Journal of Clinical Psychopharmacology
Letters to the Editors
6. Oyebode F, Rastogi A, Berrisford G, et al. Psychotropics in pregnancy: safety and other considerations. Pharmacol Ther. 2012; 135:71Y77. 7. Altshuler LL, Cohen L, Szuba MP, et al. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry. 1996; 153:592Y606. 8. Lopez L, Cohen MS, Anderson RH, et al. Unnatural history of the right ventricle in patients with congenitally malformed hearts. Cardiol Young. 2010;20:107Y112. 9. Anderson IM, Haddad PM, Scott J. Bipolar disorder. BMJ. 2012;345:e8508. 10. Bode´n R, Lundgren M, Brandt L, et al. Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study. BMJ. 2012; 345:e7085. 11. Post RM, Roy-Byrne PP, Uhde TW. Graphic representation of the life course of illness in patients with affective disorder. Am J Psychiatry. 1988;145: 844Y848. 12. Ng F, Mammen OK, Wilting I, et al. The International Society for Bipolar Disorders (ISBD) consensus guidelines for the safety monitoring of bipolar disorder treatments. Bipolar Disord. 2009;11:559Y595. 13. Viguera AC, Whitfield T, Baldessarini RJ, et al. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007;164:1817Y1824. 14. Viguera AC, Tondo L, Koukopoulos AE, et al. Episodes of mood disorders in 2,252 pregnancies and postpartum periods. Am J Psychiatry. 2011;168:1179Y1185. 15. Doyle K, Heron J, Berrisford G, et al. The management of bipolar disorder in the perinatal period and risk factors for postpartum relapse. Eur Psychiatry. 2012;27:563Y569. 16. Newport DJ, Viguera AC, Beach AJ, et al. Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy. Am J Psychiatry. 2005; 162:2162Y2170. 17. Evensen AE. Update on gestational diabetes mellitus. Prim Care. 2012;39:83Y94. 18. Santoro RC, Prejano` S. Postpartum-acquired haemophilia A: a description of three cases and literature review. Blood Coagul Fibrinolysis. 2009;20:461Y465. 19. European Surveillance of Congenital Anomalies Prevalence Data Tables [EUROCAT website]. December 4, 2012. Available at: http:// www.eurocat-network.eu/accessprevalencedata/ prevalencetables. Accessed May 13, 2013. 20. Taruscio D, Carbone P, Granata O, et al. Folic acid and primary prevention of birth defects. Biofactors. 2011;37:280Y284.
410
www.psychopharmacology.com
Takotsubo Cardiomyopathy Associated With Lithium Intoxication in Bipolar Disorder A Case Report To the Editors: ithium, a first-line agent for treatment of bipolar disorder, can induce cardiac adverse events, including myocarditis and cardiomyopathy.1Y5 There are 3 types of lithium poisoning (acute, acute on chronic, and chronic), and it is known that an elimination half-life of lithium can increase from 24 to 60 hours in patients with longterm use of lithium.2 Lithium has a narrow therapeutic window, and the severity of chronic intoxication appears to correlate with serum concentration of this mood stabilizer (ie, severe toxicity [92.5 mEq/L])2; however, delayed cardiotoxicity, manifesting even when the serum lithium content is declining from a peak level, has also been reported in chronic lithium poisoning.5 Herein, we report the case of a patient with bipolar disorder who developed Takotsubo cardiomyopathy6Y9 2 days after discontinuation of long-term lithium therapy because of its severe intoxication.
