518
BIOL PSYCHIATRY 1990,28:518-521
CASE REPORT
Fluoxetine and Neuroleptic Malignant Syndrome Mark Haiman and David S. Goldbloom
The authors present a case report of neuroleptic malignant syndrome (NMS) in a patient commencing treatment with fluoxetine alone who had previously been treated with several antipsychotic and antidepressant combinations. On reviewing the literature on the pathogenesis of NMS, the authors hypothesize a facilitative role of the neurotransmitter serotonin (5-HT) in conjunction with central dopaminergic blockade in the precipitation
of NMS. Neuroleptic malignant syndrome (NMS) is characterized by extrapyramidal symptoms (EPS), i.e., toxicity, alteration in consciousness, fever, and autonomic instability (Levenson 1985). It has been described in association with the use of most neuroleptic drugs. In addition, cases have been reported of NMS upon discontinuation of dopaminergic agents such as L-dopa and amantadine (Kellam 1987). Cases have also been reported wherein NMS was precipitated by the concomi',ant usage of neuroleptic and antidepressant medication (Rosebush and Stewart 1989). We describe a case report wherein a patient developed NMS while taking the antidepressant fluoxetine, a selective inhibitor of serotonin reuptake with little effect on central nora0renergic or dopaminergic function (Cooper i988). The patient was a 53-year-old married man with a longstanding history of a recurrent major depressive episode with mood-congruent psychotic features. He presented to another facility following an overdo~e of carbamazepine (2000 rag), methotrimeprazine (250 rag), and tryptophan (5000 rag). Methotrimeprazine is a sedating phenothiazine compound available routinely in Canada and used in the treatment of psychosis. He was treated (gastric lavage and activated charcoal) and transferred to our facility the following day in a stable condition. Medications prior to his overdose were methotfimeprazine 25 mg po qhs, carbamazepine 200 mg po bid, and tryptophan 500 mg po qhs. On admission to our facility 1-day postoverdose, physical examination was normal other than psychomotor retardation. The carbamazepine plasma level on the third day postoverdose was 24 p,m/liter (N= 17-42 ixm/liter). The patient was maintained off all medications from the time of ttie overdose. He remained quiet and downcast but displayed some increase in energy and activity level over the next few days, and a stable sleep pattern was restored. Past psychiatric history revealed a first major depressive episode with psychotic features in 1969, with recurrence in 1985 that had been refractory to multiple standard interven-
From ~':e Department of Psychiatry, Toronto General Hospital, University of Toronto, Toronto, Canada. Address reprint requests to David S. Goldbloom, M.D., F.R.C.P.(C), Department of Psychiatry, Eaton 8N219, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2(24. Received November 10, 1989; revised March 22, 1990. © 1990 Society of Biological Psychiatry
0006-3223/90/$03.50
Fluoxetine and Neuroleptic Malignant Syndrome
BIOL PSYCHIATRY 1990;28:518-521
519
tions. He had one prior course of fluoxetine in October 1987 at which time he developed a transient increase in blood press~re and was noted to be quite agitated. After a 29-day course of fluoxetine, tiffs medication was discontinued with little effect on his mood. On the ninth day following the overdose, fluoxetine was initiated alone at a dose of 20 mg po q AM. At baseline, his vital signs and white blood cell count were normal. On day 2 of fluoxetine, the patient complained of subjective feelings of restlessness and sleep disturbance, and on examination was noted to have a fine intention tremor. He became withdrawn and frightened with a marked inability to get out of bed or attend to basic U A ~ L l l:-^ l~, JLI.TUIItJ. LI.S k~...:.,-.~ ~ Ia~|U, lJLl~llL~llqb.~bJ., self-care. 0 , day 5 of aI I U....... he ,,,~o 4, . . . . a ,^ ~ . k . . . . "! and IJEJUL~,o . . . . . u:.. temperature was elevated at 37.6°C ~ i l l ~ ] . He was tachycardiac, tachypneic, and his blood pressure was 130/90. He continued to display a fine tremor of his hand and began to display cogwheel rigidity. He became markedly apprehensive and did not eat or drink for 2 days. He became incontinent of urine and feces. He denied any physical complaints. On day 7 of fiuoxetine treatment, his blood pressure was 160/90 and he was tachycardiac, tachypneic, diaphoretic, and dehydrated. His temperature was 38.6°C axillary. He displayed generalized cogwheel rigidity but no focal neurological deficits. Fhoxetine treatment was discontinued at this point. A complete blood count showed a leukocytosis (23.5 x 109/liter; normal range = 4.0-11.0 x 109/liter) with an increased neutrophil count. He had elevations of blood urea nitrogen (BUN) and creatinine. He had an elevated creatinine phosphokinase (CPK) of 736 U/litel~(muscle fraction by isoenzymatic analysis; normal range for males
