Journal of Clinical Psychopharmacology
Letters to the Editors
Arne J. Risselada, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Clinical Pharmacy Wilhelmina Hospital Assen Assen, the Netherlands [email protected]
Hans Mulder, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Clinical Pharmacy Wilhelmina Hospital Assen Assen, the Netherlands
gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. Br J Psychiatry. 2008;192:424Y428. 5. Gregoor JG, Mulder H, Cohen D, et al. Combined HTR2C-LEP genotype as a determinant of obesity in patients using antipsychotic medication. J Clin Psychopharmacol. 2010;30:702Y705. 6. Risselada AJ, Mulder H, Heerdink ER, et al. Association between HTR2C polymorphisms and obesity in patients without antipsychotic drugs. J Clin Psychopharmacol. 2012;32: 715Y740. 7. Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol. 1993;138:923Y936.
Eibert R. Heerdink, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Clinical Pharmacy University Medical Centre Utrecht Utrecht, the Netherlands
Jochem G. Gregoor, MD, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Psychiatry Psychiatric Hospital Meerkanten Ermelo, the Netherlands
Rob K. Gonera, MD Department of Internal Medicine Wilhelmina Hospital Assen Assen, the Netherlands
Toine C.G. Egberts, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Clinical Pharmacy University Medical Centre Utrecht Utrecht, the Netherlands
REFERENCES 1. Rankinen T, Zuberi A, Chagnon YC, et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring). 2006;14:529Y644. 2. De Luca V, Mueller DJ, de Bartolomeis A. Association of the HTR2C gene and antipsychotic-induced weight gain: a meta-analysis. Int J Neuropsychopharmacol. 2007;10:697Y704. 3. Sicard MN, Zai CC, Tiwari AK, et al. Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis. Pharmacogenomics. 2010;11:1561Y1571. 4. Yevtushenko OO, Cooper SJ, O’Neill R, et al. Influence of 5-HT2c receptor and leptin
268
www.psychopharmacology.com
A Case of Fatal Risperidone Poisoning Alerts Physicians To the Editors: isperidone (RIS), an atypical antipsychotic medication, is a serotonergic and dopamine receptor antagonist.1 It is used for the treatment of both positive and negative symptoms of schizophrenia, with fewer extrapyramidal symptoms than are seen with typical antipsychotics.2 Therapeutic adverse effects of RIS include lethargy, anxiety, extrapyramidal symptoms, tachycardia, and hypotension. In acute overdose cases, severe or fatal outcomes are often seen. Although acute fatal RIS poisoning has been reported, few cases have clearly shown both the blood concentration of RIS and the ingested dose.3,4 The present autopsy case, which clearly showed both the RIS blood concentration and the ingested dose, is valuable for both psychiatrists and physicians in terms of emphasizing the rigorous monitoring and management necessary for RIS overdose.
R
CASE REPORT A 52-year-old woman was found dead in her room on January 10, 2012. Eighty-two missing tablets of 1 mg RIS were found near her body. A few years previously, she had been diagnosed with a mental illness and was prescribed RIS. She stopped taking RIS upon referral to a psychiatrist. The ingested RIS had been stored in her room from that time. One year before her death, she was diagnosed with esophageal cancer and underwent esophagectomy. On the evening of January 7, she had been drinking alcohol with her friend. At midnight on January 8, she committed suicide. A forensic autopsy was performed on January 11.
&
Volume 34, Number 2, April 2014
Autopsy revealed findings of acute death (fluidity of blood, visceral congestion, and petechiae on the conjunctivae); no other abnormalities were found. Ethanol was detected in the blood and urine at concentrations of 1.83 and 2.23 mg/mL, respectively, by gas chromatography. Risperidone was detected from both the blood (447.4 ng/mL) and urine (74.6 ng/mL) by liquid chromatographyYmass spectrometry (LC-MS). No other drugs were detected by screening tests. Finally, the woman was diagnosed with sudden death due to RIS poisoning.
