Journal of Clinical Psychopharmacology
&
Volume 35, Number 1, February 2015
escitalopram use. Escitalopram, like other selective serotonin reuptake inhibitors, might induce excessive serotonergic stimulation in the brainstem, notably in the midline raphe nuclei, where the serotonergic neurons are primarily located. Possible physiological and behavioral responses include hyperthermia, muscular rigidity, and restlessness. All of these conditions may contribute to rhabdomyolysis. Additionally, the patient received a higher dose (30 mg) than that recommended for the treatment of major depressive disorder. Despite the fact that dose escalation was initially found to be tolerable in this indication,1 tolerance of psychotropic drugs is dependent on the individual, and undesirable effects have a possible dose-response relationship. Consequently, higher doses of the drug can possibly induce severe adverse effects, such as serotonin syndrome. Although an important indicator of rhabdomyolysis is an elevated serum CPK level, the 40-m fall could have produced muscular injuries, which may have contributed to his CPK elevation after escitalopram ingestion. This situation demonstrates that clinicians have to closely monitor tolerance and possible adverse effects during treatment initiation and during long-term follow-up. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Laurent Lecardeur, PhD Centre Hospitalier Universitaire de Caen Equipe Mobile de Soins Intensifs Centre Esquirol Unite´ Mixte de Recherche 6301 Imagerie et Strate´gies The´rapeutiques des pathologies Ce´re´brales et Tumorales Imagerie et Strate´gies The´rapeutiques des Schizophre´nies group Centre National de la Recherche Scientifique Commissariat a` l’E´nergie Atomique Groupement d’Inte´reˆt Public CYCERON Universite´ de Caen Basse-Normandie Caen, France [email protected]
Aline Lefebvre, Psychiatry Resident Sophie Meunier-Cussac, MD Centre Hospitalier Universitaire de Caen Equipe Mobile de Soins Intensifs Centre Esquirol Caen, France
REFERENCES 1. Wade AG, Crawford GM, Yellowlees A. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD): an open-label, pilot study. BMC Psychiatry. 2011;11:42. 2. Bennett M, Fitzpatrick G, Donnelly M. Rhabdomyolysis associated with polydipsia
induced hyponatraemia. BMJ Case Rep. 2011; doi:10.1136/bcr.08.2011.4659. 3. Bobe F, Buil ME, Palacios L. Rhabdomyolysis connected with the use of bupropion. Scand J Prim Health Care. 2004;22:191Y192. 4. Livio F. Pharmacovigilance update. Rev Med Suisse. 2013;9:72Y75. 5. Grundemar L, Wohlfart B, Lagerstedt C, et al. Symptoms and signs of severe citalopram overdose. Lancet. 1997;349:1602. 6. Richards S, Umbreit JN, Fanucchi MP, et al. Selective serotonin reuptake inhibitorYinduced rhabdomyolysis associated with irinotecan. South Med J. 2003;96:1031Y1033. 7. Hanft A, Eggleston CF, Bourgeois JA. Neuroleptic malignant syndrome in an adolescent after brief exposure to olanzapine. J Child Adolesc Psychopharmacol. 2004;14:481Y487. 8. Strawn JR, Adler CM, Strakowski SM, et al. Hyperthermia and rhabdomyolysis in an adolescent treated with topiramate and olanzapine. J Child Adolesc Psychopharmacol. 2008;18:116Y118. 9. Baumgart U, Schmid R, Spiessl H. Olanzapine-induced acute rhabdomyolysisVa case report. Pharmacopsychiatry. 2005;38:36Y37. 10. Hung CF, Huang TY, Lin PY. Hypothermia and rhabdomyolysis following olanzapine injection in an adolescent with schizophreniform disorder. Gen Hosp Psychiatry. 2009;31:376Y378. 11. Ribeyron S, Guy C, Koenig M, et al. Olanzapine induced rhabdomyolysis and serum creatine kinase increase. Rev Med Interne. 2009;30:477Y485. 12. Peano C, Leikin JB, Hanashiro PK. Seizures, ventricular tachycardia, and rhabdomyolysis as a result of ingestion of venlafaxine and lamotrigine. Ann Emerg Med. 1997;30: 704Y708. 13. Lu TC, Chu PL, Wu CS, et al. Neuroleptic malignant syndrome after the use of venlafaxine in a patient with generalized anxiety disorder. J Formos Med Assoc. 2006;105:90Y93. 14. Wilson AD, Howell C, Waring WS. Venlafaxine ingestion is associated with rhabdomyolysis in adults: a case series. J Toxicol Sci. 2007;32:97Y101. 15. Rajapakse S, Abeynaike L, Wickramarathne T. Venlafaxine-associated serotonin syndrome causing severe rhabdomyolysis and acute renal failure in a patient with idiopathic Parkinson disease. J Clin Psychopharmacol. 2010;30:620Y622. 16. Huang SS, Yang HY, Lin YC, et al. Low-dose venlafaxine-induced severe rhabdomyolysis: a case report. Gen Hosp Psychiatry. 2012;34:436Y437. 17. Phan H, Casavant MJ, Crockett S, et al. Serotonin syndrome following a single 50 mg dose of sertraline in a child. Clin Toxicol (Phila). 2008;46:845Y849.
