Indomethacin-Induced Behavioral Changes in an Elderly Patient with Dementia Louise Mallet and Jirair Kuyumjian
OBJECTIVE:
To describe a case of behavioral changes induced by indomethacin in an elderly man with a history of senile dementia of the Alzheimer type. CASE SUMMARY: A 92-year-old white man with a history of senile dementia of the Alzheimer type, glaucoma, and constipation was treated with indomethacin for an episode of pseudogout. After six doses of indomethacin 25 mg, the patient became very agitated, confused, and was physically and verbally aggressive to the nurses. Indomethacin was discontinued and the patient recovered after receiving haloperidol 0.5 mg/d po over a period of 10 days. DISCUSSION: Only a few cases of psychosis have been reported in the literature concerning the use of indomethacin in patients over the age of 60 years. The mechanism by which indomethacin causes psychosis is not well understood, but it is postulated that the acute psychosis may be related to the similarity between the molecular structure of indomethacin and serotonin. Both indomethacin and serotonin have an indolic moiety, which may explain the development of acute psychosis in this patient. CONCLUSIONS: Healthcare providers should be aware that patients with a history of dementia who are receiving indomethacin may be at risk of developing severe behavior problems along with gastrointestinal and renal adverse effects. KEY WORDS: indomethacin, Alzheimer disease. Ann Pharmacother 1998;32:201-3.
INDOMETHACIN,
a nonsteroidal antiinflammatory drug, is frequently prescribed for the treatment of acute gout. Adverse effects commonly reported with indomethacin include frontal headache, dizziness, and gastrointestinal problems. We report a case of behavioral problems in an elderly patient with senile dementia of the Alzheimer type who received indomethacin for the treatment of pseudogout. CASE REPORT
A 92-year-old white man with a history of senile dementia of the Alzheimer type, glaucoma, and constipation was admitted to the Louise Mallet PharmD BCPS, Clinical Pharmacist in Geriatrics, Department of Pharmacy and Division of Geriatrics, McGill University Health Center, Montreal, Quebec, Canada; Associate Clinical Professor, Faculty of Pharmacy, University of Montreal, Montreal; and Clinical Adjunct Professor, Faculty of Medicine, McGill University, Montreal Jirair Kuyumjian MD, Division of Geriatrics, McGill University Health Center; and Clinical Lecturer, Faculty of Medicine, McGill University Reprints: Louise Mallet PharmD BCPS, Department of Pharmacy, McGill University Health Center, 687 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada, FAX 514/843-1738, E-mail
[email protected]
geriatric unit 10 months earlier because he had some behavioral problems that presented as agitation, uncooperativeness, and aggressiveness. His wife could no longer care for him. On admission, the patient received haloperidol 0.5 mg po bid for his behavioral problems. One month following admission, the behavioral problems resolved and haloperidol was discontinued. For the past 9 months, the patient’s behavioral problems have remained stable. He was waiting for placement in a specialized Alzheimer unit. The patient had no known allergies and his weight was 38 kg. He had been stable on the following medications: aspirin one 325-mg tablet in the morning, levobunolol 0.5% one drop in the right eye twice daily, and haloperidol one 0.5-mg tablet twice daily as needed. The patient was on a pureed diet because he had problems swallowing food and his oral medications were crushed and given with applesauce. On March 6, 1996, the patient was found in his room holding his left wrist and reporting pain. His wrist was swollen, red, and warm to touch. He was given one dose of acetaminophen 300 mg and codeine 30 mg. An X-ray of the wrist was performed to rule out a fracture. Aspiration of the left joint fluid revealed calcium pyrophosphate crystals and a negative Gram stain. Serum uric acid concentration was normal at 6.3 mg/dL, and serum electrolytes and complete blood counts were within normal limits. The patient had daily bowel movements, according to the bowel record sheet, and was continent of urine. A physical examination revealed no abnormal findings other than a red, swollen left wrist. A diagnosis of pseudogout was made. Indomethacin 25 mg tid with meals was prescribed and the patient received his first dose at 0830 on March 7. At 2200 on March 8 and continuing during the night until 0300 on March 9, after six doses of indomethacin 25 mg, the patient became very agitated. He was running in the corridor and became physically and verbally aggressive when the nurses tried to bring him back to his room. The patient had been a boxer in his younger years and he tried to hit the nurses with his fists. He was screaming, swearing, and talking to himself. When he was returned to his room, he turned the bed upside down. During the night, the patient received three doses of haloperidol 0.5 mg po q2h to control his behavior. He remained calm during the rest of the night. During the day on March 9, the patient was calm and no behavioral problems were documented. On March 10 at 0100, the patient became verbally and physically aggressive. Again, he tried to hit the nurses with his fists and was swearing and screaming. A magnetic restraint was used to prevent any injury to the patient; prior permission had been obtained from the family. The patient received three doses of haloperidol 0.5 mg po q2h during the night. The patient remained calm and cooperative for the rest of the night and during the day on March 10. Indomethacin was discontinued on the morning of March 11. The patient had received a total of 12 doses of indomethacin 25 mg. A behavioral sheet was started to closely monitor his behavior. At 2000 on March 11, the patient was talking to someone who was not present in the room. He became violent toward the
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staff, trying to hit and kick, around 2230. He was given two doses of haloperidol 0.5 mg po q2h during the night. The patient remained agitated for the next 2 days. A dose of haloperidol 0.5 mg once per day was prescribed March 14 for 10 days. On March 24, haloperidol was discontinued and the patient’s behavior returned to baseline.
