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Co-occurring Anxiety Complicates Treatment Response for Those with Major Depression

Science Update

People with major depression accompanied by high levels of anxiety are significantly less likely to benefit from antidepressant medication than those without anxiety, according to a study based on data from the NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The study was published online ahead of print in January 2008, in the American Journal of Psychiatry.

The STAR*D trial examined four levels of treatment for difficult-to-treat depression, all of which tested different medications and medication combinations. Results from the four levels of treatment are available here.

This new study is the largest to date to determine if people with major depression and co-occurring high levels of anxiety respond differently to treatment than those without co-occurring anxiety. Maurizio Fava, M.D., of Massachusetts General Hospital, and colleagues examined response and remission rates among the 53 percent of STAR*D participants (1530 of the 2876 participants treated in the first two treatment steps) who were identified as having “anxious depression”—major depression coupled with significant symptoms of anxiety.

During Level 1 treatment, 42 percent of those with anxious depression responded to treatment and got somewhat better, compared to 53 percent of those without anxiety. Among those who remitted, or became symptom-free, rates were much lower—only 22 percent of those with anxious depression became symptom-free, compared to 33.4 percent of those without anxiety.

In Level 2 treatment, when participants who did not respond in Level 1 could either switch to another antidepressant or add another to the existing one, participants with anxious depression fared significantly worse than those without anxiety, regardless of whether they switched or added medication. They also experienced more frequent and more severe side effects from the medications.

The researchers also found that those with anxious depression were more likely to be unemployed, have less education, have more severe depression, have suicidal thoughts, and have more coexisting illnesses, both medical and psychiatric. They were more likely to be hospitalized during the trial, as well.

The results are consistent with previous research showing that people with depression and high levels of anxiety are less likely to respond to antidepressant medication, regardless of what medication is used. They also may lead to more recognition and possible diagnosis of anxious depression. “Clinicians should be aware of a patient’s sociodemographic situation and take note if he or she shows significant anxiety along with depression," said Dr. Fava. "The combination likely warrants a more personalized treatment approach.”

In addition to antidepressants, high levels of anxiety may be treated with anti-anxiety medications such as benzodiazepines or beta-blockers, and with psychotherapy. More information about treatment options for anxiety is available here.


Fava M, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: A STAR*D Report.  American Journal of Psychiatry. Published online ahead of print January 2, 2008.