Aripiprazole for the Treatment of Involuntary Movement Symptoms in Patients With Major Depressive Disorder

To the Editor: Somatic symptoms such as involuntary movement symptoms sometimes emerge with depressive disorder. Here, we present two cases exhibiting the remarkable therapeutic effects of aripiprazole with respect to involuntary movement symptoms with major depressive disorder.

The first patient, a 58-year-old married woman with anxiety, depressed mood, and somatic complaints, including involuntary rhythmic movements of the head and neck, was diagnosed with major depressive disorder. After prescribing 10 mg/day escitalopram, 1 month later, depressive symptoms were mildly improved, but intermittent movement symptoms remained. To reduce movement symptoms and augment antidepressant effects, aripiprazole was prescribed at 5 mg/day, then titrated to 10 mg/day. Three weeks later, involuntary movement symptoms and depressive symptoms were alleviated. Five months later, she stopped her medicine at her discretion and movement symptoms recurred. On 7.5 mg/day of aripiprazole, the patient was stabilized, with no signs of depressive symptoms or involuntary movement symptoms.

The second patient, a 62-year-old married man, presented with depressed mood and involuntary head and neck movements, was diagnosed with depressive disorder. He was given paroxetine 12.5 mg/day and escitalopram 10 mg/day, but his depressed mood remained. One month later, aripiprazole 2.5 mg/day was started because of the persistence of movement symptoms. The following week, aripiprazole was raised to 10 mg/day, resulting in a significant improvement in his involuntary movements and depressed mood. His movement symptoms reemerged after 7 months, after giving up treatment against our advice. One month after the reinitiation of aripiprazole 10 mg/day, abnormal movements were remitted considerably. During the follow-up, there were no further involuntary movement symptoms or depressive symptoms.

These involuntary movement symptoms were different from tics and parkinsonian symptoms. Also, brain magnetic resonance imaging (MRI) results showed no abnormal finding. There have been conflicting results about the relationship between aripiprazole and movement disorders. There have been case reports that aripiprazole is effective in tardive dyskinesia.¹ On the other hand, there have been other cases suggesting that aripiprazole may be more likely to cause movement disorders than other atypical antipsychotics.² Aripiprazole is considered as a dopaminergic stabilizer because of its partial agonism at postsynaptic D₂ and D₃ receptors.³ It has been postulated that aripiprazole’s 5-HT_2A receptor antagonist activity with partial D₂ agonist properties and its rapid dissociation from dopamine receptors may account for its relatively low effect of extrapyramidal symptoms.⁴

The extrapyramidal motor system has been clearly implicated in certain tremors and chorea. Furthermore, involuntary movements have been often associated with dysfunction of basal ganglia. Within the basal ganglia, the D₂ and D₃ receptors are expressed, and, thus, agonism at these receptors may result in the relief of the motor symptoms.⁵ Because of its partial agonist effect on 5-HT_1A and antagonist activity at 5-HT_2A receptors, aripiprazole has been known to exert neuromodulatory effects on the serotonergic system, which may explain the improvement in movement symptoms in our cases.

The present case reports have suggested that because of its unique feature as a dopamine stabilizer, aripiprazole’s use in depression with movement symptoms in elderly patients may be promising. However, further studies will be needed to elucidate potential mechanism of action of aripiprazole in treating depression with movement symptoms.