Journal of Clinical Psychopharmacology
Letters to the Editors
2. Finn SE, Bailey JM, Schultz RT, et al. Subjective utility ratings of neuroleptics in treating schizophrenia. Psychol Med. 1990;20:843Y848. 3. Knegtering H, van den Bosch R, Castelein S, et al. Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin? Psychoneuroendocrinology. 2008;33:711Y717. 4. Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Int Clin Psychopharmacol. 2011;26:130Y140. 5. Montejo AL, Majadas S, Rico-Villademoros F, et al. Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics. J Sex Med. 2010;7:3404Y3413. 6. Nunes LV, Moreira HC, Razzouk D, et al. Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review. J Sex Marital Ther. 2012;38:281Y301. 7. Nunes LV, Lacaz FS, Bressan RA, et al. Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-blind, crossover, placebo-controlled trial. J Sex Med. 2013;10:1136Y1145. 8. Gopalakrishnan R, Jacob KS, Kuruvilla A, et al. Sildenafil in the treatment of antipsychotic-induced erectile dysfunction: a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial. Am J Psychiatry. 2006;163:494Y499. 9. Aviv A, Shelef A, Weizman A. An open-label trial of sildenafil addition in risperidone-treated male schizophrenia patients with erectile dysfunction. J Clin Psychiatry. 2004;65:97Y103. 10. Atmaca M, Kuloglu M, Tezcan E. Sildenafil use in patients with olanzapine-induced erectile dysfunction. Int J Impot Res. 2002;14:547Y549. 11. Mitsonis CI, Mitropoulos PA, Dimopoulos NP, et al. Vardenafil in the treatment of erectile dysfunction in outpatients with chronic schizophrenia: a flexible-dose, open-label study. J Clin Psychiatry. 2008;69:206Y212. 12. Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49:822Y830. 13. Rosen RC, Cappelleri JC, Gendrano N 3rd. The International Index of Erectile Function (IIEF): a state-of-the-science review. Int J Impot Res. 2002;14:226Y244. 14. Knegtering H. Antipsychotic treatment and sexual functioning: role of prolactin. PhD Thesis, University of Groningen, University Medical Center Groningen,
382
www.psychopharmacology.com
2003, The Netherlands. Available at: http://dissertations.ub.rug.nl/faculties/ medicine/2003/h.knegtering/. Accessed July 27, 2013. 15. Diggle PJ, Liang K-Y, Zeger SL. Analysis of Longitudinal Data. Oxford, UK: Oxford Science Publications; 1994:31. 16. de Boer MK, Castelein S, Bous J, et al. The antipsychotics and sexual functioning questionnaire (ASFQ): preliminary evidence for reliability and validity. Schizophr Res. 2013;150:410Y415.
Acute Pancreatitis Associated With Quetiapine Use in Schizophrenia To the Editors: rug-related acute pancreatitis is an important safety issue. Quetiapineassociated acute pancreatitis has been reported in rare cases, all appearing shortly after the initiation of quetiapine use.1,2 Here, we report a patient with schizophrenia who experienced acute pancreatitis after quetiapine treatment for 10 years. The score of the Naranjo Scale3 was 8. Quetiapineassociated acute pancreatitis was probable. Reuse of low-dose quetiapine did not induce the disease after 6 months of observation.
