Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice

Jun 12, 2009Psychopharmacology

Increased antidepressant-like effects in mice from combining aripiprazole with antidepressants in the forced swimming test

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Abstract

Aripiprazole at doses of 0.03 and 0.06 mg/kg significantly increased the activity of various antidepressants in the forced swimming test.

The combination of aripiprazole with inactive doses of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) enhanced their antidepressant-like effects.
No significant augmentation was observed for the norepinephrine reuptake inhibitor (NRI) desipramine or the dual dopamine and norepinephrine reuptake inhibitor bupropion.
The findings align with clinical evidence that aripiprazole may improve the effectiveness of SSRIs and SNRIs.
The augmentation effect of aripiprazole appears to depend on the activation of the serotonin system.

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RATIONALE: A deficiency in brain monoamine systems (serotonin, dopamine, and/or norepinephrine) have long been hypothesized for the pathogenesis of depression. Drugs enhancing neurotransmission of those monoamines have been proven to have antidepressant effects. We hypothesized that aripiprazole, a partial D(2) agonist, could increase the activity of various antidepressants in the mice forced swimming test (FST), an animal model of depression.

OBJECTIVES: The scope of this study was to investigate the antidepressant-like effect of aripiprazole, when combined with conventional antidepressants drugs.

MATERIALS AND METHODS: This study assessed the effects of co-administration of aripiprazole with selective serotonin reuptake inhibitors (SSRIs; sertraline, paroxetine, and citalopram), selective serotonin-norepinephrine reuptake inhibitors (SNRIs; venlafaxine and minalcipran), selective norepinephrine reuptake inhibitor (NRI; desipramine), and the dual dopamine and norepinephrine reuptake inhibitor (bupropion), using the FST in mice. Subactive doses of aripiprazole and antidepressants sertraline, paroxetine, citalopram, venlafaxine, minalcipran, bupropion (4 and 8 mg/kg), and desipramine (2 and 4 mg/kg) were given i.p. 30 and 45 min, respectively, before the test.

RESULTS: Aripiprazole (0.03 and 0.06 mg/kg) combined with inactive doses of antidepressants, increased the activity of all antidepressants with the exception of bupropion and desipramine.

CONCLUSION: The augmentation effects of aripiprazole, in the present study, are in agreement with clinical evidence suggesting that aripiprazole may enhance the efficacy of therapeutic effect of SSRIs and SNRIs but not of NRI. These results suggest that augmentation effect of aripiprazole only appears when 5-HT system is activated and might implicate complex regulation between dopamine and 5-HT(1A) and 5-HT(2A) receptors.

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Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice

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