Journal of Clinical Psychopharmacology
&
Volume 35, Number 1, February 2015
2. Brown JH, Sigmundson HK. Delirium from misuse of dimenhydrinate. Can Med Assoc J. 1969;101:49Y50. 3. Malcolm R, Miller WC. Dimenhydrinate (Dramamine) abuse: hallucinogenic experiences with a proprietary antihistamine. Am J Psychiatry. 1972;128:1012Y1013. 4. Jones J, Dougherty J, Cannon L. Diphenhydramine-induced toxic psychosis. Am J Emerg Med. 1986;4:369Y371. 5. Sexton JD,PronchikDJ.Diphenhydramine-induced psychosis with therapeutic doses. Am J Emerg Med. 1997;15:548Y549. 6. Bartlik B, Galanter M, Angrist B. Dimenhydrinate addiction in a schizophrenic woman. J Clin Psychiatry. 1989;50:476. 7. Christensen RC. Misdiagnosis of anticholinergic delirium as schizophrenic psychosis. Am J Emerg Med. 1995;13:117Y118. 8. Young GB, Boyd D, Kreeft J. Dimenhydrinate: evidence for dependence and tolerance. CMAJ. 1988;138:437Y438. 9. Craig DF, Mellor CS. Dimenhydrinate dependence and withdrawal. CMAJ. 1990; 142:970Y973. 10. Thomas A, Nallur DG, Jones N, et al. Diphenhydramine abuse and detoxification: a brief review and case report. J Psychopharmacol. 2009;23:101Y105. 11. Espi Martinez F, Espi Forcen F, Shapov A, et al. Biperiden dependence: case report and literature review. Case Rep Psychiatry. 2012;2012:949256. 12. Buhrich N, Weller A, Kevans P. Misuse of anticholinergic drugs by people with serious mental illness. Psychiatr Serv. 2000;51:928Y929. 13. Prost E, Millson RC. Clozapine treatment of dimenhydrinate abuse. Am J Psychiatry. 2004;161:1500. 14. Mansheim P. A case of acute psychosis in temporal association with theophylline toxicity. J Clin Psychopharmacol. 1989;9:65Y66. 15. Wasser WG, Bronheim HE, Richardson BK. Theophylline madness. Ann Intern Med. 1981;95:191.
carbonate for bipolar disorder who developed a new-onset myasthenic syndrome while receiving adjunctive asenapine. We believe this to be a heretofore unreported adverse effect of asenapine.
CASE A 75-year-old man with bipolar disorder, depressive episode was initially managed on lithium carbonate 600 mg/d (serum level, 0.62 mmol/L [0.6Y1.2]) and venlafaxine XR 225 mg/d. Because of continued mood symptoms, he was then given adjunctive sublingual asenapine 5 mg twice daily, which was associated with improvement in his depressive symptoms. However, after 6 weeks of adjunctive asenapine, he developed sudden and progressive dysphonia, facial weakness, and asymmetric palpebral ptosis. These motor symptoms were fluctuating and progressively worse later in the day. There was a negative personal and family history for neurological and autoimmune disorders. On examination, he was alert and fully oriented, with full extraocular movements, but with hypometric vertical saccades. There was no diplopia. Hypomimia (parkinsonian facies) and increased tone bilaterally in the upper limbs were noted. Limb muscle strength was normal. Electrolytes, creatinine, and thyroid function tests were within normal range. Acetylcholine receptor (AChR) antibody test was seronegative. Brain single-photon emission computed tomography was normal. Brain magnetic resonance imaging revealed moderate chronic microvascular white matter changes. Despite significant improvement of his depression, asenapine was discontinued because of the acute onset myasthenic symptoms. Three weeks later, his ptosis, dysphonia, and facial weakness had fully resolved, but mood symptoms worsened. On repeat, his serum lithium concentration remained unchanged.