D
CASE The 58-year-old man was a nursing home resident whose condition of more than 20 years was diagnosed as schizophrenia; he had no history of diabetes or hyperlipidemia. He presented with episodes of abdominal pain, vomiting, fever, and chills. He was then brought to the emergency department of a medical center. The laboratory values on the day of admission were as follows: sodium, 141 mEq/L; potassium, 4.8 Eq/L; serum urea nitrogen, 21 mg/dL; creatinine, 1.1 mg/dL; calcium, 7.5 mg/dL; and glucose, 95 mg/dL. Lipase and amylase were significantly elevated at 5482 and 976 U/L, respectively. Liver-associated enzymes were as follows: bilirubin, 0.87 mg/dL; alkaline phosphatase, 81 U/L; aspartate aminotransferase, 26 U/L; and alanine aminotransferase, 29 U/L. Triglycerides were 74 mg/dL, thewhite blood cell count was 14240/KL, and hematocrit was 49.3%. Abdominal sonographic examination and computed tomography were also performed and revealed acute pancreatitis with a gall bladder polyp. Thus, the gastroenterologist made a diagnosis of drugrelated acute pancreatitis. The patient had chronic psychotic symptoms of auditory hallucination, poverty of thought content,
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Volume 34, Number 3, June 2014
and negative symptoms. His positive symptoms of schizophrenia were not exacerbated during the episode of acute pancreatitis. Before admission, he received quetiapine, 500 mg, plus valproic acid, 500 mg, for 10 years. Thus, valproic acid was withdrawn first. He then received antibiotics/ supportive therapy and was discharged after 12 days of admission. However, similar symptoms and signs recurred 5 days later under monotherapy of quetiapine, 500 mg/d. The laboratory values were lipase, 458 U/L; white blood cell count, 13660/KL; glucose, 102 mg/dL; and hematocrit, 41.3%. Abdominal ultrasound showed acute pancreatitis. This time, the patient was admitted from the emergency department to the department of gastroenterology for 4 days. Drug-related acute pancreatitis was highly suspected without other definite causes. Thus, we stopped quetiapine for 14 days and gradually titrated to 100 mg/d. The patient received regular monitoring in the department of gastroenterology once per month. After observation for 6 months, low-dose quetiapine did not induce acute pancreatitis. The score of the Clinical Global ImpressionVSeverity of Illness was 3.
DISCUSSION There are numerous possible etiologies of acute pancreatitis, but this patient had no causes of or risk factors for acute pancreatitis, such as alcohol abuse, or undiagnosed medical conditions, such as diabetes, elevated lipid levels, or metabolic syndrome. Other possible causes of pancreatitis were excluded with the exception of valproic acid. During the first admission, either quetiapine or valproic acid could have caused acute pancreatitis. Thus, we cannot rule out that the 2 admissions are separate events related to different drugs or combinations. It is possible that quetiapine collaborated with valproic acid in the pathogenesis of the disease. Nevertheless, a study revealed small and statistically nonsignificant pharmacokinetic interactions between quetiapine and valproic acid in patients with schizophrenia.4 It seems that quetiapine and valproic acid are independent risk factors of the disease. Valproic acidYrelated acute pancreatitis is common in children5 and may occur after a significant length of time of drug administration.1 The dosage and plasma concentration of valproic acid do not play a role in the development of pancreatitis.6 The mechanism of valproic acidYrelated acute pancreatitis remains unclear. To assess the probability of adverse effects of valproic acid, the Naranjo * 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology
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Volume 34, Number 3, June 2014
Scale was used to investigate its association. A score of 4 (1, 2, 1, 0, j1, 0, 0, 0, 0, and 1) was obtained, which means a possible probability. The circulating half-life of valproic acid is 9 to 18 hours in adults. The influence of valproic acid may disappear after withdrawal for 17 days. It should also be noted that quetiapine was the only drug associated with acute pancreatitis during the second admission of our patient. A score on the Naranjo Scale of 8 (1, 2, 1, j1, 2, 0, 0, 1, 1, and 1) was obtained, suggesting that quetiapine was associated with the acute pancreatitis. Thus, we believe that it is more likely that it was quetiapine rather than valproic acid that caused the 2 episodes of acute pancreatitis. The development of the disease may be due to the metabolic effect of quetiapine, such as is seen with the association of quetiapine in hyperglycemia and diabetic ketoacidosis.7 Whether the metabolic effects of quetiapine are similar to those of other second-generation antipsychotics8 remains unclear. It has been shown in several case reports that the characteristics of quetiapine-associated acute pancreatitis seem to occur in the first 3 months of treatment.1,2 Nevertheless, acute pancreatitis may occur with long-term use of quetiapine, as seen in our report. In our case, we withdrew quetiapine for 2 weeks and reused at a low dose of 100 mg/d and found that pancreatitis did not recur in the patient for 6 months. This suggests that a diminished dose of quetiapine may have benefited elimination of the disease in this case. Longterm or higher-dose quetiapine is often used in patients with schizophrenia. Thus, the accumulation of metabolic effects8 of quetiapine should be taken into consideration, as they may cause adverse effects. Quetiapine is widely used in the field of psychiatry owing to the development of new indications. The accumulation of metabolic effects may cause acute pancreatitis with higher-dosage or long-term use. Prescription of quetiapine should be performed cautiously in clinical practice. A well-designed study is needed to elucidate the association between quetiapine and acute pancreatitis. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Ting-Gang Chang, MD Department of Psychiatry Lu-Tung Branch of Changhua Christian Hospital LuKang, Taiwan and Department of Psychiatry Changhua Christian Hospital Changhua, Taiwan * 2014 Lippincott Williams & Wilkins
Nan-Ying Chiu, MD Department of Psychiatry Lu-Tung Branch of Changhua Christian Hospital LuKang, Taiwan and Department of Psychiatry Changhua Christian Hospital Changhua, Taiwan and Department of Psychiatry Chung Shan Medical University Taichung, Taiwan
Wen-Yu Hsu, MD Department of Psychiatry Lu-Tung Branch of Changhua Christian Hospital LuKang, Taiwan and Department of Psychiatry Changhua Christian Hospital Changhua, Taiwan and Department of Psychiatry Chung Shan Medical University Taichung, Taiwan and Graduate Institute of Clinical Medical Science China Medical University Taichung, Taiwan [email protected]
REFERENCES 1. Gropper D, Jackson CW. Pancreatitis associated with quetiapine use. J Clin Psychopharmacol. 2004;24:343Y345. 2. Potolidis E, Mandros C, Karakitsos D, et al. Quetiapine-associated pancreatitis in a geriatric critical care patient with delirium. Case Rep Psychiatry. 2012;2012:625954. 3. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239Y245. 4. Winter HR, DeVane CL, Figueroa C, et al. Open-label steady-state pharmacokinetic drug interaction study on co-administered quetiapine fumarate and divalproex sodium in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Hum Psychopharmacol. 2007;22:469Y476. 5. Sinclair DB, Berg M, Breault R. Valproic acidYinduced pancreatitis in childhood epilepsy: case series and review. J Child Neurol. 2004;19:498Y502. 6. Chapman SA, Wacksman GP, Patterson BD. Pancreatitis associated with valproic acid: a review of the literature. Pharmacotherapy. 2001;21:1549Y1560. 7. Rashid J, Starer PJ, Javaid S. Pancreatitis and diabetic ketoacidosis with quetiapine use. Psychiatry (Edgmont). 2009;6: 34Y37. 8. Kahn D, Bourgeois JA. Acute pancreatitis and diabetic ketoacidosis in a schizophrenic patient taking olanzapine. J Clin Psychopharmacol. 2007; 27:397Y400.
Letters to the Editors
Cognitive Effects of Quetiapine XR in Patients With Euthymic Bipolar Disorder To the Editors: bservational studies of patients with bipolar disorder (BD) receiving quetiapine (QTP) suggested improvements in multiple domains of cognition as compared with those who were receiving other antipsychotics.1,2 Ndesalkylquetiapine (N-QTP), a metabolite of QTP, inhibits the norepinephrine transporter with 10-fold greater potency than QTP and may account for these cognitive benefits.3 However, a randomized, placebo-controlled study is required to more definitively determine the cognitive and functional impact of QTP. We hypothesized that during the 6-week period, quetiapine extended release (QTPX) would demonstrate greater improvements on measures of cognition and functional capacity as compared with placebo. Two centers, Emory University and Duke University, conducted this study from January 2010 to June 2012. Eligible participants were adults aged 18 to 65 years with a diagnosis of BD I or II, confirmed using the Mini-International Neuropsychiatric Interview.4 Patients had to be on a mood stabilizer (lithium, valproate, lamotrigine, or any combination) with no dose changes 8 weeks before the baseline visit. Exclusion criteria included any current mood episode, a Montgomery-Asberg Depression Scale5 of 19 and above, or a Young Mania Rating Scale6 of 13 and above at screening or baseline. Carbamazepine and all medications known to enhance noradrenergic signaling were prohibited. Benzodiazepines and opiate medications were allowed but were not to be taken within 24 hours of a study visit. Subjects with substance abuse/dependence in the last 3 months, neurologic illness, or an unstable medical illness were not enrolled. This study was approved by the institutional review board at both sites and listed at ClinicalTrials.gov (NCT00746421). After providing written informed consent, subjects who completed the screening were entered into a 4-week lead-in phase to ensure mood stability. At the baseline visit, subjects were randomized to receive either QTPX or matching pill placebo. Blocked randomization by site was performed by the Emory University Investigational Drug Service. The starting dose was 200 mg nightly and flexibly dosed over the first 4 weeks to a maximum of 400 mg. Serum QTP and N-QTP levels were drawn at week 6.
