Writing in the British Journal of Psychiatry, English researchers found that “patients with mental illness showed an overall increase in risk of death of 4.9% (95% CI 2.0-7.8) per 1 degree increase in temperature above the 93rd percentile of the annual temperature distribution. (Editor’s note: research on the role of psychotropics in temperature dysregulation is presented below.)
Hot weather increases death risk in psychosis patients
Martin-Latry, K., M. P. Goumy, et al. (2007). “Psychotropic drugs use and risk of heat-related hospitalisation.” Eur Psychiatry 22(6): 335-338.
OBJECTIVE: To assess if use of psychotropic drugs is associated with an increased risk of admission for heat-related pathologies during a heat wave period. METHOD: We conducted a matched case-control study. Cases were defined as subjects admitted to an emergency department for heat-related pathology (hyperthermia or heat stroke) over the August 2003 heat wave. Controls were defined as subjects living in the same area but not hospitalised over the same period and who had at least one prescription form submitted for refunding by the social security insurance in July 2003. Multivariate analyses were used to identify psychotropic drugs independently associated with hospital referral during the heat wave period. RESULTS: Out of the 1405 patients admitted to the emergency department, 56 (4%) presented with heat-related pathology. The mean age of cases was 83 years. Multivariate analyses showed that cases were more likely than controls to be treated with anticholinergic drugs (OR 6.0, 95% CI 1.8-19.6), antipsychotics (OR 4.6, 95% CI 1.9-11.2) or anxiolytics (OR 2.4, 95% CI 1.3-4.4). CONCLUSION: In special risk situations such as heat waves, the risk/benefit ratio of psychotropic drugs which could interfere with body temperature regulation has to be carefully assessed, particularly in the elderly.
Kwok, J. S. and T. Y. Chan (2005). “Recurrent heat-related illnesses during antipsychotic treatment.” Ann Pharmacother 39(11): 1940-1942.
OBJECTIVE: To report a case of recurrent heat-related illnesses associated with the use of benzhexol, chlorpromazine, and zuclopenthixol decanoate. CASE SUMMARY: During the summer of 2004, a 48-year-old man with a history of diabetes mellitus and schizophrenia was twice admitted to the hospital because of heat-related illnesses. On both occasions, he had been working under the sun in an open car park. His medications included benzhexol 2 mg twice daily, chlorpromazine 650 mg at bedtime, and zuclopenthixol decanoate intramuscular injection 600 mg every 4 weeks. In the first admission, the clinical diagnosis was heat stroke. He was discharged home on day 14, with precautionary advice against heat stroke. In the second admission, the clinical diagnosis was heat exhaustion. He was discharged home on day 4 and reminded of the precautions against heat stroke. An objective causality assessment revealed that the adverse event was possibly drug related in the first admission and probably drug related in the second admission. DISCUSSION: Several drugs can impair thermoregulation during exercise or under conditions of environmental heat stress. Anticholinergic drugs or drugs with anticholinergic effects can inhibit sweating and reduce heat elimination. Neuroleptics (antipsychotics), such as phenothiazines, have combined anticholinergic and central thermoregulatory effects. The set point of the temperature regulation center can be elevated by the antidopaminergic effect of antipsychotics, such as phenothiazines and thioxanthenes. CONCLUSIONS: Certain drugs may induce or worsen heat-related illnesses. During a heat wave, special attention should be given to those most at risk, and the importance of preventive measures should be emphasized.
Fick, L. G., A. Fuller, et al. (2005). “Thermoregulatory, motor, behavioural, and nociceptive responses of rats to 3 long-acting neuroleptics.” Can J Physiol Pharmacol 83(6): 517-527.
We investigated physiological effects of intramuscular injections of the following 3 long-acting neuroleptics commonly used in wildlife management: haloperidol (0.05, 0.1, and 0.5 mg/kg body mass), zuclopenthixol acetate (0.5, 1, and 5 mg/kg), and perphenazine enanthate (1, 3, and 10 mg/kg), in a rat model. Body temperature and cage activity were measured by intra-abdominal telemeters. Nociceptive responses were assessed by challenges to noxious heat and pressure. Haloperidol (0.5 mg/kg) produced a significant nocturnal hypothermia (p < 0.05) and decreased nighttime cage activity and food intake. Zuclopenthixol (5 mg/kg) significantly decreased nighttime body temperature and cage activity and, at 1 mg/kg and 5 mg/kg, significantly decreased food intake 5-17 h after injection (p < 0.05). Perphenazine (10 mg/kg) significantly decreased nighttime body temperature and cage activity and, at all doses, significantly decreased food intake 5-17 h after injection (p < 0.05). Significant analgesic activity was evident in rats given 5 mg/kg zuclopenthixol up to 40 h after injection, and 10 mg/kg perphenazine from 48 to 96 h after injection (p < 0.0001). Zuclopenthixol (5 mg/kg) and perphenazine (10 mg/kg) had significant antihyperalgesic activities at 16 h postinjection and 24-48 h postinjection, respectively (p < 0.0001). Haloperidol had no significant antinociceptive activity at doses tested. Motor function was impaired in rats given 0.5 mg/kg haloperidol, 5 mg/kg zuclopenthixol and 10 mg/kg perphenazine. Effects of long-acting neuroleptics on body temperature, feeding, and activity were short-lasted and should not preclude their use in wildlife. Antinociceptive actions were longer-lasting, but were nonspecific, and we recommend additional analgesics for painful procedures during wildlife management.