L
CASE REPORT A 78-year-old woman with bipolar disorder, who had been treated with lithium (600 mg/d) for 2 years, developed ataxia, tremor, and myoclonus and was admitted to our hospital. She had a history of hypertension, and her blood pressure and pulse rate on admission were 140/80 mm Hg and 68 bpm, respectively. After admission, she suddenly vomited and lost her consciousness. The results of brain magnetic resonance imaging and cerebrospinal fluid investigations were normal. An electroencephalogram demonstrated diffuse slowing. Dehydration and renal dysfunction were recognized, and the serum lithium concentration was very high (2.9 mEq/L). Her condition was diagnosed as having severe lithium intoxication, and her lithium treatment was discontinued. She was treated with intravenous crystalloids to restore adequate hydration and tissue perfusion. Two days later, she had difficulty in breathing; at that time, her blood pressure and pulse rate were 96/54 mm Hg and 94 bpm, respectively. The electrocardiogram showed ST-segment elevation in the anterior leads, and the serum troponin T level was elevated. Although she was immediately treated for possible ST-segment elevation myocardial infarction, coronary angiography was not conducted because of her renal dysfunction10; the estimated glomerular filtration
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Volume 34, Number 3, June 2014
rate was severely decreased (22.7 mL/min per 1.73 m2), and the levels of serum creatinine and serum urea nitrogen were substantially increased (1.72 mg/dL and 71 mg/dL, respectively). The subsequent echocardiography demonstrated left ventricular dysfunction (her ejection fraction was decreased to 0.30) caused by apical kinesis and basal hyperkinesis (which resulted in characteristic shape of the left ventricle, resembling a round-bottomed, narrow-necked Japanese pot ‘‘Takotsubo’’ to trap octopuses), and her condition was diagnosed as having Takotsubo cardiomyopathy (not otherwise specified6,7). Eight days later, we confirmed that her serum lithium concentration was not elevated at all (0.06 mEq/L). All of the neurologic and cardiac abnormalities disappeared within 3 weeks, and she had no manic episode during this period.
DISCUSSION To our knowledge, this is the first report of Takotsubo cardiomyopathy associated with lithium poisoning in bipolar disorder. Lithium stimulates catecholamine release from the adrenal gland and induces dose-dependent increases in plasma catecholamines in rats, evokes catecholamine release from the perfused adrenal gland of cats, and increases catecholamine synthesis as well as secretion in the cultured bovine adrenal medullary cells.11Y15 Moreover, lithium administration can increase plasma and urine norepinephrine in humans, and catecholamine overload may play a crucial role in the pathogenesis of Takotsubo cardiomyopathy.8,16 Thus, increased peripheral catecholamines caused by lithium intoxication could trigger Takotsubo cardiomyopathy. One of the reasons why Takotsubo cardiomyopathy most commonly occurs in postmenopausal women might be related to exaggerated response to circulating catecholamines in these women who lose possibly protective effects of estrogens.9 Recently, Maldonado and colleagues17 attributed Takotsubo cardiomyopathy, which was manifested 1 week after lithium withdrawal because of thyroid-stimulating hormone elevation (not accompanied by any symptoms due to lithium intoxication), to acute mania in their patient with bipolar disorder. In contrast, in our patient, no manic episode was observed for at least 3 weeks. Reported ‘‘delayed cardiotoxicity in chronic lithium poisoning (recognized 2 days after lithium discontinuation in a patient with bipolar disorder having the peak level at 2.6 mEq/L5)’’ could contribute to the development of Takotsubo cardiomyopathy in our patient. Cardiovascular manifestations of lithium toxicity were reported to be * 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
delayed by several days, and the interval was attributed to progressive equilibration of lithium concentrations between extracellular and tissue compartments.1,5 Takotsubo cardiomyopathy is characterized by transient left ventricular dysfunction and electrocardiographic changes that can mimic acute myocardial infarction.6Y9,17 Considering comorbid medical illnesses, including cardiac diseases, are common in patients with bipolar disorder,4,18 the observed association in our patient might be coincidental. Nevertheless, clinicians should be aware that Takotsubo cardiomyopathy could be induced by lithium intoxication because therapeutic approach is different between this cardiomyopathy and acute myocardial infarction. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Makiko Kitami, MD Department of Neurology Juntendo Tokyo Koto Geriatric Medical Center and Department of Neurology Faculty of Medicine University & Post Graduate University of Juntendo Tokyo, Japan [email protected]
Hideki Oizumi, MD Department of Neurology Juntendo Tokyo Koto Geriatric Medical Center and Department of Neurology Faculty of Medicine University & Post Graduate University of Juntendo Tokyo, Japan
Stephen J. Kish, PhD Human Brain Laboratory Centre for Addiction and Mental Health and Departments of Psychiatry and Pharmacology University of Toronto Toronto, Ontario, Canada
Yoshiaki Furukawa, MD Department of Neurology Juntendo Tokyo Koto Geriatric Medical Center and Department of Neurology Faculty of Medicine University & Post Graduate University of Juntendo Tokyo, Japan [email protected]
REFERENCES 1. Tilkian AG, Schroeder JS, Kao JJ, et al. The cardiovascular effects of lithium in man. A review of the literature. Am J Med. 1976; 61:665Y670.