DISCUSSION
Asenapine-Associated Myasthenic Syndrome To the Editors:
P
sychopharmacological agents (including lithium) can affect neuromuscular transmission, which can be associated with myasthenia symptoms in previously asymptomatic patients.1Y4 Asenapine is a newer second-generation antipsychotic used in the treatment of bipolar disorder, as monotherapy or adjunctive therapy to mood stabilizers (eg, lithium or valproate).5 We present a patient on long-term use of lithium
The sudden and progressive development of weakness of extraocular, facial, and laryngeal muscles after the initiation of asenapine treatment, associated with marked variability throughout the day, were consistent with a clinical presentation of myasthenic syndrome. Myasthenia gravis is an autoimmune disorder with marked weakness, where antibodies form against acetylcholine nicotinic postsynaptic receptors at the myoneural junction.6,7 Muscular weakness becomes progressively worse with prolonged use of the affected muscles or later in the day and improves after periods of rest.6 Muscles that control ocular and extraocular movement, facial
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editors
expression, chewing, talking, and swallowing are especially susceptible, although other muscles can also be affected.6 As in our case, the physical examination often yields nonspecific findings.6 Multiple factors can influence the duration of neuromuscular blockade including the mode of drug administration, dosage and duration of treatment, concomitant drug use, severity of underlying disease, and end-organ dysfunction (eg, renal insufficiency can lead to increased drug concentrations).8 In our patient, his neuroimaging studies excluded brainstem lesions and Parkinson plus syndromes. There was no trauma, renal, thyroid or electrolyte disturbance, malignancy, or use of corticosteroids or diuretics, which may have impaired his neuromuscular transmission. However, it is plausible that concomitant use of lithium may have played a partial role. Treatment with lithium can produce muscle weakness as a transient adverse effect early in the course of treatment,4 can unmask antibodyseropositive myasthenic syndromes in asymptomatic patients with myasthenia gravis,9 and can also cause antibodyseronegative myasthenic syndromes with motor weakness, which fully remits after lithium discontinuation.4 The long-term lithium treatment without associated myasthenia in our patient seemed to favor a new-onset, asenapine-associated syndrome rather than an underlying myasthenia. In this view, he became asymptomatic after asenapine discontinuation, whereas his lithium was continued. However, a cumulative/ additive effect of lithium and asenapine was impossible to rule out. Furthermore, assays for AChR antibodies are less sensitive for ocular myasthenia than for generalized myasthenia7 because up to 50% of patients with ocular myasthenia have been found seronegative.6 In our case, the temporal relationship of the onset of myasthenic symptoms and use of asenapine (despite the absence of AChR antibodies) may yet have suggested an asenapine-associated autoimmune attack. A PubMed search with the search terms asenapine and myasthenia produced no citations. In conclusion, our patient had physiological findings pointing to a myasthenic syndrome with the adjunctive use of asenapine. Asenapine was stopped, and the patient’s neurological status improved, whereas lithium was continued. Although the patient may have had a coincidental chance association of asenapine administration and myasthenic syndrome, the report is notable for the following reasons. It may provide an association between the onset of myasthenia symptoms and temporally related use of asenapine. In this www.psychopharmacology.com
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
107
Journal of Clinical Psychopharmacology
Letters to the Editors
case, the concurrent use of lithium may have been a factor in the onset of myasthenia symptoms once the patient was exposed to adjunctive asenapine. Whether he would have experienced myasthenic symptoms from asenapine without concurrent use of lithium remains speculative. Clinicians should closely monitor for unusual symptoms possibly associated with neuromuscular junction dysfunction in patients taking asenapine. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Ana Hategan, MD Division of Geriatric Psychiatry Department of Psychiatry and Behavioural Neurosciences Michael G. DeGroote School of Medicine Faculty of Health Sciences McMaster University Hamilton, Ontario, Canada [email protected]
