What predict non response to first line depression treatments? Biol Psy. Oct.2014


Remission of depression with the first  antidepressant occur in  40% of patients only. Second steps benefit another 15-20%. Lack of response to initial agents usually indicate  a poor outcome.There are many predictors that can help us in choosing a particular treatment. However, for these to be clinically meaningful, these predictors should tell us the possibility of response to a range of treatments that are available rather than to a single agent.

Metabolic activity in right anterior insula has been shown to predict the response to either escitalopram or CBT. The same group (  McGrath et al Emory University) is now reporting predictors of non response two either of these two treatments ( SSRI or cBT). If we can predict who will not respond to these strategies, patents could straight away try some other treatments.

Patients received CBT or Escitalopram for 3 months ( random) and then combined for the next 3 months. Non response= no response over 6 months. Hamilton score 15 or above was needed to be randomised. Those with substance use, medical conditions,psychotic features, suicidal features etch ere excluded. Escitalopram was given 10mg/day with option to increase to 20mg/day. 16 CBT sessions were given.


82 patients were randomised. Phase 1 remission rates were similar (36% for CBT and 40% for  Escitalopram). Baseline Sub Callosal Cingulate (SCC) metabolism was higher in patients who failed to respond to both treatments compared with patients who achieved remission with either treatment. Superior temporal sulcus activity was also increased in the non remitters.

Hyperactivity of SCC was previously reported in resistant depression. Increased connectivity of SCC to default mode network is also reported in recurrent depression. Deep brain stimulation for resistant depression targets this area. All these are converging evidence to suggest that SCC activity is a crucial factor in non response.

Limitations– Patients achieving response were excluded from significance tests. This was because  researchers wanted clear differences in clinical picture and link that to structural/ functional parameters. Small number of participants, need replication.

Conclusions: SCC hyperactivity could be predictor of non response to first line treatments ( SSRI or CBT). if consistently and significantly shown, such predictors may one day help clinicians to fast track patents to most appropriate treatments.

Summary of the article:

Pretreatment brain States identify likely nonresponse to standard treatments for depression.

McGrath CL, Kelley ME, Dunlop BW, Holtzheimer Iii PE, Craighead WE, Mayberg HS.

Biol Psychiatry. 2014 Oct 1;76(7):527-35.

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