DISCUSSION As atypical antipsychotic medications have largely replaced older antipsychotic medications, overdoses of these medications have become common. The potential for cardiovascular toxicity of these medications, characterized by tachycardia, hypotension, and prolongation of the corrected QT (QTc) interval, has also been of concern.5 Acute effects of these drugs in terms of cardiac toxicity include serious ventricular arrhythmias probably due to blockade of potassium channels, prolongation of cardiac repolarization, autonomic effects, and so on.6 In a retrospective cohort study, users of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs with an adjusted incidence rate of 2.26.6 For RIS, the incidence rate ratio was 2.49, and a significant dose-dependent relationship was also obtained.6 There have been some reports summarizing the reported RIS overdose cases. Kuspis et al7 reported 31 cases of RIS overdose and noted that no patient developed any moderate to life-threatening toxic effects following ingestion of up to 150 mg. Heather and Vicas8 reported 6 cases of RIS overdose ranging from 5 to 270 mg and concluded that RIS overdose appears to have a relatively benign course. Acri and Henretig4 reported 31 cases of RIS poisoning, including 15 sole ingestion cases. The authors concluded that RIS overdoses of 180 mg or less are associated with mild changes in the central nervous system or neuromuscular status, heart rate, and blood pressure.4 However, fatal cases have also been reported, and RIS overdose can become life-threatening if not adequately treated.3,4 The previously mentioned series of RIS overdoses revealed that cardiovascular abnormalities are frequently observed in both RIS-only poisoning (60.0%) and RIS-plus-coingestant poisoning (75.0%) cases.4 A 29-year-old man who had ingested 240 mg of RIS showed prolongation of the QRS duration and QTc * 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology
&
Volume 34, Number 2, April 2014
interval (peaked at 565 milliseconds).9 A 41-year-old man who had ingested 270 mg of RIS and benzodiazepines showed sinus bradycardia and a prolonged QTc interval (peaked at 520 milliseconds).10 Therefore, in RIS overdose cases, fatal arrhythmia is the most common cause of death, which is consistent with the findings of the present case and those of previous cases.4 Considering the fatal toxic threshold, information regarding both the ingested dose and blood concentration of RIS is of great value. Furthermore, when the data on clinical characteristics and blood levels are accumulated, measurement of the blood concentration may provide useful information for initial management or prediction of patient outcome. A few reports have shown the blood concentration of RIS in victims who had taken high doses.1,3,11 Among the fatal cases, only the present case revealed both the ingested dose (82 mg) and blood concentration (447.4 ng/mL) by LC-MS analysis. The detected value was well in accordance with a nonfatal poisoning case in which a 45-year-old woman ingested 90 mg of RIS and revealed a maximum plasma concentration of 325 ng/mL by LCYtandem MS.1 In addition, 1.83 mg/mL of ethanol was detected in the blood of the present patient. Although the detailed mechanism and clinical characteristics of the interaction between RIS and alcohol have not been fully investigated, the metabolism of RIS by cytochrome P450 2D6 may be somewhat inhibited under the influence of alcohol, which is also metabolized by cytochrome P450. Therefore, the present case suggests that even if 82 mg of RIS is ingested under the influence of alcohol, the victim may suffer a fatal outcome if untreated. Routine alcohol checkups are also recommended for patients with RIS overdose. The RIS concentrations in our patient and the previously mentioned 45year-old patient differ from those in 2 previous reports in which the blood concentrations were higher and were mea sured by high-performance LC.1,3,11 With