Letters On "Psychological Factors Affecting a Physical Condition" SIR: I am greatly pleased to see that the DSMIV committee on "Psychological Factors Affecting a Physical Condition" (PFAPC) are fundamentally rethinking the metatheory upon which the diagnosis is based. even if a radical new scheme has not yet emerged. I I have been troubled for some time by the lack of specificity in this syndrome. For example. we now have replicated. controlled. prospective evidence that anger! hostility,2 major and minor depression;1.4 anxiety.5 social isolation!alienation.6-8 and sleep apnea9 . 10 are major risk factors for ischemic heart disease (IHD). And at least one well-controlled treatment study has confirmed causal status for anger and hostility.11.I2 Yet all these conditions are lumped together. The clinical functions of a diagnostic category are I) to predict course of illness. and!or 2) to predict response to treatment regimens. Given that the treatment implications of each of the above risk factors are different. one major rationale for splitting these categories is met. D I am troubled. though. by one briefstatement by Drs. Stoudemire and Hales' that appears to misconstrue the meaning of controlled prospective studies. If statistically significant residual variance between a putative risk factor and a disease is found in a primary analysis. but not after controlling for other known risk factors. it does not prove that the risk factor is not causal. Rather. it may imply that the risk factor's effect is mediated by one or more of the control variables. As an example. let us suppose that the primary relationship between depression and IHD disappears when smoking is controlled. Let us further suppose that successful achievement of smoking cessation or relapse avoidance in depressed patients requires that the depression first be treated. The clinical implication. then. is that. while mediated by smoking. the effect of depression on IHD is (indirectly) causal and clinically important. It seems to me that a distinction should be made here between direct "psychophysiological" and indirect "behavioral" mechanisms. The forVOLUME 32· NUMBER 4 • FALL 1991

mer encompass the neural or neuroendocrine effects of mental states or characteristics. The latter encompass behaviorally mediated mechanisms. such as increased smoking. noncompliance. symptom denial leading to treatment delay. etc. These behaviorally mediated mechanisms are of no less medical significance than the psychophysiological mechanisms. For example. smoking cessation after receiving a diagnosis of IHD is associated with a 50% reduction in risk for new cardiac events. 14 an effect larger than any other medical or surgical treatment. 15.16 Can we responsibly ignore those psychological characteristics that influence the indirect behavioral mechanisms? Mark W. Ketterer. Ph.D. ConsultationlLiaison Psychiatry Henry Ford Hospital Detroit. Michigan

References I. Stoudemire A. Hales RE: Psychological and behavioral factors affecting medical conditions and the OSM-IV: an overview. Psychosomatics 32:5-13, 1991 2. Dembroski TN. MacDougall JM, Costa PT. et al: Components of hostility as predictors of sudden death and myocardial infarction in the multiple risk factor intervention trial. Psychosom Med 51 :514-522.1989 3. Carney RM, Rich MW, Freedland KE, et al: Major depressive disorder predicts cardiac events in patients with coronary anery disease. Psychosom Med 50:627--{)33, 1988 4. Patillo J, Thoreson CE, Buchanan GM, et al: Depressive behavior pattern, explanatory style, anger and type A as predictors of coronary recurrence. ProuedinRS of the Society ofBehavioral Medicine II :64, 1990 5. Haines AP, Imeson JO, Meade TW: Phobic anxiety and ischemic hean disease. BMJ295(6593):297-299. 1987 6. Seeman TE. Syme SL: Social networks and coronary anery disease: a comparison of the structure and function of social relations as predictors of disease. Psychosom Med49:341-354,1987 7. Blumenthal JA. Burg MM. Barefoot J, et al: Social suppon, type A behavior and coronary anery disease. PsychosomMed49:331-340.1987 8. Onh-Gomer K, Unden A-L: Type A behavior, social suppon and coronary risk interaction and significance for monality in cardiac patients. Psychosom Med 52:59-72, 1990 9. Hung J. Whitford EG, Parsons RW, et al: Association of sleep apnoea with myocardial infarction in men. Lancet 336(8710):261-263.1990

