Benzodiazepines and antipsychotic medications for treatment of acute cocaine toxicity in animal models – A systematic review and meta-analysis

Abstract

<jats:p> There are no controlled human studies to determine the efficacy of benzodiazepines or antipsychotic medications for prevention or treatment of acute cocaine toxicity. The only available controlled data are from animal models and these studies have reported inconsistent benefits. The objective of this study was to quantify the reported efficacy of benzodiazepines and antipsychotic medication for the prevention of mortality due to cocaine poisoning. We conducted a systematic review to identify English language articles describing experiments that compared a benzodiazepine or antipsychotic medication to placebo for the prevention of acute cocaine toxicity in an animal model. We then used these articles in a meta-analysis with a random-effects model to quantify the absolute risk reduction observed in these experiments. We found 10 articles evaluating antipsychotic medications and 15 articles evaluating benzodiazepines. Antipsychotic medications reduced the risk of death by 27% (95% CI, 15.2%–38.7%) compared to placebo and benzodiazepines reduced the risk of death by 52% (42.8%–60.7%) compared to placebo. Both treatments showed evidence of a dose-response effect, and no experiment found a statistically significant increase in risk of death. We conclude that both benzodiazepines and antipsychotic medications are effective for the prevention of lethality from cocaine toxicity in animal models. </jats:p>

Experimental Treatments for Cocaine Toxicity: A Difficult Transition to the Bedside

“…Success using short-onset benzodiazepines such as midazolam or diazepam has been a cornerstone of the treatment of acute cocaine toxicity since the 1980s. Large human trials assessing their efficacy are lacking, but recent meta-analysis data demonstrate a 51.7% improvement in survival in cocaine-poisoned animals treated with benzodiazepines compared with animals receiving placebo (Heard et al, 2011). In humans, a beneficial effect of benzodiazepine treatment is best demonstrated for patients with cocainerelated chest pain.…”

“…The use of atypical antipsychotics in cocaine toxicity exploits their mechanisms as dopamine, serotonin, and muscarinic inhibitors. Animal studies show antipsychotics as a class increase survival by 27% over placebo (Heard et al, 2011). Olanzapine, specifically, is an antagonist at the dopamine D 1 , D 2 , muscarinic, and serotonin 5HT 2A receptors.…”

Beim Zahnarzt

“…Aufgrund von Herzrasen, Schwäche und Koordinationsstörungen war sie jedoch im Treppenhaus "steckengeblieben" und habe nur noch laut um Hilfe gerufen. überlegen, obgleich letztere im Tierversuch auch keine Verschlechterung bewirkt hatten [3]. Hochgradig agitierte Patienten weisen oftmals auch exzessiv erhöhten Blutdruck und erhöhte Herzfrequenzen auf.…”

Implementation of systematic reviews in EFSA scientific outputs workflow

“…One important area where the number of systematic reviews has increased is animal-based biomedical research (Macleod and Sandercock, 2005;Macleod and van der Worp, 2010;Macleod et al, 2004;O'Collins et al, 2006;Perel et al, 2007;Sena et al, 2010;. This increase is relevant to environmental and chemical risk assessment, which frequently uses animal-based studies as the only evidence base (Heard et al, 2011;van der Zande et al, 2011).…”

“…This increase is relevant to environmental and chemical risk assessment, which frequently uses animal-based studies as the only evidence base (Heard et al, 2011;van der Zande et al, 2011).…”