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Insect Repellant Toxicity Associated With Psychosis
Case Reports Insect Repellant Toxicity Associated With Psychosis RAPHAEL J. LEO, M.D., PAULA A. DEL REGNO, M.D. CHARMAINE GREGORY, KRISTIN L. CLARK
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cute onset of atypical psychotic symptoms in a patient with no prior psychiatric history necessitates evaluation for possible organic etiologies. Clarification of the cause of an organic psychosis can be quite puzzling in the absence of definitive neurologic symptoms, metabolic abnormalities, sepsis, or obvious medication toxicity. We report an unusual case of psychosis related to excess use of insect repellents. Only two cases of comparable psychosis associated with insect repellent use have been reported previously in the literature.1,2
Case Report
Mr. G. is a 41-year-old, single, man who presented to the hospital with lethargy, headaches, nausea, vomiting, and abdominal pain. He brought a sample of vomit with him from home, convinced that it contained “worms.” His beliefs remained fixed, despite reassurances from medical staff who found no abnormalities in the contents of the vomit. Mr. G. reported poor sleep and appetite in recent weeks. His medical history is significant for insulin-dependent diabetes mellitus and end-stage renal disease. Mr. G. was on peritoneal dialysis. Neither Mr. G. nor his family had a prior psychiatric history. He denied (and his family corroborated) any history of alcohol or illicit substance use. Mr. G.’s family provided collateral information, indicating that Mr. G. first made a passing reference to fleas in his apartment approximately 6 weeks earlier, when he mentioned that he sought out an exterminator. At the time, no one had been particularly concerned about the allegation of the flea problem, although in retrospect, no one could recall being particularly impressed by any evidence to suggest that fleas were present. Furthermore, Mr. G.’s family were puzzled because Mr. G. did not own any pets and Received June 1, 2000; revised September 7, 2000; accepted October 3, 2000. From Department of Psychiatry, School of Medicine and Biomedical Sciences, State University of New York. Buffalo, New York. Address correspondence and reprint requests to Dr. Leo, Department of Psychiatry, School of Medicine and Biomedical Sciences, State University of New York, Erie County Medical Center, 462 Grider Street, Buffalo, New York 14215. Copyright 䉷 2001 The Academy of Psychosomatic Medicine.
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could not account for why he thought that there were fleas in his apartment. Family members prompted hospitalization after Mr. G. had become increasingly withdrawn and seclusive, his self-care progressively declined, and he kept minimal food in his house. Mr. G. had discarded much of his food and bedding for fear that they had become infested with fleas. When approached with this information, he conceded to these beliefs, although Mr. G. could not account for why he thought this. He believed that the fumigation was unsuccessful, which led to the repeated applications of insecticides on his food, his mattress, and himself. Family members, who returned to the Mr. G.’s home, discovered upwards of 20 empty cans of insect repellents throughout his house. Despite all of these attempts, Mr. G. was convinced that the fleas were not eliminated. He insisted that they were entering his body through his nose and mouth, laying eggs, which would then become the worms that he reported were in his vomit. The repetitive use of the insecticide accounted for his physical symptoms. Aside from the aforementioned sleep and appetite disturbances, Mr. G. did not endorse significant symptoms of depression or mania. His mood was “slightly depressed,” but he attributed this to his physical symptoms. His thoughts were goal directed. He denied experiencing auditory or tactile hallucinations (e.g., formication). He denied having any grandiose, paranoid, or persecutory beliefs. Cognitively, there was no evidence of delirium or significant deficits in higher executive functions. Medical work-up failed to reveal any metabolic abnormalities or evidence of sepsis. Computerized tomography of the head failed to demonstrate any abnormalities. Neuropsychological testing failed to reveal significant cognitive deficiencies suggestive of organicity. Antipsychotic medication was not prescribed, as the decision was made to first monitor Mr. G. during the course of organicity work-up. His symptoms began to abate within days, and within 2 weeks, the psychosis was completely resolved. He gained insight into the excessive and deleterious effects of his insecticide use. Mr. G. resumed usual levels of self-care and had returned to baseline functioning.
