Letter to the Editor

Letters to the Editor are invited for comment on a topic of current interest or on Table material published in GENERAL HOSPITAL PSYCHIATRY. Letters should be typed doubled spaced and are subject to editing according to space limitations. -

Memory Deficits Associated with Attent KnO Clonidine WA Verbal WA Drugs used in the treatment of essential hyperten- Initiation of clonidine therapy (0.1 mg b.i.d.) in WA sion are among the most commonly prescribed. April 1984 resulted in well-controlled hypertension Tactilc Some of these agents have primary effects on neu- without immediately apparent adverse effects. Fulc rotransmitter systems and are centrally active. However, the coincidence of the onset of memory Verba Thus, drugs such as a-methyldopa, propranalol, complaints and the beginning of clonidine treat- 3% ment suggested that clonidine might be respon- List Ll and reserpine have well-established neuropsychia- Fulc tric complications, ranging from depression to cog- sible. si nitive impairments and psychosis [l].Since the use After consultation with the patient's internist, a R of these drugs is widespread and unavoidable, we switch was made to captopril, an angiotensin-con- T must be alert to the possibility that these drugs verting enzyme inhibitor. Before the change we T administered tests of attention, concentration, and contribute to psychologic complaints and symp- -R toms of our patients. verbal skills as well as the Fuld Object-Memory Evaluation, which includes a measure of verbal 'Age-a Clonidine, a presynaptic adrenergic a2agonist, bNonc has become well established as a useful and rela- fluency as well as a selective reminding list learning tively safe therapeutic agent. Its potential for psy- task. This test was developed to assess memory chiatric morbidity is still incompletely understood. function in aged populations, and has appropriate the a We have recently treated an elderly hypertensive normative data [2]. As shown in Table 1, the pa- chara diabetic who developed a memory deficit second- tient's performance on tests of attention and con- anisn since ary to the use of clonidine hydrochloride. centration, verbal abilities, and verbal fluency were average to superior. However, he had a deficit in The patient was a 74-year-old retired white male o'y 1 short-term memory, with low scores in initial re- and ( with insulin-dependent diabetes and hyperten- call, recall of the same items on consecutive trials, of Cll sion. He had been hospitalized in September 1983 and recall after a 5-minute delay. geste for a depressive illness precipitated by the breakup One month after the medication change the pa- with of his marrige of 42 years. At the time of admission tient reported that his memory problems had dis- cloni he manifested symptoms of depression, anxiety, appeared. Repeat testing, using the alternate form SUrpl insomnia, and suicidal ideation. His depression re- of the Fuld test, showed a marked improvement studi sponded well to doxepin and supportive psycho- in the list learning task. As Table 1 demonstrates, tiona therapy; doxepin was discontinued after only a few his performance was now above the mean on all in hi months. By January 1985 he had been free of clin- subtests. Five months later the patient reported Ek ical signs of depression for over 1 year. In addition that the improved level of functioning was stable. pres to his continuing distress over his marriage, he Clonidine has been associated with the emer- long now complained of significant memory lapses, gence of psychiatric symptomatology. Three an- PEd which he had noticed only in the previous 6-9 ecdotal reports describe delirium or dementia in defic months. Specific instances included opening the patients on clonidine, with remission of symptoms to th refrigerator and forgetting what he had come for, after its discontinuance [3-51. Hallucinations and plaa and frequently forgetting why he had left the delusions associated with a clear sensorium have nitiV house. He reported going for the wrong ball during also been reported [6, 71. A study of adolescent ager pool games and, on two occasions, forgetting to patients failed to find any significant deficits, take his regular insulin dose. whereas withdrawing opiate addicts may expen- The patient had been treated for hypertension ence psychomotor slowing [8, 91. Cognitive func- for over 10 years, usually with thiazide diuretics. tion in elderly and/or medically ill patients has not When these became less effective, other treatments been studied. were initiated. A trial of prazosin hydrochloride The case reported here differs from those cited had been terminated due to postural hypotension. in that a discrete memory deficit was present in

