Intrathecal Injection of Amitriptyline and Doxepin for Spinal Anesthesia in Animal Studies

I read with a great interest the recent article by Alebouyeh et al. about intrathecal administration of amitriptyline and doxepin to induce spinal blockade and comparison of their effects with those of bupivacaine (1). Alebouyeh et al. reported that intrathecal injection of various drugs with different mechanisms is an intriguing issue in anesthesiology and pain management. Antidepressants are complex drugs having multiple actions, including effects on serotoninergic, adrenergic, and opioid mechanisms, and may modulate the levels of various neurotransmitters (gamma-amino butyric acid [GABA], adenosine, N-methyl D-aspartate [NMDA], and cholecystokinin) and ion channels (Na+, K+, Ca++) (2). Thus, the different of pharmacological actions of antidepressants contributes to their efficacy in relieving depression at central sites, in producing analgesia at supraspinal, spinal, and peripheral sites, as well as in the side effects observed at multiple sites. Antidepressants belonging to a same class also show difference in the intensities of pharmacological actions, some accounting for differential actions and side effects, similar to the findings of amitryptyline and doxepin reported by Alebouyeh et al. Tricyclic antidepressants (TCAs) have very different efficacy as local anesthetics in vivo (3). Among various TCAs, amitriptyline and doxepin have been studied as local anesthetics in most studies. Chen YW et al. evaluated the spinal anesthetic effect of various TCAs after a single intrathecal injection (4). In this study, the effects of 9 TCAs, including amitriptyline and doxepin, and 3 traditional local anesthetics (bupivacaine, lidocaine, and mepivacaine) were evaluated in rats. The results showed that intrathecal amitriptyline had a more potent and longer duration of spinal anesthetic effect than bupivacaine (under a given concentration of 5 mM), whereas the potency of other TCAs was similar to or less than that of bupivacaine. Although meta-analyses on the maximum allowable dose for intrathecal injection of these drugs have not been performed, several studies have reported the administration of these drugs in different doses. The study performed by Alebouyeh et al. has contributed to these findings; In a study performed by Cerda et al. , intratheIntrathecal Injection of Amitriptyline and Doxepin for Spinal Anesthesia in Animal Studies G. Ulufer Sivrikaya 1*