A recent study in geriatric patients with MDD showed that escitalopram therapy was associated with significant memory improvement.35 Similarly, a study with the serotonin-norepinephrine reuptake inhibitor duloxetine showed that memory and verbal learning significantly improved with treatment.36

The noradrenergic-dopaminergic antidepressant bupropion has also been reported to improve a variety of cognitive symptoms in a group of young (mean age, 24 years) adults with MDD.37 Bupropion led to robust improvements in visual memory and mental processing speed. Low pretreatment measures of visual memory and slow mental processing speed were predictors of good overall antidepressant response to bupropion.37

However, several studies have found that moderate cognitive dysfunction predicts failure to achieve antidepressant response in geriatric patients.38,39 Nonresponders to fluoxetine showed increased perseverative errors in one study.38 Another study showed that impairments in initiation/perseveration were associated with poor response in a group of geriatric patients with MDD who were treated with citalopram.15 In addition, fluoxetine was found to be less effective in MDD patients with psychomotor slowing.40 Finally, some investigators have proposed that SSRI response could be predicted in 85% of patients with MDD by using a battery of cognitive function tests.41

Conclusions
While many studies have noted significant cognitive abnormalities in persons with MDD, on average these disturbances tend to be mild to moderate in younger adults and of lesser frequency and severity than those found in people with bipolar disorder or schizophrenia. In younger adults, some data suggest that mental slowing and reduced motivation and attention may contribute to the apparent dysfunction in other cognitive domains. Cognitive dysfunction in younger adults tends to improve with treatment, although some patients continue to have residual mild impairment.2 Although a bupropion study showed that this drug was more likely to lead to an antidepressant response in patients who had evidence of cognitive dysfunction at baseline, no comparative data are available. Studies with SSRIs suggest that baseline cognitive impairment, reduced hippocampal volume, greater burden of white matter hyperintensities, and microstructural abnormalities in white matter may predict poor antidepressant response, especially in older patients.42

Cognitive dysfunction may be an endophenotype for a specific subset of MDD, and brain imaging abnormalities are possible biomarkers for this and other subsets of MDD. Whether these or other attempts will be successful in defining a more biologically homogeneous group of people within the syndrome of MDD is still unclear. Future research needs to focus on subsets of patients with MDD defined by a certain severity of cognitive dysfunction, a certain density of white matter abnormality, or markedly reduced hippocampal volume. To advance treatment, MDD studies need to more explicitly address the likelihood that this syndrome includes an exceptionally broad range of causal pathways and underlying mechanisms.

Based on what we currently know, patients with MDD should receive standard antidepressant treatment, regardless of cognitive dysfunction. Clinicians should be watchful for nonresponse in patients with more severe cognitive dysfunction at baseline and for progression to frank dementia in patients with significant residual cognitive dysfunction after successful antidepressant response.

While the fact that bupropion showed greater efficacy in younger adults with cognitive dysfunction in one study is interesting, no comparator was used and this has not been demonstrated in geriatric patients. Therefore, the available data do not favor the use of one antidepressant over another in patients with cognitive dysfunction. If dementia develops or co-occurs with MDD, combination treatment with antidepressants and drugs approved for treatment of dementia should be used in an integrated fashion.43

Drugs Mentioned in this Article
Bupropion (Wellbutrin, Zyban)
Citalopram (Celexa)
Duloxetine (Cymbalta)
Escitalopram (Lexapro)
Fluoxetine (Prozac, Sarafem)
Fluvoxamine (Luvox)
Imipramine (Tofranil)
Nortriptyline (Aventyl, Pamelor)
Paroxetine (Paxil)
Pages: 1  2  3  4