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ANTICHOLINERGIC EFFECTS AND HAZARDS
Abstracts favorable side-effect profile associated with few or no drug interactions. This aids in compliance.
elderly or those ⱖ75, although this group may be the most difficult to treat.
DEPRESSION AND DEMENTIA. Ira R. Katz, M.D., Ph.D.
ANTICHOLINERGIC EFFECTS Larry E. Tune, M.D.
L
B
ate-life depression, in general, occurs in the context of comorbid medical/neurological illnesses or other psychiatric disorders, such as dementia. There is evidence that depression remains a diagnosable and treatable disorder in the presence of comorbid conditions as diverse as AD, stroke, Parkinson’s disease, arthritis, cancer, cardiac disease, chronic obstructive pulmonary disease, and diabetes. With increasing knowledge, the questions facing clinicians have advanced from whether depression should be diagnosed and treated to how it should be done. Recent research findings in this area include differential effects of selective serotonin reuptake inhibitors vs. tricyclic antidepressants on glucose control in diabetes, and changes in plasma level-response relationships for nortriptyline in AD. There are ongoing questions about optimal methods for screening for and identifying depression in the face of significant medical illness, and the impact of subcortical/deep white matter hyperintensities on treatment responses.
REVIEW OF AVAILABLE TREATMENTS FOR LATELIFE DEPRESSION. Craig Nelson, M.D.
D
epression is common in late life, especially in patients with medical illness or in institutional health care settings. Fortunately, a variety of treatments are available for patients who develop late-life depression. Both psychotherapy and pharmacotherapy appear to be effective, although the latter has been better studied. In 1988, Gershon et al. found 25 double-blind studies examining depression in late life. Almost all of these were studies of the tricyclic antidepressants (TCAs). Although only 13 of these studies were placebo controlled, in general, they found antidepressants to be effective. In a subsequent review of recent studies by Nelson in 1997, 19 studies of selective serotonin reuptake inhibitor compounds were identified. Thirteen of these studies provided a comparison with a TCA. These studies demonstrated comparable efficacy for the two groups of drugs, but with higher dropout rates associated with the TCAs due to adverse effects. Several studies also demonstrated less adverse effects on cognitive function for the selective serotonin reuptake inhibitors than for the TCAs. The studies provide information about special issues in older adults, such as appropriate dosing and duration of treatment, sensitivity to side effects, resistance to treatment, and drug interactions. Much of the data on elderly patients comes from samples of reasonably healthy patients ⬍ 75. Few studies have been completed in the frail
Am J Geriatr Psychiatry Supplement, Fall 1999
AND
HAZARDS.
ecause of age- and disease-related (e.g., dementia) changes in cholinergic neurotransmission, one important source of “cognitive toxicity” in older adults is the antimuscarinic effect of psychotropic medications either alone (direct anticholinergic toxicity) or in combination with other medications (cumulative anticholinergic toxicity). Data from preclinical and clinical investigations strongly suggest that many antidepressants have significant adverse effects on tests of recent memory, attention, and motor performance. The most toxic of these agents include amitriptyline, imipramine, doxepin, and clomipramine. Preclinical and clinical data include in vitro measurements of the relative antimuscarinic effects of these medications using radioreceptor assay methods. The use of antidepressants in older adults raises greater concerns because of the number of concomitant nonpsychiatric medications with modest antimuscarinic effects. These include commonly prescribed medications like digoxin, furosemide, prednisolone, and cimetidine. Data from published and ongoing studies show significant effects of these medication combinations on measures of behavior, cognition, and activities of daily living. Many antidepressants have little or no cognitive toxicity. In some cases, subtle cognitive enhancing effects have been shown, e.g., sertraline, fluoxetine, and citalopram. These agents should be considered first-line therapy. Antidepressants associated with cognitive toxicity should be avoided.
PHARMACOLOGICAL INTERACTIONS. David J. Greenblatt, M.D.
T
he availability of selective serotonin reuptake inhibitors and related mixed-mechanism antidepressants during the last 10 to 15 years has increased the therapeutic options available for patients with depression but has also reopened the general clinical problem of drug interactions in psychopharmacology. This is of particular concern for older adults, who may be receiving multiple pharmacologic treatments for psychiatric disorders coexisting with other medical disease. Understanding the function and regulation of the human cytochrome P450 (CYP) family of drug-metabolizing enzymes is of considerable value in bringing a vast amount of data on drug interactions into a manageable perspective. The major human CYP enzymes (1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) have distinct mechanisms of geriatric control, substrate specificities, and susceptibility to induction and inhibition. Many drug inter-
23
elderly or those ⱖ75, although this group may be the most difficult to treat.
