Effect of a combination of duloxetine with hydroxyzine on experimental models of anxiety in mice

Abstract

Objective:There is a strong association between depression and anxiety. Duloxetine, an antidepressant agent, is also used in the treatment of anxiety. Hydroxyzine is preferred over benzodiazepines in the treatment of anxiety. Present study was designed to study the impact of a combination of duloxetine with hydroxyzine in treatment of anxiety.Materials and Methods:Mice received intraperitoneal injection of normal saline (10 ml/kg), duloxetine alone (10 mg/kg), hydroxyzine alone (10 mg/kg), and hydroxyzine plus duloxetine (5 mg/kg, each).Results:The in vivo results (elevated plus maze and light/dark transition tests) showed significant anxiolytic activity with the hydroxyzine treatment than the control group. The brain monoamines were significantly increased in hippocampi, cerebral cortices, and whole brain in drug-treated groups than in the control group. The group receiving the combination showed similar results in the in vivo models and in vitro tests (brain monoamine estimations) than respective monotherapies, with the exception of a greater increase of norepinephrine levels in cerebral cortices in duloxetine-treated group.Conclusion:Combination of duloxetine with hydroxyzine is not beneficial in anxiolytic treatment than the respective monotherapies. There is a need to study the pharmacokinetic drug-drug interactions to understand the present study outcomes.

Evaluation of anxiolytic effects of aripiprazole and hydroxyzine as a combination in mice

“…[30] H1 receptor blockers are known to increase the level of serotonin and no effect on dopamine level in the brain. [17] The results of hydroxyzine treatment-induced brain monoamine changes observed in the present study are also in agreement with the in-house finding reports. [17] All drug-treated groups showed benefits in terms of dopamine and serotonin levels in hippocampi, cerebral cortices, and whole brains, as compared to control group.…”

“…[12] The monotherapy of aripiprazole[1228] and hydroxyzine[15] has shown a considerable anxiolytic effect in different preclinical studies. The present study outcomes of aripiprazole monotherapy[122829] and hydroxyzine monotherapy[17] are in line with the available reports. [12172829] The combination-treated group showed benefits in terms of exploratory activity in EPM, light and dark transition test, and marble burying test as compared to control group and aripiprazole-treated group, however anxiolytic effect was not better than hydroxyzine treatment in open field test and novelty suppressed feeding test.…”

“…Group I, II, III, and IV received treatment of 5% of Tween 80 in 0.9% saline (10 ml/kg; control group), aripiprazole (1 mg/kg), hydroxyzine (3 mg/kg), and aripiprazole (0.5 mg/kg) + hydroxyzine (1.5 mg/kg), respectively. [121517]…”

“…These data were used for further calculations of percentage of OAT (%OAT) and the percentage of OAE (%OAE). [17]…”

“…[16] Changes in dopaminergic and serotonergic systems through hippocampus are related to the anxiety disorders. [1718] Aripiprazole is categorized as an antipsychotic drug that acts as a partial dopamine agonist and serotonin antagonist. Hydroxyzine belongs to the class of antihistaminic drugs as well as anxiolytic agents that acts as an inverse histamine agonist and serotonin antagonist.…”