LC-MS or LCYtandem MS, specific ions originating from RIS can be detected; however, with high-performance LC, part of the structure of RIS can be detected by UV absorption. Further reports will clarify the differences in these values by specific measurement methods. All atypical antipsychotic agents have significant adverse effects if taken in excess. Therefore, special care is warranted in all cases of atypical antipsychotic overdose, including rigorous monitoring and highintensity clinical setting to manage respiratory compromise or cardiac difficulty. A prolonged QTc interval and wide QRS * 2014 Lippincott Williams & Wilkins
complex have been reported in some cases of RIS overdose, and some cases have ended in death, possibly because of asystole preceded by a QTc interval of 520 or 565 milliseconds.3,9,11 ACKNOWLEDGMENTS The authors thank Mr Takumi Kobayashi of Jansen Pharmaceutical Companies for his scientific suggestion. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Masahito Hitosugi, MD, PhD Department of Legal Medicine Dokkyo Medical University School of Medicine Tochigi, Japan [email protected]
Chie Tsukada, BSc Shinobu Yamauchi, PhD Toshiaki Nagai, PhD Department of Legal Medicine Dokkyo Medical University School of Medicine Tochigi, Japan
REFERENCES 1. Nishikage H, Nakanishi T, Takamitsu Y, et al. sequential changes in the plasma concentration of risperidone following intentional overdose. Clin Neuropharmacol. 2002;25:307Y309. 2. Keegan D. Risperidone: neurochemical pharmacologic and clinical properties of new antipsychotic drug. Can J Psychiatry. 1994;39(suppl 2):46Y52. 3. Springfield AC, Bodiford Ed. An overdose of risperidone. J Anal Toxicol. 1996;20:202Y203. 4. Acri AA, Henretig FM. Effects of risperidone in overdose. Am J Emerg Med. 1998;16:498Y501. 5. Tan HH, Hoppe J, Heard K. A systematic review of cardiovascular effects following atypical antipsychotic medication overdose. Am J Emerg Med. 2009;27:607Y616. 6. Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009;360:225Y235. 7. Kuspis D, Dean B, Krenzelok EP. Risperidone overdose assessment. J Toxicol Clin Toxicol. 1995;33:552. 8. Heather GS, Vicas IMO. Risperidone overdose: a case series. Vet Hum Toxicol. 1994;36:371. 9. Brown K, Levy H, Brenner C, et al. Overdose of risperidone. Ann Emerg Med. 1993;22:1908Y1910. 10. Duenas-Latia A, Castro-villamor M, Martin-Escudero JC, et al. New clinical manifestations of acute risperidone poisoning. Clin Toxicol. 1999;37:893Y894.
Letters to the Editors
11. Sung LH, Hoon TS, Lydia A, et al. Serum and urine risperidone concentrations in an acute overdose. J Clin Psychopharmacol. 1997;17:325Y326.
Paliperidone-Related Peripheral Edema A Case Report and Review of the Literature To the Editors: eripheral edema as an infrequent adverse drug reaction to an antipsychotic medication has been reported to occur in 1% to 3% of patients taking antipsychotic drugs.1 A MEDLINE search from January 1950 to December 2012 using the MeSH terms ‘‘antipsychotic agents’’ and ‘‘edema’’ yielded only 28 relevant studies. Among them, risperidone (7 case studies and 2 clinical trials) and olanzapine (7 case studies) were the most frequently reported antipsychotic drugs associated with peripheral edema. They were followed by quetiapine (5 case studies), haloperidol (2 case studies), chlorpromazine (1 case study and 1 clinical trial), and other antipsychotics (1 case study each), including clozapine, ziprasidone, and amisulpride. Although the published information about antipsychotic-related peripheral edema is sparse, this adverse effect has been known to lead to discontinuation of the antipsychotic treatment in patients.2,3 To the best of our knowledge, paliperidone, a benzisoxazole drug that antagonizes the dopamine type 2 receptors and serotonin (5-HT) type 2A receptors, has not been reported to induce peripheral edema.4 Herein, we report a case of peripheral edema occurring in a patient being treated with paliperidone alone.