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editors 18. Wu ML, Deng JF. Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose. Chang Gung Med J. 2011;34:644Y649. 19. Boulanger-Gobeil C, St-Onge M, Laliberte M, et al. Seizures and hyponatremia related to ethcathinone and methylone poisoning. J Med Toxicol. 2012;8:59Y61. 20. Lewien A, Kranaster L, Hoyer C, et al. Escitalopram-related rhabdomyolysis. J Clin Psychopharmacol. 2011;31:251Y253.
Effects of Trazodone on Night Eating Behavior A Case Report To the Editors:
N
ight eating syndrome (NES) has been recently introduced in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) category of Other Specified Feeding or Eating Disorder. A delay in the circadian rhythm of food intake is considered the main feature of this pervasive eating disorder: patients affected present recurrent episodes of night eating, intended as consumption of more than a fourth of their daily food intake between dinner and bedtime or during nocturnal awakenings.1 Patients could feel the need to eat and to sleep and this leads to a potentially severe sleep dysregulation. However, NES differs from sleep-related eating disorder because patients are awake during episodes and present awareness and recall of the night eating.2 Morning anorexia is common as well as restrictive eating at lunch, but these symptoms are not specific for NES.3 Likewise, night eating cannot be solely ascribed as a symptom of depression, although most of these patients have a depressed mood.4 Some authors observed that in NES, mood is euthymic in the morning, then gradually worsens until a marked distress, which results in overeating in the evening and in the night.5 The description of the feeding behavior of these patients remains controversial as well as its treatment.
CASE REPORT The patient is a 55-year-old woman who worked as an employee at a government agency. Fatherless at the age of 6, she married twice, the first time at the age of 18 to leave her mother’s home. She had 2 children with her second husband from whom she divorced after 5 years of marriage. When she was 46 years, she lost her mother to a carcinoma and then she www.psychopharmacology.com
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
109
Journal of Clinical Psychopharmacology
Letters to the Editors
developed a major depressive episode treated effectively in 5 weeks with fluoxetine 40 mg/d. She presented also opposite polarity symptoms and severe, accompanied by multiple early awakenings and hypnagogic hallucination, that resolved, respectively, with topiramate 150 mg/d and mianserin 60 mg/d plus delorazepam 15 drops/d. She followed the therapy for 2 years and then suspended autonomously all medications. Nine years later, after a personal disappointment, she had a relapse of insomnia worsened with night eating episodes. Her consultant prescribed again fluoxetine, topiramate, and mianserin without results. She was referred to our outpatient service for Eating Disorders, and a polysomnography showed nonspecific alteration of sleep (‘‘destructured sleep’’) excluding a parasomnia. When we met the patient for the first time, night eating had occurred 9 months before and treatment was ongoing for 3 months. She referred to ‘‘wake up every night’’ but she failed to quantify the exact frequency per night and the food intake. She presented morning anorexia and she used to fast at lunch because she was worried about having gained 25 lb in the last 6 months. Her body mass index (BMI) was 33.5 kg/m2. She slept approximately 4 hours a night, resulting in daytime sleepiness with strong impact on work and social life. Psychic status showed somatized anxiety and moderate impulsivity; she reported feelings of sadness and ideas of guilt closely related to insomnia and overeating; thoughts were normal in process and content. As usual, Eating Disorder Inventory26 and Minnesota Multiphasic Personality Inventory-27 were administered and, given the unusual symptoms, the Night Eating Questionnaire (NEQ)8 and the Hamilton Rating Scale for Depression (HRSD-29)9 were completed (Table 1, T0). The patient was aware of her pathological eating behavior but had clouded consciousness, as many other NES patients, and described night eating as ‘‘automatic,’’ as a depersonalization phenomenon. For this purpose, the food diary has been useful to promote awareness, to increase compliance to treatment, and to help the clinician to recognize and quantify the symptoms.3 We discovered that night eating occurred about 3 times per week, especially during the weekends or holidays. She woke one time per night and she ate up to 2500 calories of almost exclusively comfort foods in a single night eating episode. During the rest of the day, all the meals together did not reach 800 calories. These symptoms fulfilled both DSM-5 and the International NES Research Group criteria.1 The NEQ score attests a severe NES symptom. The patient does not meet DSM-5 criteria for bulimia nervosa,
110
www.psychopharmacology.com
&
Volume 35, Number 1, February 2015
TABLE 1. Clinical and Psychopathological Assessment at First Visit and After 6 Months
BMI NEQ Tot. NEQVnocturnal ingestion NEQVevening hyperphagia NEQVmorning anorexia NEQVmood/sleep HRSD-29 EDI-2Vdrive for thinness EDI-2Vbulimia EDI-2Vbody dissatisfaction EDI-2Vineffectiveness EDI-2Vperfectionism EDI-2Vinterpersonal distrust EDI-2Vinteroceptive awareness EDI-2Vmaturity fears EDI-2Vasceticism EDI-2Vimpulse regulation EDI-2Vsocial insecurity MMPI-2Vhypochondriasis MMPI-2Vdepression MMPI-2Vhysteria MMPI-2Vpsychopathic deviate MMPI-2Vmasculinity/femininity MMPI-2Vparanoia MMPI-2Vpsychasthenia MMPI-2Vschizophrenia MMPI-2Vhypomania MMPI-2Vsocial introversion
T0
T1 (6th Month)
33.5 41* 19 10 7 5 26* 14* 11* 24* 14* 1 3 10 5 7 4 4 69* 78* 77* 70* 38 63 64 60 47 56
30.1 12 0 2 1 6 18 10 6* 7 1 4 2 12* 0 9 0 0 48 64 50 58 50 41 44 43 42 50
*Marks points exceeding the cut-off value of the corresponding domain. BMI indicates body mass index; EDI-2, Eating Disorder Inventory-2; MMPI-2, Minnesota Multiphasic Personality Inventory-2.
