a/Medical Psychiatry. Edited by Stoudemire A. Fogel BS. Orlando FL. Grune and Stratton. 1987. pp 79-112 4. Stoudemire A. Fogel BS. Gulley L: Psychopharmacology in the medically ill: an update. in Medical Psychiatric Practice. Edited by Stoudemire A. Fogel BS. Washington DC. American Psychiatric Press (in press) 5. Goodman WK. Charney OS: Therapeutic applications and mechanisms of action of monoamine oxidase inhibitor and heterocyclic antidepressant drugs.} Clin Psychiatry 46:6-22. 1985 6. Cohen LS. Heller VL. Rosenbaum JF: Treatment guidelines for psychotropic drug use in pregnancy. Psychosomatics 30:25-33. 1989 7. Cohen LS. Heller VL. Rosenbaum JF: Psychotropic drug use in pregnancy: an update. in Medical Psychiatric Practice. Edited by Stoudemire A. Fogel BS. Washington DC. American Psychiatric Press (in press) 8. Goldstein MG: Intensive care unit syndromes. in Principles of Medical Psychiatry. Edited by Stoudemire A. Fogel BS. Orlando FL. Grune and Stratton. 1987. pp 403-421 9. Adverse reactions to the tricyclic-anlidepressant drugs: repon from Boston Collaborative Drug Surveillance Program. Lancet 1:529-531. 1972 10. Bigger JT. Giardina EGV. Perel JM. et al: Cardiac antiarrhythmic effect of imipramine hydrochloride. N Engl } Med 296:206-208.1977 II. Roose SP. Glassman AH. Giardina EGV. et al: Tricyclic antidepressants in depressed patients with cardiac conduction disease. Arch Cen Psychiatry 44:273-275. 1987 12. Stoudemire A. Atkinson P: Use of cyclic antidepressants in patients with cardiac conduction disturbances. Cen Hosp Psychiatry 10:389-397. 1988 13. Fricchione GL. Vlay SC: Psychiatric aspects of patients with malignant ventricular arrhythmias. Am} Psychiatry 143: 1518-1526. 1986 14. Schwanz P. Wolf S: QT interval prolongation as predictor of sudden death in patients with MIA. Circulation 57:1074-1077. 1978 15. Janowsky O. Cunis G. Zisook S: Ventricular arrhythmias possibly aggravated by trazodone. Am} Psychiatry 140:796-797. 1983 16. Rausch JL. Pavlinac OM. Newman PE: Complete heart block following a single dose of trazodone. Am} Psychiatry 141:1472-1473. 1984 17. Spar JE: Plasma trazodone concentrations in elderly depressed inpatients: cardiac effects and shon-term efficacy.} Clin Psychopharmaco/7:406-409. 1987 18. Sommi RW. Crismon ML. Bowden CL.et al: Fluoxetine: a serotonin-specific second-generation antidepressant.

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37. Falk WE: Trazodone and priapism. Biological Therapies ill PsvciliaTry 10:9-10. 1987 38. Stevenson DD. Simon RA. Lumry WR. et al: Adverse reactions to tartrazine. } AI/ergv Clill Imnllll/ol 78: 182191. 1986 39. Pohl R. Balon R. Berchou R. et al: Allergy to tanrazine in antidepressants. Am} PsychiaTry 144:237-238. 1987 40. Edwards JG. Long SK. Sedgwick EM. et al: Antidepressants and convulsive seizures: clinical. electroencephalog.raphic. and pharmacological aspects. Clill NeuropharmacoI9:329-360. 1986 41. Fogel BS: Combining anticonvulsants with conventional psychopharmacologic agents. in Use of AllIiCOII l'/tlsalll.\· ill P.n'ciliaTrv: Realll Ad'·alla.L Edited by McElroy SL. Pope HG. C1inon. NJ. Oxford Health Care. 1988. pp 77-94 42. Davidson J: Seizures and bupropion: a review. } Cfill PsvchiaTrv 50: 256-261. 1989 43. GlassmanJN. DugasJE. Tsuang MT: Idiosyncratic pharmacokinetics complicating treatment of major depression in an elderly woman.} NOT Melli Dis 173:573-576. 19H5 44. Rockwell E. Lam RW. Zisook S: Antidepressant drug studies in the elderly. PsvciliaTr Cfill NorTh Am 11:215233. 19HH 45. Nies A. Robinson DS. Friedman MJ. et al: Relationship between age and tricyclic antidepressant plasma levels. Am} Psychia/lT 134:790-793. 1977 46. Abernethy DR. Greenblan DJ. Shader RI: Imipramine and desipramine disposition in the elderly.} Pharmacol Exp Tiler 232: 183-1 HH. 19H5 47. Antal EJ. Lawson IR. Alderson LM. et al: Estimating steady-state desipramine levels in noninstitutionalized elderly patients using single dose disposition parameters. .! Clill Psychol'lwrmacoI2:193-19H. 1982 4H. Cutler NR. Zavadil AP III. Eisdorfer C: Concentrations of desipramine in elderly women are not elevated. Am.! PsychiaTry. 138:1235-1237.1981 49. Cutler NR. Narang PK: Implications of dosing tricyclic antidepressants and benzodiaz.epines in geriatrics. Psychilll/' Clill No,.,11 Am 7:845-H61. 1984 50. Kutcher SP. Shulman KI. Reed K: Desipramine plasma concentration and therapeutic response in elderly depressives: a naturalistic pilot study. Call} PsychiaTry 31:752-754.1986 51. Levy NB: Chronic renal disease. dialysis. and transplantation. in Prillciples of Medical PsychiaTry. Edited by Stoudemire A. Fogel BS. Orlando FL. Grune and Stratton. 19H7. pp 583-594 52. Dawling S. Lynn K. Rosser R. et al: Nortriptyline metabol ism in chronic renal failure: metabol ite elimination. Clill Pllarmacol Til('/' 32:322-329. 19H2 53. Lieberman JA. Cooper TB. Suckow RF. et al: Tricyclic psychopharmacology antidepressant and metabolite levels in chronic renal failure. Clill Pharmacol Ther 37:301-307. 1985 54. American Psychiatric Association: Task force repon on antidepressant drug levels. Am .! PsychiaTry 142: 155-