BIOL PSYCHIATRY 1990,28:518-521
CASE REPORT
Fluoxetine and Neuroleptic Malignant Syndrome Mark Haiman and David S. Goldbloom
The authors present a case report of neuroleptic malignant syndrome (NMS) in a patient commencing treatment with fluoxetine alone who had previously been treated with several antipsychotic and antidepressant combinations. On reviewing the literature on the pathogenesis of NMS, the authors hypothesize a facilitative role of the neurotransmitter serotonin (5-HT) in conjunction with central dopaminergic blockade in the precipitation
of NMS. Neuroleptic malignant syndrome (NMS) is characterized by extrapyramidal symptoms (EPS), i.e., toxicity, alteration in consciousness, fever, and autonomic instability (Levenson 1985). It has been described in association with the use of most neuroleptic drugs. In addition, cases have been reported of NMS upon discontinuation of dopaminergic agents such as L-dopa and amantadine (Kellam 1987). Cases have also been reported wherein NMS was precipitated by the concomi',ant usage of neuroleptic and antidepressant medication (Rosebush and Stewart 1989). We describe a case report wherein a patient developed NMS while taking the antidepressant fluoxetine, a selective inhibitor of serotonin reuptake with little effect on central nora0renergic or dopaminergic function (Cooper i988). The patient was a 53-year-old married man with a longstanding history of a recurrent major depressive episode with mood-congruent psychotic features. He presented to another facility following an overdo~e of carbamazepine (2000 rag), methotrimeprazine (250 rag), and tryptophan (5000 rag). Methotrimeprazine is a sedating phenothiazine compound available routinely in Canada and used in the treatment of psychosis. He was treated (gastric lavage and activated charcoal) and transferred to our facility the following day in a stable condition. Medications prior to his overdose were methotfimeprazine 25 mg po qhs, carbamazepine 200 mg po bid, and tryptophan 500 mg po qhs. On admission to our facility 1-day postoverdose, physical examination was normal other than psychomotor retardation. The carbamazepine plasma level on the third day postoverdose was 24 p,m/liter (N= 17-42 ixm/liter). The patient was maintained off all medications from the time of ttie overdose. He remained quiet and downcast but displayed some increase in energy and activity level over the next few days, and a stable sleep pattern was restored. Past psychiatric history revealed a first major depressive episode with psychotic features in 1969, with recurrence in 1985 that had been refractory to multiple standard interven-
From ~':e Department of Psychiatry, Toronto General Hospital, University of Toronto, Toronto, Canada. Address reprint requests to David S. Goldbloom, M.D., F.R.C.P.(C), Department of Psychiatry, Eaton 8N219, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2(24. Received November 10, 1989; revised March 22, 1990. © 1990 Society of Biological Psychiatry
0006-3223/90/$03.50
Fluoxetine and Neuroleptic Malignant Syndrome
BIOL PSYCHIATRY 1990;28:518-521
519
tions. He had one prior course of fluoxetine in October 1987 at which time he developed a transient increase in blood press~re and was noted to be quite agitated. After a 29-day course of fluoxetine, tiffs medication was discontinued with little effect on his mood. On the ninth day following the overdose, fluoxetine was initiated alone at a dose of 20 mg po q AM. At baseline, his vital signs and white blood cell count were normal. On day 2 of fluoxetine, the patient complained of subjective feelings of restlessness and sleep disturbance, and on examination was noted to have a fine intention tremor. He became withdrawn and frightened with a marked inability to get out of bed or attend to basic U A ~ L l l:-^ l~, JLI.TUIItJ. LI.S k~...:.,-.~ ~ Ia~|U, lJLl~llL~llqb.~bJ., self-care. 0 , day 5 of aI I U....... he ,,,~o 4, . . . . a ,^ ~ . k . . . . "! and IJEJUL~,o . . . . . u:.. temperature was elevated at 37.6°C ~ i l l ~ ] . He was tachycardiac, tachypneic, and his blood pressure was 130/90. He continued to display a fine tremor of his hand and began to display cogwheel rigidity. He became markedly apprehensive and did not eat or drink for 2 days. He became incontinent of urine and feces. He denied any physical complaints. On day 7 of fiuoxetine treatment, his blood pressure was 160/90 and he was tachycardiac, tachypneic, diaphoretic, and dehydrated. His temperature was 38.6°C axillary. He displayed generalized cogwheel rigidity but no focal neurological deficits. Fhoxetine treatment was discontinued at this point. A complete blood count showed a leukocytosis (23.5 x 109/liter; normal range = 4.0-11.0 x 109/liter) with an increased neutrophil count. He had elevations of blood urea nitrogen (BUN) and creatinine. He had an elevated creatinine phosphokinase (CPK) of 736 U/litel~(muscle fraction by isoenzymatic analysis; normal range for males
