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New-onset diabetic ketoacidosis associated with quetiapine: a case report
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General Hospital Psychiatry 30 (2008) 587 – 588
Letter to the Editor New-onset diabetic ketoacidosis associated with quetiapine: a case report To the Editor: 1. Introduction Atypical antipsychotics are known to foster weight gain and hyperglycemia. Patients under such medication are at risk for metabolic syndrome. So far, the biological pattern was mainly associated with diabetes type 2 or exacerbation of pre-existing diabetes. Recent reports [1–3] suggest that a significant portion of patients under quetiapine might develop new-onset diabetes. The increasing concern about the metabolic consequences of atypical antipsychotic therapy is related to the fulminant and dramatic onset of diabetes with metabolic acidosis. The present case features typical clinical aspects of such complication and highlights clinical guidelines.
and ideas of reference like people talking in her back; she had started wearing sunglasses at work as to avoid being looked at. A month later, she was hospitalized for 19 days as paranoid symptoms crept into her relationship with her husband whom she wanted to leave as she felt neglected by him. During hospitalization, she was put on risperidone 1 mg tid and haloperidol 7.5 mg hs while being kept on the same dosage of venlafaxine. After discharge from hospital with the same medication, she reported mammary congestion, and risperidone was decreased to 1 mg hs (prolactin levels were unavailable) up to the current admission. On follow-up, haloperidol was discontinued early, and 5 months after her psychiatric hospitalisation, she was started on quetiapine. She had no previous psychiatric history before the current episode. Diagnosis was psychotic depression; the breakdown was linked to the menarche of her daughter as the patient started worrying about being neglected by her husband, was preoccupied with her daughter's breasts, and felt more and more unable to leave home for fear of people talking about her. 3. Discussion
2. Case report A 41-year-old black woman was admitted in hyperglycemic coma, with a Glasgow 5/15. Glycemia was 81.8 mmol/L (N 3.6–5.8). Other laboratory measures were as follows: pH 7.022, pCo2 32.1 mmHg, HCo3 8.3 mmol/L (N 21–29), anion gap 31.1 mmol/L (N 7–16), hydroxybutyric acid 4.0 (N b0.6) and glyk HB 0.117 (N 0.043–0.062). She recovered within few days when glycemic control was restored but remained under insulin treatment. She had started quetiapine 37 days earlier at 300 mg for 4 days, then 400 mg/day. She was not known for diabetes and was without family history. On admission, her body mass index (BMI) was 37.2. Previous fasting glucose tests from traceable medical records prior to exposition to quetiapine showed that her glycemic levels were within normal limits (N 3.6–5.8 mmol/L): February 2002, 4.9; August 2004, 5.3; November 2006, 5.0. During the year prior to diabetic ketoacidosis (DKA), she had been followed by a psychiatrist for depression, initially treated with sertraline 50 mg for a few weeks and later with venlafaxineXR 75 mg, which she was still taking at admission. About 8 months prior to her current admission, her employer suggested a leave of absence from work as she developed paranoid ideation 0163-8343/$ – see front matter © 2008 Elsevier Inc. All rights reserved.
While the metabolic effects of atypical antipsychotics have been known for some time [1], recent reports [2,3] about quetiapine-associated hyperglycemia point towards a shift: new-onset diabetes accounts for 50% of hyperglycemic reactions, with DKA in half of those new-onset diabetes. Patients under quetiapine appear to have diabetes 2.5 times more frequently than the general US population [3]. Populations at risk with a 2:1 ratio are African-stock persons and female [2,4]. Daily drug dosage averages 400 mg/day [3]. Time to onset after initiating treatment is about a month as median time, with a mean of 81 days. Monitoring of blood glucose for outpatients with limited follow-up should be mandatory in the first 6 months [2] given the unpredictability of such serious side effect as DKA and the 10-fold higher incidence of DKA in psychotic patients than that reported in the general population [7]. In such cases, monitoring weight gain measure alone is insufficient [5,6]. Henderson et al. [7] have argued that cases of DKA with quetiapine occur mainly in patients with known diabetes mellitus. It appears that our case had no diabetes prior to exposure to quetiapine, and the hemoglobin test also showed diabetes present for some weeks, probably from the onset of quetiapine intake. Reversibility is an unsettled issue as well as rechallenging with the
588
Letter to the Editor / General Hospital Psychiatry 30 (2008) 587–588
same drug. Eight out of 13 patients with new-onset diabetes mellitus with DKA reported by Henderson et al. were continued on the same drug regimen with insulin treatment later switched in many cases to oral hypoglycemic agents. François Sirois, M.D. Clinical Professor of Psychiatry, Laval University Quebec, Canada E-mail address: [email protected] doi:10.1016/j.genhosppsych.2008.06.007 References [1] Wilson D, D’Souza L, Sarkar N, Newton M, Hammond C. New-onset diabetes and ketoacidosis with atypical antipsychotics. Schizophr Res 2002;59:1–6.
