Monday, April 17, 2017

When and Where Does Depression End?

For the past 7 years I have been seeing patients who have been carefully selected for having an alcohol or other substance use disorder.  My task is to determine if there is an associated psychiatric disorder, whether or not it can be treated, initiate treatment, and follow up.  Most of the people I see have anxiety and/or mood disorders and determining adequacy of treatment and the actual diagnosis can be a challenge.  I have highlighted a couple of the problems in the past including a high prevalence of primary sleep disorders and the issue of people with disorders of temperament that might seem like a primary disorder but that are fundamentally different.  These distinctions are critically important in terms of when the disorder ends if it is treated.  I don't think the problem have been adequately addressed in the literature.  In many ways it is a failure to recognize that conscious states exist out there that are not easily captured by a handful of descriptors or the derivative checklists.  Checklists are frequently seen are the endpoints in clinical research.  They are used to determine if treatments are effective.

A couple of texts (1,2) describe typical endpoints for depression.  In the first reference the authors discuss the concept and how it has evolved since the 1970s from broad terms like treatment resistant to more specific antidepressant resistant or refractory.  They discuss staging methods including the Thase and Rush staging method (TRSM), the European Staging Method (ESM), the Massachusetts General Staging Method (MGH-S) and the Maudsley Staging Method (MSM).  The ratings vary in how they rate the treatment resistant dimension (antidepressant resistant,  electroconvulsive resistant, duration of trials).  The MSM is the only scale that rates multiple dimension including symptoms severity at baseline, duration and specific number of treatment failures.  Treatment resistance is a biological psychiatry based term that is not applied to psychotherapy.

Looking at what is available, there should be concerns about people being able to recall that level of detail.  I prompt people with a list of all known medications.  A substantial number of people cannot recall medication names, even when prompted.  Unless the medication regimen has been uncomplicated like: "I took fluoxetine for 10 years and then changed to venlafaxine" specific duration will not be recalled (the ESM has 5 specific intervals of treatments demarcated in weeks). Unless medical records are available for review by researchers, I would be skeptical of a large population of research subjects being able to provide the information necessary to make these classifications.

I generally try to reconstruct the history from late childhood and adolescence through adulthood.  That allows for the determination of global subtypes of depression from persistent depressive disorder or what used to be called dysthymia to discrete episodes of major depression.  When I was trained we had an entity of double depression or episodes of major depression superimposed on dysthymia.  In DSM-5 parlance that would be called persistent depressive disorder with intermittent major depressive episodes with or without current episode.  Since the diagnostic criteria for persistent depressive disorder involves having at least two of six symptoms that results in a total of 15 combinations of two symptoms.

In focusing on how to determine if the depression is gone most clinicians like myself are looking at binary outcomes.  We are treating depression until the symptoms are gone.  Research studies depend more on metrics like rating scales that are done directly by the research subjects or researchers.  Remission or partial remission is based on the scores of those rating scales.  For example, a typical psychopharmacological study would look at either the amount of decrease on a depression rating scale or where the rating scale score is relative to the established cutoff.  For example, treatment resistance could be defined as less than a 50% reduction in depression rating scale scores after a course of treatment.  It could also be defined as a failure to attain the require responder score or remission score after an adequate course of antidepressant therapy.  In primary care these days, a lot of people are diagnosed and treated with a depression rating scale - the PHQ-9.  Their PHQ-9 scores are tracked and their depression is classified as remitted if their score is 5 or less (the total score ranges from 0-27).

For the purpose of this post consider the following scenario.  I see a person back after they have been treated with an antidepressant.  In reviewing whether the medication has been working the patient reports his sleep has normalized, he is eating and exercising well, he has gone back to enjoying his previous activities, and most of his depressogenic thinking has resolved.  He no longer has any hopelessness or suicidal thinking - the original reason for the referral.  For further clarification, the discussion proceeds to the issue of dysthymia:

MD:  "Do you remember the first time we talked and you told me that you had been depressed since middle school and it had never gone away?  With the improvement you are noticing right now - do you feel like it has gone away?"
Pt:  " I am a lot better but I still feel depressed.  I would say that I am about 60-70% better."
MD:  "We have covered pretty much all of the critical symptoms for depression.  Let me ask you - what else would need to clear up right now in order for the depression to be completely gone?"
Pt:  "I guess my wife and family would need to treat me better.  I know that you can't do much about that - but that is a big problem.  If that happened I would be feeling a lot better?"

What to do about what seems to be an external factor affecting our neat little conceptualization of depression?  A typical formulation considers this to be an external factor.  A factor amenable to environmental engineering or adaptation.  Either way, the patient is still depressed despite what appears to have been a significant treatment effect.  On dichotomous analysis of depressive symptoms appear to have resolved for the most part.  He could be handed a rating scale and score in the mild to moderate range.  But the most important part of the assessment is that he still feels subjectively depressed.  In the 1970s or 1980s general systems theorists proposed that the brain is able to develop models of the environment so well that becomes an important part of any central nervous modulated process.  Motor activity provides the most obvious models.  A person walking with a cane has a much different cortical representation of what walking with a cane is than before they walked with a cane.  The cane is an actual extension of the CNS process.  You can easily demonstrate this by going through the motions of brushing your teeth without the tooth brush.  Within seconds it is obvious that you are not engaged in the same process and the parts are much more than the weight and feel of the toothbrush.  Can this exist in depression?  Can there be brain representations of relationships that are disturbed and lead to chronic depression?

I don't see why not.  Many psychiatrists would see this as a bad thing.  Many critics of psychiatry would see this as a good thing.  I see it as a brain thing.  A person would have to be fairly naive to believe that the most complex object in the universe could be parsed into a couple hundred diagnoses based on verbal criteria.  That is why psychiatrists are extensively trained.  Trained psychiatrists should be able to do much more than read the DSM-5.  I think that this is where Kendler's idea about indexing is valuable.  These are ballpark estimates of problems that need further refinement both over the course of treatment and by active research.  Formulations of these estimates can allow for successful medical treatment as well as successful psychotherapy.

These formulations can also suggest when active treatment can stop and a person can pick up the ball and start to make a lot of discoveries on their own - whether they consider themselves to be chronically depressed or not.

There is more to life than a score on a rating scale.


George Dawson, MD, DFAPA


1: Carvalho ACCF, McIntyre RS. Treatment-resistant mood disorders. Oxford: Oxford University Press; 2015.

2: Greden JF, Riba MB, McInnis MG. Treatment Resistant Depression, A Roadmap for Effective Care. American Psychiatric Pub; 2011.

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