New therapies show promise for vascular depression

Researchers see new treatments on the horizon for a a recently recognized type of depression related to blood vessels that affects the elderly, and have discovered why some elderly people fail to respond to current medications.

Vascular depression usually develops in patients older than age 60 and is associated with loss of blood supply to the brain. This condition is a serious problem for elderly patients and highly effective treatments have yet to be developed, but several research teams now report progress in understanding and treating this condition.

"Mental health practitioners and patients should be aware of the relationship between vascular problems and depression, and should understand the value of preventing vascular changes that might lead to difficult-to-treat depressions, for example through early recognition and treatment of high blood pressure," says John Newcomer, MD, of Washington University in St. Louis.

Drugs Show Promise for Vascular Depression

George Alexopoulos, MD of the Weill Cornell Medical College in White Plains, NY, and his colleagues, are investigating the specific brain abnormalities linked to blood vessel problems. Using a new magnetic resonance imaging technique called diffusion tensor imaging, the team have found that, in late life depression, higher blood pressure readings are linked to tiny abnormalities in the brain white matter (white-matter hyperintensities), mainly in the brain's frontal lobes and in subcortical areas. Some of these structural abnormalities were linked to impairment in specific frontal lobe functions.

The researchers are also studying the brain abnormalities that prevent depressed older patients from responding to antidepressant medication. In a study of 112 elderly patients with major depression treated with the antidepressant citalopram (Celexa^®), they found that patients were less likely to recover from their depression if they had cardiovascular disease or performed poorly on a 'response inhibition' task testing an aspect of cognition requiring frontal lobe function. This timed task asks a person to suppress the reading of a word (e.g., the word red) and identify the color of ink by which the word is written (e.g., blue).

In a subsequent study of 48 depressed older patients treated with the antidepressant escitalopram (Lexapro^®), which is more potent than citalopram, Alexopoulos and his colleagues demonstrated for the first time that patients who failed to achieve remission had more of the tiny structural abnormalities in several areas of frontal lobe and in subcortical structures compared with those who got well.

"With further refinement, the findings may improve physicians' ability to predict who will fail to respond to antidepressants," Alexopoulos says. "Such patients may need close follow-up and different treatments such as psychotherapy or novel medications. Second, our findings can be used in the development of new treatments for those who do not respond to classical antidepressants."

Alexopoulos is now working to pinpoint activation and processing abnormalities in frontal and subcortical brain structures that predict failure to respond to antidepressants. He is studying how parts of the frontal lobe are activated when depressed patients perform cognitive tasks known to engage this area. "Preliminary findings show that depressed older patients cannot activate these frontal lobe parts as efficiently as non-depressed older adults," Alexopoulos, says.

Stimulation Therapy Tested for Vascular Depression

In other treatment strategies, Robert Robinson, MD, a professor of psychiatry at the University of Iowa, and his colleagues have found for the first time that vascular depression can be effectively treated with repetitive transcranial magnetic stimulation (rTMS), an experimental technique that also has been tested in other psychiatric disorders.

Among 92 depressed people with an average of three prior treatment failures, the researchers found that rTMS produced better remission rates than those associated with standard medication treatment. They also found that increasing the number of magnetic pulses delivered significantly improved remission rates. "These findings suggest that this new method of treatment may be particularly useful for these late life onset depressions and that even greater response rates might be achieved by utilizing more pulses of magnetic stimulation," Robinson says. The findings of this study were published in the March 2008 issue of the Archives of General Psychiatry.

The study participants had clinical or imaging evidence indicating lack of blood flow in the brain, and had failed to respond to standard treatments for depression. They were given either 12,000 or 18,000 pulses of rTMS or a sham (inactive) treatment over a two-week period. Neither the patient nor the examiner knew if the treatment was actual rTMS or sham, thus removing any possible bias. Improvement of depression was documented by scores on the Hamilton Depression Scale. The next step in this research is to determine precisely how many magnetic stimulations will achieve the maximum response among patients with vascular depression.

---

Alexopoulos GS, Gunning-Dixon F, Murphy C, et al. Fronto-Striato-Limbic Abnormalities Linked to Late- Life Depression and to Treatment Resistance. Symposium presentation 27-B, APA Annual meeting Washington DC, 2008 May 6.

Robinson RG, Jorge RE, Moser DJ. Repetitive Transcranial Magnetic Stimulation and Vascular Depression. Symposium presentation 27-C, APA Annual meeting Washington DC 2008 May 6