154 General Hospital Psychiatry 9, 154-155 1987 ISSN 01638343/87/$3.50 0 1987 Elsevier Science Publishing Co., In(. 52 Vanderbiit Ave., New York, NY 10017 Letter to the Editor

Table 1. Results of cognitive testing during (session 1) and after cessation (session 2) of clonidine treatment T Session 1 Session 2 Attention and Concentration: Knox Cube Test, total raw score (rating) 15 (superior) not repeated WAIS-R Digit Span, AASS (range) 15 (superior) not repeated Verbal Abilities: WAIS-R Vocabulary, AASS' (range) 11 (average) not repeated in WAIS-R Similarities, AASS (range) 13 (high average) not repeated ion Tactile Recognition of Common Objects: 3s. Fuld Object-Memory Evaluation 8 of 10 10 of 10 Verbal Fluency: 3'y tat- 3 Semantic Categories, total (Z-score) 38 (1.5) 43 (2.2) m- List Learning: Fuld Object-Memory Evaluation Storage after 5 trials 10 of 10 10 of 10 t, a Recall on 1st trial, raw (Z-score) 5(-1.5) 7 (0.5) on- Total recall on consecutive trials 20 (-0.9) 30 (0.7) we Total recall for 5 trials 36 (-0.5) 42 (0.4) md Retention after 5-minute delayh 7 9 o'y bal 'Age-adjusted scale score. hNonorms available. ing o'y ate the absence of the global intellectual impairment References characteristic of dementia or delirium. The mech- Pa- 1. Henning M: Adverse reactions to ant,.ypertensive on- anism of this impairment is not immediately clear, drug therapy: central nervous system. Acta Med ere since the role of noradrenergic functions in mem- %and Suppl628:33, 1979 t in ory has yet to be established. Recently, Arnsted 2. Fuld PA: The Fuld Object-Memory Evaluation Test. re- and Goldman-Rakic [ 101 reported facilitative effects Chicago, Stoelting Instrument Co., 1981 als, of clonidine on cognition in primates and sug- 3. Allen RM, Flemenbaum A: Delirium associated with combined fluphenazine-clonidine therapy. J Clin gested that it may prove useful in therapeutic trials Psychiatry 40236-237, 1979 Pa- with demented patients. This makes the effect of 4. Hoffman WF, Ladogana L: Delirium secondary to iis- clonidine on memory function in our patient more clonidine therapy. NY State J Med 81:382-383, 1981 )rm surprising, and underlines the need for clinical 5. Lavin P, Alexander CP: Dementia associated with ent studies before drawing conclusions about the func- clonidine therapy (letter). Br Med J 1:628, 1975 6. Enoch MD, Hammad GEM: Acute hallucinosis due tes, tional significance of specific transmitter systems to clonidine. Curr Med Res Opin 4:670-671, 1977 all in humans. 7. Brown MJ, Salmon D, Rendell M: Clonidine hallu- ted Because this patient's deficit was discrete, its cinations. Ann Intern Med 93:456-457, 1980 3le. presence might easily have been overlooked. His 8. Falkner 8, Koffler S, Lowenthal DT: Effects of anti- ier- long-standing diabetes and hypertension may have hypertensive drugs on cognitive function in adoles- cents. Ped Pharmacol4239-244, 1984 an- predisposed him to the development of memory 9. Preston KL, Bigelow GE, Liebson IA: Self-adminis- tin deficits. Patients in this age group are often subject tration of clonidine, oxazepam, and hydromorphone )ms to these risk factors and are also very likely to be by patients undergoing methadone detoxification. and placed on this agent. Controlled studies of the cog- Clin Pharmacol Ther 38:219-227, 1985 ave nitive effects of clonidine and other hypertensive 10. Arnsten AFT, Goldman-Rakic PS: a2 adrenergic mechanisms in prefrontal cortex associated with cog- :ent agents in elderly populations are necessary. nitive decline in aged nonhuman primates. Science its, 230:1273-1276, 1985 eri- inc- George Fein, Ph.D. Edward L. Memn, M.D. not Linda Davenport, M.S. John C. Buffum, Pharm.D. ited University of California, Sun Francisco, California tin VAMC, Sun Francisco, California 155 387 ., Inc. 11 7 i .-