binge eating disorder (BED), or other specific eating disorders. We reduced mianserin and fluoxetine, to gradually introduce trazodone. The switch had been programmed as follows: (1) from the first to the seventh day: interruption of fluoxetine, and maintenance of mianserin 30 mg and topiramate 150 mg, introduction of trazodone 75 mg; (2) from the eighth day: interruption of mianserin and increase of trazodone up to 150 mg/d. At follow-up, after 4 weeks of full dose of trazodone, the patient’s condition improved: feelings of sadness and anxiety cleared, and normal sleep patterns were restored. Pathological eating behaviors improved after 2 weeks from the introduction of trazodone and they resolved with the regularization of the sleep-wake rhythm in an additional week. Low selfesteem and body dissatisfaction persisted, as well as affective instability that led to inadequacy, seclusion, and social phobia. As usual in our service, the patient was invited to start a supportive psychotherapy to consolidate results and prevent relapses. After 6 months, NEQ shows a complete remission of night eating, Eating Disorder Inventory-2 and HRSD-29 evidence
a relevant improvement of pathological eating behaviors and depressive symptoms (Table 1, T1). The patient asked to discontinue the medications and we proceeded to reduce trazodone from 150 to 75 mg but insomnia and nocturnal overeating reappeared in 2 weeks. Thus, therapy was restored and she continued psychotherapy. A state of symptom remission persists, 10 months after the resolution of the night eating syndrome. She lacks depressive symptoms or pathological eating behaviors and drug therapy remains unchanged.
DISCUSSION This case presented an unusual mixture of depressive symptoms, pathological eating behaviors, and sleep disruption that allows us to reflect on the therapy of the core features of NES. There have been few reports on the treatment of NES. Although evidence is not available on night eating, no benefit was reported from treatment with fluoxetine and fluvoxamine in BED in terms of weight loss or episode frequency.10 Furthermore, mianserin is completely ineffective in the treatment of BED, although
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Journal of Clinical Psychopharmacology
&
Volume 35, Number 1, February 2015
it is effective in the therapy of chronic insomnia.11 There are anecdotal reports of efficacy of topiramate,12,13 but our patient took topiramate for months without any benefit. Sertraline is to date the only selective serotonin reuptake inhibitor successfully used in the treatment of NES: 3 clinical trials report a decrease in evening hyperphagia, mean body weight, and frequency of awakenings.14 Because central modulation of serotonin seems to be promising, trazodone may represent an effectual alternative. Trials demonstrate similar results to those obtained with tricyclics and selective serotonin reuptake inhibitors in patients with bulimia nervosa and atypical eating disorders.15 It also increases slow-wave sleep when given as a monotherapy and this can be helpful in restoring circadian rhythm.16 The woman’s night eating symptoms improved after 2 weeks of treatment and the NEQ score dropped by 29 points (70.7%) at 6-month follow-up with Nocturnal Ingestion scale achieving remission. At the same time, her body mass index decreased by 3 points, approximately 10% of her body weight. These results overlap with that obtained with sertraline in term of remission in night eating symptoms, weight loss, and speed of response. The patient has also been monitored for a longer time than the other studies available on literature and positive results have been stable for 10 months after remission. The antidepressive dose of trazodone (>150 mg/d) seems to be the most suitable, although results seem dose-independent.17 Trazodone was also well tolerated: the patient did not report any adverse effect, except for daytime sleepiness that could have been avoided through a slower titration. Lastly, we recommended psychotherapy, as well as for other eating and feeding disorders,18 to consolidate the results achieved and support the patients in remission.19 Limitation of this case is the relevant depressive symptoms, as assessed with the HRSD-29 (score > 20), which does not allow to deduce in a definitive way that change in depressive symptoms was not the principal driver of changes in night eating symptoms. However, Minnesota Multiphasic Personality Inventory-2 profile assesses for a depressive temperament and not for a full-blown depression. These observations are promising but further investigations are needed. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Flavio Giuseppe Di Leone, MD Department of Neurology and Psychiatry Sapienza University of Rome Rome, Italy
Dalila Talevi, MD Department of Neurology and Psychiatry Sapienza University of Rome Rome, Italy [email protected]
Camillo Loriedo, MD, PhD Department of Neurology and Psychiatry Sapienza University of Rome Rome, Italy
REFERENCES 1. Allison KC, Lundgren JD, O’Reardon JP, et al. Proposed diagnostic criteria for night eating syndrome. Int J Eat Disord. 2010;43:241Y247. 2. Winkelman JW. Clinical and polysomnographic features of sleep-related eating disorder. J Clin Psychiatry. 1998;59:14Y19. 3. Allison KC, Grilo CM, Masheb RM, et al. Binge eating disorder and night eating syndrome: a comparative study of disordered eating. J Consult Clin Psychol. 2005;73:1107Y1115. 4. Stunkard AJ, Allison KC. Two forms of disordered eating in obesity: binge eating and night eating. Int J Obes Relat Metab Disord. 2003;27:1Y12. 5. Stunkard AJ, Allison KC, Lundgren JD, et al. A biobehavioural model of the night eating syndrome. Obes Rev. 2009;10:69Y77. 6. Garner DM. EDI-2: Eating Disorder Inventory-2: Manuale. Rizzardi M, Trombini E, Trombini G, eds. Firenze, Italy: Giunti O.S. Organizzazioni Speciali; 1995. 7. Sirigatti S, Stefanile C. MMPI-2: aggiornamento all’adattamento italiano: scale di validita`, Harris-Lingoes, supplementari, di contenuto e PSY-5. Firenze: Giunti O.S. Organizzazioni Speciali; 2011. 8. Allison KC, Lundgren JD, O’Reardon JP, et al. The Night Eating Questionnaire (NEQ): psychometric properties of a measure of severity of the Night Eating Syndrome. Eat Behav. 2008;9:62Y72. 9. Trajkovi( G, Star*evi( V, Latas M, et al. Reliability of the Hamilton Rating Scale for Depression: a meta-analysis over a period of 49 years. Psychiatry Res. 2011;189:1Y9. 10. Marcus MD, Wing RR, Ewing L, et al. A double-blind, placebo-controlled trial of fluoxetine plus behavior modification in the treatment of obese binge-eaters and non-binge-eaters. Am J Psychiatry. 1990;147: 876Y881. 11. Sabine EJ, Yonace A, Farrington AJ, et al. Bulimia nervosa: a placebo controlled double-blind therapeutic trial of mianserin. Br J Clin Pharmacol. 1983;15:195SY202S. 12. Winkelman JW. Treatment of nocturnal eating syndrome and sleep-related eating disorder with topiramate. Sleep Med. 2003;4:243Y246. 13. Cooper-Kazaz R. Treatment of night eating syndrome with topiramate: dawn of a new day. J Clin Psychopharmacol. 2012;32:143Y145.
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editors 14. Howell MJ, Schenck CH, Crow SJ. A review of nighttime eating disorders. Sleep Med Rev. 2009;13:23Y34. 15. Hudson JI, Pope HG Jr, Keck PE Jr, et al. Treatment of bulimia nervosa with trazodone: short-term response and long-term follow-up. Clin Neuropharmacol. 1989;12:S38YS46. 16. James SP, Mendelson WB. The use of trazodone as a hypnotic: a critical review. J Clin Psychiatry. 2004;65:752Y755. 17. Karhu D, Gossen ER, Mostert A, et al. Safety, tolerability, and pharmacokinetics of once-daily trazodone extended-release caplets in healthy subjects. Int J Clin Pharmacol Ther. 2011;49:730Y743. 18. Vander Wal JS. Night eating syndrome: a critical review of the literature. Clin Psychol Rev. 2012;32:49Y59. 19. Loriedo C, Costa E, Carrus D, et al. In: Biondi M, Loriedo C. La mente nella ricerca. Attivita` scientifica in psichiatria e psicologia medica. Milano, Italy: Franco Angeli; 2007:90Y127.