Hadad, E., A. A. Weinbroum, et al. (2003). “Drug-induced hyperthermia and muscle rigidity: a practical approach.” Eur J Emerg Med 10(2): 149-154.
Body thermoregulation can be violently offset by drugs capable of altering the balance between heat production and dissipation. Such events may rapidly become fatal. The drugs that are involved in the eruption of such syndromes include inhalation anaesthetics, sympathomimetic agents, serotonin antagonists, antipsychotic agents and compounds that exhibit anticholinergic properties. The resultant hyperthermia is frequently accompanied by an intense skeletal muscle hypermetabolic reaction that leads to rapidly evolving rigidity, extensive rhabdomyolysis and hyperkalemia. The differential diagnosis should, however, rule out non-drug-induced causes, such as lethal catatonia, central nervous system infection or tetanus, strychnine poisoning, thyrotoxic storm and pheochromocytoma. Prompt life-saving procedures include aggressive body temperature reduction. Patients with a suspected drug (or non-drug) hypermetabolic reaction should be admitted into an intensive care area for close monitoring and system-oriented supportive treatment. We present six conditions, in decreasing order of gravity and potential lethality, in which hyperthermia plays an essential role, and suggest a clinical approach in such conditions.
(2002). “As temperatures soar: antipsychotics increase risk for heat-related conditions.” J Psychosoc Nurs Ment Health Serv 40(8): 12.
Hermesh, H., R. Shiloh, et al. (2000). “Heat intolerance in patients with chronic schizophrenia maintained with antipsychotic drugs.” Am J Psychiatry 157(8): 1327-1329.
OBJECTIVE: Schizophrenia may be associated with hyperthermic syndromes such as febrile catatonia, neuroleptic malignant syndrome, and heatstroke. The authors hypothesized that an exercise-heat tolerance test would disclose abnormal thermoregulation in schizophrenic patients. METHOD: Seven male schizophrenic outpatients in remission maintained on depot antipsychotic treatment and eight healthy comparison subjects completed a heat tolerance test that consisted of two 50-minute bouts of walking a motor-driven treadmill at 40xC (relative humidity=40%). RESULTS: A significantly higher rise in rectal and skin temperatures was observed in the patient group. No differences in heart rate, blood pressure, or perspiration were detected. CONCLUSIONS: Schizophrenic patients maintained on antipsychotic drugs exhibit impaired heat tolerance. Possible explanations are a reduced ability to convey heat from the body’s core to the periphery with or without excessive heat production. The hyperthermic response to the heat tolerance test may reflect a dysfunction associated with schizophrenia, a neuroleptic-induced side effect, or both.
Epstein, Y., D. Albukrek, et al. (1997). “Heat intolerance induced by antidepressants.” Ann N Y Acad Sci 813: 553-558.
A case in which prescription medications induced heat intolerance which led to heat stroke is presented. A subject who suffered from depression and was treated with fluoxetine HCL (prozac) and lithium carbonate was engaged in mild intermittent work for 4 hours under hot/dry climatic conditions (Ta = 37 degrees C, rh = 15%). The subject lost consciousness, was hyperthermic and suffered from disseminated intravascular coagulation. A year later residual cerebellar symptoms were still evident and severe atrophy of the cerebellar tissue was demonstrated in a CT scan. It is suggested that drug-induced heat intolerance was the predisposing factor that reduced the patient ability to sustain exercise-heat stress, and under the favorable environmental circumstances led to excessive heat accumulation which ultimately caused heat stroke. This is the first description, to our knowledge, of heat intolerance of a patient treated by a combination of fluoxetine and lithium carbonate.
Tanii, H., N. Taniguchi, et al. (1996). “Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level.” Brain Res 743(1-2): 263-270.
The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.
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