James A. Bourgeois, OD, MD Consultation-Liaison Service Department of Psychiatry Langley Porter Psychiatric Institute University of California, San Francisco San Francisco, CA
REFERENCES 1. Wilson CL, Ferguson J. Myasthenia gravis unmasked by antipsychotic medication. Prog Neurol Psychiatry. 2013;17:17Y19. 2. Crews EL, Daw J. Neuroleptic-induced syndrome mimicking myasthenia gravis. Psychosomatics. 1981;22:67Y68. 3. Chiu YH, Yang AC, Chern CH, et al. Myasthenic crisis may mimic antipsychotic-induced extrapyramidal syndromes. J Neuropsychiatry Clin Neurosci. 2011;23:E36YE37. 4. Ronziere T, Auzou P, Ozsancak C, et al. Myasthenic syndrome induced by lithium [in French]. Presse Med. 2000;29:1043Y1044. 5. Samalin L, Charpeaud T, Llorca PM. Asenapine in bipolar I disorder: evidence and place in patient management. Ther Adv Chronic Dis. 2013;4:5Y14. 6. Scherer K, Bedlack RS, Simel DL. Does this patient have myasthenia gravis? JAMA. 2005; 293:1906Y1914. 7. Barton JJ, Fouladvand M. Ocular aspects of myasthenia gravis. Semin Neurol. 2000;20:7Y20. 8. Watling SM, Dasta JF. Prolonged paralysis in intensive care unit patients after the use of neuromuscular blocking agents: a review of the literature. Crit Care Med. 1994;22: 884Y893. 9. Alevizos B, Gatzonis S, Anagnostara CH. Myasthenia gravis disclosed by lithium carbonate. J Neuropsychiatry Clin Neurosci. 2006;18:427Y429.
108
www.psychopharmacology.com
Rhabdomyolysis After Escitalopram Treatment in a Young Adult With Melancholic Depression
&
Volume 35, Number 1, February 2015
CASE REPORT
Manual of Mental Disorders, Fourth Edition-Text Revision criteria) who developed rhabdomyolysis after his treatment of escitalopram. He was brought to the emergency department after a suicide attempt (December 2012) by jumping and falling 40 m. During his initial intake, the patient presented with vertebral fractures and a bilateral pneumothorax. A complete medical examination, including blood sample analysis, was performed after his admission to the emergency department. Abnormal (but low) levels of creatine phosphokinase (CPK, 465 UI/L) were found on the day of the fall. Another blood sample analysis was performed 6 hours after the first one and showed a decrease in CPK levels (from 465 to 430 UI/L). Abnormal levels of CPK were attributed to his muscular injuries sustained due to the fall, and, consequently, rhabdomyolysis was not diagnosed. To the best of our knowledge, no excessive physical activity, intramuscular injection, or drug use were reported by the patient. After somatic stabilization, he was transferred to the psychiatric care unit for 1 week. After his discharge (end of December 2012), he was admitted to the Intensive Care Mobile Unit at the University Hospital of Caen (France). On the basis of his symptoms, melancholic depression was diagnosed. He reported having a personal history of obsessive-compulsive disorder during adolescence and a family history of bipolar disorder (maternal uncle). Aripiprazole (10 mg) was initially given to him as treatment, but the patient stopped treatment after 1 day due to adverse effects (major sedation). Thereafter, he received escitalopram, which was progressively titrated from 5 to 20 mg/d (from January to February 2013). The medication was well tolerated, but euthymia was not achieved. Escitalopram at 30 mg led to greater improvement in depressive symptoms, and he reached a euthymic state 2 months later (April 2013). The patient reported bilateral myalgias of inferior members (quadriceps muscles) and intensive abdominal pain for a week. The psychiatrist suspected rhabdomyolysis and prescribed a dosage of muscular enzymes because of the urgent situation. Due to his blood analysis showing a severely elevated CPK level of 1245 UI/L (K+, 4.5 mmol/L; creatinine, 11.4 g/L), escitalopram was immediately stopped. Aches lasted for 13 days and then decreased as his CPK level decreased to a normal level (CPK, 143 UI/L). The patient’s clinical state was stabilized with lithium (625 mg/d) and mianserin (90 mg/d).