Manic Episodes Associated With Tramadol A Case Report To the Editors:
T
ramadol is an atypical centrally acting opioid analgesic used for the treatment of moderate to severe pain. Tramadol weakly binds to K-receptors, and it also enhances the action of serotonin and norepinephrine through interfering in their reuptake and release mechanisms.1 In diverse animal models, tramadol has been shown to induce antidepressantlike effects similar to those of monoaminergic system drugs, and it has been demonstrated that the molecular structure of tramadol is similar to that of the antidepressant venlafaxine.2 Recent animal studies demonstrated that tramadol pretreatment reinforces the antidepressant effects of ketamine, a sedative/hypnotic, anesthetic induction agent with antidepressant effects and increases the levels of brain-derived neurotrophic factor and tropomyosin-related kinase B.3,4 In clinical settings, tramadol has reportedly been effective in the treatment of obsessive-compulsive disorder and depression.5Y8 Excessive doses of tramadol or the combination of tramadol with monoaminergic antidepressants have been reported to be associated with serotonergic syndrome.7 Tramadol has been reported to trigger manic episodes in bipolar patients.8Y10 A patient with no previous psychiatric history, who had 2 manic episodes possibly associated with tramadol, is described here. www.psychopharmacology.com
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
111
&
Volume 35, Number 1, February 2015
escitalopram use. Escitalopram, like other selective serotonin reuptake inhibitors, might induce excessive serotonergic stimulation in the brainstem, notably in the midline raphe nuclei, where the serotonergic neurons are primarily located. Possible physiological and behavioral responses include hyperthermia, muscular rigidity, and restlessness. All of these conditions may contribute to rhabdomyolysis. Additionally, the patient received a higher dose (30 mg) than that recommended for the treatment of major depressive disorder. Despite the fact that dose escalation was initially found to be tolerable in this indication,1 tolerance of psychotropic drugs is dependent on the individual, and undesirable effects have a possible dose-response relationship. Consequently, higher doses of the drug can possibly induce severe adverse effects, such as serotonin syndrome. Although an important indicator of rhabdomyolysis is an elevated serum CPK level, the 40-m fall could have produced muscular injuries, which may have contributed to his CPK elevation after escitalopram ingestion. This situation demonstrates that clinicians have to closely monitor tolerance and possible adverse effects during treatment initiation and during long-term follow-up. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Laurent Lecardeur, PhD Centre Hospitalier Universitaire de Caen Equipe Mobile de Soins Intensifs Centre Esquirol Unite´ Mixte de Recherche 6301 Imagerie et Strate´gies The´rapeutiques des pathologies Ce´re´brales et Tumorales Imagerie et Strate´gies The´rapeutiques des Schizophre´nies group Centre National de la Recherche Scientifique Commissariat a` l’E´nergie Atomique Groupement d’Inte´reˆt Public CYCERON Universite´ de Caen Basse-Normandie Caen, France [email protected]
Aline Lefebvre, Psychiatry Resident Sophie Meunier-Cussac, MD Centre Hospitalier Universitaire de Caen Equipe Mobile de Soins Intensifs Centre Esquirol Caen, France
REFERENCES 1. Wade AG, Crawford GM, Yellowlees A. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD): an open-label, pilot study. BMC Psychiatry. 2011;11:42. 2. Bennett M, Fitzpatrick G, Donnelly M. Rhabdomyolysis associated with polydipsia
induced hyponatraemia. BMJ Case Rep. 2011; doi:10.1136/bcr.08.2011.4659. 3. Bobe F, Buil ME, Palacios L. Rhabdomyolysis connected with the use of bupropion. Scand J Prim Health Care. 2004;22:191Y192. 4. Livio F. Pharmacovigilance update. Rev Med Suisse. 2013;9:72Y75. 5. Grundemar L, Wohlfart B, Lagerstedt C, et al. Symptoms and signs of severe citalopram overdose. Lancet. 1997;349:1602. 6. Richards S, Umbreit JN, Fanucchi MP, et al. Selective serotonin reuptake inhibitorYinduced rhabdomyolysis associated with irinotecan. South Med J. 2003;96:1031Y1033. 7. Hanft A, Eggleston CF, Bourgeois JA. Neuroleptic malignant syndrome in an adolescent after brief exposure to olanzapine. J Child Adolesc Psychopharmacol. 2004;14:481Y487. 8. Strawn JR, Adler CM, Strakowski SM, et al. Hyperthermia and rhabdomyolysis in an adolescent treated with topiramate and olanzapine. J Child Adolesc Psychopharmacol. 2008;18:116Y118. 9. Baumgart U, Schmid R, Spiessl H. Olanzapine-induced acute rhabdomyolysisVa case report. Pharmacopsychiatry. 2005;38:36Y37. 10. Hung CF, Huang TY, Lin PY. Hypothermia and rhabdomyolysis following olanzapine injection in an adolescent with schizophreniform disorder. Gen Hosp Psychiatry. 2009;31:376Y378. 11. Ribeyron S, Guy C, Koenig M, et al. Olanzapine induced rhabdomyolysis and serum creatine kinase increase. Rev Med Interne. 2009;30:477Y485. 12. Peano C, Leikin JB, Hanashiro PK. Seizures, ventricular tachycardia, and rhabdomyolysis as a result of ingestion of venlafaxine and lamotrigine. Ann Emerg Med. 1997;30: 704Y708. 13. Lu TC, Chu PL, Wu CS, et al. Neuroleptic malignant syndrome after the use of venlafaxine in a patient with generalized anxiety disorder. J Formos Med Assoc. 2006;105:90Y93. 14. Wilson AD, Howell C, Waring WS. Venlafaxine ingestion is associated with rhabdomyolysis in adults: a case series. J Toxicol Sci. 2007;32:97Y101. 15. Rajapakse S, Abeynaike L, Wickramarathne T. Venlafaxine-associated serotonin syndrome causing severe rhabdomyolysis and acute renal failure in a patient with idiopathic Parkinson disease. J Clin Psychopharmacol. 2010;30:620Y622. 16. Huang SS, Yang HY, Lin YC, et al. Low-dose venlafaxine-induced severe rhabdomyolysis: a case report. Gen Hosp Psychiatry. 2012;34:436Y437. 17. Phan H, Casavant MJ, Crockett S, et al. Serotonin syndrome following a single 50 mg dose of sertraline in a child. Clin Toxicol (Phila). 2008;46:845Y849.
