- Email: [email protected]
Suicide attempts with mirtazapine overdose without complications
CASE REPORTS Suicide Attempts with Mirtazapine Overdose without Complications Ru¨diger Holzbach, Holger Jahn, Frank-Gerald Pajonk, and Christiane Ma¨hne Background: One important aim of pharmacotherapy in depressed patients is the prevention of suicide attempts. Therefore, the medication given should be efficient and safe in overdose. Results: We saw two patients after they had overdosed with mirtazapine because of suicidal intention. Both patients had taken 30 and 50 times a normal daily dose and achieved a full recovery without any complications or harm. Conclusions: Mirtazapine seems to be a safe compound in overdose. Therefore, it is an important therapeutic agent in depressed and suicidal patients. Key words: Suicide attempt, overdose, depression, mirtazapine
Introduction In the management of patients with depressive disorders and suicidal ideation, the choice of antidepressants should be done with care to prevent suicide attempts or completed suicides. Classical tricyclic antidepressants (TCA) are often chosen by physicians to treat this group of patients, primarily because of their strong efficacy and their favorable clinical profile combining sedative and anxiolytic properties. One serious disadvantage of TCA is their cardiotoxicity in overdose. Whereas serotonin reuptake inhibitors (SSRI) in overdose rarely cause death (Kasper et al 1996), many psychiatrists hesitate to prescribe SSRI in agitated suicidal patients unless they are hospitalized or comedicated with benzodiazepines (Benkert and Hippius 1996). Mirtazapin is a new antidepressant with antidepressive efficacy equivalent to TCA (Davis and Wilde 1996). First cases of suicide attempts with the compound were without serious effects (Hoes and Zeijpveld 1996; Gerritsen 1997). Here we report on two additional cases.
From the Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany. Address reprint requests to Ru¨diger Holzbach, Department of Psychiatry and Psychotherapy, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. Received September 10, 1997; revised January 20, 1998; accepted February 16, 1998.
© 1998 Society of Biological Psychiatry
Case 1 A female patient, 44 years of age, was referred to the clinic with a diagnosis of a major depressive disorder (recurrent, severe, without psychotic features ICD-10: F33.2; DSM-IV: 296.33). The patient had a history of four suicide attempts by drug overdoses in the past. On admission the patient presented with low mood and continuous and overt suicidality. Treatment with mirtazapine was started at 15 mg/day increasing to 30 mg/day. The patient remitted within 3 weeks. Four weeks after discharge her condition worsened, and she attempted suicide by taking 900 mg mirtazapine in combination with an unknown dose of amitriptyline and 0.5 L of wine. Eighteen hours later the patient was hospitalized, presenting with fluctuating somnolence and severely depressed mood. Neurological examination and vital signs including blood pressure and electrocardiogram were normal. The plasma level of mirtazapine upon admission measured by high-performance liquid chromatography was 2300 ng/ mL, decreased to 1370 ng/mL after 26 hours, and to 1060 ng/mL 40 hours after intake (fourth day 80 ng/mL, ninth day 25 ng/mL). The patient recovered without complications.
Case 2 Another female patient, 51 years of age, was admitted to our clinic as an emergency case (major depressive disorder, single episode, severe without psychotic features ICD-10: F32.2; DSM-IV: 296.23). On admission, the mood of the patient was dysphoric, showing despair and hopelessness facing the chronic drug problem of her husband. She was treated with mirtazapine 30 mg/day. Seven weeks after admission the patient was discharged in a stabilized condition. At home she stopped all medication, and her condition worsened rapidly. Three weeks later she attempted suicide by taking 1500 mg of mirtazapine and 1 L of wine. She was admitted to a medical ward, presenting with somnolence, minor sinus tachycardia, and mild leukocytosis, but in a stable condition. Gastric lavage was performed on admission. Twenty hours after drug intake the plasma concentration of mirtazapine was 480 ng/mL. This patient recovered without any complications as well as the first patient. 0006-3223/98/$19.00 PII S0006-3223(98)00081-X
926
R. Holzbach et al
BIOL PSYCHIATRY 1998;44:925–926
Discussion
References
Both cases show that even after intake of high doses of mirtazapine no arrhythmias, respiratory depression, delirium, or epileptic seizures occurred. The respective plasma concentrations at admission were 100 –500 times higher than levels obtained with a single 15-mg dose (4.2 6 1.5 ng/mL; Voortman and Paanakker 1995). The respective increase in peak concentrations were 460 and 915 times that level. Repeated dosing (15–75 mg/day) yielded plasma levels from 0.49 6 0.21 ng/mL per mg dosage to 2.68 6 0.80 ng/mL per mg dosage, which means that with a conventional dosing regime (30 – 60 mg/day) plasma levels are regularly 30 – 80 ng/mL (Timmer et al 1995). The average lethal dose of tricyclic antidepressants is estimated at approximately 30 mg/kg (Fritze 1993), equivalent to 15 times the therapeutic dose. The 2 patients reported here had taken 30 and 50 times a normal daily dose, respectively, which is in line with the measured plasma levels, and recovered fully from their intoxications. Since mirtazapine combines a wide therapeutic range and good antidepressive efficacy with anxiolytic, mild sedative, and sleep-improving properties with considerable few other side effects, it seems particularly suitable in the management of suicidal patients.
