People with an anxious form of depression are not as likely to respond to
antidepressants and may be more sensitive to medication side effects than
people with depression who don't experience the anxiety symptoms, according to
a new report (for a different opinion see Anxiety in Depression: Findings
The study's researchers said that clinicians should be sure to include
questions about anxiety on depression-screening instruments so they better
know what to expect during treatment.
In a report in the March American Journal of Psychiatry, lead
author Mauricio Fava, M.D., noted that the presence of anxiety symptoms in
patients with depression is likely to complicate treatment.
Such symptoms "would indicate to us that we need to be more attentive
to the management of medication side effects and the potential for patients
dropping out of treatment," he told Psychiatric News.
It may be advisable for clinicians to schedule office visits more closely
together for patients with what Fava and his coauthors termed "anxious
depression," so that treatment progress can be more closely
The report defines anxious depression as major depressive disorder with
high levels of anxiety symptoms indicated by a Hamilton Depression Rating
Scale (HAM-D) anxiety/somatization score of 7 or higher.
Fava is vice chair of psychiatry at Massachusetts General Hospital.
To obtain their results, Fava and his colleagues analyzed data from adult
outpatients with major depressive disorder enrolled at 18 primary care and 23
specialty care settings across the United States as part of the Sequenced
Treatment Alternatives to Relieve Depression (STAR*D) Study.
To be eligible for the study, patients had to be between ages 18 and 75 and
meet DSM-IV criteria for major depressive disorder, with a score of
14 or higher on the HAM-D.
Researchers obtained data on 2,876 patients who completed at least one
visit after baseline measurements in level 1 of the study. In level 1,
patients were treated with citalopram with the goal of achieving symptom
remission, which was defined as having a score of 5 or less on the Quick
Inventory of Depressive Symptomatology.
Dose adjustments were guided by manualized treatment protocols that allowed
for individualized starting doses and adjustments to minimize side effects.
The protocol recommended treatment visits at baseline and weeks 2, 4, 6, 9,
and 12, with an optional visit at week 14 if necessary.
Those who did not achieve symptom remission were encouraged to enter level
2 of the study, in which 1,292 patients were randomized to switch to
sustained-release bupropion (n=239), sertraline (n=238), or extended-release
venlafaxine (n=250). The rest of the patients continued taking citalopram with
sustained-release bupropion (n=279) or buspirone (n=286). This trial also
lasted up to 14 weeks.
The authors noted that anxious depression tended to be more common among
minorities and those who were unemployed and had public insurance, lower
levels of education, and lower income than those without anxious
Patients with more severe depression at baseline, greater perceived
physical impairment, more diminished quality of life, and later onset of major
depression were also more likely to have anxious depression.
For level 1 subjects, Fava found that remission rates were significantly
lower in patients with anxious depression as measured by HAM-D scores: 22.2
percent of patients with anxious depression experienced remission of symptoms,
while 33.4 percent of those with nonanxious depression did.
Anxiety May Hinder Remission in Depressed Patients
Fava also analyzed data from a self-report version of the Quick Inventory
of Depressive Symptomatology (QIDS-SR) for both groups enrolled in level 1. He
found a similar pattern, with 27.5 percent of those with anxious depression
showing symptom remission and 38.9 percent of those with nonanxious depression
Response rates, defined as 50 percent or greater reduction from baseline
scores on the QIDS-SR, were also lower in patients with anxious depression
(41.7 percent) than in those with nonanxious depression (52.8 percent).
The findings also showed that despite having similar citalopram dosages,
patients with anxious depression experienced greater frequency, intensity, and
burden of side effects and adverse events (including death, suicidal ideation,
substance abuse, and psychiatric hospitalization) than those with nonanxious
In addition, the number of hospitalizations for general medical conditions
was higher for those with anxious depression during the study than it was for
those without anxious depression (40 versus 18, respectively).
Level 2 participants with anxious depression, according to the report,"
fared significantly worse in both the switching and augmentation
The authors noted that since there was not a placebo control group, it was
impossible to determine whether patients with anxious depression were less
responsive to true drug effects or less responsive to certain nonspecific
aspects of treatment.
Also, the report highlighted the fact that patients with anxious depression
had a higher physical illness burden, lower socioeconomic status, and greater
severity of depression, factors that alone could have contributed to poorer
"In general, these patients may be tougher to treat," Fava
commented. "We're not sure exactly why."
He suggested that patients with anxious depression may need more aggressive
treatment, which may include closer monitoring of symptoms and side effects.
He said more research is needed to understand what specific treatments will be
effective for patients with anxious depression.
"Difference in Treatment Outcome in Outpatients With Anxious
Versus Nonanxious Depression: A STAR*D Report" is posted at<http://ajp.psychiatryonline.org/cgi/content/full/165/3/342>.▪