Hypothermie unter antipsychotischer Medikation

Zusammenfassung

Veränderungen der Körpertemperatur nach Applikation antipsychotisch wirksamer Substanzen werden im klinischen Alltag seit jeher beobachtet. Die Entwicklung von Fieber im Sinne einer unerwünschten Arzneimittelwirkung von antipsychotisch wirksamen Substanzen (isoliert vorliegend bzw. im Rahmen des malignen neuroleptischen Syndroms) ist jedem Medizinstudenten bekannt. Weitaus geringere Beachtung finden dagegen gegenläufige Störungen der Thermoregulation im Sinne einer Erniedrigung der Körpertemperatur nach Applikation von antipsychotisch wirksamen Substanzen. Dies verwundert umso mehr, da bereits vor der Entdeckung des antipsychotischen Effekts des ersten Neuroleptikums Chlorpromazin im Jahr 1952 dessen temperatursenkende Wirkung in der Anästhesiologie gut bekannt war und sogar therapeutischen Nutzen fand.

Hier stellen wir den Fall einer 93-jährigen Patientin mit demenziellem Syndrom vor, die unter einer psychopharmakologischen Polymedikation mit Risperidon, Doxepin und Buspiron eine Hypothermie von 29,5°C entwickelte. Eine Literaturübersicht zeigt, dass Antipsychotika bei individueller Disposition und in Kombination mit unabhängigen Risikofaktoren wie Umgebungstemperatur, somatischer Begleiterkrankung, endokrinen Störungen (z. B. Hypothyreose) oder organischer ZNS-Vorschädigung sowohl zu Hypo- wie auch zu Hyperthermie führen können. Ursächlich verantwortlich erscheint ein komplexes Zusammenspiel dopaminerger Regulationsmechanismen im ventralen Hypothalamus mit peripherer vasomotorischer Dysregulation.

Summary

Thermoregulatory dysfunction is a well-known side effect of central acting drugs. Particularly there is a high awareness that fever can develop in patients receiving antipsychotic medication. It may occur either unescorted or in the context of the malignant neuroleptic syndrome (NMS). However, in comparison to neuroleptics induced hyperthermia, a neuroleptics induced reduction of body temperature draws only minor attention. This is especially surprising as even before the discovery of the antipsychotic effect of the first neuroleptic drug (chlorpromazine) in the year 1952, anaesthesiologists have already tried to use its hypothermia-inducing effects for therapeutic reasons. Here we present the case of a 93-year-old lady with dementia developing a hypothermic episode of 29.5°C receiving a poly-psychopharmacological therapy consisting of risperidone, doxepin, and buspirone. A literature search illustrated that antipsychotic drugs may lead to both hypo- and hyperthermia, which is additionally based on individual predisposition and independent risk factors such as environmental temperature, somatic comorbidity, endocrinological dysfunction and structural brain damage. A complex interaction between dopaminergic regulatory mechanisms concerning the ventral hypothalamus, and peripheral vasomotoric dysregulation may play a vital pathophysiological role.

Schlüsselwörter

Hypothermie - Neuroleptika - Antipsychotika - Thermoregulation - Hypothalamus

Keywords

Hypothermia - antipsychotic medication - neuroleptics - thermoregulation - hypothalamus