4. Aichhorn W, Huber R, Stuppaeck C, et al. Cardiomyopathy after long-term treatment with lithiumVmore than a coincidence? J Psychopharmacol. 2006;20:589Y591. 5. Waring WS. Delayed cardiotoxicity in chronic lithium poisoning: discrepancy between serum lithium concentrations and clinical status. Basic Clin Pharmacol Toxicol. 2007;100:353Y355. 6. Kawai S, Kitabatake A, Tomoike H. Guidelines for diagnosis of Takotsubo (ampulla) cardiomyopathy. Circ J. 2007;71:990Y992. 7. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. 2008; 155:408Y417. 8. Nef HM, Mo¨llmann H, Akashi YJ, et al. Mechanisms of stress (Takotsubo) cardiomyopathy. Nat Rev Cardiol. 2010; 7:187Y193. 9. Zeb M, Sambu N, Scott P, et al. Takotsubo cardiomyopathy: a diagnostic challenge. Postgrad Med J. 2011;87:51Y59. 10. Lameire N, Adam A, Becker CR, et al. Baseline renal function screening. Am J Cardiol. 2006;98:21KY26K. 11. Abajo FJ, Castro MA, Garijo B, et al. Catecholamine release evoked by lithium from the perfused adrenal gland of the cat. Br J Pharmacol. 1987;91:539Y546. 12. O’Connor EF, Naylor SK, Cox RH, et al. Lithium chloride stabilizes systolic blood pressure and increases adrenal catecholamines in the spontaneously hypertensive rat. Physiol Behav. 1988;44:69Y74. 13. Chaouloff F, Gunn SH, Young JB. Serotonin does not mediate the adrenal catecholamine-releasing effect of acute lithium administration in rats. Psychoneuroendocrinology. 1992; 17:135Y144. 14. Terao T, Yanagihara N, Abe K, et al. Lithium chloride stimulates catecholamine synthesis and secretion in cultured bovine adrenal medullary cells. Biol Psychiatry. 1992; 31:1038Y1049. 15. Chaudhuri-Sengupta S, Sarkar R, Maiti BR. Lithium action on adrenomedullary and adrenocortical functions and serum ionic balance in different age-groups of albino rats. Arch Physiol Biochem. 2003;111:246Y253. 16. Manji HK, Hsiao JK, Risby ED, et al. The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects. Arch Gen Psychiatry. 1991; 48:505Y512.
2. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999;10:666Y674.
17. Maldonado JR, Pajouhi P, Witteles R. Broken heart syndrome (Takotsubo cardiomyopathy) triggered by acute mania: a review and case report. Psychosomatics. 2013;54:74Y79.
3. Coulter DM, Bate A, Meyboom RH, et al. Antipsychotic drugs and heart muscle disorder in international pharmacovigilance: data mining study. BMJ. 2001;322:1207Y1209.
18. Beyer J, Kuchibhatla M, Gersing K, et al. Medical comorbidity in a bipolar outpatient clinical population. Neuropsychopharmacology. 2005;30:401Y404.