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editors 18. Wu ML, Deng JF. Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose. Chang Gung Med J. 2011;34:644Y649. 19. Boulanger-Gobeil C, St-Onge M, Laliberte M, et al. Seizures and hyponatremia related to ethcathinone and methylone poisoning. J Med Toxicol. 2012;8:59Y61. 20. Lewien A, Kranaster L, Hoyer C, et al. Escitalopram-related rhabdomyolysis. J Clin Psychopharmacol. 2011;31:251Y253.
Effects of Trazodone on Night Eating Behavior A Case Report To the Editors:
N
ight eating syndrome (NES) has been recently introduced in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) category of Other Specified Feeding or Eating Disorder. A delay in the circadian rhythm of food intake is considered the main feature of this pervasive eating disorder: patients affected present recurrent episodes of night eating, intended as consumption of more than a fourth of their daily food intake between dinner and bedtime or during nocturnal awakenings.1 Patients could feel the need to eat and to sleep and this leads to a potentially severe sleep dysregulation. However, NES differs from sleep-related eating disorder because patients are awake during episodes and present awareness and recall of the night eating.2 Morning anorexia is common as well as restrictive eating at lunch, but these symptoms are not specific for NES.3 Likewise, night eating cannot be solely ascribed as a symptom of depression, although most of these patients have a depressed mood.4 Some authors observed that in NES, mood is euthymic in the morning, then gradually worsens until a marked distress, which results in overeating in the evening and in the night.5 The description of the feeding behavior of these patients remains controversial as well as its treatment.
CASE REPORT The patient is a 55-year-old woman who worked as an employee at a government agency. Fatherless at the age of 6, she married twice, the first time at the age of 18 to leave her mother’s home. She had 2 children with her second husband from whom she divorced after 5 years of marriage. When she was 46 years, she lost her mother to a carcinoma and then she www.psychopharmacology.com
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
109
Journal of Clinical Psychopharmacology
Letters to the Editors
developed a major depressive episode treated effectively in 5 weeks with fluoxetine 40 mg/d. She presented also opposite polarity symptoms and severe, accompanied by multiple early awakenings and hypnagogic hallucination, that resolved, respectively, with topiramate 150 mg/d and mianserin 60 mg/d plus delorazepam 15 drops/d. She followed the therapy for 2 years and then suspended autonomously all medications. Nine years later, after a personal disappointment, she had a relapse of insomnia worsened with night eating episodes. Her consultant prescribed again fluoxetine, topiramate, and mianserin without results. She was referred to our outpatient service for Eating Disorders, and a polysomnography showed nonspecific alteration of sleep (‘‘destructured sleep’’) excluding a parasomnia. When we met the patient for the first time, night eating had occurred 9 months before and treatment was ongoing for 3 months. She referred to ‘‘wake up every night’’ but she failed to quantify the exact frequency per night and the food intake. She presented morning anorexia and she used to fast at lunch because she was worried about having gained 25 lb in the last 6 months. Her body mass index (BMI) was 33.5 kg/m2. She slept approximately 4 hours a night, resulting in daytime sleepiness with strong impact on work and social life. Psychic status showed somatized anxiety and moderate impulsivity; she reported feelings of sadness and ideas of guilt closely related to insomnia and overeating; thoughts were normal in process and content. As usual, Eating Disorder Inventory26 and Minnesota Multiphasic Personality Inventory-27 were administered and, given the unusual symptoms, the Night Eating Questionnaire (NEQ)8 and the Hamilton Rating Scale for Depression (HRSD-29)9 were completed (Table 1, T0). The patient was aware of her pathological eating behavior but had clouded consciousness, as many other NES patients, and described night eating as ‘‘automatic,’’ as a depersonalization phenomenon. For this purpose, the food diary has been useful to promote awareness, to increase compliance to treatment, and to help the clinician to recognize and quantify the symptoms.3 We discovered that night eating occurred about 3 times per week, especially during the weekends or holidays. She woke one time per night and she ate up to 2500 calories of almost exclusively comfort foods in a single night eating episode. During the rest of the day, all the meals together did not reach 800 calories. These symptoms fulfilled both DSM-5 and the International NES Research Group criteria.1 The NEQ score attests a severe NES symptom. The patient does not meet DSM-5 criteria for bulimia nervosa,
110
www.psychopharmacology.com
&
Volume 35, Number 1, February 2015
TABLE 1. Clinical and Psychopathological Assessment at First Visit and After 6 Months
BMI NEQ Tot. NEQVnocturnal ingestion NEQVevening hyperphagia NEQVmorning anorexia NEQVmood/sleep HRSD-29 EDI-2Vdrive for thinness EDI-2Vbulimia EDI-2Vbody dissatisfaction EDI-2Vineffectiveness EDI-2Vperfectionism EDI-2Vinterpersonal distrust EDI-2Vinteroceptive awareness EDI-2Vmaturity fears EDI-2Vasceticism EDI-2Vimpulse regulation EDI-2Vsocial insecurity MMPI-2Vhypochondriasis MMPI-2Vdepression MMPI-2Vhysteria MMPI-2Vpsychopathic deviate MMPI-2Vmasculinity/femininity MMPI-2Vparanoia MMPI-2Vpsychasthenia MMPI-2Vschizophrenia MMPI-2Vhypomania MMPI-2Vsocial introversion
T0
T1 (6th Month)
33.5 41* 19 10 7 5 26* 14* 11* 24* 14* 1 3 10 5 7 4 4 69* 78* 77* 70* 38 63 64 60 47 56
30.1 12 0 2 1 6 18 10 6* 7 1 4 2 12* 0 9 0 0 48 64 50 58 50 41 44 43 42 50
*Marks points exceeding the cut-off value of the corresponding domain. BMI indicates body mass index; EDI-2, Eating Disorder Inventory-2; MMPI-2, Minnesota Multiphasic Personality Inventory-2.