• Literatur

• 1 Lopez-Munoz F, Alamo C, Cuenca E, Shen WW, Clervoy P, Rubio G. History of the discovery and clinical introduction of chlorpromazine. Ann Clin Psychiatry 2005; 17 (03) 113-35.
• 2 Delay J, Pichot P, Lemperiere T, Elissalde B, Peigne F. [A non-phenothiazine and non-reserpine major neuroleptic, haloperidol, in the treatment of psychoses]. Ann Med Psychol (Paris) 1960; 118 (01) 145-52.
• 3 Khaldi S, Kornreich C, Choubani Z, Gourevitch R. [Neuroleptic malignant syndrome and atypical antipsychotics: a brief review]. Encephale 2008; 34 (06) 618-24.
• 4 Young DM. Risk factors for hypothermia in psychiatric patients. Ann Clin Psychiatry 1996; 8 (02) 93-7.
• 5 Blass DM, Chuen M. Olanzapine-associated hypothermia. Psychosomatics 2004; 45 (02) 135-9.
• 6 Mehtonen OP, Aranko K, Malkonen L, Vapaatalo H. A survey of sudden death associated with the use of antipsychotic or antidepressant drugs: 49 cases in Finland. Acta Psychiatr Scand 1991; 84 (01) 58-64.
• 7 van Marum RJ, Wegewijs MA, Loonen AJ, Beers E. Hypothermia following antipsychotic drug use. Eur J Clin Pharmacol 2007; 63 (06) 627-31.
• 8 Harada H, Igarashi M, Sugae S, Okamoto K, Tsuji M, Nakajima T. A schizophrenic patient who developed extreme hypothermia after an increase in the dose of haloperidol: a case report. Jpn J Psychiatry Neurol 1994; 48 (03) 595-8.
• 9 Schwaninger M, Weisbrod M, Schwab S, Schroder M, Hacke W. Hypothermia induced by atypical neuroleptics. Clin Neuropharmacol 1998; 21 (06) 344-6.
• 10 Kreuzer P, Landgrebe M, Wittmann M, Hajak G, Schecklmann M, Poeppl TB. et al. [Hypothermia under olanzapine treatment : Clinical case series and review of current literature.]. Nervenarzt 2011 Jun 1. E-Pub.
• 11 Benkert O, Hippius H. Kompendium der Psychiatrischen Pharmakotherapie. Berlin: Springer 2015
• 12 Sessler DI. Thermoregulatory defense mechanisms. Crit Care Med 2009; 37 (Suppl. 07) S203-10.
• 13 Gillman PK. Neuroleptic malignant syndrome: mechanisms, interactions, and causality. Mov Disord 2010; 25 (12) 1780-90.
• 14 Kiyatkin EA. Brain hyperthermia as physiological and pathological phenomena. Brain Res Brain Res Rev 2005; 50 (01) 27-56.
• 15 Boulant JA. Role of the preoptic-anterior hypothalamus in thermoregulation and fever. Clin Infect Dis 2000; 31 (Suppl. 05) S157-61.
• 16 Chai CY, Lin MT. The enhancement of chlorpromazine-induced hypothermia by lesions in the anterior hypothalamus. Br J Pharmacol 1977; 61 (01) 77-82.
• 17 de la Cruz F. Hypothermia elicited by haloperidol in rats with hypothalamic lesions. Exp Neurol 1988; 99 (01) 234-8.
• 18 Dimicco JA, Zaretsky DV. The dorsomedial hypothalamus: a new player in thermoregulation. Am J Physiol Regul Integr Comp Physiol 2007; 292 (01) R47-63.
• 19 Barros RC, Branco LG, Carnio EC. Evidence for thermoregulation by dopamine D1 and D2 receptors in the anteroventral preoptic region during normoxia and hypoxia. Brain Res 2004; 1030 (02) 165-71.
• 20 Oerther S, Ahlenius S. Atypical antipsychotics and dopamine D(1) receptor agonism: an in vivo experimental study using core temperature measurements in the rat. J Pharmacol Exp Ther 2000; 292 (02) 731-6.
• 21 Maier U, Aigner JM, Klein HE. [Hypothermia caused by neuroleptics. 2 case reports and review of the literature]. Nervenarzt 1994; 65 (07) 488-91.
• 22 Eikenboom HC, Janssens AR, Rosekrans PC, Molendijk W. [Hypothermia during use of pipamper-one]. Ned Tijdschr Geneeskd 1997; 141 (06) 301-3.
• 23 van Marum RJ, Jansen S, Ponssen HH. [Antipsychotic medication as a cause of deep hypothermia]. Ned Tijdschr Geneeskd 2003; 147 (25) 1201-4.
• 24 Kreuzer P, Landgrebe M, Hajak G, Burger SJ, Langguth B. A case of severe hypothermia following single-dose administration of olanzapine: A case report. J Clin Pharmacol. 2011 Feb 22; E-Pub.
• 25 Kreuzer P, Landgrebe M, Wittmann M, Schecklmann M, Poeppl TB, Hajak G. et al. Hypothermia associated with antipsychotic drug use: A clinical case series and review of current literature. J Clin Pharmacol. 2011 Sep 28; E-Pub.
• 26 Lin MT, Wang HS, Wang Z, Chern YF. Haloperidol produces hypothermic effects in rats. Experientia 1979; 35 (11) 1469-70.
• 27 Sharma RP, Janicak PG, Bissette G, Nemeroff CB. CSF neurotensin concentrations and antipsychotic treatment in schizophrenia and schizoaffective disorder. Am J Psychiatry 1997; 154 (07) 1019-21.
• 28 Blessing E, Kader L, Arpandy R, Ootsuka Y, Blessing WW, Pantelis C. Atypical antipsychotics cause an acute increase in cutaneous hand blood flow in patients with schizophrenia and schizoaffective disorder. Aust NZJ Psychiatry 2011; 45 (08) 646-53.
• 29 Shiloh R, Weizman A, Epstein Y, Rosenberg SL, Valevski A, Dorfman-Etrog P. et al. Abnormal thermoregulation in drug-free male schizophrenia patients. Eur Neuropsychopharmacol 2001; 11 (04) 285-8.
• 30 Vandijck D, Decruyenaere JM, Blot SI. The value of sepsis definitions in daily ICU-practice. Acta Clin Belg 2006; 61 (05) 220-6.
• 31 Dilsaver SC. Effects of neuroleptics on body temperature. J Clin Psychiatry 1988; 49 (02) 78-9.
• 32 Loffler S, Danos P, Schillen TB, Klimke A. [Recurrent dysregulation of body temperature during antipsychotic pharmacotherapy]. Psychiatr Prax 2008; 35 (02) 91-3.