Antidepressant drugs appear to enhance cocaine-induced toxicity.

Abstract

It has been shown that cocaine-induced convulsions and lethality appear to be mediated by serotonin and dopamine neurotransmission, respectively. However, many antidepressants considered for treatment of cocaine addiction target these monoamine systems and may thus amplify these toxic effects during relapse. In this study, the authors assessed whether pretreatment with antidepressants influences cocaine-induced toxicity in mice as well as the potency of these medications at cocaine-binding sites previously shown to be associated with cocaine toxicity. Overall, selective serotonin reuptake inhibitors (SSRIs) facilitated cocaine-induced convulsions but not lethality. Dopamine uptake inhibition facilitated cocaine-induced lethality, but not convulsion. The SSRI sertraline enhanced neither convulsions nor lethality and may be unique due to its high affinity for sigma receptors. These results have important implications for safe and effective addiction treatments.

Thalamocortical functional connectivity and behavioral disruptions in neonates with prenatal cocaine exposure

“…Therefore, pending further validation, potential interplay between cocaine-affected serotonin signaling and that from SSRIs may underlie the observed interaction. Consistent with our findings, antidepressant drugs have been shown to enhance cocaine-induced toxicity (Macedo et al, 2004; O'Dell et al, 2000) and the manipulation of the serotonin system has been shown to alter, and often enhance, the behavioral effects of cocaine in animal models (Muller et al, 2003; Walsh and Cunningham, 1997). Given the common practice of SSRI prescription for depressed pregnant women with drug dependence (Yamamoto et al, 2014), the discovered interaction may have significant clinical implications.…”

Mechanisms of Acute Cocaine Toxicity

“…In a mouse model, pretreatment with fluoxetine, a potent inhibitor of the SERT, decreased the latency of cocaine-induced convulsions by 53% and increased the occurrence of seizures in a dose-dependent manner [58]. Similar effects have been reported for other SERT inhibitors [59]. Serotonin receptor antagonists (5HT2 and 5HT3) decrease the incidence of seizures [60].…”

Preclinical antiepileptic actions of selective serotonin reuptake inhibitors—Implications for clinical trial design

“…Cocaine may exert its ictogenic effects through inhibition of serotonin reuptake (Ritz & George, 1993). Consistent with a proconvulsant effect of 5-HT in this model, the SSRIs fluoxetine, citalopram, and paroxetine facilitated convulsions, although sertraline did not have this effect (O'Dell et al, 2000). In another study, cocaineinduced seizures were shown to be aggravated by fluoxetine at 20-40 mg/kg, but inhibited by lower doses (10 mg/kg) (MacÞdo et al, 2004).…”