[2] van Winkel R, De Hert M, Wampers M, Van Eyck D, Hanssens L, Schee A, Peuskens J. Major changes in glucose metbolism, including newonset diabetes, within 3 months after initiation of or switch to atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2008:e1–8. [3] Koller EA, Weber J, Murali P, Bruce S. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry 2004;65:857–63. [4] Procyshyn RM, Pande S, Tse G. New-onset diabetes mellitus associated with quetiapine. Can J Psychiatry 2000;45:668–9. [5] Marlowe KF, Howard D, Chung A. New onset diabetes with ketoacidosis attributed to quetiapine. South Med J 2007;100:829–31. [6] Meyer JM, Leckband SG, Loh C, Moutier CY. Quetiapine-induced diabetes with metabolic acidosis. Int Clin Psychopharmacol 2004;19: 169–71. [7] Henderson DC, Cagliero E, Copeland PM, Louie PM, Borba CP, Fan X, Freudenreich O, Goff DC. Elevated hemoglobin A1c as possible indicator of diabetes mellitus and diabetic ketoacidosis in schizophrenia patients receiving atypical antipsychotics. J Clin Psychiatry 2007;68: 533–41.
General Hospital Psychiatry 30 (2008) 587 – 588
Letter to the Editor New-onset diabetic ketoacidosis associated with quetiapine: a case report To the Editor: 1. Introduction Atypical antipsychotics are known to foster weight gain and hyperglycemia. Patients under such medication are at risk for metabolic syndrome. So far, the biological pattern was mainly associated with diabetes type 2 or exacerbation of pre-existing diabetes. Recent reports [1–3] suggest that a significant portion of patients under quetiapine might develop new-onset diabetes. The increasing concern about the metabolic consequences of atypical antipsychotic therapy is related to the fulminant and dramatic onset of diabetes with metabolic acidosis. The present case features typical clinical aspects of such complication and highlights clinical guidelines.
and ideas of reference like people talking in her back; she had started wearing sunglasses at work as to avoid being looked at. A month later, she was hospitalized for 19 days as paranoid symptoms crept into her relationship with her husband whom she wanted to leave as she felt neglected by him. During hospitalization, she was put on risperidone 1 mg tid and haloperidol 7.5 mg hs while being kept on the same dosage of venlafaxine. After discharge from hospital with the same medication, she reported mammary congestion, and risperidone was decreased to 1 mg hs (prolactin levels were unavailable) up to the current admission. On follow-up, haloperidol was discontinued early, and 5 months after her psychiatric hospitalisation, she was started on quetiapine. She had no previous psychiatric history before the current episode. Diagnosis was psychotic depression; the breakdown was linked to the menarche of her daughter as the patient started worrying about being neglected by her husband, was preoccupied with her daughter's breasts, and felt more and more unable to leave home for fear of people talking about her. 3. Discussion
2. Case report A 41-year-old black woman was admitted in hyperglycemic coma, with a Glasgow 5/15. Glycemia was 81.8 mmol/L (N 3.6–5.8). Other laboratory measures were as follows: pH 7.022, pCo2 32.1 mmHg, HCo3 8.3 mmol/L (N 21–29), anion gap 31.1 mmol/L (N 7–16), hydroxybutyric acid 4.0 (N b0.6) and glyk HB 0.117 (N 0.043–0.062). She recovered within few days when glycemic control was restored but remained under insulin treatment. She had started quetiapine 37 days earlier at 300 mg for 4 days, then 400 mg/day. She was not known for diabetes and was without family history. On admission, her body mass index (BMI) was 37.2. Previous fasting glucose tests from traceable medical records prior to exposition to quetiapine showed that her glycemic levels were within normal limits (N 3.6–5.8 mmol/L): February 2002, 4.9; August 2004, 5.3; November 2006, 5.0. During the year prior to diabetic ketoacidosis (DKA), she had been followed by a psychiatrist for depression, initially treated with sertraline 50 mg for a few weeks and later with venlafaxineXR 75 mg, which she was still taking at admission. About 8 months prior to her current admission, her employer suggested a leave of absence from work as she developed paranoid ideation 0163-8343/$ – see front matter © 2008 Elsevier Inc. All rights reserved.