Discussion In the present case, the abrupt onset of psychosis in Mr. G. without prior psychiatric history, or family psychiatric history, strongly suggested an organic psychotic disorder. Psychosomatics 42:1, January-February 2001
Leo et al. Common causes (e.g., metabolic disturbances or intracranial lesions) were quickly ruled out. Psychiatric consultation was requested days after admission because of a suspected functional psychiatric disorder. The psychiatric consultants elicited the collateral information from Mr. G.’s family that helped to establish the temporal relationship between the insecticide use and psychosis. The active agent, N,N-diethyl-m-toluamide (DEET), contained in insecticides can produce acute onset of physical and psychiatric disturbances. Usually, DEET toxicity is caused by prolonged, continuous and repetitive use of insecticides. Physical symptoms include urticaria or, as in the present case, gastrointestinal disturbances (e.g., abdominal pain, nausea, vomiting and diarrhea). Neuropsychiatric symptoms include lethargy, anxiety, behaviorial disturbances, ataxia, delirium, seizures, and coma.1–5 DEET is rapidly absorbed percutaneously, reaching peak plasma concentrations within an hour after application.6 Normally, it is rapidly metabolized in the liver and excreted in the urine within 24 hours. DEET is also highly lipophilic, thus, repeated use can lead to accumulation of DEET within adipose tissue. Metabolites can accumulate in skin and adipose tissue for as much as 2 months.6,7 DEET can likewise accumulate in the central nervous system, readily passing through the blood-brain barrier, producing lethargy, confusion, delusions, illusions, and/or hallucinations.1,2,4,5,8–10 Toxicity associated with insecticide exposure has been noted to occur more commonly in children.7,11 There are only two cases in which psychosis and mood disturbances have been associated with DEET exposure in adults.1,2 Usually, patients with DEET toxicity present with the clinical picture of delirium.3–5 However, some cases reported, as in Mr. G.’s case, a clinical syndrome suggestive of a functional psychiatric disorder.1,2 In the present case, the issue of cause becomes problematic. It is reasonable to argue that the psychosis preceded, and thereby led to, the excess use of the insecticides. For example, pruritis can occur in end-stage renal disease. A psychotic misinterpretation of pruritis (e.g., believing the pruritis to be due to fleabites) might lead to insecticide use. On the other hand, a psychological process (e.g., anxiety) could have led to the excess use of the insecticide, with its resultant toxicity and psychosis (including delusions, behavioral disturbances, and diminished adaptive functioning). The rapid resolution of the psychosis, without the use of antipsychotic medications, suggested that the psychosis was related to extensive DEET exposure. The symptoms resolved presumably because of the washout of DEET through peritoneal dialysis. This suggests the possibility Psychosomatics 42:1, January-February 2001
that the psychosis may have been because of the DEET exposure. Conclusive evidence for the association between DEET toxicity and neuropsychiatric disturbances is lacking. Although DEET can be detected using gas chromatography,6 prior case reports showed no detectable levels in urine, presumably because of delays in acquiring sufficient samples within 24 hours of initial toxicity.3 Additionally, although three cases reported elevated serum or urine levels of DEET among patients with mania, psychosis, or delirium, it has not been possible to establish clear doseresponse relationships.1,2,5 Effects on behavior are likely to be influenced by the rate and amount of DEET accumulation and rates of metabolism and excretion. The limited number of cases reported in the literature preclude making clear statements about levels at which psychiatric symptoms can appear, or resolve. Hence, in the literature, the link between DEET toxicity and psychopathology is based on the temporal relationship between symptom onset and excess exposure to insecticides. In the present case, attempts at generating quantifiable DEET levels in urine proved unsuccessful. The yield of DEET assays in urine is best early in the hospital course, as DEET levels are rapidly reduced to nondetectable levels by hepatic metabolism and urinary excretion. Several days had elapsed before collateral informants provided the link between repetitive insecticide use and behaviorial disturbances. Mr. G.’s renal disease and resultant production of negligible amounts of urine also delayed obtaining urine samples in a timely manner, which would have been likely to generate detectable DEET levels. Furthermore, he received peritoneal dialysis routinely, which reduced measurable DEET levels. The fact that the psychosis resolved in the absence of antipsychotic medication use suggests that DEET toxicity contributed to the perceptual disturbances, delusions, and bizarre behaviors observed here. Whether it is the cause or result of the psychosis, toxicities associated with insecticide exposure can lead to serious physical sequelae or even death, and can prove to be a vexing problem in the work-up of an organic etiology to an acute psychotic episode. Regardless of whether the position is taken that the psychosis was because of DEET toxicity or the cause of toxicity, Mr. G.’s case illustrates the seriousness associated with insecticide overexposure. DEET toxicity can lead to delirium, seizures, coma, and death.4,10 The timely response of the Mr. G.’s family likely prevented more serious sequelae. Previous literature suggests that DEET exposure can produce neuropsychiatric symptoms. Abrupt onset of 79
Toxicity Associated With Psychosis mood disturbances, thought disturbances, delusions, and hallucinations, suggestive of an organic etiology naturally prompt a work-up for an organic cause. When organic eti-
ology is suggested, exposure to toxins, such as those in insecticides, should be considered as a potential cause.