Benkert O, Hippius H (1996): Antidepressiva. In: Benkert O, Hippius H, editors. Psychiatrische Pharmakotherapie. Berlin: Springer Verlag, pp 11–56. Davis R, Wilde MI (1996): Mirtazapine: A review of its pharmacology and therapeutic potential in the management of major depression. CNS Drugs 5:389 – 407. Fritze J (1993): Unerwu¨nschte Begleitwirkungen der Antidepressiva und ihre Behandlung. In: Mo¨ller HJ, editor. Therapie psychiatrischer Erkrankungen. Stuttgart: Enke, pp 287–301. Gerritsen AW (1997): Safety in overdose of mirtazepine: A case report. J Clin Psychiatry 58:271. Hoes MJAJM, Zeijpveld JHB (1996): First report of mirtazapine overdose. Int Clin Psychopharmacol 2:147. Kasper S, Schindler S, Neumeister A (1996): Risk of suicide in depression and its implication for psychopharmacological treatment. Int Clin Psychopharmacol 11:71–79. Timmer CJ, Lohmann AAM, Mink CPA (1995): Pharmacokinetic dose-proportionality study at steady state of mirtazapine from Remeront tablets. Hum Psychopharmacol 10:97–106. Voortman G, Paanakker JE (1995): Bioavailability of mirtazapine from Remeront tablets after single and multiple oral dosing. Hum Psychopharmacol 10:83–96.
Introduction In the management of patients with depressive disorders and suicidal ideation, the choice of antidepressants should be done with care to prevent suicide attempts or completed suicides. Classical tricyclic antidepressants (TCA) are often chosen by physicians to treat this group of patients, primarily because of their strong efficacy and their favorable clinical profile combining sedative and anxiolytic properties. One serious disadvantage of TCA is their cardiotoxicity in overdose. Whereas serotonin reuptake inhibitors (SSRI) in overdose rarely cause death (Kasper et al 1996), many psychiatrists hesitate to prescribe SSRI in agitated suicidal patients unless they are hospitalized or comedicated with benzodiazepines (Benkert and Hippius 1996). Mirtazapin is a new antidepressant with antidepressive efficacy equivalent to TCA (Davis and Wilde 1996). First cases of suicide attempts with the compound were without serious effects (Hoes and Zeijpveld 1996; Gerritsen 1997). Here we report on two additional cases.
From the Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany. Address reprint requests to Ru¨diger Holzbach, Department of Psychiatry and Psychotherapy, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. Received September 10, 1997; revised January 20, 1998; accepted February 16, 1998.
© 1998 Society of Biological Psychiatry
Case 1 A female patient, 44 years of age, was referred to the clinic with a diagnosis of a major depressive disorder (recurrent, severe, without psychotic features ICD-10: F33.2; DSM-IV: 296.33). The patient had a history of four suicide attempts by drug overdoses in the past. On admission the patient presented with low mood and continuous and overt suicidality. Treatment with mirtazapine was started at 15 mg/day increasing to 30 mg/day. The patient remitted within 3 weeks. Four weeks after discharge her condition worsened, and she attempted suicide by taking 900 mg mirtazapine in combination with an unknown dose of amitriptyline and 0.5 L of wine. Eighteen hours later the patient was hospitalized, presenting with fluctuating somnolence and severely depressed mood. Neurological examination and vital signs including blood pressure and electrocardiogram were normal. The plasma level of mirtazapine upon admission measured by high-performance liquid chromatography was 2300 ng/ mL, decreased to 1370 ng/mL after 26 hours, and to 1060 ng/mL 40 hours after intake (fourth day 80 ng/mL, ninth day 25 ng/mL). The patient recovered without complications.
