DR HAGIKURA AND COLLEAGUES successfully illustrated the potentiality of mirtazapine for treating depression in patients with Parkinson's disease (PD), providing clinically relevant action mechanisms concerning blockade of serotonin 5-HT3 and 5-HT2A receptors, which may result in less dopamine-related side-effects (e.g., loss of appetite and nausea) and extrapyramidal symptoms.[1] Here, I would like to add and update biological treatment issues to the authors' suggestions.

Although the first randomized controlled trial (RCT)[2] has suggested the superiority of older antidepressants, such as nortriptyline, over paroxetine, and previous studies have frequently reported that selective serotonin re-uptake inhibitors (SSRIs) may be no more effective than placebo in PD patients with depression, another recent, adequately powered RCT has demonstrated comparable efficacy and safety of paroxetine in PD patients.[3] In fact, even though SSRIs are commonly prescribed for PD patients with depression in clinical practice, clinical trial data favoring dual-re-uptake inhibitors (e.g., venlafaxine) over SSRIs have been increasing recently.[4] Hence, large-scale subsequent studies with broader entrance criteria and antidepressants acting on multiple neurotransmitters other than serotonin are particularly needed to establish advanced treatment options for such patients.[2-4] Clinical heterogeneity of depression symptom profile should also be taken into account in selection of antidepressants as some PD patients may suffer more anxiety, agitation, and disturbance in sleep, while others may feel more concentration difficulties, lack of energy/interest, feeling hopeless, and somnolence.[4] Discrete consideration of the pharmacodynamic profile of individual antidepressants should also be kept in mind.

In addition, we may have effective augmentation agents for antidepressants to be continuously explored in PD patients with depression. In fact, a recent RCT has clearly demonstrated the efficacy and safety of omega-3 fatty acid as augmentation treatment or monotherapy for treating depression in PD patients.[5] Preliminary studies also suggest that repetitive trans-cranial magnetic stimulation (rTMS) may be effective for treating depression in PD patients, especially for such patients with tolerability issues.[4]

Finally, the American Academy of Neurology declared that there is insufficient evidence to recommend specific antidepressant treatments for MDD in PD patients. Therefore, currently available evidence proposes that the choice of antidepressants to treat PD patients with depression should be tailored to the individual's clinical situation, including PD medications and lifestyle characteristics, based on careful consideration of benefits and risks.


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  2. References
  • 1
    Hagikura M, Iwamoto K, Aleksic B, Ozaki N. What is a rational antidepressant treatment for major depression in patients with Parkinson's disease? Psychiatry Clin. Neurosci. 2012; 66: 463.
  • 2
    Menza M, Dobkin RD, Marin H et al. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology 2009; 72: 886892.
  • 3
    Richard IH, McDermott MP, Kurlan R et al. A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology 2012; 78: 12291236.
  • 4
    Aarsland D, Pahlhagen S, Ballard CG, Ehrt U, Svenningsson P. Depression in Parkinson disease: epidemiology, mechanisms and management. Nat. Rev. Neurol. 2012; 8: 3547.
  • 5
    da Silva TM, Munhoz RP, Alvarez C et al. Depression in Parkinson's disease: A double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation. J. Affect. Disord. 2008; 111: 351359.