Discussion Only a few cases of psychosis have been reported in the literature concerning the use of indomethacin in patients over the age of 60 years. Carney1 reported the case of a 65year-old woman with rheumatoid arthritis who had been treated with indomethacin 100–150 mg over a 4-year period. No dosing interval for the indomethacin was specified. During this period, other agents such as salicylates, gold, and steroids were also prescribed but without therapeutic success. When indomethacin was continued alone, the patient developed paranoid delusions, morbid jealousy of her husband, visual and olfactory hallucinations, and weight loss. Indomethacin was discontinued and chlorpromazine 100 mg/d was prescribed. The patient became free of symptoms within 4 weeks after discontinuation of indomethacin. Gotz2 described an 80-year-old woman who was prescribed indomethacin 25 mg three times daily for pseudogout. The patient had no previous history of psychiatric disturbances and was receiving no other medications associated with this type of reaction. Eight hours after the first dose of indomethacin, the patient became verbally hostile, had hallucinations and paranoia, fearing that people were trying to kill her. She responded to one dose of chlorpromazine intramuscularly. The dose of chlorpromazine was not specified. She was later challenged with indomethacin 25 mg three times daily for 5 more days without further symptoms. Acute paranoid psychosis was described in an 83-yearold woman who was treated with indomethacin 50 mg tid for the management of acute gouty arthritis.3 The patient had no history of psychiatric illness. Six days after beginning indomethacin, the patient became very agitated and delusional. Indomethacin was discontinued and the patient recovered with haloperidol 5 mg po twice daily over a period of 7 days. Bessa4 reported a 71-year-old woman with no history of psychiatric problems who developed acute psychosis after 3 days of indomethacin 200 mg/d for acute gout. She presented with hallucinations and paranoid ideas, and was unable to recognize her surroundings or immediate relatives. Indomethacin was discontinued and the patient returned to baseline within 48 hours. Schwartz and Moura5 reported severe depersonalization and anxiety in a 61-year-old woman after receiving two doses of indomethacin 50 mg for an acute attack of gout. The patient described herself as feeling like a “body without a mind” after the second dose of indomethacin. Indomethacin was discontinued and the patient recovered by the next day. The development of symptoms in each of these reports began shortly after indomethacin was introduced and disappeared rapidly after the drug was discontinued. None of these patients were rechallenged and indomethacin was 202
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implicated in the presentation of these reactions by the temporal relationship of the drug to the symptoms. The mechanism by which indomethacin produces acute psychosis still remains unknown. Spittle6 postulated that the acute psychosis associated with indomethacin may be related to the similarity in molecular structure between indomethacin and serotonin. Both indomethacin and serotonin have an indolic moiety that may be related to the development of acute psychosis.6,7 The dosage of indomethacin prescribed for this elderly man was appropriate. The recommended starting dosage in the elderly is 25 mg given two to three times per day.8 Psychiatric adverse events with indomethacin are reported in most standard references.7-9 The clinical problem is that psychosis is a relatively rare event, not often recognized as being due to indomethacin. The presence of acute psychosis associated with the use of indomethacin may be underreported in elderly patients with dementia, since uninformed clinicians treat the psychiatric or agitated behaviors inappropriately as primary psychotic events, not as a potential adverse effect requiring discontinuation of indomethacin. Our patient had a history of dementia of the Alzheimer type and had been clinically stable for 9 months before indomethacin was introduced. According to the algorithm for establishing a causal relationship between a drug and an adverse event, it is probable that indomethacin was associated with the presence of the behavioral changes described in our patient.10 Healthcare providers should be aware that patients with dementia receiving indomethacin may be at risk of developing severe behavior problems in addition to gastrointestinal and renal adverse effects.
