Q: How are functional outcomes defined in MDD, and what place does cognitive function have in that definition?

Regarding cognition, while the Mini–Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are known for their screening role in dementia, they are clearly insufficient in MDD because of the so-called ceiling effect. That is, both tests have a limited ability to detect milder impairments.

But I also think that there is a broader issue here, and I think we all can agree that measurement of cognitive functioning has not taken place nearly as frequently as it should and could be taken. The dreamer in me would like to see cognition measured in just about every patient. I realize that is a quixotic fantasy, and so on, but I think that in certain patients – for example, that Silicon Valley CEO type that we considered in a previous discussion – I see a role for it.

The impact of cognition is so huge that I would say that a short version like your THINC-it^®, Dr McIntyre, or an even shorter instrument – and measuring cognition in a wider population than just the CEOs – I think that may be worthwhile. If you have a chronic lung disease or a chronic liver disease, your internist or primary care provider will spend a fair amount of time measuring a lot of things before he or she continues treating you, and I think we need to unapologetically recommend a similar approach for depression.

We now have a series of papers on work productivity, quality of life, and psychosocial functioning. We have not traditionally been paying enough attention to this area, nor have we included these parameters in our outcome assessments. We have now published about 9 papers that look at work productivity. In people who are not employed, we examine their daily activities, and we find impairments in these daily activities. Looking at psychosocial function, quality of life, social adjustment, all in different domains, there continues to be a proportion of patients who are better symptomatically but who are not yet fully recovered functionally.

Dr McIntyre:
Agreed, and I think very relevant here is Dr Trivedi’s work with the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) data set, and the CO-MED (Combining Medications to Enhance Depression Outcomes) trial. The paper that he and his team published dealt with the probability of improvements in work measures and productivity measures as functions of failed initial treatment.

Over the last 3 to 5 years, I’ve been quite struck by the data from various studies showing that, across the panoply of depressive symptoms, cognitive symptoms may disproportionately account for impairments in work productivity and attendance.

I don’t think this comes as a surprise to anyone, given the requirements in the workplace today for cognitively demanding, complex, nonroutine skill sets.

However, hitherto, cognitive symptoms have really not been extensively studied. So, as we attempt to reduce the burden of illness to individuals, families, and populations, I think addressing any dimension of cognition that is mediating these outcomes holds promise. It seems as though when it comes to workplace performance and workplace attendance among those with depression, the presence, severity, and maybe also the type of cognitive symptoms are particularly germane.

I think of cognition and functioning as being separate entities that should be simultaneously assessed. The instruments that allow us to assess cognition are different from those that allow us to assess day-to-day functioning.

Functioning is assessed by the activities of daily living (ADL) and instrumental ADL (IADL) measures. The IADL measure assesses functional abilities such as managing one’s own checkbook, driving, paying the bills, and going to the grocery store. The ADLs are the more basic daily living skills such as dressing, bathing, and grooming that become impaired in more severe cognitive syndromes like dementia. A neuropsychological evaluation will evaluate the domains of cognitive impairment in more depth and help to differentiate between dementia syndromes and depression.

I think that this is a very interesting issue and one that we need to deal more with. Of particular value are the assessments of performance, on, say, cognitive IADL. In our experience, this can be performed in the home environment of study participants, for instance, such as the older patient with post-stroke depression. Some of our occupational therapists go into the homes of some of the participants of our clinical trials and watch them prepare meals, change a light bulb, wash clothes, go to the grocery store, and carry out a shopping list. These activities that tell us a lot about how well someone is doing and whether he or she can remain functionally independent for very much longer. I think that’s what matters to patients and to their family caregivers.