binge eating disorder (BED), or other specific eating disorders. We reduced mianserin and fluoxetine, to gradually introduce trazodone. The switch had been programmed as follows: (1) from the first to the seventh day: interruption of fluoxetine, and maintenance of mianserin 30 mg and topiramate 150 mg, introduction of trazodone 75 mg; (2) from the eighth day: interruption of mianserin and increase of trazodone up to 150 mg/d. At follow-up, after 4 weeks of full dose of trazodone, the patient’s condition improved: feelings of sadness and anxiety cleared, and normal sleep patterns were restored. Pathological eating behaviors improved after 2 weeks from the introduction of trazodone and they resolved with the regularization of the sleep-wake rhythm in an additional week. Low selfesteem and body dissatisfaction persisted, as well as affective instability that led to inadequacy, seclusion, and social phobia. As usual in our service, the patient was invited to start a supportive psychotherapy to consolidate results and prevent relapses. After 6 months, NEQ shows a complete remission of night eating, Eating Disorder Inventory-2 and HRSD-29 evidence
a relevant improvement of pathological eating behaviors and depressive symptoms (Table 1, T1). The patient asked to discontinue the medications and we proceeded to reduce trazodone from 150 to 75 mg but insomnia and nocturnal overeating reappeared in 2 weeks. Thus, therapy was restored and she continued psychotherapy. A state of symptom remission persists, 10 months after the resolution of the night eating syndrome. She lacks depressive symptoms or pathological eating behaviors and drug therapy remains unchanged.
DISCUSSION This case presented an unusual mixture of depressive symptoms, pathological eating behaviors, and sleep disruption that allows us to reflect on the therapy of the core features of NES. There have been few reports on the treatment of NES. Although evidence is not available on night eating, no benefit was reported from treatment with fluoxetine and fluvoxamine in BED in terms of weight loss or episode frequency.10 Furthermore, mianserin is completely ineffective in the treatment of BED, although
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Journal of Clinical Psychopharmacology
&
Volume 35, Number 1, February 2015
it is effective in the therapy of chronic insomnia.11 There are anecdotal reports of efficacy of topiramate,12,13 but our patient took topiramate for months without any benefit. Sertraline is to date the only selective serotonin reuptake inhibitor successfully used in the treatment of NES: 3 clinical trials report a decrease in evening hyperphagia, mean body weight, and frequency of awakenings.14 Because central modulation of serotonin seems to be promising, trazodone may represent an effectual alternative. Trials demonstrate similar results to those obtained with tricyclics and selective serotonin reuptake inhibitors in patients with bulimia nervosa and atypical eating disorders.15 It also increases slow-wave sleep when given as a monotherapy and this can be helpful in restoring circadian rhythm.16 The woman’s night eating symptoms improved after 2 weeks of treatment and the NEQ score dropped by 29 points (70.7%) at 6-month follow-up with Nocturnal Ingestion scale achieving remission. At the same time, her body mass index decreased by 3 points, approximately 10% of her body weight. These results overlap with that obtained with sertraline in term of remission in night eating symptoms, weight loss, and speed of response. The patient has also been monitored for a longer time than the other studies available on literature and positive results have been stable for 10 months after remission. The antidepressive dose of trazodone (>150 mg/d) seems to be the most suitable, although results seem dose-independent.17 Trazodone was also well tolerated: the patient did not report any adverse effect, except for daytime sleepiness that could have been avoided through a slower titration. Lastly, we recommended psychotherapy, as well as for other eating and feeding disorders,18 to consolidate the results achieved and support the patients in remission.19 Limitation of this case is the relevant depressive symptoms, as assessed with the HRSD-29 (score > 20), which does not allow to deduce in a definitive way that change in depressive symptoms was not the principal driver of changes in night eating symptoms. However, Minnesota Multiphasic Personality Inventory-2 profile assesses for a depressive temperament and not for a full-blown depression. These observations are promising but further investigations are needed. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Flavio Giuseppe Di Leone, MD Department of Neurology and Psychiatry Sapienza University of Rome Rome, Italy