While the metabolic effects of atypical antipsychotics have been known for some time [1], recent reports [2,3] about quetiapine-associated hyperglycemia point towards a shift: new-onset diabetes accounts for 50% of hyperglycemic reactions, with DKA in half of those new-onset diabetes. Patients under quetiapine appear to have diabetes 2.5 times more frequently than the general US population [3]. Populations at risk with a 2:1 ratio are African-stock persons and female [2,4]. Daily drug dosage averages 400 mg/day [3]. Time to onset after initiating treatment is about a month as median time, with a mean of 81 days. Monitoring of blood glucose for outpatients with limited follow-up should be mandatory in the first 6 months [2] given the unpredictability of such serious side effect as DKA and the 10-fold higher incidence of DKA in psychotic patients than that reported in the general population [7]. In such cases, monitoring weight gain measure alone is insufficient [5,6]. Henderson et al. [7] have argued that cases of DKA with quetiapine occur mainly in patients with known diabetes mellitus. It appears that our case had no diabetes prior to exposure to quetiapine, and the hemoglobin test also showed diabetes present for some weeks, probably from the onset of quetiapine intake. Reversibility is an unsettled issue as well as rechallenging with the
588
Letter to the Editor / General Hospital Psychiatry 30 (2008) 587–588
same drug. Eight out of 13 patients with new-onset diabetes mellitus with DKA reported by Henderson et al. were continued on the same drug regimen with insulin treatment later switched in many cases to oral hypoglycemic agents. François Sirois, M.D. Clinical Professor of Psychiatry, Laval University Quebec, Canada E-mail address: [email protected] doi:10.1016/j.genhosppsych.2008.06.007 References [1] Wilson D, D’Souza L, Sarkar N, Newton M, Hammond C. New-onset diabetes and ketoacidosis with atypical antipsychotics. Schizophr Res 2002;59:1–6.
[2] van Winkel R, De Hert M, Wampers M, Van Eyck D, Hanssens L, Schee A, Peuskens J. Major changes in glucose metbolism, including newonset diabetes, within 3 months after initiation of or switch to atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2008:e1–8. [3] Koller EA, Weber J, Murali P, Bruce S. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry 2004;65:857–63. [4] Procyshyn RM, Pande S, Tse G. New-onset diabetes mellitus associated with quetiapine. Can J Psychiatry 2000;45:668–9. [5] Marlowe KF, Howard D, Chung A. New onset diabetes with ketoacidosis attributed to quetiapine. South Med J 2007;100:829–31. [6] Meyer JM, Leckband SG, Loh C, Moutier CY. Quetiapine-induced diabetes with metabolic acidosis. Int Clin Psychopharmacol 2004;19: 169–71. [7] Henderson DC, Cagliero E, Copeland PM, Louie PM, Borba CP, Fan X, Freudenreich O, Goff DC. Elevated hemoglobin A1c as possible indicator of diabetes mellitus and diabetic ketoacidosis in schizophrenia patients receiving atypical antipsychotics. J Clin Psychiatry 2007;68: 533–41.