We report the case of a 20-year-old man (1.60 m, 66 kg; body mass index, 25.78 kg/m2) with melancholic depression (according to Diagnostic and Statistical
This report illustrates a case of severe adverse effect, rhabdomyolysis, after
To the Editors:
E
scitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is the S-enantiomer of citalopram, and it works by preventing the neurotransmitter serotonin from being taken into the nerve cells in the brain and spinal cord again. This antidepressant has been approved for the treatment of major depression, including severe forms of depression and generalized anxiety disorder. Escitalopram reaches maximum plasma concentration 3 to 4 hours after ingestion. The initial recommended dose is 10 mg/d, and the dose can be increased to 20 mg/d. Moreover, dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with treatmentresistant major depressive disorder.1 Escitalopram is generally well tolerated by patients. The most frequent adverse effects during treatment are headache, nausea, insomnia, fatigue, diarrhea, ejaculation impairment, drowsiness, dry mouth, dizziness, increased sweating, and tiredness. There have been a small number of reported cases of escitalopram-related serotonin syndrome. Severe serotonin toxicity may induce muscular hyperactivity that can exceed 40-C/ 104-F, seizures or rhabdomyolysis. Rhabdomyolysis is a condition that induces a rapid breakdown of skeletal muscle cells, which are released into the blood. The pathological pathway involves an increased concentration of intracellular calcium. Rhabdomyolysis has many etiologies, such as physical (eg, excessive muscular activity, compression of the muscles, thermal maximum, prolonged immobilization) or nonphysical (eg, electrolyte abnormalities, such as hyponatraemia2; hypophosphatemia or hypokalemia;or infections, such as influenzas, legionella, and salmonella) causes. Rhabdomyolysis has also been associated with the use of several substances: bupropion,3 fusidic acid,4 citalopram,5,6 olanzapine,7Y11 venlafaxine,12Y16 sertraline,17 moclobemide associated with fluoxetine,18 alcohol, cocaine, amphetaminelike molecules19 and ingestion, in one reported case, of escitalopram.20
DISCUSSION
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
&
Volume 35, Number 1, February 2015
2. Brown JH, Sigmundson HK. Delirium from misuse of dimenhydrinate. Can Med Assoc J. 1969;101:49Y50. 3. Malcolm R, Miller WC. Dimenhydrinate (Dramamine) abuse: hallucinogenic experiences with a proprietary antihistamine. Am J Psychiatry. 1972;128:1012Y1013. 4. Jones J, Dougherty J, Cannon L. Diphenhydramine-induced toxic psychosis. Am J Emerg Med. 1986;4:369Y371. 5. Sexton JD,PronchikDJ.Diphenhydramine-induced psychosis with therapeutic doses. Am J Emerg Med. 1997;15:548Y549. 6. Bartlik B, Galanter M, Angrist B. Dimenhydrinate addiction in a schizophrenic woman. J Clin Psychiatry. 1989;50:476. 7. Christensen RC. Misdiagnosis of anticholinergic delirium as schizophrenic psychosis. Am J Emerg Med. 1995;13:117Y118. 8. Young GB, Boyd D, Kreeft J. Dimenhydrinate: evidence for dependence and tolerance. CMAJ. 1988;138:437Y438. 9. Craig DF, Mellor CS. Dimenhydrinate dependence and withdrawal. CMAJ. 1990; 142:970Y973. 10. Thomas A, Nallur DG, Jones N, et al. Diphenhydramine abuse and detoxification: a brief review and case report. J Psychopharmacol. 2009;23:101Y105. 11. Espi Martinez F, Espi Forcen F, Shapov A, et al. Biperiden dependence: case report and literature review. Case Rep Psychiatry. 2012;2012:949256. 12. Buhrich N, Weller A, Kevans P. Misuse of anticholinergic drugs by people with serious mental illness. Psychiatr Serv. 2000;51:928Y929. 13. Prost E, Millson RC. Clozapine treatment of dimenhydrinate abuse. Am J Psychiatry. 2004;161:1500. 14. Mansheim P. A case of acute psychosis in temporal association with theophylline toxicity. J Clin Psychopharmacol. 1989;9:65Y66. 15. Wasser WG, Bronheim HE, Richardson BK. Theophylline madness. Ann Intern Med. 1981;95:191.
carbonate for bipolar disorder who developed a new-onset myasthenic syndrome while receiving adjunctive asenapine. We believe this to be a heretofore unreported adverse effect of asenapine.
