Even people who show a clear treatment response with antidepressant medications continue to experience symptoms like insomnia, sadness and decreased concentration, researchers at UT Southwestern Medical Center have found after analyzing data from the largest study on the treatment of depression.

"Widely used antidepressant medications, while working overall, missed these symptoms. If patients have persistent residual symptoms, these individuals have a high probability of incomplete recovery," said Dr. Shawn McClintock, assistant professor of psychiatry and lead author of the analysis available in the April print issue of the Journal of Clinical Psychopharmacology.

UT Southwestern researchers tracked a wide range of symptoms of depression -- including sadness, suicidal thoughts, and changes in sleep patterns, appetite/weight, concentration, outlook and energy/fatigue -- at the start of the trial and at the end of the antidepressant treatment course.

Dr. McClintock's research used data from the Sequenced Treatment Alternatives to Relieve Depression, or STAR*D study, the largest ever on the treatment of major depressive disorder and considered a benchmark in the field of depression research. The six-year, National Institute of Mental Health-sponsored study initially included more than 4,000 patients with major depressive disorder from clinics across the country. Dr. Madhukar Trivedi, professor of psychiatry at UT Southwestern, was co-principal investigator of STAR*D and an author on this paper that analyzed data.

All responders reported between three to 13 residual depressive symptoms, and 75 percent of participants reported five symptoms or more.

Some of their symptoms included insomnia that occurs in the middle of the night (nearly 79 percent); sadness (nearly 71 percent); and decreased concentration and decision-making skills (nearly 70 percent). Moderately severe midnoctural insomnia was reported in nearly 60 percent of participants -- more than twice as frequently as other symptoms.

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Thoughts of suicide rarely persisted or emerged during treatment, researchers found.

"Some people fear that antidepressant medication increases thoughts of suicide," Dr. McClintock said. "This provided counterevidence of that."

Researchers in the STAR*D trial found that only 33 percent of people go into remission in the first 12 weeks of treatment with an antidepressant medication known as an SSRI, or selective serotonin reuptake inhibitor. Of the available antidepressant medications, SSRIs are the most commonly prescribed for the treatment of depression.

Individuals on SSRIs often still exhibit symptoms of depression. For one of first times, researchers sought with this analysis in a large sample to identify residual symptoms of the disease and whether these symptoms began before or during treatment.

Dr. McClintock and colleagues looked at data from the 2,876 STAR*D participants who completed the first phase of the trial -- treatment with an SSRI for 12 weeks. About 15 percent of those participants, or 428 people, responded to treatment with no remission. Response was defined as a 50 percent decrease in severity of depression. The average age of participants was 40, 73 percent were white, and 66 percent were female.

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Each year about 19 million adults in America struggle with depression. People with depression are often at increased risk of heart disease, diabetes, asthma and obesity. Depression cost the U.S. an estimated $83 billion a year.

The next step, Dr. McClintock said, will be to develop more targeted antidepressant therapies to decrease depressive symptoms, and to understand better the association between depression and concentration.

Dr. Trivedi said, "Our findings do suggest that the use of measurement-based care techniques to identify and target residual depressive symptoms is essential to help patients return to normal function and recover from depression in the long term."

Other UT Southwestern researchers involved in this paper were Dr. Mustafa Husain, professor of psychiatry, internal medicine, and neurology and neurotherapeutics; Dr. David Morris, assistant professor of psychiatry; and Dr. Diane Warden, associate professor of psychiatry. Dr. A. John Rush, formerly of UT Southwestern Medical Center, now at NUS Graduate Medical School in Singapore, is co-principal investigator of STAR*D and an author of this analysis. Researchers from New York State Psychiatric Institute; Columbia University; the University of Pittsburgh; Massachusetts General Hospital, Harvard University; and the University of California, Los Angeles also participated.

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