References
1. Poe RO, Snyder JW, Stubbins JF, et al: Psychotic reaction to an insect repellent. Am J Psychiatry 1987; 144:1103–1104 2. Snyder JW, Poe RO, Stubbins JF, et al: Acute manic psychosis following the dermal application of N,N-diethyl-m-toluamide (DEET) in an adult. Clin Toxicol 1986; 24:429–439 3. de Garbino JP, Laborde A: Toxicity of an insect repellent: N-Ndiethyltoluamide. Vet Hum Toxicol 1983; 25:422–423 4. Gryboski J, Weinstein D, Ordway NK: Toxic encephalopathy apparently related to the use of an insect repellent. N Engl J Med 1961; 264:289–291 5. Hampers LC, Oker E, Leikin JB: Topical use of DEET insect repellent as a cause of severe encephalopathy in a healthy adult male. Acad Emerg Med 1999; 6:1295–1297 6. Ellenhorn MJ: Ellenhorn’s Medical Toxicology: Diagnosis and
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Treatment of Human Poisoning, Second Edition. Baltimore, MD, Williams and Wilkins, 1997, pages 1655–1656 7. Lur’e AA, Gleiberman SE, Tsizin IuS: Pharmacokinetics of insect repellent N,N-diethyltoluamide. Med Parazitol (Mosk) 1978; 47:72–77 8. Edwards DL, Johnson CE: Insect-repellent-induced toxic encephalopathy in a child. Clin Pharm 1987; 6:496–498 9. Osimitz TG, Murphy JV: Neurological effects associated with use of the insect repellent N,N-diethyl-m-toluamide (DEET). Clin Toxicol 1997; 35:435–441 10. Tenenbein M: Severe toxic reactions and death following the ingestion of diethyltoluamide-containing insect repellents. JAMA 1987; 258:1509–1511 11. Roland EH, Jan JE, Rigg JM: Toxic encephalopathy in a child after brief exposure to insect repellents. Can Med Assoc J 1985; 132:155–156
Psychosomatics 42:1, January-February 2001
A
cute onset of atypical psychotic symptoms in a patient with no prior psychiatric history necessitates evaluation for possible organic etiologies. Clarification of the cause of an organic psychosis can be quite puzzling in the absence of definitive neurologic symptoms, metabolic abnormalities, sepsis, or obvious medication toxicity. We report an unusual case of psychosis related to excess use of insect repellents. Only two cases of comparable psychosis associated with insect repellent use have been reported previously in the literature.1,2
Case Report
Mr. G. is a 41-year-old, single, man who presented to the hospital with lethargy, headaches, nausea, vomiting, and abdominal pain. He brought a sample of vomit with him from home, convinced that it contained “worms.” His beliefs remained fixed, despite reassurances from medical staff who found no abnormalities in the contents of the vomit. Mr. G. reported poor sleep and appetite in recent weeks. His medical history is significant for insulin-dependent diabetes mellitus and end-stage renal disease. Mr. G. was on peritoneal dialysis. Neither Mr. G. nor his family had a prior psychiatric history. He denied (and his family corroborated) any history of alcohol or illicit substance use. Mr. G.’s family provided collateral information, indicating that Mr. G. first made a passing reference to fleas in his apartment approximately 6 weeks earlier, when he mentioned that he sought out an exterminator. At the time, no one had been particularly concerned about the allegation of the flea problem, although in retrospect, no one could recall being particularly impressed by any evidence to suggest that fleas were present. Furthermore, Mr. G.’s family were puzzled because Mr. G. did not own any pets and Received June 1, 2000; revised September 7, 2000; accepted October 3, 2000. From Department of Psychiatry, School of Medicine and Biomedical Sciences, State University of New York. Buffalo, New York. Address correspondence and reprint requests to Dr. Leo, Department of Psychiatry, School of Medicine and Biomedical Sciences, State University of New York, Erie County Medical Center, 462 Grider Street, Buffalo, New York 14215. Copyright 䉷 2001 The Academy of Psychosomatic Medicine.