P
CASE REPORT In January 2010, a 50-year-old man with a 30-year history of paranoid schizophrenia and on a maintenance dosage of haloperidol (10 mg/d) was admitted to our psychiatric ward because of worsening persecutory delusions and auditory hallucinations. His medical history was unremarkable. Upon examination, he exhibited fearfulness, suspiciousness, and self-talking. He also had mild tremor and rigidity. Results of laboratory studies, chest radiograph, electrocardiography, and electroencephalography were all normal. We replaced the haloperidol with paliperidone. The dosage was increased from 6 to 9 mg/d over 2 weeks. By the end of this 2-week period, although his psychotic symptoms improved, a 3+ pitting edema developed dorsally in both of the patient’s feet, causing enough pain to interfere with his daily www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
269
Letters to the Editors
Arne J. Risselada, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Clinical Pharmacy Wilhelmina Hospital Assen Assen, the Netherlands [email protected]
Hans Mulder, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Clinical Pharmacy Wilhelmina Hospital Assen Assen, the Netherlands
gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. Br J Psychiatry. 2008;192:424Y428. 5. Gregoor JG, Mulder H, Cohen D, et al. Combined HTR2C-LEP genotype as a determinant of obesity in patients using antipsychotic medication. J Clin Psychopharmacol. 2010;30:702Y705. 6. Risselada AJ, Mulder H, Heerdink ER, et al. Association between HTR2C polymorphisms and obesity in patients without antipsychotic drugs. J Clin Psychopharmacol. 2012;32: 715Y740. 7. Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol. 1993;138:923Y936.
Eibert R. Heerdink, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Clinical Pharmacy University Medical Centre Utrecht Utrecht, the Netherlands
Jochem G. Gregoor, MD, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Psychiatry Psychiatric Hospital Meerkanten Ermelo, the Netherlands
Rob K. Gonera, MD Department of Internal Medicine Wilhelmina Hospital Assen Assen, the Netherlands
Toine C.G. Egberts, PhD Department of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht, the Netherlands and Department of Clinical Pharmacy University Medical Centre Utrecht Utrecht, the Netherlands
REFERENCES 1. Rankinen T, Zuberi A, Chagnon YC, et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring). 2006;14:529Y644. 2. De Luca V, Mueller DJ, de Bartolomeis A. Association of the HTR2C gene and antipsychotic-induced weight gain: a meta-analysis. Int J Neuropsychopharmacol. 2007;10:697Y704. 3. Sicard MN, Zai CC, Tiwari AK, et al. Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis. Pharmacogenomics. 2010;11:1561Y1571. 4. Yevtushenko OO, Cooper SJ, O’Neill R, et al. Influence of 5-HT2c receptor and leptin
268
www.psychopharmacology.com
A Case of Fatal Risperidone Poisoning Alerts Physicians To the Editors: isperidone (RIS), an atypical antipsychotic medication, is a serotonergic and dopamine receptor antagonist.1 It is used for the treatment of both positive and negative symptoms of schizophrenia, with fewer extrapyramidal symptoms than are seen with typical antipsychotics.2 Therapeutic adverse effects of RIS include lethargy, anxiety, extrapyramidal symptoms, tachycardia, and hypotension. In acute overdose cases, severe or fatal outcomes are often seen. Although acute fatal RIS poisoning has been reported, few cases have clearly shown both the blood concentration of RIS and the ingested dose.3,4 The present autopsy case, which clearly showed both the RIS blood concentration and the ingested dose, is valuable for both psychiatrists and physicians in terms of emphasizing the rigorous monitoring and management necessary for RIS overdose.
R
CASE REPORT A 52-year-old woman was found dead in her room on January 10, 2012. Eighty-two missing tablets of 1 mg RIS were found near her body. A few years previously, she had been diagnosed with a mental illness and was prescribed RIS. She stopped taking RIS upon referral to a psychiatrist. The ingested RIS had been stored in her room from that time. One year before her death, she was diagnosed with esophageal cancer and underwent esophagectomy. On the evening of January 7, she had been drinking alcohol with her friend. At midnight on January 8, she committed suicide. A forensic autopsy was performed on January 11.
&
Volume 34, Number 2, April 2014
Autopsy revealed findings of acute death (fluidity of blood, visceral congestion, and petechiae on the conjunctivae); no other abnormalities were found. Ethanol was detected in the blood and urine at concentrations of 1.83 and 2.23 mg/mL, respectively, by gas chromatography. Risperidone was detected from both the blood (447.4 ng/mL) and urine (74.6 ng/mL) by liquid chromatographyYmass spectrometry (LC-MS). No other drugs were detected by screening tests. Finally, the woman was diagnosed with sudden death due to RIS poisoning.