CASE A 75-year-old man with bipolar disorder, depressive episode was initially managed on lithium carbonate 600 mg/d (serum level, 0.62 mmol/L [0.6Y1.2]) and venlafaxine XR 225 mg/d. Because of continued mood symptoms, he was then given adjunctive sublingual asenapine 5 mg twice daily, which was associated with improvement in his depressive symptoms. However, after 6 weeks of adjunctive asenapine, he developed sudden and progressive dysphonia, facial weakness, and asymmetric palpebral ptosis. These motor symptoms were fluctuating and progressively worse later in the day. There was a negative personal and family history for neurological and autoimmune disorders. On examination, he was alert and fully oriented, with full extraocular movements, but with hypometric vertical saccades. There was no diplopia. Hypomimia (parkinsonian facies) and increased tone bilaterally in the upper limbs were noted. Limb muscle strength was normal. Electrolytes, creatinine, and thyroid function tests were within normal range. Acetylcholine receptor (AChR) antibody test was seronegative. Brain single-photon emission computed tomography was normal. Brain magnetic resonance imaging revealed moderate chronic microvascular white matter changes. Despite significant improvement of his depression, asenapine was discontinued because of the acute onset myasthenic symptoms. Three weeks later, his ptosis, dysphonia, and facial weakness had fully resolved, but mood symptoms worsened. On repeat, his serum lithium concentration remained unchanged.
DISCUSSION
Asenapine-Associated Myasthenic Syndrome To the Editors:
P
sychopharmacological agents (including lithium) can affect neuromuscular transmission, which can be associated with myasthenia symptoms in previously asymptomatic patients.1Y4 Asenapine is a newer second-generation antipsychotic used in the treatment of bipolar disorder, as monotherapy or adjunctive therapy to mood stabilizers (eg, lithium or valproate).5 We present a patient on long-term use of lithium
The sudden and progressive development of weakness of extraocular, facial, and laryngeal muscles after the initiation of asenapine treatment, associated with marked variability throughout the day, were consistent with a clinical presentation of myasthenic syndrome. Myasthenia gravis is an autoimmune disorder with marked weakness, where antibodies form against acetylcholine nicotinic postsynaptic receptors at the myoneural junction.6,7 Muscular weakness becomes progressively worse with prolonged use of the affected muscles or later in the day and improves after periods of rest.6 Muscles that control ocular and extraocular movement, facial
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editors
expression, chewing, talking, and swallowing are especially susceptible, although other muscles can also be affected.6 As in our case, the physical examination often yields nonspecific findings.6 Multiple factors can influence the duration of neuromuscular blockade including the mode of drug administration, dosage and duration of treatment, concomitant drug use, severity of underlying disease, and end-organ dysfunction (eg, renal insufficiency can lead to increased drug concentrations).8 In our patient, his neuroimaging studies excluded brainstem lesions and Parkinson plus syndromes. There was no trauma, renal, thyroid or electrolyte disturbance, malignancy, or use of corticosteroids or diuretics, which may have impaired his neuromuscular transmission. However, it is plausible that concomitant use of lithium may have played a partial role. Treatment with lithium can produce muscle weakness as a transient adverse effect early in the course of treatment,4 can unmask antibodyseropositive myasthenic syndromes in asymptomatic patients