Case 2 Another female patient, 51 years of age, was admitted to our clinic as an emergency case (major depressive disorder, single episode, severe without psychotic features ICD-10: F32.2; DSM-IV: 296.23). On admission, the mood of the patient was dysphoric, showing despair and hopelessness facing the chronic drug problem of her husband. She was treated with mirtazapine 30 mg/day. Seven weeks after admission the patient was discharged in a stabilized condition. At home she stopped all medication, and her condition worsened rapidly. Three weeks later she attempted suicide by taking 1500 mg of mirtazapine and 1 L of wine. She was admitted to a medical ward, presenting with somnolence, minor sinus tachycardia, and mild leukocytosis, but in a stable condition. Gastric lavage was performed on admission. Twenty hours after drug intake the plasma concentration of mirtazapine was 480 ng/mL. This patient recovered without any complications as well as the first patient. 0006-3223/98/$19.00 PII S0006-3223(98)00081-X
926
R. Holzbach et al
BIOL PSYCHIATRY 1998;44:925–926
Discussion
References
Both cases show that even after intake of high doses of mirtazapine no arrhythmias, respiratory depression, delirium, or epileptic seizures occurred. The respective plasma concentrations at admission were 100 –500 times higher than levels obtained with a single 15-mg dose (4.2 6 1.5 ng/mL; Voortman and Paanakker 1995). The respective increase in peak concentrations were 460 and 915 times that level. Repeated dosing (15–75 mg/day) yielded plasma levels from 0.49 6 0.21 ng/mL per mg dosage to 2.68 6 0.80 ng/mL per mg dosage, which means that with a conventional dosing regime (30 – 60 mg/day) plasma levels are regularly 30 – 80 ng/mL (Timmer et al 1995). The average lethal dose of tricyclic antidepressants is estimated at approximately 30 mg/kg (Fritze 1993), equivalent to 15 times the therapeutic dose. The 2 patients reported here had taken 30 and 50 times a normal daily dose, respectively, which is in line with the measured plasma levels, and recovered fully from their intoxications. Since mirtazapine combines a wide therapeutic range and good antidepressive efficacy with anxiolytic, mild sedative, and sleep-improving properties with considerable few other side effects, it seems particularly suitable in the management of suicidal patients.
Benkert O, Hippius H (1996): Antidepressiva. In: Benkert O, Hippius H, editors. Psychiatrische Pharmakotherapie. Berlin: Springer Verlag, pp 11–56. Davis R, Wilde MI (1996): Mirtazapine: A review of its pharmacology and therapeutic potential in the management of major depression. CNS Drugs 5:389 – 407. Fritze J (1993): Unerwu¨nschte Begleitwirkungen der Antidepressiva und ihre Behandlung. In: Mo¨ller HJ, editor. Therapie psychiatrischer Erkrankungen. Stuttgart: Enke, pp 287–301. Gerritsen AW (1997): Safety in overdose of mirtazepine: A case report. J Clin Psychiatry 58:271. Hoes MJAJM, Zeijpveld JHB (1996): First report of mirtazapine overdose. Int Clin Psychopharmacol 2:147. Kasper S, Schindler S, Neumeister A (1996): Risk of suicide in depression and its implication for psychopharmacological treatment. Int Clin Psychopharmacol 11:71–79. Timmer CJ, Lohmann AAM, Mink CPA (1995): Pharmacokinetic dose-proportionality study at steady state of mirtazapine from Remeront tablets. Hum Psychopharmacol 10:97–106. Voortman G, Paanakker JE (1995): Bioavailability of mirtazapine from Remeront tablets after single and multiple oral dosing. Hum Psychopharmacol 10:83–96.