The Frequency of Cognitive Impairment in Patients With Anxiety, Depression, and Bipolar Disorder: An Unaccounted Source of Variance in Clinical Trials
J Clin Psychiatry 2008;69(7):1122-1130
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: Patients with anxiety,
depression, and bipolar disorder are known to be
impaired relative to healthy controls on
neurocognitive tests, but the degree of impairment may
be obscured if the data are analyzed in terms of group means.
Method: Patients and controls were
administered a comprehensive neurocognitive assessment that measured performance in 5
domains: memory, psychomotor speed, reaction time,
attention, and cognitive flexibility. Clinic patients
diagnosed per DSM-IV-TR criteria with generalized anxiety disorder (N = 63), major depressive
disorder (N = 285), and bipolar I or II disorder (N
= 96) were compared with 907 controls. Subjects' age range was 18 to 65 years. Patients had
no comorbid psychiatric disorders and no medical, neurologic, or developmental conditions
that might affect cognition (e.g.,
attention-deficit/hyperactivity disorder, brain injury, mild
cognitive impairment, chronic pain). Data on patients
and controls (collected from March 2003 through February 2007) were taken from a clinical
database that also contained neurocognitive test scores.
Results: There were small differences
between patients and controls, between different
patient groups, and between treated and untreated
patients when neurocognitive results in terms of group means were compared. Comparisons
of results in terms of the frequency with which patients and controls fell below certain cutoff
scores amplified the importance of these
differences. Only 4% of controls fell below a standard
score of 70 (2 standard deviations below the mean) on
2 or more cognitive domains, but 19% of anxiety patients, 21% of depressed patients, and 30%
of bipolar patients fell below the standard score.
Conclusions: Substantial numbers of
patients with anxiety, depression, and bipolar disorder
are cognitively impaired. A score that is 2
standard deviations below the mean is usually
clinically important, and 2 domain scores in that range
is cause for serious concern. The importance of
this finding is discussed, with respect to clinical
trials, in terms of establishing a homogeneous
trial population and minimizing the placebo