Guidelines for Clinical Trials Assessing Cognitive Impairment in Major Depressive Disorder

depressed Women sitting head in hands on the bed in the dark bedroom with low light environment, dramatic concept
While the relationship between current mood state and cognitive impairment is unclear, more severe depression has been linked to greater impairment.

A review published in the British Journal of Psychiatry Open provided methodological guidelines for clinical trials assessing the psychological treatment of depression associated cognitive impairment. The investigators provided guidance on cohort selection, treatment duration and dose, choice of outcomes, and improving adherence.  

While cognitive impairment is a well-known hallmark of major depressive disorder, research assessing the psychological treatments of cognitive impairment is limited. Katie M. Douglas, PhD, of the department of psychological medicine, University of Otago, Dunedin, New Zealand, and colleagues outlined methodological considerations for the study of cognitive impairment treatments. They emphasized that a concise definition of cognitive impairment should be used in participant selection.

Common approaches to defining cognitive impairment in depression include: (1) comparing patients’ cognitive test results with those from a healthy population; (2) comparing patients’ test results prior to and after depression onset; and (3) allowing patients to self-identify their impairments. It is also important to screen for patient mood state and medication use at the start of the trial. While the relationship between current mood state and cognitive impairment is unclear, more severe depression has been linked to greater impairment. Studies should be clear in their reasons for applying certain treatments to patients of varying depression levels.

The investigators noted the potential benefits of a cognitive activation vs remediation approach. They also identified 3 pillars of treatment: computerized cognitive training, strategy monitoring, and transfer of cognitive change to functioning.

Medication use should be monitored throughout trial duration, and changes in drug regimens should be noted. Use of concomitant therapy may also be a confounder, although prior research suggests that psychotherapy alone rarely improves cognitive impairment. Even so, analyses should adjust for medication use and other therapy types.

Regarding outcome selection, the investigators endorsed the use of multiple cognitive metrics, including attention, processing speed, memory, and executive function. Treatment “success” may be defined as a function of these test results; for example, as a 1 standard deviation increase from baseline in any cognitive measure.

Cognitive treatment trials may also benefit from added endpoints addressing real world functioning. Few recommendations exist regarding appropriate cognitive therapy “dose” and duration, although follow-up of 3 to 6 months is recommended to properly capture outcomes.

To maintain adherence, the investigators suggested using reminders tailored to patients’ needs such as workbooks or check-in phone calls. They noted that motivational interviewing techniques has been associated with improved treatment adherence among patients with schizophrenia. Additionally, incorporating at-home practice into treatment may help patients maintain an active role in their treatment.

While further study is necessary to provide evidence-based guidelines for cognitive treatment trials, the present review provided substantial advice to researchers and clinicians alike. Efforts to identify the best methods of cognitive treatment are crucial to protect the well-being of patients with major depressive disorder.

Disclosure: Study authors declared affiliations with the pharmaceutical industry.

Please see the original reference for a full list of authors’ disclosures.


Douglas KM, Milanovic M, Porter RJ, Bowie CR. Clinical and methodological considerations for psychological treatment of cognitive impairment in major depressive disorder. BJPsych Open. 2020;6(4):e67.