* 2014 Lippincott Williams & Wilkins
Letters to the Editors
Case Series of 21 Synthetic Cathinones Abuse To the Editors: he pattern of recreational drug use has changed over the last decade and now includes a range of substances sold as ‘‘research chemicals.’’1,2 In recent years, hundreds of new drugs appeared on the drug market. Synthetic cathinones (SCs) are alternatives to traditionally abused stimulants. Psychoactive cathinone is an alkaloid derived from the khat plant (Catha edulis), used in East Africa for stimulant properties. Synthetic cathinone family contains A-ketoamfetamine derivatives,3 which are quite inexpensive and are commonly available in so-called ‘‘head shops’’ under such names as MDPV, NRG2, NRG3, I (as powder, or in pill or capsule form). The prevalence of SC is difficult to appraise. In a Finnish study, 8.6% of analyzed blood, from individuals suspected by police to drive under the effect of drugs, contained 3,4-methylenedioxypyrovalerone (MDPV).4 Pursuant to an Irish study completed on patients receiving methadone, maintenance found that 14% of urine samples were positive to mephedrone and 3% to methylone.5 A self-report study completed on students of UK high schools and colleges revealed that 20% had used mephedrone on at least 1 occasion.6 The difficulty to determine cathinones exposure is increased by the analytical testing: chromatography/mass spectrometry7 is required (not detected via standard drug tests). In France, SCs emerged in 20087 and have grown to become popular drugs of abuse. In June 2010, mephedrone was the first SC to be listed as a narcotic, but since July 2012, all its congenerics have been listed as narcotics following the example of the United Kingdom. We report a case series of SC abuse notified by physicians directly to the Centre for Evaluation and Information on Drug Dependence and Addiction surveillance observed between January 2011 and December 2012.
T
CASE REPORTS Over this 2-year period, 21 cases of SC abuse were identified of 264 stimulants notifications (cocaine, MDMA, methylphenidate, etc), among 698 total notifications. Users were mostly men (20/21), with mean age of 38 years (26Y53 years old), having occasional cathinones exposure in a sexual gay party (14/21) with intakes ranging between 400 mg to 8 g (on average, 2.6 g). Synthetic cathinones reported by users (declarative information cf. Table 1 enclosed) are NRG3 (n = 11), mephedrone (n = 9), and MDPV (n = 4). The duration of cathinones use is available for 62% of www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
411
Letters to the Editors
6. Oyebode F, Rastogi A, Berrisford G, et al. Psychotropics in pregnancy: safety and other considerations. Pharmacol Ther. 2012; 135:71Y77. 7. Altshuler LL, Cohen L, Szuba MP, et al. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry. 1996; 153:592Y606. 8. Lopez L, Cohen MS, Anderson RH, et al. Unnatural history of the right ventricle in patients with congenitally malformed hearts. Cardiol Young. 2010;20:107Y112. 9. Anderson IM, Haddad PM, Scott J. Bipolar disorder. BMJ. 2012;345:e8508. 10. Bode´n R, Lundgren M, Brandt L, et al. Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study. BMJ. 2012; 345:e7085. 11. Post RM, Roy-Byrne PP, Uhde TW. Graphic representation of the life course of illness in patients with affective disorder. Am J Psychiatry. 1988;145: 844Y848. 12. Ng F, Mammen OK, Wilting I, et al. The International Society for Bipolar Disorders (ISBD) consensus guidelines for the safety monitoring of bipolar disorder treatments. Bipolar Disord. 2009;11:559Y595. 13. Viguera AC, Whitfield T, Baldessarini RJ, et al. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007;164:1817Y1824. 14. Viguera AC, Tondo L, Koukopoulos AE, et al. Episodes of mood disorders in 2,252 pregnancies and postpartum periods. Am J Psychiatry. 2011;168:1179Y1185. 15. Doyle K, Heron J, Berrisford G, et al. The management of bipolar disorder in the perinatal period and risk factors for postpartum relapse. Eur Psychiatry. 2012;27:563Y569. 16. Newport DJ, Viguera AC, Beach AJ, et al. Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy. Am J Psychiatry. 2005; 162:2162Y2170. 17. Evensen AE. Update on gestational diabetes mellitus. Prim Care. 2012;39:83Y94. 18. Santoro RC, Prejano` S. Postpartum-acquired haemophilia A: a description of three cases and literature review. Blood Coagul Fibrinolysis. 2009;20:461Y465. 19. European Surveillance of Congenital Anomalies Prevalence Data Tables [EUROCAT website]. December 4, 2012. Available at: http:// www.eurocat-network.eu/accessprevalencedata/ prevalencetables. Accessed May 13, 2013. 20. Taruscio D, Carbone P, Granata O, et al. Folic acid and primary prevention of birth defects. Biofactors. 2011;37:280Y284.