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10. Koskenvuo M, Kaprio J, Telakivi T. et al: Snoring as a risk factor for ischemic heart disease and stroke in men. BMJ294(6563):1&-19.1987 II. Friedman M. Thoreson CE, Gill JJ, et al: Alteration of type A behavior and its effect on cardiac recurrences in post myocardial infarction patients: summary results of the recurrent coronary prevention project. Am Heart 1 112(4):65~5, 1986 12. Friedman M. Powell LH. Thoreson CE, et al: Effect of discontinuance of type A behavioral counseling on type A behavior and cardiac recurrence rate of post myocardial infarction patients. Am Heart 1 114(3):483-490, 1987 13. Kendler KS: Toward a scientific psychiatric nosology. Arch Gen Psychiatry 47:969-973. 1990 14. Koop CE: The Health Benefits of Smoking Cessation: A Report of the Surgeon General. 1990. Rockville, MD, Public Health Service. 1990 15. Yusuf S. Wittes J, Friedman L: Overview of results of randomized clinical trials in heart disease I and II. lAMA 260:2088-2093.2259-2263.1988 16. Ketterer MW: Randomized clinical trials in heart disease [Ietterl. lAMA 261 :2952-2953. 1989

Depersonalization Syndrome Induced by Fluoxetine SIR: We recently observed a patient who developed a depersonalization syndrome from fluoxetine, a complication hitherto unreported.

Case Reporr A 32-year-old woman had a 10- to 15-year history of DSM-III-R bipolar disorder not otherwise specified. She was admitted due to a deterioration in her clinical condition. She had become progressively more depressed and had developed suicidal ideations. She had been treated with a combination of carbamazepine, trazodone, and prazepam for the 5 months prior to admission, but the medications were discontinued I week before admission because of their lack of efficacy and her worsening condition. The patient was started on both lithium carbonate and amitriptyline. Over a period of 3 weeks, her amitriptyline was increased to 250 mg and her lithium adjusted to 600 mg bid; her blood level was 0.97 mEqlL. Her mood failed to improve with this combination, although she was no longer suicidal. Amitriptyline then was tapered over 3 days, and fluoxetine 20 mg qam was substituted. On the third day of treatment with fluoxetine, the patient reported

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feelings of unreality. She was noted to have a bizarre and fixed smile on her face and to ask: "Where am I? I know where I am, but don't know where I am." She stated that she felt detached from her surroundings, as though she were part of a movie or dream, although she realized that these sensations were not real. She remained alert and oriented, and her level of depression was unchanged. She had not developed suicidal ideas or psychotic symptoms, but she slept poorly and reported being "wound up." Feelings of depersonalization fluctuated over the next 3 days. Fluoxetine was finally discontinued, and within 24 hours the patient reported being free of these bizarre experiences. She remained free of depersonalization symptoms during a 6-month follow-up.

F1uoxetine is a relatively new medication reported to be safe and efficacious in treatment of depression. 1.2 A depersonalization syndrome has not specifically been reported as a side effect offluoxetine, but in one of the six cases (case 5) recently reported by Teicher et aL 3 a woman developed "prominent dissociative symptoms, sedation, and abulia" (p. 208) at 80 mg. We cannot dismiss the possibility that a drug interaction could explain our patient's symptoms. Biologically significant levels of amitriptyline may have been present in the central nervous system, which, combined with fluoxetine, may have contributed to the development of depersonalization. Also, the combination of lithium and fluoxetine together may have led to the behavioral reaction through their synergistic action on the serotonin system.It is unlikely that there are other explanations for our patient's depersonalization syndrome. The patient had no history of depersonalization; nor was there any history of benzodiazepine, alcohol, or illicit drug use. Furthermore, there was no evidence from laboratory examinations of a medical condition that could have explained her symptoms. The patient's vital signs remained stable during this episode, and there was no evidence of a febrile illness. Donald W. Black, M.D. Joanne Wojcieszek, M.D. University of Iowa Hospitals and Clinics Iowa City, IA

PSYCHOSOMATICS