How is depression treated in patients with Parkinson disease (PD)?

Updated: Aug 29, 2019
  • Author: Robert A Hauser, MD, MBA; Chief Editor: Selim R Benbadis, MD  more...
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Imaging, cerebrospinal fluid, and autopsy studies indicate that depression in Parkinson disease is associated with dysfunction of basal ganglia dopaminergic circuits that project to the frontal lobes, as well as noradrenergic limbic and brainstem structures. [107] Whether serotonin (5-HT) dysfunction plays a role in depression in PD is unclear.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used medications to treat depression in Parkinson disease in clinical practice. However, several randomized controlled trials, systematic reviews, and meta-analyses have suggested that SSRIs may be no more effective than placebo in this situation. [47, 107, 110]

Positive results in randomized clinical trials have been demonstrated for nortriptyline (a tricyclic antidepressant [TCA] with serotoninergic and adrenergic activity), desipramine (a predominantly noradrenergic reuptake inhibitor TCA), venlafaxine (a serotonin-noradrenaline uptake inhibitor), citalopram (an SSRI), and paroxetine (an SSRI). [107] For example, in Parkinson disease patients that were diagnosed with depressive disorder or operationally-defined subsyndromal depression, venlafaxine extended release or paroxetine significantly reduced scores on the Hamilton Rating Scale for Depression compared to placebo. Both venlafaxine and paroxetine were well tolerated and did not worsen motor function. [111]

There is a suggestion that noradrenergic or dual action (noradrenergic/serotoninergic) antidepressants may be more effective for treating depression in Parkinson disease than SSRIs. However, whether this is an artifact of clinical-trials methodology is not yet clear, and more research is necessary.

Antiparkinsonian medications can also exert an antidepressant effect. In a large, randomized trial, pramipexole (mean daily dose, 2.18 mg) significantly reduced depression scores relative to placebo. [112] The monoamine oxidase (MAO)-B inhibitor selegiline was also demonstrated to provide an antidepressant effect in patients with early Parkinson disease who were not clinically depressed. [113]

Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be effective for depression in Parkinson disease, but more research is required. Electroconvulsive therapy (ECT) can be considered for refractory moderate to severe depression.

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