“How do antidepressant drugs work? Can we use this information to improve depression treatment of the future? ”

This talk is arranged as part of the Toronto-Oxford Psychiatry Collaboration, Catherine Harmer is giving the Paul Garfinkel Lecture at the University of Toronto (virtually).

Psychological and pharmacological approaches to the treatment of depression are often considered separately. However, recent evidence challenges this division and shows that antidepressants affect cognitive psychological mechanisms important for the maintenance of depression very early in treatment [1]. At a neural level, these early changes in emotional processing are related to re-tuning fronto-limbic circuitry important for the detection and response to biologically salient information [2]. Although these changes in neurocognitive processing occur before clinical changes in depression are seen, they are predictive of later clinical response [3]. These results are therefore consistent with the view that antidepressants work via early correction of negative bias and the delay in response reflects the need for changes in processing to interact with everyday events, stressors and cues. This work raises the possibility that early change in emotional processing may be able to predict later clinical response, allowing for treatment to be modified earlier for non-responders. This idea was recently tested in the Predict study across 5 EU countries in depressed patients. The results suggest that adjusting medication based on initial change in emotional processing may have value for clinical decision making.The implications for translating lab based assessments to the clinic will be discussed.
[1] Harmer, C.J., Duman, R.S., Cowen, P.J., 2017. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry. 4(5), 409-418. doi: 10.1016/S2215-0366(17)30015-9
[2] Godlewska, B.R., Browning, M., Norbury, R., Cowen, P.J., Harmer, C.J., 2016. Early changes inemotional processing as a marker of clinical response to SSRI treatment indepression. Transl Psychiatry. 6(11), e957.
[3] Godlewska, B.R., Norbury, R., Selvaraj, S., Cowen, P.J., Harmer, C.J., 2012. Short-term SSRI treatment normalises amygdala hyperactivity in depressed patients.Psychol Med. 42(12), 2609-261

Learning objectives
1. An understanding of the role of cognitive biases in depression and in response to antidepressant drug treatment
2. An understanding of the neural circuitry underpinning changes in cognitive bias with treatment
3. Reflections on our ability to translate lab based mechanistic studies into the clinic and ideas about how to improve translation