O
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
383
Letters to the Editors
2. Finn SE, Bailey JM, Schultz RT, et al. Subjective utility ratings of neuroleptics in treating schizophrenia. Psychol Med. 1990;20:843Y848. 3. Knegtering H, van den Bosch R, Castelein S, et al. Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin? Psychoneuroendocrinology. 2008;33:711Y717. 4. Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Int Clin Psychopharmacol. 2011;26:130Y140. 5. Montejo AL, Majadas S, Rico-Villademoros F, et al. Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics. J Sex Med. 2010;7:3404Y3413. 6. Nunes LV, Moreira HC, Razzouk D, et al. Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review. J Sex Marital Ther. 2012;38:281Y301. 7. Nunes LV, Lacaz FS, Bressan RA, et al. Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-blind, crossover, placebo-controlled trial. J Sex Med. 2013;10:1136Y1145. 8. Gopalakrishnan R, Jacob KS, Kuruvilla A, et al. Sildenafil in the treatment of antipsychotic-induced erectile dysfunction: a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial. Am J Psychiatry. 2006;163:494Y499. 9. Aviv A, Shelef A, Weizman A. An open-label trial of sildenafil addition in risperidone-treated male schizophrenia patients with erectile dysfunction. J Clin Psychiatry. 2004;65:97Y103. 10. Atmaca M, Kuloglu M, Tezcan E. Sildenafil use in patients with olanzapine-induced erectile dysfunction. Int J Impot Res. 2002;14:547Y549. 11. Mitsonis CI, Mitropoulos PA, Dimopoulos NP, et al. Vardenafil in the treatment of erectile dysfunction in outpatients with chronic schizophrenia: a flexible-dose, open-label study. J Clin Psychiatry. 2008;69:206Y212. 12. Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49:822Y830. 13. Rosen RC, Cappelleri JC, Gendrano N 3rd. The International Index of Erectile Function (IIEF): a state-of-the-science review. Int J Impot Res. 2002;14:226Y244. 14. Knegtering H. Antipsychotic treatment and sexual functioning: role of prolactin. PhD Thesis, University of Groningen, University Medical Center Groningen,
382
www.psychopharmacology.com
2003, The Netherlands. Available at: http://dissertations.ub.rug.nl/faculties/ medicine/2003/h.knegtering/. Accessed July 27, 2013. 15. Diggle PJ, Liang K-Y, Zeger SL. Analysis of Longitudinal Data. Oxford, UK: Oxford Science Publications; 1994:31. 16. de Boer MK, Castelein S, Bous J, et al. The antipsychotics and sexual functioning questionnaire (ASFQ): preliminary evidence for reliability and validity. Schizophr Res. 2013;150:410Y415.
Acute Pancreatitis Associated With Quetiapine Use in Schizophrenia To the Editors: rug-related acute pancreatitis is an important safety issue. Quetiapineassociated acute pancreatitis has been reported in rare cases, all appearing shortly after the initiation of quetiapine use.1,2 Here, we report a patient with schizophrenia who experienced acute pancreatitis after quetiapine treatment for 10 years. The score of the Naranjo Scale3 was 8. Quetiapineassociated acute pancreatitis was probable. Reuse of low-dose quetiapine did not induce the disease after 6 months of observation.
