Skip to main content
Erschienen in: International Journal of Legal Medicine 6/2005

01.11.2005 | Original Article

Newer antidepressants: evaluation of fatal toxicity index and interaction with alcohol based on Finnish postmortem data

verfasst von: Anna Koski, Erkki Vuori, Ilkka Ojanperä

Erschienen in: International Journal of Legal Medicine | Ausgabe 6/2005

Einloggen, um Zugang zu erhalten

Abstract

Finnish postmortem toxicology data from 1995 to 2002 was analyzed to obtain improved estimates of fatal toxicity indices for the newer antidepressants and to evaluate their interaction with alcohol. Altogether 284 fatal poisonings were attributed to 12 different newer antidepressants. Venlafaxine, mianserin, moclobemide, and mirtazapine were responsible for significantly more deaths than expected from their sales. Their fatal toxicity indices were higher than those of selective serotonin reuptake inhibitors (SSRIs) but lower than those of tricyclic antidepressants. In fatal poisonings involving alcohol in combination with venlafaxine, mianserin, moclobemide, or mirtazapine, the median blood alcohol concentration (BAC) ranged from 2.35 to 2.7 mg/g, whereas in those involving alcohol in combination with citalopram or fluoxetine the median BAC was 2.9 and 3.4 mg/g, respectively. The BAC was significantly lower in venlafaxine-related deaths than in those involving fluoxetine or citalopram. We conclude that among the newer antidepressants differences are present both in toxicity and in interaction potential with alcohol. The SSRIs appear to present a low risk of fatal poisoning when taken alone or in combination with alcohol, whereas venlafaxine is associated with an elevated risk.
Literatur
1.
Zurück zum Zitat Anderson IM (2001) Meta-analytical studies on new antidepressants. Br Med Bull 57:161–178 Anderson IM (2001) Meta-analytical studies on new antidepressants. Br Med Bull 57:161–178
2.
Zurück zum Zitat Peretti S, Judge R, Hindmarch I (2000) Safety and tolerability considerations: tricyclic antidepressants vs. selective serotonin reuptake inhibitors. Acta Psychiatr Scand, Suppl 403:17–25 Peretti S, Judge R, Hindmarch I (2000) Safety and tolerability considerations: tricyclic antidepressants vs. selective serotonin reuptake inhibitors. Acta Psychiatr Scand, Suppl 403:17–25
3.
Zurück zum Zitat Nelson JC (1997) Safety and tolerability of the new antidepressants. J Clin Psychiatry 58:26–31 Nelson JC (1997) Safety and tolerability of the new antidepressants. J Clin Psychiatry 58:26–31
4.
Zurück zum Zitat Barbey JT, Roose SP (1998) SSRI safety in overdose. J Clin Psychiatry 59(Suppl 15):42–48 Barbey JT, Roose SP (1998) SSRI safety in overdose. J Clin Psychiatry 59(Suppl 15):42–48
5.
Zurück zum Zitat Henry JA, Alexander CA, Sener EK (1995) Relative mortality from overdose of antidepressants. Br Med J 310:221–224 Henry JA, Alexander CA, Sener EK (1995) Relative mortality from overdose of antidepressants. Br Med J 310:221–224
6.
Zurück zum Zitat Whyte IM, Dawson AH, Buckley NA (2003) Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM 96:369–374 Whyte IM, Dawson AH, Buckley NA (2003) Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM 96:369–374
7.
Zurück zum Zitat Ray WA, Meredith S, Thapa PB, Hall K, Murray KT (2004) Cyclic antidepressants and the risk of sudden cardiac death. Clin Pharmacol Ther 75:234–241 Ray WA, Meredith S, Thapa PB, Hall K, Murray KT (2004) Cyclic antidepressants and the risk of sudden cardiac death. Clin Pharmacol Ther 75:234–241
8.
Zurück zum Zitat Delgado PL (2004) How antidepressants help depression: mechanisms of action and clinical response. J Clin Psychiatry 65(Suppl 4):25–30 Delgado PL (2004) How antidepressants help depression: mechanisms of action and clinical response. J Clin Psychiatry 65(Suppl 4):25–30
9.
Zurück zum Zitat Elhwuegi AS (2004) Central monoamines and their role in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 28:435–451 Elhwuegi AS (2004) Central monoamines and their role in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 28:435–451
10.
Zurück zum Zitat Cheeta S, Schifano F, Oyefeso A, Webb L, Ghodse AH (2004) Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998–2000. Br J Psychiatry 184:41–47 Cheeta S, Schifano F, Oyefeso A, Webb L, Ghodse AH (2004) Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998–2000. Br J Psychiatry 184:41–47
11.
Zurück zum Zitat Frey R, Schreinzer D, Stimpfl T, Vycudilik W, Berzlanovich A, Kasper S (2000) Suicide by antidepressant intoxication identified at autopsy in Vienna from 1991–1997: the favourable consequences of the increasing use of SSRIs. Eur Neuropsychopharmacol 10:133–142 Frey R, Schreinzer D, Stimpfl T, Vycudilik W, Berzlanovich A, Kasper S (2000) Suicide by antidepressant intoxication identified at autopsy in Vienna from 1991–1997: the favourable consequences of the increasing use of SSRIs. Eur Neuropsychopharmacol 10:133–142
12.
Zurück zum Zitat Buckley NA, McManus PR (2002) Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. Br Med J 325:1332–1333 Buckley NA, McManus PR (2002) Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. Br Med J 325:1332–1333
13.
Zurück zum Zitat Cassidy S, Henry J (1987) Fatal toxicity of antidepressant drugs in overdose. Br Med J 295:1021–1024 Cassidy S, Henry J (1987) Fatal toxicity of antidepressant drugs in overdose. Br Med J 295:1021–1024
14.
Zurück zum Zitat Öhberg A, Vuori E, Klaukka T, Lönnqvist J (1998) Antidepressants and suicide mortality. J Affect Disord 50:225–233 Öhberg A, Vuori E, Klaukka T, Lönnqvist J (1998) Antidepressants and suicide mortality. J Affect Disord 50:225–233
15.
