ABOUT 50% OF PARKINSON'S disease (PD) patients suffer from depression.1 As the quality of life (QOL) impairment in PD patients is partly caused by psychiatric symptomatology, the treatment for depression in PD is clinically important. Although a meta-analysis raises questions about the efficacy of selective serotonin reuptake inhibitors (SSRI) for treatment of depression in PD patients,2 SSRI are often the first choice for treatment of these patients. A recent study suggested that the efficacy of SSRI may be inferior to that of tricyclic antidepressants (TCA) for depression in PD. SSRI have the potential to worsen parkinsonian motor function and TCA have a strong anticholinergic effect and impair cardiac conduction, causing poor tolerability. Here, we describe a PD patient with depression successfully treated with mirtazapine and consider the optimal treatment strategy for depression comorbid with PD, which remains a matter of debate.

The patient is a 62-year-old woman with mild dilated cardiomyopathy. At age 61, she was diagnosed with major depression based on the symptoms of psychomotor retardation and prescribed milnacipran 75 mg/day without improvement of the symptoms. Four months later, she was diagnosed with PD by a neurologist after developing motor symptoms, including resting tremor, rigidity, and gait disturbance. Although parkinsonian symptoms were well controlled with levodopa 300 mg/day and pramipexole 1.5 mg/day during 6 months, she had gradually developed insomnia, severe appetite and weight loss, loss of interest and suicidal ideation. She was sent by a neurologist to our outpatient department of psychiatric service, diagnosed as having major depression comorbid with PD, and subsequently hospitalized. Milnacipran 75 mg/day was switched to mirtazapine 30 mg/day over 2 weeks while keeping her anti-parkinsonian medication unchanged. After fixing mirtazapine 30 mg/day, her depressive symptoms were improved without the exacerbation of parkinsonian symptoms. She was discharged home and remained in remission at 1 month after hospitalization.

Dopamine agonists (DA) are first-line therapy for motor symptoms and effective for depression in PD as well. DA can cause nausea and appetite loss by stimulating dopamine D2 receptor in the chemoreceptor trigger zone, thus DA are not suitable for patients who have digestive symptoms. The blockade of serotonin (5-HT)3 receptor in the same region (e.g. by mirtazapine), can reduce DA-induced digestive symptoms. Furthermore, the worsening of extrapyramidal symptoms involving SSRI is attributed to an agonistic effect on the 5-HT2A receptor at the dopaminergic nerve terminal in the substantia nigra and inhibition of dopamine release.3 The blockade of 5-HT2A receptor with mirtazapine might reduce this risk. According to these pharmacological profiles, mirtazapine appears to be a rational treatment option for depression in PD patients. Randomized clinical trials are warranted to confirm the effectiveness of mirtazapine in PD patients with depression.


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