DEPRESSION AND DEMENTIA. Ira R. Katz, M.D., Ph.D.
ANTICHOLINERGIC EFFECTS Larry E. Tune, M.D.
L
B
ate-life depression, in general, occurs in the context of comorbid medical/neurological illnesses or other psychiatric disorders, such as dementia. There is evidence that depression remains a diagnosable and treatable disorder in the presence of comorbid conditions as diverse as AD, stroke, Parkinson’s disease, arthritis, cancer, cardiac disease, chronic obstructive pulmonary disease, and diabetes. With increasing knowledge, the questions facing clinicians have advanced from whether depression should be diagnosed and treated to how it should be done. Recent research findings in this area include differential effects of selective serotonin reuptake inhibitors vs. tricyclic antidepressants on glucose control in diabetes, and changes in plasma level-response relationships for nortriptyline in AD. There are ongoing questions about optimal methods for screening for and identifying depression in the face of significant medical illness, and the impact of subcortical/deep white matter hyperintensities on treatment responses.
REVIEW OF AVAILABLE TREATMENTS FOR LATELIFE DEPRESSION. Craig Nelson, M.D.
D
epression is common in late life, especially in patients with medical illness or in institutional health care settings. Fortunately, a variety of treatments are available for patients who develop late-life depression. Both psychotherapy and pharmacotherapy appear to be effective, although the latter has been better studied. In 1988, Gershon et al. found 25 double-blind studies examining depression in late life. Almost all of these were studies of the tricyclic antidepressants (TCAs). Although only 13 of these studies were placebo controlled, in general, they found antidepressants to be effective. In a subsequent review of recent studies by Nelson in 1997, 19 studies of selective serotonin reuptake inhibitor compounds were identified. Thirteen of these studies provided a comparison with a TCA. These studies demonstrated comparable efficacy for the two groups of drugs, but with higher dropout rates associated with the TCAs due to adverse effects. Several studies also demonstrated less adverse effects on cognitive function for the selective serotonin reuptake inhibitors than for the TCAs. The studies provide information about special issues in older adults, such as appropriate dosing and duration of treatment, sensitivity to side effects, resistance to treatment, and drug interactions. Much of the data on elderly patients comes from samples of reasonably healthy patients ⬍ 75. Few studies have been completed in the frail
Am J Geriatr Psychiatry Supplement, Fall 1999
AND
HAZARDS.
ecause of age- and disease-related (e.g., dementia) changes in cholinergic neurotransmission, one important source of “cognitive toxicity” in older adults is the antimuscarinic effect of psychotropic medications either alone (direct anticholinergic toxicity) or in combination with other medications (cumulative anticholinergic toxicity). Data from preclinical and clinical investigations strongly suggest that many antidepressants have significant adverse effects on tests of recent memory, attention, and motor performance. The most toxic of these agents include amitriptyline, imipramine, doxepin, and clomipramine. Preclinical and clinical data include in vitro measurements of the relative antimuscarinic effects of these medications using radioreceptor assay methods. The use of antidepressants in older adults raises greater concerns because of the number of concomitant nonpsychiatric medications with modest antimuscarinic effects. These include commonly prescribed medications like digoxin, furosemide, prednisolone, and cimetidine. Data from published and ongoing studies show significant effects of these medication combinations on measures of behavior, cognition, and activities of daily living. Many antidepressants have little or no cognitive toxicity. In some cases, subtle cognitive enhancing effects have been shown, e.g., sertraline, fluoxetine, and citalopram. These agents should be considered first-line therapy. Antidepressants associated with cognitive toxicity should be avoided.
PHARMACOLOGICAL INTERACTIONS. David J. Greenblatt, M.D.
T
he availability of selective serotonin reuptake inhibitors and related mixed-mechanism antidepressants during the last 10 to 15 years has increased the therapeutic options available for patients with depression but has also reopened the general clinical problem of drug interactions in psychopharmacology. This is of particular concern for older adults, who may be receiving multiple pharmacologic treatments for psychiatric disorders coexisting with other medical disease. Understanding the function and regulation of the human cytochrome P450 (CYP) family of drug-metabolizing enzymes is of considerable value in bringing a vast amount of data on drug interactions into a manageable perspective. The major human CYP enzymes (1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) have distinct mechanisms of geriatric control, substrate specificities, and susceptibility to induction and inhibition. Many drug inter-
23