410
www.psychopharmacology.com
Takotsubo Cardiomyopathy Associated With Lithium Intoxication in Bipolar Disorder A Case Report To the Editors: ithium, a first-line agent for treatment of bipolar disorder, can induce cardiac adverse events, including myocarditis and cardiomyopathy.1Y5 There are 3 types of lithium poisoning (acute, acute on chronic, and chronic), and it is known that an elimination half-life of lithium can increase from 24 to 60 hours in patients with longterm use of lithium.2 Lithium has a narrow therapeutic window, and the severity of chronic intoxication appears to correlate with serum concentration of this mood stabilizer (ie, severe toxicity [92.5 mEq/L])2; however, delayed cardiotoxicity, manifesting even when the serum lithium content is declining from a peak level, has also been reported in chronic lithium poisoning.5 Herein, we report the case of a patient with bipolar disorder who developed Takotsubo cardiomyopathy6Y9 2 days after discontinuation of long-term lithium therapy because of its severe intoxication.
L
CASE REPORT A 78-year-old woman with bipolar disorder, who had been treated with lithium (600 mg/d) for 2 years, developed ataxia, tremor, and myoclonus and was admitted to our hospital. She had a history of hypertension, and her blood pressure and pulse rate on admission were 140/80 mm Hg and 68 bpm, respectively. After admission, she suddenly vomited and lost her consciousness. The results of brain magnetic resonance imaging and cerebrospinal fluid investigations were normal. An electroencephalogram demonstrated diffuse slowing. Dehydration and renal dysfunction were recognized, and the serum lithium concentration was very high (2.9 mEq/L). Her condition was diagnosed as having severe lithium intoxication, and her lithium treatment was discontinued. She was treated with intravenous crystalloids to restore adequate hydration and tissue perfusion. Two days later, she had difficulty in breathing; at that time, her blood pressure and pulse rate were 96/54 mm Hg and 94 bpm, respectively. The electrocardiogram showed ST-segment elevation in the anterior leads, and the serum troponin T level was elevated. Although she was immediately treated for possible ST-segment elevation myocardial infarction, coronary angiography was not conducted because of her renal dysfunction10; the estimated glomerular filtration
&
Volume 34, Number 3, June 2014
rate was severely decreased (22.7 mL/min per 1.73 m2), and the levels of serum creatinine and serum urea nitrogen were substantially increased (1.72 mg/dL and 71 mg/dL, respectively). The subsequent echocardiography demonstrated left ventricular dysfunction (her ejection fraction was decreased to 0.30) caused by apical kinesis and basal hyperkinesis (which resulted in characteristic shape of the left ventricle, resembling a round-bottomed, narrow-necked Japanese pot ‘‘Takotsubo’’ to trap octopuses), and her condition was diagnosed as having Takotsubo cardiomyopathy (not otherwise specified6,7). Eight days later, we confirmed that her serum lithium concentration was not elevated at all (0.06 mEq/L). All of the neurologic and cardiac abnormalities disappeared within 3 weeks, and she had no manic episode during this period.