with myasthenia gravis,9 and can also cause antibodyseronegative myasthenic syndromes with motor weakness, which fully remits after lithium discontinuation.4 The long-term lithium treatment without associated myasthenia in our patient seemed to favor a new-onset, asenapine-associated syndrome rather than an underlying myasthenia. In this view, he became asymptomatic after asenapine discontinuation, whereas his lithium was continued. However, a cumulative/ additive effect of lithium and asenapine was impossible to rule out. Furthermore, assays for AChR antibodies are less sensitive for ocular myasthenia than for generalized myasthenia7 because up to 50% of patients with ocular myasthenia have been found seronegative.6 In our case, the temporal relationship of the onset of myasthenic symptoms and use of asenapine (despite the absence of AChR antibodies) may yet have suggested an asenapine-associated autoimmune attack. A PubMed search with the search terms asenapine and myasthenia produced no citations. In conclusion, our patient had physiological findings pointing to a myasthenic syndrome with the adjunctive use of asenapine. Asenapine was stopped, and the patient’s neurological status improved, whereas lithium was continued. Although the patient may have had a coincidental chance association of asenapine administration and myasthenic syndrome, the report is notable for the following reasons. It may provide an association between the onset of myasthenia symptoms and temporally related use of asenapine. In this www.psychopharmacology.com
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
107
Journal of Clinical Psychopharmacology
Letters to the Editors
case, the concurrent use of lithium may have been a factor in the onset of myasthenia symptoms once the patient was exposed to adjunctive asenapine. Whether he would have experienced myasthenic symptoms from asenapine without concurrent use of lithium remains speculative. Clinicians should closely monitor for unusual symptoms possibly associated with neuromuscular junction dysfunction in patients taking asenapine. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Ana Hategan, MD Division of Geriatric Psychiatry Department of Psychiatry and Behavioural Neurosciences Michael G. DeGroote School of Medicine Faculty of Health Sciences McMaster University Hamilton, Ontario, Canada [email protected]
James A. Bourgeois, OD, MD Consultation-Liaison Service Department of Psychiatry Langley Porter Psychiatric Institute University of California, San Francisco San Francisco, CA
REFERENCES 1. Wilson CL, Ferguson J. Myasthenia gravis unmasked by antipsychotic medication. Prog Neurol Psychiatry. 2013;17:17Y19. 2. Crews EL, Daw J. Neuroleptic-induced syndrome mimicking myasthenia gravis. Psychosomatics. 1981;22:67Y68. 3. Chiu YH, Yang AC, Chern CH, et al. Myasthenic crisis may mimic antipsychotic-induced extrapyramidal syndromes. J Neuropsychiatry Clin Neurosci. 2011;23:E36YE37. 4. Ronziere T, Auzou P, Ozsancak C, et al. Myasthenic syndrome induced by lithium [in French]. Presse Med. 2000;29:1043Y1044. 5. Samalin L, Charpeaud T, Llorca PM. Asenapine in bipolar I disorder: evidence and place in patient management. Ther Adv Chronic Dis. 2013;4:5Y14. 6. Scherer K, Bedlack RS, Simel DL. Does this patient have myasthenia gravis? JAMA. 2005; 293:1906Y1914. 7. Barton JJ, Fouladvand M. Ocular aspects of myasthenia gravis. Semin Neurol. 2000;20:7Y20. 8. Watling SM, Dasta JF. Prolonged paralysis in intensive care unit patients after the use of neuromuscular blocking agents: a review of the literature. Crit Care Med. 1994;22: 884Y893. 9. Alevizos B, Gatzonis S, Anagnostara CH. Myasthenia gravis disclosed by lithium carbonate. J Neuropsychiatry Clin Neurosci. 2006;18:427Y429.