D
CASE The 58-year-old man was a nursing home resident whose condition of more than 20 years was diagnosed as schizophrenia; he had no history of diabetes or hyperlipidemia. He presented with episodes of abdominal pain, vomiting, fever, and chills. He was then brought to the emergency department of a medical center. The laboratory values on the day of admission were as follows: sodium, 141 mEq/L; potassium, 4.8 Eq/L; serum urea nitrogen, 21 mg/dL; creatinine, 1.1 mg/dL; calcium, 7.5 mg/dL; and glucose, 95 mg/dL. Lipase and amylase were significantly elevated at 5482 and 976 U/L, respectively. Liver-associated enzymes were as follows: bilirubin, 0.87 mg/dL; alkaline phosphatase, 81 U/L; aspartate aminotransferase, 26 U/L; and alanine aminotransferase, 29 U/L. Triglycerides were 74 mg/dL, thewhite blood cell count was 14240/KL, and hematocrit was 49.3%. Abdominal sonographic examination and computed tomography were also performed and revealed acute pancreatitis with a gall bladder polyp. Thus, the gastroenterologist made a diagnosis of drugrelated acute pancreatitis. The patient had chronic psychotic symptoms of auditory hallucination, poverty of thought content,
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Volume 34, Number 3, June 2014
and negative symptoms. His positive symptoms of schizophrenia were not exacerbated during the episode of acute pancreatitis. Before admission, he received quetiapine, 500 mg, plus valproic acid, 500 mg, for 10 years. Thus, valproic acid was withdrawn first. He then received antibiotics/ supportive therapy and was discharged after 12 days of admission. However, similar symptoms and signs recurred 5 days later under monotherapy of quetiapine, 500 mg/d. The laboratory values were lipase, 458 U/L; white blood cell count, 13660/KL; glucose, 102 mg/dL; and hematocrit, 41.3%. Abdominal ultrasound showed acute pancreatitis. This time, the patient was admitted from the emergency department to the department of gastroenterology for 4 days. Drug-related acute pancreatitis was highly suspected without other definite causes. Thus, we stopped quetiapine for 14 days and gradually titrated to 100 mg/d. The patient received regular monitoring in the department of gastroenterology once per month. After observation for 6 months, low-dose quetiapine did not induce acute pancreatitis. The score of the Clinical Global ImpressionVSeverity of Illness was 3.
DISCUSSION There are numerous possible etiologies of acute pancreatitis, but this patient had no causes of or risk factors for acute pancreatitis, such as alcohol abuse, or undiagnosed medical conditions, such as diabetes, elevated lipid levels, or metabolic syndrome. Other possible causes of pancreatitis were excluded with the exception of valproic acid. During the first admission, either quetiapine or valproic acid could have caused acute pancreatitis. Thus, we cannot rule out that the 2 admissions are separate events related to different drugs or combinations. It is possible that quetiapine collaborated with valproic acid in the pathogenesis of the disease. Nevertheless, a study revealed small and statistically nonsignificant pharmacokinetic interactions between quetiapine and valproic acid in patients with schizophrenia.4 It seems that quetiapine and valproic acid are independent risk factors of the disease. Valproic acidYrelated acute pancreatitis is common in children5 and may occur after a significant length of time of drug administration.1 The dosage and plasma concentration of valproic acid do not play a role in the development of pancreatitis.6 The mechanism of valproic acidYrelated acute pancreatitis remains unclear. To assess the probability of adverse effects of valproic acid, the Naranjo * 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology
&
Volume 34, Number 3, June 2014
Scale was used to investigate its association. A score of 4 (1, 2, 1, 0, j1, 0, 0, 0, 0, and 1) was obtained, which means a possible probability. The circulating half-life of valproic acid is 9 to 18 hours in adults. The influence of valproic acid may disappear after withdrawal for 17 days. It should also be noted that quetiapine was the only drug associated with acute pancreatitis during the second admission of our patient. A score on the Naranjo Scale of 8 (1, 2, 1, j1, 2, 0, 0, 1, 1, and 1) was obtained, suggesting that quetiapine was associated with the acute pancreatitis. Thus, we believe that it is more likely that it was quetiapine rather than valproic acid that caused the 2 episodes of acute pancreatitis. The development of the disease may be due to the metabolic effect of quetiapine, such as is seen with the association of quetiapine in hyperglycemia and diabetic ketoacidosis.7 Whether the metabolic effects of quetiapine are similar to those of other second-generation antipsychotics8 remains unclear. It has been shown in several case reports that the characteristics of quetiapine-associated acute pancreatitis seem to occur in the first 3 months of treatment.1,2 Nevertheless, acute pancreatitis may occur with long-term use of quetiapine, as seen in our report. In our case, we withdrew quetiapine for 2 weeks and reused at a low dose of 100 mg/d and found that pancreatitis did not recur in the patient for 6 months. This suggests that a diminished dose of quetiapine may have benefited elimination of the disease in this case. Longterm or higher-dose quetiapine is often used in patients with schizophrenia. Thus, the accumulation of metabolic effects8 of quetiapine should be taken into consideration, as they may cause adverse effects. Quetiapine is widely used in the field of psychiatry owing to the development of new indications. The accumulation of metabolic effects may cause acute pancreatitis with higher-dosage or long-term use. Prescription of quetiapine should be performed cautiously in clinical practice. A well-designed study is needed to elucidate the association between quetiapine and acute pancreatitis. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Ting-Gang Chang, MD Department of Psychiatry Lu-Tung Branch of Changhua Christian Hospital LuKang, Taiwan and Department of Psychiatry Changhua Christian Hospital Changhua, Taiwan * 2014 Lippincott Williams & Wilkins
Nan-Ying Chiu, MD Department of Psychiatry Lu-Tung Branch of Changhua Christian Hospital LuKang, Taiwan and Department of Psychiatry Changhua Christian Hospital Changhua, Taiwan and Department of Psychiatry Chung Shan Medical University Taichung, Taiwan
Wen-Yu Hsu, MD Department of Psychiatry Lu-Tung Branch of Changhua Christian Hospital LuKang, Taiwan and Department of Psychiatry Changhua Christian Hospital Changhua, Taiwan and Department of Psychiatry Chung Shan Medical University Taichung, Taiwan and Graduate Institute of Clinical Medical Science China Medical University Taichung, Taiwan [email protected]
REFERENCES 1. Gropper D, Jackson CW. Pancreatitis associated with quetiapine use. J Clin Psychopharmacol. 2004;24:343Y345. 2. Potolidis E, Mandros C, Karakitsos D, et al. Quetiapine-associated pancreatitis in a geriatric critical care patient with delirium. Case Rep Psychiatry. 2012;2012:625954. 3. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239Y245. 4. Winter HR, DeVane CL, Figueroa C, et al. Open-label steady-state pharmacokinetic drug interaction study on co-administered quetiapine fumarate and divalproex sodium in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Hum Psychopharmacol. 2007;22:469Y476. 5. Sinclair DB, Berg M, Breault R. Valproic acidYinduced pancreatitis in childhood epilepsy: case series and review. J Child Neurol. 2004;19:498Y502. 6. Chapman SA, Wacksman GP, Patterson BD. Pancreatitis associated with valproic acid: a review of the literature. Pharmacotherapy. 2001;21:1549Y1560. 7. Rashid J, Starer PJ, Javaid S. Pancreatitis and diabetic ketoacidosis with quetiapine use. Psychiatry (Edgmont). 2009;6: 34Y37. 8. Kahn D, Bourgeois JA. Acute pancreatitis and diabetic ketoacidosis in a schizophrenic patient taking olanzapine. J Clin Psychopharmacol. 2007; 27:397Y400.
Letters to the Editors
Cognitive Effects of Quetiapine XR in Patients With Euthymic Bipolar Disorder To the Editors: bservational studies of patients with bipolar disorder (BD) receiving quetiapine (QTP) suggested improvements in multiple domains of cognition as compared with those who were receiving other antipsychotics.1,2 Ndesalkylquetiapine (N-QTP), a metabolite of QTP, inhibits the norepinephrine transporter with 10-fold greater potency than QTP and may account for these cognitive benefits.3 However, a randomized, placebo-controlled study is required to more definitively determine the cognitive and functional impact of QTP. We hypothesized that during the 6-week period, quetiapine extended release (QTPX) would demonstrate greater improvements on measures of cognition and functional capacity as compared with placebo. Two centers, Emory University and Duke University, conducted this study from January 2010 to June 2012. Eligible participants were adults aged 18 to 65 years with a diagnosis of BD I or II, confirmed using the Mini-International Neuropsychiatric Interview.4 Patients had to be on a mood stabilizer (lithium, valproate, lamotrigine, or any combination) with no dose changes 8 weeks before the baseline visit. Exclusion criteria included any current mood episode, a Montgomery-Asberg Depression Scale5 of 19 and above, or a Young Mania Rating Scale6 of 13 and above at screening or baseline. Carbamazepine and all medications known to enhance noradrenergic signaling were prohibited. Benzodiazepines and opiate medications were allowed but were not to be taken within 24 hours of a study visit. Subjects with substance abuse/dependence in the last 3 months, neurologic illness, or an unstable medical illness were not enrolled. This study was approved by the institutional review board at both sites and listed at ClinicalTrials.gov (NCT00746421). After providing written informed consent, subjects who completed the screening were entered into a 4-week lead-in phase to ensure mood stability. At the baseline visit, subjects were randomized to receive either QTPX or matching pill placebo. Blocked randomization by site was performed by the Emory University Investigational Drug Service. The starting dose was 200 mg nightly and flexibly dosed over the first 4 weeks to a maximum of 400 mg. Serum QTP and N-QTP levels were drawn at week 6.
O
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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