Zurück zum Zitat Koski A, Ojanperä I, Vuori E (2003) Interaction of alcohol and drugs in fatal poisonings. Human Exp Toxicol 22:281–287 Koski A, Ojanperä I, Vuori E (2003) Interaction of alcohol and drugs in fatal poisonings. Human Exp Toxicol 22:281–287
16.
Zurück zum Zitat Jönsson A, Holmgren P, Ahlner J (2004) Fatal intoxications in a Swedish forensic autopsy material during 1992–2002. Forensic Sci Int 143:53–59 Jönsson A, Holmgren P, Ahlner J (2004) Fatal intoxications in a Swedish forensic autopsy material during 1992–2002. Forensic Sci Int 143:53–59
17.
Zurück zum Zitat Vuori E, Ojanperä I, Rasanen I (1997) Fatal poisonings in Finland during 1993–1995 based on forensic toxicological investigations. Suom Laakaril 54:421–425 Vuori E, Ojanperä I, Rasanen I (1997) Fatal poisonings in Finland during 1993–1995 based on forensic toxicological investigations. Suom Laakaril 54:421–425
18.
Zurück zum Zitat Vuori E, Ojanperä I, Ojansivu RL, Nieminen R (1999) Drug, poison, drug of abuse, or alcohol again? Duodecim 115:1531–1535 Vuori E, Ojanperä I, Ojansivu RL, Nieminen R (1999) Drug, poison, drug of abuse, or alcohol again? Duodecim 115:1531–1535
19.
Zurück zum Zitat Vuori E, Ojanperä I, Nokua J, Ojansivu RL (2001) Fatal poisonings in Finland during 1998 and 1999 based on forensic toxicological investigations. Suom Laakaril 56:2521–2525 Vuori E, Ojanperä I, Nokua J, Ojansivu RL (2001) Fatal poisonings in Finland during 1998 and 1999 based on forensic toxicological investigations. Suom Laakaril 56:2521–2525
20.
Zurück zum Zitat Vuori E, Ojanperä I, Nokua J, Ojansivu RL (2003) Fatal poisonings in Finland during 2000 and 2001 based on forensic toxicological investigations. Suom Laakaril 58:3403–3407 Vuori E, Ojanperä I, Nokua J, Ojansivu RL (2003) Fatal poisonings in Finland during 2000 and 2001 based on forensic toxicological investigations. Suom Laakaril 58:3403–3407
21.
Zurück zum Zitat Jones AW, Schuberth J (1989) Computer-aided headspace gas chromatography applied to blood-alcohol analysis: importance of online process control. J Forensic Sci 34:1116–1127 Jones AW, Schuberth J (1989) Computer-aided headspace gas chromatography applied to blood-alcohol analysis: importance of online process control. J Forensic Sci 34:1116–1127
22.
Zurück zum Zitat Rasanen I, Ojanperä I, Vuori E (2000) Quantitative screening for benzodiazepines in blood by dual-column gas chromatography and comparison of the results with urine immunoassay. J Anal Toxicol 24:46–53 Rasanen I, Ojanperä I, Vuori E (2000) Quantitative screening for benzodiazepines in blood by dual-column gas chromatography and comparison of the results with urine immunoassay. J Anal Toxicol 24:46–53
23.
Zurück zum Zitat Koski A, Ojanperä I, Vuori E (2002) Alcohol and benzodiazepines in fatal poisonings. Alcohol Clin Exp Res 26:956–959 Koski A, Ojanperä I, Vuori E (2002) Alcohol and benzodiazepines in fatal poisonings. Alcohol Clin Exp Res 26:956–959
24.
Zurück zum Zitat Worm K, Dragsholt C, Simonsen K, Kringsholm B (1998) Citalopram concentrations in samples from autopsies and living persons. Int J Leg Med 111:188–190 Worm K, Dragsholt C, Simonsen K, Kringsholm B (1998) Citalopram concentrations in samples from autopsies and living persons. Int J Leg Med 111:188–190
25.
Zurück zum Zitat Kelly CA, Dhaun N, Laing WJ, Strachan FE, Good AM, Bateman DN (2004) Comparative toxicity of citalopram and the newer antidepressants after overdose. J Toxicol Clin Toxicol 42:67–71 Kelly CA, Dhaun N, Laing WJ, Strachan FE, Good AM, Bateman DN (2004) Comparative toxicity of citalopram and the newer antidepressants after overdose. J Toxicol Clin Toxicol 42:67–71
26.
Zurück zum Zitat Egberts AC, Lenderink AW, de Koning FH, Leufkens HG (1997) Channeling of three newly introduced antidepressants to patients not responding satisfactorily to previous treatment. J Clin Psychopharmacol 17:149–155 Egberts AC, Lenderink AW, de Koning FH, Leufkens HG (1997) Channeling of three newly introduced antidepressants to patients not responding satisfactorily to previous treatment. J Clin Psychopharmacol 17:149–155
27.
Zurück zum Zitat Heerdink ER, Hugenholtz GW, Meijer WE, Egberts AC (2003) Channelling new antidepressants to problem patients may be factor in fatal toxicity. Br Med J 325:600 Heerdink ER, Hugenholtz GW, Meijer WE, Egberts AC (2003) Channelling new antidepressants to problem patients may be factor in fatal toxicity. Br Med J 325:600
28.
Zurück zum Zitat Preskorn SH (1997) Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 32(Suppl 1):1–21 Preskorn SH (1997) Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 32(Suppl 1):1–21
29.
Zurück zum Zitat Bateman DN, Chick J, Good AM, Kelly CA, Masterton G (2004) Are selective serotonin re-uptake inhibitors associated with an increased risk of self-harm by antidepressant overdose? Eur J Clin Pharmacol 60:221–224 Bateman DN, Chick J, Good AM, Kelly CA, Masterton G (2004) Are selective serotonin re-uptake inhibitors associated with an increased risk of self-harm by antidepressant overdose? Eur J Clin Pharmacol 60:221–224
30.
Zurück zum Zitat Bentur Y, Raikhlin-Eisenkraft B, Lavee M (2004) Toxicological features of deliberate self-poisonings. Human Exp Toxicol 23:331–337 Bentur Y, Raikhlin-Eisenkraft B, Lavee M (2004) Toxicological features of deliberate self-poisonings. Human Exp Toxicol 23:331–337
Metadaten
Titel
Newer antidepressants: evaluation of fatal toxicity index and interaction with alcohol based on Finnish postmortem data
verfasst von
Anna Koski
Erkki Vuori
Ilkka Ojanperä
Publikationsdatum
01.11.2005
Erschienen in
International Journal of Legal Medicine / Ausgabe 6/2005
Print ISSN: 0937-9827
Elektronische ISSN: 1437-1596
DOI
https://doi.org/10.1007/s00414-005-0528-x