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could not account for why he thought that there were fleas in his apartment. Family members prompted hospitalization after Mr. G. had become increasingly withdrawn and seclusive, his self-care progressively declined, and he kept minimal food in his house. Mr. G. had discarded much of his food and bedding for fear that they had become infested with fleas. When approached with this information, he conceded to these beliefs, although Mr. G. could not account for why he thought this. He believed that the fumigation was unsuccessful, which led to the repeated applications of insecticides on his food, his mattress, and himself. Family members, who returned to the Mr. G.’s home, discovered upwards of 20 empty cans of insect repellents throughout his house. Despite all of these attempts, Mr. G. was convinced that the fleas were not eliminated. He insisted that they were entering his body through his nose and mouth, laying eggs, which would then become the worms that he reported were in his vomit. The repetitive use of the insecticide accounted for his physical symptoms. Aside from the aforementioned sleep and appetite disturbances, Mr. G. did not endorse significant symptoms of depression or mania. His mood was “slightly depressed,” but he attributed this to his physical symptoms. His thoughts were goal directed. He denied experiencing auditory or tactile hallucinations (e.g., formication). He denied having any grandiose, paranoid, or persecutory beliefs. Cognitively, there was no evidence of delirium or significant deficits in higher executive functions. Medical work-up failed to reveal any metabolic abnormalities or evidence of sepsis. Computerized tomography of the head failed to demonstrate any abnormalities. Neuropsychological testing failed to reveal significant cognitive deficiencies suggestive of organicity. Antipsychotic medication was not prescribed, as the decision was made to first monitor Mr. G. during the course of organicity work-up. His symptoms began to abate within days, and within 2 weeks, the psychosis was completely resolved. He gained insight into the excessive and deleterious effects of his insecticide use. Mr. G. resumed usual levels of self-care and had returned to baseline functioning.
Discussion In the present case, the abrupt onset of psychosis in Mr. G. without prior psychiatric history, or family psychiatric history, strongly suggested an organic psychotic disorder. Psychosomatics 42:1, January-February 2001
Leo et al. Common causes (e.g., metabolic disturbances or intracranial lesions) were quickly ruled out. Psychiatric consultation was requested days after admission because of a suspected functional psychiatric disorder. The psychiatric consultants elicited the collateral information from Mr. G.’s family that helped to establish the temporal relationship between the insecticide use and psychosis. The active agent, N,N-diethyl-m-toluamide (DEET), contained in insecticides can produce acute onset of physical and psychiatric disturbances. Usually, DEET toxicity is caused by prolonged, continuous and repetitive use of insecticides. Physical symptoms include urticaria or, as in the present case, gastrointestinal disturbances (e.g., abdominal pain, nausea, vomiting and diarrhea). Neuropsychiatric symptoms include lethargy, anxiety, behaviorial disturbances, ataxia, delirium, seizures, and coma.1–5 DEET is rapidly absorbed percutaneously, reaching peak plasma concentrations within an hour after application.6 Normally, it is rapidly metabolized in the liver and excreted in the urine within 24 hours. DEET is also highly lipophilic, thus, repeated use can lead to accumulation of DEET within adipose tissue. Metabolites can accumulate in skin and adipose tissue for as much as 2 months.6,7 DEET can likewise accumulate in the central nervous system, readily passing through the blood-brain barrier, producing lethargy, confusion, delusions, illusions, and/or hallucinations.1,2,4,5,8–10 Toxicity associated with insecticide exposure has been noted to occur more commonly in children.7,11 There are only two cases in which psychosis and mood disturbances have been associated with DEET exposure in adults.1,2 Usually, patients with DEET toxicity present with the clinical picture of delirium.3–5 However, some cases reported, as in Mr. G.’s case, a clinical syndrome suggestive of a functional psychiatric disorder.1,2 In the present case, the issue of cause becomes problematic. It is reasonable to argue that the psychosis preceded, and thereby led to, the excess use of the insecticides. For example, pruritis can occur in end-stage renal disease. A psychotic misinterpretation of pruritis (e.g., believing the pruritis to be due to fleabites) might lead to insecticide use. On the other hand, a psychological process (e.g., anxiety) could have led to the excess use of the insecticide, with its resultant toxicity and psychosis (including delusions, behavioral disturbances, and diminished adaptive functioning). The rapid resolution of the psychosis, without the use of antipsychotic medications, suggested that the psychosis was related to extensive DEET exposure. The symptoms resolved presumably because of the washout of DEET through peritoneal dialysis. This suggests the possibility Psychosomatics 42:1, January-February 2001