108
www.psychopharmacology.com
Rhabdomyolysis After Escitalopram Treatment in a Young Adult With Melancholic Depression
&
Volume 35, Number 1, February 2015
CASE REPORT
Manual of Mental Disorders, Fourth Edition-Text Revision criteria) who developed rhabdomyolysis after his treatment of escitalopram. He was brought to the emergency department after a suicide attempt (December 2012) by jumping and falling 40 m. During his initial intake, the patient presented with vertebral fractures and a bilateral pneumothorax. A complete medical examination, including blood sample analysis, was performed after his admission to the emergency department. Abnormal (but low) levels of creatine phosphokinase (CPK, 465 UI/L) were found on the day of the fall. Another blood sample analysis was performed 6 hours after the first one and showed a decrease in CPK levels (from 465 to 430 UI/L). Abnormal levels of CPK were attributed to his muscular injuries sustained due to the fall, and, consequently, rhabdomyolysis was not diagnosed. To the best of our knowledge, no excessive physical activity, intramuscular injection, or drug use were reported by the patient. After somatic stabilization, he was transferred to the psychiatric care unit for 1 week. After his discharge (end of December 2012), he was admitted to the Intensive Care Mobile Unit at the University Hospital of Caen (France). On the basis of his symptoms, melancholic depression was diagnosed. He reported having a personal history of obsessive-compulsive disorder during adolescence and a family history of bipolar disorder (maternal uncle). Aripiprazole (10 mg) was initially given to him as treatment, but the patient stopped treatment after 1 day due to adverse effects (major sedation). Thereafter, he received escitalopram, which was progressively titrated from 5 to 20 mg/d (from January to February 2013). The medication was well tolerated, but euthymia was not achieved. Escitalopram at 30 mg led to greater improvement in depressive symptoms, and he reached a euthymic state 2 months later (April 2013). The patient reported bilateral myalgias of inferior members (quadriceps muscles) and intensive abdominal pain for a week. The psychiatrist suspected rhabdomyolysis and prescribed a dosage of muscular enzymes because of the urgent situation. Due to his blood analysis showing a severely elevated CPK level of 1245 UI/L (K+, 4.5 mmol/L; creatinine, 11.4 g/L), escitalopram was immediately stopped. Aches lasted for 13 days and then decreased as his CPK level decreased to a normal level (CPK, 143 UI/L). The patient’s clinical state was stabilized with lithium (625 mg/d) and mianserin (90 mg/d).
We report the case of a 20-year-old man (1.60 m, 66 kg; body mass index, 25.78 kg/m2) with melancholic depression (according to Diagnostic and Statistical
This report illustrates a case of severe adverse effect, rhabdomyolysis, after
To the Editors:
E
scitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is the S-enantiomer of citalopram, and it works by preventing the neurotransmitter serotonin from being taken into the nerve cells in the brain and spinal cord again. This antidepressant has been approved for the treatment of major depression, including severe forms of depression and generalized anxiety disorder. Escitalopram reaches maximum plasma concentration 3 to 4 hours after ingestion. The initial recommended dose is 10 mg/d, and the dose can be increased to 20 mg/d. Moreover, dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with treatmentresistant major depressive disorder.1 Escitalopram is generally well tolerated by patients. The most frequent adverse effects during treatment are headache, nausea, insomnia, fatigue, diarrhea, ejaculation impairment, drowsiness, dry mouth, dizziness, increased sweating, and tiredness. There have been a small number of reported cases of escitalopram-related serotonin syndrome. Severe serotonin toxicity may induce muscular hyperactivity that can exceed 40-C/ 104-F, seizures or rhabdomyolysis. Rhabdomyolysis is a condition that induces a rapid breakdown of skeletal muscle cells, which are released into the blood. The pathological pathway involves an increased concentration of intracellular calcium. Rhabdomyolysis has many etiologies, such as physical (eg, excessive muscular activity, compression of the muscles, thermal maximum, prolonged immobilization) or nonphysical (eg, electrolyte abnormalities, such as hyponatraemia2; hypophosphatemia or hypokalemia;or infections, such as influenzas, legionella, and salmonella) causes. Rhabdomyolysis has also been associated with the use of several substances: bupropion,3 fusidic acid,4 citalopram,5,6 olanzapine,7Y11 venlafaxine,12Y16 sertraline,17 moclobemide associated with fluoxetine,18 alcohol, cocaine, amphetaminelike molecules19 and ingestion, in one reported case, of escitalopram.20
DISCUSSION
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
