Treatment of Mood Disorders: Neurological Illnesses
Cerebrovascular accident and Parkinson’s disease are two neurological illnesses associated with a high incidence of comorbid depression after initial neurological insult. Within a week of experiencing a stroke, more than half of patients fulfill DSM-IV criteria for a major depressive disorder or minor depression. The longitudinal course of poststroke depression has been investigated thoroughly, and it has been found that by 8-9 months after their initial evaluation, 67% who are initially depressed remain depressed. Controlled studies show effectiveness of trazodone and nortriptyline as well as of psychostimulants in this population. As previously mentioned, the side-effect pattern of the TCAs in this population can lead to intolerable reactions including syncope and the potential for delirium. Monitoring blood levels can increase cost, which is a significant issue with these patients. Side effects reported for psychostimulants include increased blood pressure, insomnia, and irritability, and at least one case of hypomania has been reported; however, 40% of the patients saw an improvement of at least 50% in their Hamilton Rating Scale for Depression scores. None of the reports cited mentioned an arrhythmia or angina as a side effect of the medication. Serotonergic agents are much better tolerated than the TCAs, but the efficacy of any of these agents in this population is incompletely studied. One study of interest with citalopram revealed a significant improvement over a 6-week trial in poststroke depression.
Among patients with Parkinson’s disease, rates of depression are estimated to be between 20% and 70%, and the occurrence of symptoms often presents months or weeks before worsening motor symptoms. Many authors believe that the occurrence of depression in Parkinson’s disease arises from neurochemical dysfunction involving specific brain areas. It is believed that the depressive symptoms may be a signal of accelerated cognitive decline.
All of the available agents have been used in mood disorders with regard to Parkinson’s disease. Double-blind, placebo-controlled trials have been conducted with imipramine, nortriptyline, desipramine, and bupropion. Each of the aforementioned studies was found to show improvement of mood symptoms except the study with nortriptyline. Most studies involving the SSRIs in use with Parkinson’s disease have shown a positive effect on mood symptoms, but these studies were not adequately blinded or well controlled. In 1995, a meta-analysis of 12 papers describing investigations of treatment of depression in Parkinson’s disease concluded that the majority of studies examined were inadequate as a result of the small numbers of subjects and the lack of standardized scales. The use of SSRIs, including fluoxetine, paroxetine, and fluvoxamine, has been reported to increase motor disability in Parkinson’s disease. In a survey of the Parkinson’s Disease Study Group, it was found that SSRIs were the most commonly prescribed antidepressants in these patients. Forty-three percent of the investigators polled believed that the SSRI might worsen motor function, but the actual number of patients affected was not reported.
Selegiline was first shown to potentiate the efficacy of levodopa in 1975. It is postulated that selegiline is metabolized into l-desmethyl-deprenyl, l-amphetamine, and l-methamphetamine and that these metabolites stimulate the release and block the reuptake of dopamine, enhancing the dopaminergic medication l-dopa. Although selegiline lacks an indication for use in depression, it has been shown to be effective in relieving mood symptoms and in motor improvement at high doses. It was noted that at these high doses the specificity to the MAO-B receptor is lost, and this effect was a result of activity at both receptors. Without further evidence, the effectiveness of an additional response of selegiline for use in patients with Parkinson’s disease and depression is not clinically indicated.
ECT has been shown to be effective in the treatment of depression in patients with Parkinson’s disease, and both mood and movement difficulties improve. However, Kellner and Bernstein (1993) demonstrated that the motor improvement associated with ECT in patients with Parkinson’s disease is only transient, whereas the increase in mood symptoms remains with multiple treatments. Considering the potential for drug interactions, cognitive or interpersonal psychotherapy can be considered as primary or adjunctive therapy.
Revision date: June 22, 2011
Last revised: by Janet A. Staessen, MD, PhD