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August 2009

Folate and Depression
L-methylfolate (Deplin) shows theoretical promise as an augmenting strategy for treatment-resistant depression, but so far there is little clinical evidence of its efficacy.

In Brief
Lithium in Drinking Water May Decrease Suicide Risk; No Association Found Between Fish Consumption and Dementia

Breast Cancer, Tamoxifen, and 2D6 Inhibitors
Antidepressants and other drugs that inhibit the cytochrome P450 2D6 isoenzyme may cause low levels of tamoxifen in women with breast cancer.

Treating Depression in Parkinson's Disease
Two studies provide preliminary but encouraging data about nortriptyline and omega-3 fatty acids as potential treatments for depression in patients with Parkinson's disease.

Treating Depression in Parkinson's Disease

August 2009

Parkinson's disease (PD) is the second most prevalent neurodegenerative illness in the United States, afflicting about 1 million people.1 The classic motor triad of PD is tremor, rigidity, and bradykinesia. Common nonmotor features of PD are depression, dementia, drug-induced psychosis, impulsivity, and sleep disturbances.

Depression affects an estimated 40% to 50% of patients with PD. It is associated with a faster progression of physical symptoms, greater decline in cognitive and self-care abilities, worse compliance with treatment and quality of life, and greater caregiver distress.

A recent Cochrane review concluded that there is insufficient data to make recommendations for the treatment of depression in PD.2 Nonetheless, faced with the clinical problem, physicians commonly prescribe antidepressants. One recent survey found that 26% of patients with PD were taking antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). In the Veterans Affairs system, 63% of patients with PD were taking SSRIs, and 7% were taking tricyclic antidepressants. Recently, Menza and coworkers compared nortriptyline (Pamelor and others), controlled-release paroxetine (Paxil CR and others), and placebo in patients with PD and depression in a study funded by the National Institutes of Health.1

In this double-blind, placebo-controlled trial, 52 patients were randomly assigned to take paroxetine CR, 12.5 to 37.5 mg/day; nortriptyline, 25 to 75 mg/day, or placebo. At both 2 and 8 weeks, the decrease in scores on the Hamilton Depression Rating Scale (HAM-D) was superior to placebo (P < .029 and P < .002) for nortriptyline but not for paroxetine. Defined as a 50% or greater improvement in the HAM-D total score, "response" was achieved by 53% of patients taking nortriptyline, 11% of those taking paroxetine, and 24% of patients taking placebo. Both antidepressants were relatively well tolerated. The most common adverse effects with nortriptyline were constipation and dry mouth, and with paroxetine, fatigue and orthostatic hypotension.

In a pilot project, da Silva and coworkers in Brazil randomly assigned 31 patients with PD and major depressive disorder to receive supplementation with omega-3 fatty acids or placebo for 12 weeks.3 Patients were also taking antiparkinson medication, and about half were taking antidepressants. Subjects who received omega-3 fatty acids, with or without antidepressants, showed significant improvement in depressive symptoms compared with those taking placebo.

The study by Menza et al found a clear benefit in depressed patients with PD from the tricyclic antidepressant nortriptyline and none from the SSRI paroxetine. However, it was a small study and requires replication. Although both antidepressants were well tolerated in this trial, tricyclic antidepressants can cause substantial anticholinergic effects, both peripheral and central. Tricyclics also increase the cardiac QT interval, which can be deadly for some patients, particularly the elderly and those with heart disease. While a growing body of evidence suggests omega-3 fatty acids may have some efficacy in treating depressed patients, along with other health benefits and minimal adverse effects, the study by Dr da Silva's group must be considered preliminary.

Parkinson's disease is a highly prevalent condition. Depression presents a common and substantial burden to this population. There is a huge unmet need for better understanding of treatments.

1Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Buyske S, Bienfait K, Dicke A: A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology 2009;72:886-892.

2Shabnam GN, Th C, Kho D, H R, Ce C: Therapies for depression in Parkinson's disease. Cochrane Database Syst Rev 2003;3:CD003465.

3da Silva TM, Munhoz RP, Alvarez C, Naliwaiko K, Kiss A, Andreatini R, Ferraz AC: Depression in Parkinson's disease: A double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation. J Affect Disord 2008;111:351-359.