DISCUSSION As atypical antipsychotic medications have largely replaced older antipsychotic medications, overdoses of these medications have become common. The potential for cardiovascular toxicity of these medications, characterized by tachycardia, hypotension, and prolongation of the corrected QT (QTc) interval, has also been of concern.5 Acute effects of these drugs in terms of cardiac toxicity include serious ventricular arrhythmias probably due to blockade of potassium channels, prolongation of cardiac repolarization, autonomic effects, and so on.6 In a retrospective cohort study, users of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs with an adjusted incidence rate of 2.26.6 For RIS, the incidence rate ratio was 2.49, and a significant dose-dependent relationship was also obtained.6 There have been some reports summarizing the reported RIS overdose cases. Kuspis et al7 reported 31 cases of RIS overdose and noted that no patient developed any moderate to life-threatening toxic effects following ingestion of up to 150 mg. Heather and Vicas8 reported 6 cases of RIS overdose ranging from 5 to 270 mg and concluded that RIS overdose appears to have a relatively benign course. Acri and Henretig4 reported 31 cases of RIS poisoning, including 15 sole ingestion cases. The authors concluded that RIS overdoses of 180 mg or less are associated with mild changes in the central nervous system or neuromuscular status, heart rate, and blood pressure.4 However, fatal cases have also been reported, and RIS overdose can become life-threatening if not adequately treated.3,4 The previously mentioned series of RIS overdoses revealed that cardiovascular abnormalities are frequently observed in both RIS-only poisoning (60.0%) and RIS-plus-coingestant poisoning (75.0%) cases.4 A 29-year-old man who had ingested 240 mg of RIS showed prolongation of the QRS duration and QTc * 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology
&
Volume 34, Number 2, April 2014
interval (peaked at 565 milliseconds).9 A 41-year-old man who had ingested 270 mg of RIS and benzodiazepines showed sinus bradycardia and a prolonged QTc interval (peaked at 520 milliseconds).10 Therefore, in RIS overdose cases, fatal arrhythmia is the most common cause of death, which is consistent with the findings of the present case and those of previous cases.4 Considering the fatal toxic threshold, information regarding both the ingested dose and blood concentration of RIS is of great value. Furthermore, when the data on clinical characteristics and blood levels are accumulated, measurement of the blood concentration may provide useful information for initial management or prediction of patient outcome. A few reports have shown the blood concentration of RIS in victims who had taken high doses.1,3,11 Among the fatal cases, only the present case revealed both the ingested dose (82 mg) and blood concentration (447.4 ng/mL) by LC-MS analysis. The detected value was well in accordance with a nonfatal poisoning case in which a 45-year-old woman ingested 90 mg of RIS and revealed a maximum plasma concentration of 325 ng/mL by LCYtandem MS.1 In addition, 1.83 mg/mL of ethanol was detected in the blood of the present patient. Although the detailed mechanism and clinical characteristics of the interaction between RIS and alcohol have not been fully investigated, the metabolism of RIS by cytochrome P450 2D6 may be somewhat inhibited under the influence of alcohol, which is also metabolized by cytochrome P450. Therefore, the present case suggests that even if 82 mg of RIS is ingested under the influence of alcohol, the victim may suffer a fatal outcome if untreated. Routine alcohol checkups are also recommended for patients with RIS overdose. The RIS concentrations in our patient and the previously mentioned 45year-old patient differ from those in 2 previous reports in which the blood concentrations were higher and were mea sured by high-performance LC.1,3,11 With LC-MS or LCYtandem MS, specific ions originating from RIS can be detected; however, with high-performance LC, part of the structure of RIS can be detected by UV absorption. Further reports will clarify the differences in these values by specific measurement methods. All atypical antipsychotic agents have significant adverse effects if taken in excess. Therefore, special care is warranted in all cases of atypical antipsychotic overdose, including rigorous monitoring and highintensity clinical setting to manage respiratory compromise or cardiac difficulty. A prolonged QTc interval and wide QRS * 2014 Lippincott Williams & Wilkins