DISCUSSION To our knowledge, this is the first report of Takotsubo cardiomyopathy associated with lithium poisoning in bipolar disorder. Lithium stimulates catecholamine release from the adrenal gland and induces dose-dependent increases in plasma catecholamines in rats, evokes catecholamine release from the perfused adrenal gland of cats, and increases catecholamine synthesis as well as secretion in the cultured bovine adrenal medullary cells.11Y15 Moreover, lithium administration can increase plasma and urine norepinephrine in humans, and catecholamine overload may play a crucial role in the pathogenesis of Takotsubo cardiomyopathy.8,16 Thus, increased peripheral catecholamines caused by lithium intoxication could trigger Takotsubo cardiomyopathy. One of the reasons why Takotsubo cardiomyopathy most commonly occurs in postmenopausal women might be related to exaggerated response to circulating catecholamines in these women who lose possibly protective effects of estrogens.9 Recently, Maldonado and colleagues17 attributed Takotsubo cardiomyopathy, which was manifested 1 week after lithium withdrawal because of thyroid-stimulating hormone elevation (not accompanied by any symptoms due to lithium intoxication), to acute mania in their patient with bipolar disorder. In contrast, in our patient, no manic episode was observed for at least 3 weeks. Reported ‘‘delayed cardiotoxicity in chronic lithium poisoning (recognized 2 days after lithium discontinuation in a patient with bipolar disorder having the peak level at 2.6 mEq/L5)’’ could contribute to the development of Takotsubo cardiomyopathy in our patient. Cardiovascular manifestations of lithium toxicity were reported to be * 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
delayed by several days, and the interval was attributed to progressive equilibration of lithium concentrations between extracellular and tissue compartments.1,5 Takotsubo cardiomyopathy is characterized by transient left ventricular dysfunction and electrocardiographic changes that can mimic acute myocardial infarction.6Y9,17 Considering comorbid medical illnesses, including cardiac diseases, are common in patients with bipolar disorder,4,18 the observed association in our patient might be coincidental. Nevertheless, clinicians should be aware that Takotsubo cardiomyopathy could be induced by lithium intoxication because therapeutic approach is different between this cardiomyopathy and acute myocardial infarction. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Makiko Kitami, MD Department of Neurology Juntendo Tokyo Koto Geriatric Medical Center and Department of Neurology Faculty of Medicine University & Post Graduate University of Juntendo Tokyo, Japan [email protected]
Hideki Oizumi, MD Department of Neurology Juntendo Tokyo Koto Geriatric Medical Center and Department of Neurology Faculty of Medicine University & Post Graduate University of Juntendo Tokyo, Japan
Stephen J. Kish, PhD Human Brain Laboratory Centre for Addiction and Mental Health and Departments of Psychiatry and Pharmacology University of Toronto Toronto, Ontario, Canada
Yoshiaki Furukawa, MD Department of Neurology Juntendo Tokyo Koto Geriatric Medical Center and Department of Neurology Faculty of Medicine University & Post Graduate University of Juntendo Tokyo, Japan [email protected]
REFERENCES 1. Tilkian AG, Schroeder JS, Kao JJ, et al. The cardiovascular effects of lithium in man. A review of the literature. Am J Med. 1976; 61:665Y670.
4. Aichhorn W, Huber R, Stuppaeck C, et al. Cardiomyopathy after long-term treatment with lithiumVmore than a coincidence? J Psychopharmacol. 2006;20:589Y591. 5. Waring WS. Delayed cardiotoxicity in chronic lithium poisoning: discrepancy between serum lithium concentrations and clinical status. Basic Clin Pharmacol Toxicol. 2007;100:353Y355. 6. Kawai S, Kitabatake A, Tomoike H. Guidelines for diagnosis of Takotsubo (ampulla) cardiomyopathy. Circ J. 2007;71:990Y992. 7. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. 2008; 155:408Y417. 8. Nef HM, Mo¨llmann H, Akashi YJ, et al. Mechanisms of stress (Takotsubo) cardiomyopathy. Nat Rev Cardiol. 2010; 7:187Y193. 9. Zeb M, Sambu N, Scott P, et al. Takotsubo cardiomyopathy: a diagnostic challenge. Postgrad Med J. 2011;87:51Y59. 10. Lameire N, Adam A, Becker CR, et al. Baseline renal function screening. Am J Cardiol. 2006;98:21KY26K. 11. Abajo FJ, Castro MA, Garijo B, et al. Catecholamine release evoked by lithium from the perfused adrenal gland of the cat. Br J Pharmacol. 1987;91:539Y546. 12. O’Connor EF, Naylor SK, Cox RH, et al. Lithium chloride stabilizes systolic blood pressure and increases adrenal catecholamines in the spontaneously hypertensive rat. Physiol Behav. 1988;44:69Y74. 13. Chaouloff F, Gunn SH, Young JB. Serotonin does not mediate the adrenal catecholamine-releasing effect of acute lithium administration in rats. Psychoneuroendocrinology. 1992; 17:135Y144. 14. Terao T, Yanagihara N, Abe K, et al. Lithium chloride stimulates catecholamine synthesis and secretion in cultured bovine adrenal medullary cells. Biol Psychiatry. 1992; 31:1038Y1049. 15. Chaudhuri-Sengupta S, Sarkar R, Maiti BR. Lithium action on adrenomedullary and adrenocortical functions and serum ionic balance in different age-groups of albino rats. Arch Physiol Biochem. 2003;111:246Y253. 16. Manji HK, Hsiao JK, Risby ED, et al. The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects. Arch Gen Psychiatry. 1991; 48:505Y512.
2. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999;10:666Y674.
17. Maldonado JR, Pajouhi P, Witteles R. Broken heart syndrome (Takotsubo cardiomyopathy) triggered by acute mania: a review and case report. Psychosomatics. 2013;54:74Y79.
3. Coulter DM, Bate A, Meyboom RH, et al. Antipsychotic drugs and heart muscle disorder in international pharmacovigilance: data mining study. BMJ. 2001;322:1207Y1209.
18. Beyer J, Kuchibhatla M, Gersing K, et al. Medical comorbidity in a bipolar outpatient clinical population. Neuropsychopharmacology. 2005;30:401Y404.
* 2014 Lippincott Williams & Wilkins
Letters to the Editors
Case Series of 21 Synthetic Cathinones Abuse To the Editors: he pattern of recreational drug use has changed over the last decade and now includes a range of substances sold as ‘‘research chemicals.’’1,2 In recent years, hundreds of new drugs appeared on the drug market. Synthetic cathinones (SCs) are alternatives to traditionally abused stimulants. Psychoactive cathinone is an alkaloid derived from the khat plant (Catha edulis), used in East Africa for stimulant properties. Synthetic cathinone family contains A-ketoamfetamine derivatives,3 which are quite inexpensive and are commonly available in so-called ‘‘head shops’’ under such names as MDPV, NRG2, NRG3, I (as powder, or in pill or capsule form). The prevalence of SC is difficult to appraise. In a Finnish study, 8.6% of analyzed blood, from individuals suspected by police to drive under the effect of drugs, contained 3,4-methylenedioxypyrovalerone (MDPV).4 Pursuant to an Irish study completed on patients receiving methadone, maintenance found that 14% of urine samples were positive to mephedrone and 3% to methylone.5 A self-report study completed on students of UK high schools and colleges revealed that 20% had used mephedrone on at least 1 occasion.6 The difficulty to determine cathinones exposure is increased by the analytical testing: chromatography/mass spectrometry7 is required (not detected via standard drug tests). In France, SCs emerged in 20087 and have grown to become popular drugs of abuse. In June 2010, mephedrone was the first SC to be listed as a narcotic, but since July 2012, all its congenerics have been listed as narcotics following the example of the United Kingdom. We report a case series of SC abuse notified by physicians directly to the Centre for Evaluation and Information on Drug Dependence and Addiction surveillance observed between January 2011 and December 2012.
T
CASE REPORTS Over this 2-year period, 21 cases of SC abuse were identified of 264 stimulants notifications (cocaine, MDMA, methylphenidate, etc), among 698 total notifications. Users were mostly men (20/21), with mean age of 38 years (26Y53 years old), having occasional cathinones exposure in a sexual gay party (14/21) with intakes ranging between 400 mg to 8 g (on average, 2.6 g). Synthetic cathinones reported by users (declarative information cf. Table 1 enclosed) are NRG3 (n = 11), mephedrone (n = 9), and MDPV (n = 4). The duration of cathinones use is available for 62% of www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
411
