Urgent need to optimize treatment in major depression

Residual symptoms reduce the likelihood of return to pre-depression functioning and increase the risk of relapse. Since patients with Major Depressive Disorder (MDD) want full restoration of functioning, and since repeated relapse is devastating for the brain, we should aim to do the best we can and as quickly as we can, Siegfried Kasper (Medical University of Vienna, Austria) told at an ECNP symposium on recovery in the era of personalized medicine.

The Europe-wide Group for Studies of Resistant Depression (GSRD) does what it says on the box: data have been collected on approaching 3000 patients across at least six countries. To reflect real-world practice, patients are recruited from both university and non-university settings, represent both in- and out-patients, span the range of disease severity, and include those with mental health and physical comorbidities that would prevent their participation on clinical trials.

To date, the GSRD has published 65 peer-reviewed papers. An important recent finding (based on tertiary referral centers) is that polypharmacy for MDD is common. A third of patients were co-prescribed a benzodiazepine or related drug, 29% more than one antidepressant, and 24% an antipsychotic.

The brain deteriorates with each episode of major depression

Professor Kasper attributes the high rate of benzodiazepine prescription to the presence in many patients of agitation and anxiety. This is important, in his view, since the presence of comorbid anxiety disorder is associated with a four-fold increase in risk of treatment resistant depression.2 This is greater than the increased risk associated with non-response to the first antidepressant ever received, and presence of melancholic features. 

Depression is devastating for the brain

A publication now in press will confirm that the presence of an anxiety disorder – along with severity of symptoms and higher number of prior episodes of MDD -- predict treatment resistance. The adverse effect of repeated episodes of major depression, in particular, is something that Siegfried Kasper argues which should be more widely acknowledged.

The likelihood of response falls from 43% in first-episode MDD to 31% with the fourth episode. In its effects, both on structure and on function, depression is bad for the brain.3 And an old but still relevant study shows a clear relationship between duration of untreated depression and reduced hippocampal volume.4

We should aim for early detection of MDD, and its early and effective treatment

Can subtyping help us improving the rates of response and remission?

An approach using clustering of symptoms to identify subtypes of depression reflects the widely-held belief that people with depression differ from one another in ways that can potentially help the logical choice of treatments. One such system advocates subtyping based on anxiety, fatigue, insomnia and pain. 5

Aim for measurement-based care

Assessment of depressive symptoms has become more feasible with the development of computerized tools such as, THINC-It and structured interviews

In the future, we may very well have genetic and other biomarkers to guide selection of treatment. In the meantime, however, we are left with clinical characteristics. Comorbid anxiety has attracted Professor Kasper’s particular concern: if it is not taken care of, the risk of treatment resistance is high.

These themes were taken up by Eva Českova (Masaryk University, Brno, Czech Republic). We should regularly assess depressive symptoms, she urged. Persistent problems include disrupted sleep and cognitive dysfunction, and she further noted that their assessment has become more feasible with the development of computerized tools such as, THINC-It and structured interviews.

Residual symptoms increase the risk of relapse and recurrence, shorten the duration between depressive episodes, and impair function and quality of life

Our aim should be to deal with residual symptoms, which are present even in patients with remission. Such residual symptoms increase the risk of relapse and recurrence, shorten the duration between depressive episodes, and impair function and quality of life.

Educational financial support for this symposium was provided by Angelini


  1. Dold M et al. Eur Neuropsychopharmacol 2016;26:1960-1971
  2. Schosser A et al. Eur Neuropsychopharmacol 2012;22:453-468
  3. Maletic V et al. Int J Clin Pract 2007;61:2030-2040
  4. Shelin YI et al. Am J Psychiatry 2003;160:1516-1518
  5. Lin SY et al. J Am Board Fam Med 2014;27:151-159
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