Dalila Talevi, MD Department of Neurology and Psychiatry Sapienza University of Rome Rome, Italy [email protected]
Camillo Loriedo, MD, PhD Department of Neurology and Psychiatry Sapienza University of Rome Rome, Italy
REFERENCES 1. Allison KC, Lundgren JD, O’Reardon JP, et al. Proposed diagnostic criteria for night eating syndrome. Int J Eat Disord. 2010;43:241Y247. 2. Winkelman JW. Clinical and polysomnographic features of sleep-related eating disorder. J Clin Psychiatry. 1998;59:14Y19. 3. Allison KC, Grilo CM, Masheb RM, et al. Binge eating disorder and night eating syndrome: a comparative study of disordered eating. J Consult Clin Psychol. 2005;73:1107Y1115. 4. Stunkard AJ, Allison KC. Two forms of disordered eating in obesity: binge eating and night eating. Int J Obes Relat Metab Disord. 2003;27:1Y12. 5. Stunkard AJ, Allison KC, Lundgren JD, et al. A biobehavioural model of the night eating syndrome. Obes Rev. 2009;10:69Y77. 6. Garner DM. EDI-2: Eating Disorder Inventory-2: Manuale. Rizzardi M, Trombini E, Trombini G, eds. Firenze, Italy: Giunti O.S. Organizzazioni Speciali; 1995. 7. Sirigatti S, Stefanile C. MMPI-2: aggiornamento all’adattamento italiano: scale di validita`, Harris-Lingoes, supplementari, di contenuto e PSY-5. Firenze: Giunti O.S. Organizzazioni Speciali; 2011. 8. Allison KC, Lundgren JD, O’Reardon JP, et al. The Night Eating Questionnaire (NEQ): psychometric properties of a measure of severity of the Night Eating Syndrome. Eat Behav. 2008;9:62Y72. 9. Trajkovi( G, Star*evi( V, Latas M, et al. Reliability of the Hamilton Rating Scale for Depression: a meta-analysis over a period of 49 years. Psychiatry Res. 2011;189:1Y9. 10. Marcus MD, Wing RR, Ewing L, et al. A double-blind, placebo-controlled trial of fluoxetine plus behavior modification in the treatment of obese binge-eaters and non-binge-eaters. Am J Psychiatry. 1990;147: 876Y881. 11. Sabine EJ, Yonace A, Farrington AJ, et al. Bulimia nervosa: a placebo controlled double-blind therapeutic trial of mianserin. Br J Clin Pharmacol. 1983;15:195SY202S. 12. Winkelman JW. Treatment of nocturnal eating syndrome and sleep-related eating disorder with topiramate. Sleep Med. 2003;4:243Y246. 13. Cooper-Kazaz R. Treatment of night eating syndrome with topiramate: dawn of a new day. J Clin Psychopharmacol. 2012;32:143Y145.
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editors 14. Howell MJ, Schenck CH, Crow SJ. A review of nighttime eating disorders. Sleep Med Rev. 2009;13:23Y34. 15. Hudson JI, Pope HG Jr, Keck PE Jr, et al. Treatment of bulimia nervosa with trazodone: short-term response and long-term follow-up. Clin Neuropharmacol. 1989;12:S38YS46. 16. James SP, Mendelson WB. The use of trazodone as a hypnotic: a critical review. J Clin Psychiatry. 2004;65:752Y755. 17. Karhu D, Gossen ER, Mostert A, et al. Safety, tolerability, and pharmacokinetics of once-daily trazodone extended-release caplets in healthy subjects. Int J Clin Pharmacol Ther. 2011;49:730Y743. 18. Vander Wal JS. Night eating syndrome: a critical review of the literature. Clin Psychol Rev. 2012;32:49Y59. 19. Loriedo C, Costa E, Carrus D, et al. In: Biondi M, Loriedo C. La mente nella ricerca. Attivita` scientifica in psichiatria e psicologia medica. Milano, Italy: Franco Angeli; 2007:90Y127.
Manic Episodes Associated With Tramadol A Case Report To the Editors:
T
ramadol is an atypical centrally acting opioid analgesic used for the treatment of moderate to severe pain. Tramadol weakly binds to K-receptors, and it also enhances the action of serotonin and norepinephrine through interfering in their reuptake and release mechanisms.1 In diverse animal models, tramadol has been shown to induce antidepressantlike effects similar to those of monoaminergic system drugs, and it has been demonstrated that the molecular structure of tramadol is similar to that of the antidepressant venlafaxine.2 Recent animal studies demonstrated that tramadol pretreatment reinforces the antidepressant effects of ketamine, a sedative/hypnotic, anesthetic induction agent with antidepressant effects and increases the levels of brain-derived neurotrophic factor and tropomyosin-related kinase B.3,4 In clinical settings, tramadol has reportedly been effective in the treatment of obsessive-compulsive disorder and depression.5Y8 Excessive doses of tramadol or the combination of tramadol with monoaminergic antidepressants have been reported to be associated with serotonergic syndrome.7 Tramadol has been reported to trigger manic episodes in bipolar patients.8Y10 A patient with no previous psychiatric history, who had 2 manic episodes possibly associated with tramadol, is described here. www.psychopharmacology.com
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
111