complex have been reported in some cases of RIS overdose, and some cases have ended in death, possibly because of asystole preceded by a QTc interval of 520 or 565 milliseconds.3,9,11 ACKNOWLEDGMENTS The authors thank Mr Takumi Kobayashi of Jansen Pharmaceutical Companies for his scientific suggestion. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Masahito Hitosugi, MD, PhD Department of Legal Medicine Dokkyo Medical University School of Medicine Tochigi, Japan [email protected]
Chie Tsukada, BSc Shinobu Yamauchi, PhD Toshiaki Nagai, PhD Department of Legal Medicine Dokkyo Medical University School of Medicine Tochigi, Japan
REFERENCES 1. Nishikage H, Nakanishi T, Takamitsu Y, et al. sequential changes in the plasma concentration of risperidone following intentional overdose. Clin Neuropharmacol. 2002;25:307Y309. 2. Keegan D. Risperidone: neurochemical pharmacologic and clinical properties of new antipsychotic drug. Can J Psychiatry. 1994;39(suppl 2):46Y52. 3. Springfield AC, Bodiford Ed. An overdose of risperidone. J Anal Toxicol. 1996;20:202Y203. 4. Acri AA, Henretig FM. Effects of risperidone in overdose. Am J Emerg Med. 1998;16:498Y501. 5. Tan HH, Hoppe J, Heard K. A systematic review of cardiovascular effects following atypical antipsychotic medication overdose. Am J Emerg Med. 2009;27:607Y616. 6. Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009;360:225Y235. 7. Kuspis D, Dean B, Krenzelok EP. Risperidone overdose assessment. J Toxicol Clin Toxicol. 1995;33:552. 8. Heather GS, Vicas IMO. Risperidone overdose: a case series. Vet Hum Toxicol. 1994;36:371. 9. Brown K, Levy H, Brenner C, et al. Overdose of risperidone. Ann Emerg Med. 1993;22:1908Y1910. 10. Duenas-Latia A, Castro-villamor M, Martin-Escudero JC, et al. New clinical manifestations of acute risperidone poisoning. Clin Toxicol. 1999;37:893Y894.
Letters to the Editors
11. Sung LH, Hoon TS, Lydia A, et al. Serum and urine risperidone concentrations in an acute overdose. J Clin Psychopharmacol. 1997;17:325Y326.
Paliperidone-Related Peripheral Edema A Case Report and Review of the Literature To the Editors: eripheral edema as an infrequent adverse drug reaction to an antipsychotic medication has been reported to occur in 1% to 3% of patients taking antipsychotic drugs.1 A MEDLINE search from January 1950 to December 2012 using the MeSH terms ‘‘antipsychotic agents’’ and ‘‘edema’’ yielded only 28 relevant studies. Among them, risperidone (7 case studies and 2 clinical trials) and olanzapine (7 case studies) were the most frequently reported antipsychotic drugs associated with peripheral edema. They were followed by quetiapine (5 case studies), haloperidol (2 case studies), chlorpromazine (1 case study and 1 clinical trial), and other antipsychotics (1 case study each), including clozapine, ziprasidone, and amisulpride. Although the published information about antipsychotic-related peripheral edema is sparse, this adverse effect has been known to lead to discontinuation of the antipsychotic treatment in patients.2,3 To the best of our knowledge, paliperidone, a benzisoxazole drug that antagonizes the dopamine type 2 receptors and serotonin (5-HT) type 2A receptors, has not been reported to induce peripheral edema.4 Herein, we report a case of peripheral edema occurring in a patient being treated with paliperidone alone.
P
CASE REPORT In January 2010, a 50-year-old man with a 30-year history of paranoid schizophrenia and on a maintenance dosage of haloperidol (10 mg/d) was admitted to our psychiatric ward because of worsening persecutory delusions and auditory hallucinations. His medical history was unremarkable. Upon examination, he exhibited fearfulness, suspiciousness, and self-talking. He also had mild tremor and rigidity. Results of laboratory studies, chest radiograph, electrocardiography, and electroencephalography were all normal. We replaced the haloperidol with paliperidone. The dosage was increased from 6 to 9 mg/d over 2 weeks. By the end of this 2-week period, although his psychotic symptoms improved, a 3+ pitting edema developed dorsally in both of the patient’s feet, causing enough pain to interfere with his daily www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
269