References 1. Carney MWP. Paranoid psychosis with indomethacin (letter). Br Med J 1977;2:994-5. 2. Gotz V. Paranoid psychosis with indomethacin (letter). Br Med J 1978;1: 49. 3. Tollefson GD, Garvey MJ. Indomethacin and prostaglandins: their behavioral relationships in an acute toxic psychosis. J Clin Psychopharmacol 1982;2:62-4. 4. Bessa O. Acute psychosis due to indomethacin. Conn Med 1994;58:395-6. 5. Schwartz JI, Moura RJ. Severe depersonalization and anxiety associated with indomethacin. South Med J 1983;76:679-80. 6. Spittle BJ. Drug-induced psychiatric syndromes. N Z Med J 1982;95: 349-52. 7. Insel PA. Analgesic–antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1995:617-57. 8. Semla TP, Beizer JL, Higbee MD, eds. Geriatric dosage handbook 1997– 1998. 3rd ed. Hudson, OH: Lexi-Comp Inc., 1997:440. 9. AHFS drug information 97. Bethesda, MD: American Society of HealthSystem Pharmacists, Inc., 1997:1508. 10. Drug evaluations annual 1994. Chicago: American Medical Association, 1994:39-50.
EXTRACTO OBJETIVO:
Informar un caso de cambios en conducta inducidos por indometacina en un envejeciente varón con historial de demencia senil del tipo Alzheimer.
1998 February, Volume 32
Case Reports RESUMEN DEL CASO: Un hombre blanco de 92 años con historial de demencia senil del tipo Alzheimer, glaucoma, y constipación fue tratado con indometacina para un episodio de pseudogota. Después de seis dosis de indometacina de 25 mg, el paciente se puso bien agitado, confuso, y física y verbalmente agresivo con las enfermeras. Indometacina fue descontinuada y el paciente se recuperó con una dosis de haloperidol 0.5 mg oral diario por un período de 10 días. DISCUSIÓN: Solo algunos casos de psicosis han sido reportados en la literatura con el uso de indometacina en pacientes sobre 60 años. El mecanismo por el cual indometacina produce la psicosis no es bien comprendido pero se cree que la psicosis aguda puede estar relacionada a la similaridad de la estructura molecular de indometacina y serotonina. Tanto la indometacina y serotonina tienen un componente indólico que podría explicar el desarrollo de psicosis aguda en éste paciente. CONCLUSIONES: Los proveedores de cuidado de la salud deben estar concientes que los pacientes con historial de demencia que están recibiendo indometacina podrían desarrollar severos problemas de conducta asi como efectos secundarios gastrointestinal y renal.
WILMA M GUZMAN
RÉSUMÉ DU CAS: Un homme blanc de 92 ans présentant avec une histoire de démence de type Alzheimer, de glaucome, et de constipation a été traité avec de l’indométhacine 25 mg trois fois par jour pour un épisode de pseudogoutte. Après 2 jours de traitement avec l’indométhacine, à raison de 25 mg trois fois par jour, le patient a présenté avec de l’agitation et de la confusion. Il est devenu agressif physiquement et verbalement envers le personnel infirmier. L’indométhacine a été discontinué et le patient a reçu de haloperidol 0.5 mg chaque jour pour une période de 10 jours. DISCUSSION: Seulement quelques cas de psychose induite par l’indométhacine ont été rapportés dans la littérature chez des patients de plus de 60 ans. Le mécanisme d’action par lequel la psychose se manifeste n’est pas encore bien élucidé. Il a été postulé que la psychose serait associée à la similarité dans les structures chimiques de l’indométhacine et la sérotonine. La molécule de l’indométhacine et celle de la sérotonine possèdent un groupe indolique, ce qui pourrait expliquer le développement d’une psychose aiguë. CONCLUSIONS: Il est important de surveiller les changements de comportement chez les patients souffrant de démence lorsque l’indométhacine est prescrit.
LOUISE MALLET
RÉSUMÉ OBJECTIF: Décrire le cas d’une personne âgée présentant avec des troubles de comportement suite à la prise d’indométhacine.
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