Aripiprazole Monotherapy Can Relieve Ruminations in a Case With Nonpsychotic Depression

“Mr. J” is a 37-year-old male patient with major depressive disorder who received antidepressant treatment for 2 years without significant improvements of his depression symptoms (Hamilton Rating Scale for Depression score: 27). The name and approximate treatment duration of the antidepressants are as follows: sertraline, 150 mg/day for 6 months; escitalopram, 20 mg/day for 3 months; bupropion, 300 mg/day for 3 months; duloxetine, 120 mg/day for 6 months; and venlafaxine, 225 mg/day for 6 months. He complained of the gastrointestinal side effects of the antidepressants. Other than the major depressive disorder symptoms, he had significant brooding ruminations, such as “repetitively thinking how lonely he feels,” “what is he doing to deserve this major depressive disorder,” and “why can’t I get going.” The scores of the 22-item Rumination Response Scale were 59. For the past treatment-resistant characteristics and intolerable side effects of the antidepressants, he started to receive aripiprazole monotherapy as 5 mg/day. After the 3-month treatment, his major depressive disorder symptoms gradually responded (Hamilton Rating Scale for Depression scores: 27 → 15; Rumination Response Scale scores: 59 → 38; “repetitively thinking how lonely he feels” item scores: 4 → 1; “what is he doing to deserve this major depressive disorder” item scores: 4 → 2; “why can’t I get going” item scores: 4 → 1). No intolerable side effects were mentioned.

Recently, it has been understood that major depressive disorder is mediated and formed by ruminations and reappraisal mechanisms.² Higher levels of depression are associated with decreased connectivity between the anterior cingulate cortex and the middle frontal gyrus. The severity of ruminations in major depressive disorder is also inversely correlated with the functional connectivity between the anterior cingulate cortex and frontal regions.³ A meta-analytic structural study of major depressive disorder showed decreased gray matter in the anterior cingulate cortex.⁴ Pizzagalli also mentioned that the brain activity of the anterior cingulate cortex could predict treatment response, and fronto-cingulate dysfunctions would be a model for the pathophysiology of major depressive disorder and the treatment response.⁵ The severity of ruminations seemed to be related to a decreased ability of the anterior cingulate cortex to modulate the functional connection to the amygdala and dorsolateral prefrontal cortex.⁵ Han et al. reported that the combination treatment of aripiprazole and escitalopram would modulate the activities of the anterior cingulate cortex for the presentation of alcohol cue in the alcoholic patients comorbid with major depressive disorder.⁶ Aripiprazole might relieve the ruminations through enhancement of cerebral blood flow in the anterior cingulate cortex.⁷ Schlagenhauf et al. also reported that aripiprazole treatment could normalize the deficits of working memory tasks and the hypoactivity of the anterior cingulate cortex.⁸ Apart from the above neuroimaging evidence, aripiprazole’s D2 partial agonist, 5-HT1A partial agonist, 5-HT2C antagonist, and 5-HT2A antagonist theory contributes to its therapeutic role for ruminations in major depressive disorder.⁹