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162.1985 55. Kragh-Sorensen P. Asherg M. Hansen CE: Plasma nortriptyline levels in endogenous depression. LallceT 1:113-115.1973 56. Montgomery S. Braithwaite R. Dawling S. et al: High plasma nortriptyline levels in the treatment of depression. Cfill Pharmacol Ther 28:309-314. 1978 57. Ziegler VE. Clayton PJ. Taylor JR. et al: Nonriptyline plasma levels and therapeutic response. Cfin Pharmacol Ther 20:45~63. 1976 5H. Tariot PN. Cohen RM. Sunderland T. et al: L-Deprenyl in Alzheimer's disease. Arch GI'll P.H'chiaTry 44:427433. 1987 59. Ford MF: Treatment of depression in Huntington's disease with monoamine oxidase inhibitors. Br} Psychiatn' 149:654-656. 1986 60. Summergrad P: Depression in Binswanger's encephalopathy responsive to tranylcypromine: case repon. } Cfill Psychiatry 46:69-70. 19H5 61. Rabkin J. Quitkin F. McGrath P. et al: Adverse reactions to monoamine oxidase inhibitors. II: Treatment correlates and clinical management.} Cfill P.n'chopharmacol 5:2-9. 19H5 62. Lazarus LW. Groves L. Gierl B. et al: Efficacy of phenelzine in geriatric depression. 8iol PsychiaTry 21 :699701. 19H6 63. Buigues J. Vallejo J: Therapeutic response to phenelzine in patients with panic disorder and agomphobia with panic anacks.} Clin Psychiatry 48:55-59. 1987 64. Kronig MH. Roose SP. Walsh BT. et al: Blood pressure effects of phenelzine. } Clill P.n'chopharmacol 3:307310.19H3 65. Lin Soc. Hsu T. Fredrickson PA. et al: Yohimbine- and tranylcypromine-induced postural hypotension (leHer). Am} Psychiatry 144:119. 1987 66. Mallinger AG. Edwards DJ. Himmelhoch JM. et al: Pharmacokinetics of tranylcypromine in patients who are depressed: relationship to cardiovascular effects. Cfill Pharmacol Ther 40:444-450. 1986 67. Georgotas A. McCue RE. Friedman E. et al: A placebocontrolled comparison of the effect of nortriptyline and phenelzine on orthostatic hypotension in elderly depressed patients. J Clin Psyclwpharmacol 7:413-416. 1987 68. Braverman B. McCanhy RJ. Ivankovich AD: Vasopressor challenges during chronic MAOI or TCA treatment in anesthetized dogs. Life Sciellce 40:2587-2595. 1987 69. Clary C. Schweizer E: Treatment of MAOI hypenensive crisis with sublingual nifedipine. J Clin Psychiatry 4H:249-250.19K7 70. Merikangas JR. Merikangas KR: Calcium channel blockers in MAOI-induced hypenensive crisis. Psychopharmacology 96(suppl):229. 1988 71. Harris B. Young J. Hughes B: Comparative effects of seven antidepressant regimes on appetite. weight and carbohydrate preference. Br J Psychiatry 148:590-592. 1986 72. Robinson DS. Kayser A. Bennen B. et al: Maintenance

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