that the psychosis may have been because of the DEET exposure. Conclusive evidence for the association between DEET toxicity and neuropsychiatric disturbances is lacking. Although DEET can be detected using gas chromatography,6 prior case reports showed no detectable levels in urine, presumably because of delays in acquiring sufficient samples within 24 hours of initial toxicity.3 Additionally, although three cases reported elevated serum or urine levels of DEET among patients with mania, psychosis, or delirium, it has not been possible to establish clear doseresponse relationships.1,2,5 Effects on behavior are likely to be influenced by the rate and amount of DEET accumulation and rates of metabolism and excretion. The limited number of cases reported in the literature preclude making clear statements about levels at which psychiatric symptoms can appear, or resolve. Hence, in the literature, the link between DEET toxicity and psychopathology is based on the temporal relationship between symptom onset and excess exposure to insecticides. In the present case, attempts at generating quantifiable DEET levels in urine proved unsuccessful. The yield of DEET assays in urine is best early in the hospital course, as DEET levels are rapidly reduced to nondetectable levels by hepatic metabolism and urinary excretion. Several days had elapsed before collateral informants provided the link between repetitive insecticide use and behaviorial disturbances. Mr. G.’s renal disease and resultant production of negligible amounts of urine also delayed obtaining urine samples in a timely manner, which would have been likely to generate detectable DEET levels. Furthermore, he received peritoneal dialysis routinely, which reduced measurable DEET levels. The fact that the psychosis resolved in the absence of antipsychotic medication use suggests that DEET toxicity contributed to the perceptual disturbances, delusions, and bizarre behaviors observed here. Whether it is the cause or result of the psychosis, toxicities associated with insecticide exposure can lead to serious physical sequelae or even death, and can prove to be a vexing problem in the work-up of an organic etiology to an acute psychotic episode. Regardless of whether the position is taken that the psychosis was because of DEET toxicity or the cause of toxicity, Mr. G.’s case illustrates the seriousness associated with insecticide overexposure. DEET toxicity can lead to delirium, seizures, coma, and death.4,10 The timely response of the Mr. G.’s family likely prevented more serious sequelae. Previous literature suggests that DEET exposure can produce neuropsychiatric symptoms. Abrupt onset of 79
Toxicity Associated With Psychosis mood disturbances, thought disturbances, delusions, and hallucinations, suggestive of an organic etiology naturally prompt a work-up for an organic cause. When organic eti-
ology is suggested, exposure to toxins, such as those in insecticides, should be considered as a potential cause.
References
1. Poe RO, Snyder JW, Stubbins JF, et al: Psychotic reaction to an insect repellent. Am J Psychiatry 1987; 144:1103–1104 2. Snyder JW, Poe RO, Stubbins JF, et al: Acute manic psychosis following the dermal application of N,N-diethyl-m-toluamide (DEET) in an adult. Clin Toxicol 1986; 24:429–439 3. de Garbino JP, Laborde A: Toxicity of an insect repellent: N-Ndiethyltoluamide. Vet Hum Toxicol 1983; 25:422–423 4. Gryboski J, Weinstein D, Ordway NK: Toxic encephalopathy apparently related to the use of an insect repellent. N Engl J Med 1961; 264:289–291 5. Hampers LC, Oker E, Leikin JB: Topical use of DEET insect repellent as a cause of severe encephalopathy in a healthy adult male. Acad Emerg Med 1999; 6:1295–1297 6. Ellenhorn MJ: Ellenhorn’s Medical Toxicology: Diagnosis and
80
Treatment of Human Poisoning, Second Edition. Baltimore, MD, Williams and Wilkins, 1997, pages 1655–1656 7. Lur’e AA, Gleiberman SE, Tsizin IuS: Pharmacokinetics of insect repellent N,N-diethyltoluamide. Med Parazitol (Mosk) 1978; 47:72–77 8. Edwards DL, Johnson CE: Insect-repellent-induced toxic encephalopathy in a child. Clin Pharm 1987; 6:496–498 9. Osimitz TG, Murphy JV: Neurological effects associated with use of the insect repellent N,N-diethyl-m-toluamide (DEET). Clin Toxicol 1997; 35:435–441 10. Tenenbein M: Severe toxic reactions and death following the ingestion of diethyltoluamide-containing insect repellents. JAMA 1987; 258:1509–1511 11. Roland EH, Jan JE, Rigg JM: Toxic encephalopathy in a child after brief exposure to insect repellents. Can Med Assoc J 1985; 132:155–156
Psychosomatics 42:1, January-February 2001