Weitere Artikel der Ausgabe 6/2005

International Journal of Legal Medicine 6/2005 Zur Ausgabe

Neu im Fachgebiet Rechtsmedizin

Molekularpathologische Untersuchungen im Wandel der Zeit

Open Access Biomarker Leitthema

Um auch an kleinen Gewebeproben zuverlässige und reproduzierbare Ergebnisse zu gewährleisten ist eine strenge Qualitätskontrolle in jedem Schritt des Arbeitsablaufs erforderlich. Eine nicht ordnungsgemäße Prüfung oder Behandlung des …

Vergleichende Pathologie in der onkologischen Forschung

Pathologie Leitthema

Die vergleichende experimentelle Pathologie („comparative experimental pathology“) ist ein Fachbereich an der Schnittstelle von Human- und Veterinärmedizin. Sie widmet sich der vergleichenden Erforschung von Gemeinsamkeiten und Unterschieden von …

Gastrointestinale Stromatumoren

Open Access GIST CME-Artikel

Gastrointestinale Stromatumoren (GIST) stellen seit über 20 Jahren ein Paradigma für die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren dar. Eine elementare Voraussetzung für eine mögliche neoadjuvante oder adjuvante Behandlung bei …

Personalisierte Medizin in der Onkologie

Aufgrund des erheblichen technologischen Fortschritts in der molekularen und genetischen Diagnostik sowie zunehmender Erkenntnisse über die molekulare Pathogenese von Krankheiten hat in den letzten zwei Jahrzehnten ein grundlegender …