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When SSRI Fails in Elderly, Augmentation May Help

Many older patients who do not respond well to initial SSRI therapy for major depression can achieve recovery with augmented treatment.

Half of elderly depressed patients who initially responded poorly to selective serotonin reuptake inhibitors (SSRIs) achieved recovery after a second medication was added to their regimen, according to University of Pittsburgh researchers. They also found that patients with clinically significant anxiety and higher medical burden took longer to recover than did other patients.

Augmenting antidepressant therapy is not a new idea in treating younger adults, but it has been used less commonly in older patients, study leader Mary Amanda Dew, Ph.D., a professor of psychiatry, psychology, and epidemiology at the University of Pittsburgh School of Medicine, told Psychiatric News.

The findings appear in the June American Journal of Psychiatry.

"Doctors have hesitated to add medications for older patients because they are concerned about the risks of polypharmacy, but this study shows response rates as good as those among younger ones," said Dew. Untreated or undertreated depression also carries risks, she said.

Many older individuals diagnosed with major depression do not respond well to the initial drug regimen prescribed for them, said Dew. Guidelines have been developed clinically, but there have been no studies in this age group following a protocol specifying the steps for augmentation.

So, Dew and her team monitored depression levels of 195 patients over age 70 during their treatment for unipolar major depressive disorder. They were being treated openly with the SSRI paroxetine, titrated from 10 mg to 40 mg, as needed. These patients also received interpersonal psychotherapy weekly until registering a clinical response, then biweekly for up to 16 weeks.

At that point, 90 patients (46.2 percent) had responded without relapse; 77 (39.5 percent) had an inadequate response; and 28 (14.4 percent) responded but experienced an early relapse. These last two groups were eligible for augmentation treatment, but 36 of them did not receive it, because they either withdrew consent or had worsening medical conditions that precluded continuation.

The treatment teams used a standardized protocol and expert consensus to decide which of three drugs to add to the paroxetine members of the target study group were receiving: sustained-release bupropion, nortriptyline, or lithium carbonate.

Patients who required and received augmented treatment had lower recovery rates than did those who responded well initially. After nearly a year, 86.7 percent of patients who didn't need augmentation had recovered. However, half (24 of 48) with an initial inadequate treatment response recovered, as did 66.7 percent (14 of 21) of those who relapsed.

The researchers recorded a variety of demographic, clinical, and medical comorbidity information in an attempt to predict outcomes. Besides their first response to treatment, only anxiety and a high general medical burden appeared to be associated with a longer time to recovery. Given the sample size, they did not break out response by the drugs used to augment treatment.

"Our findings show that the response to treatment and to augmentation among older people is at odds with the conventional thinking that assumes the young do better," said Dew. The study indicates the value of a wider range of options for treating this age cohort, she said.

"For older adults, we need a wider set of strategies for treating depression," said Dew. "Although many patients can't or won't take an additional drug, augmentation is one more possibility, like switching medications or using psychotherapy."

Dew and her colleagues are continuing research that compares switching medications with augmenting them.

The study was funded by the National Institute of Mental Health.

"Recovery From Major Depression in Older Adults Receiving Augmentation of Antidepressant Pharmacotherapy" is posted at <http://ajp.psychiatryonline.org/cgi/content/full/164/6/892>.

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