As a psychiatrist, I have long worked to address mental diseases such as schizophrenia and depression. Experiencing first-hand the suffering and heavy burden these ailments place on people motivated me early on in my career to better understand the underlying mechanisms of these diseases and to help find new treatment possibilities. This is why I have devoted the majority of my professional life to neuroscience preclinical research, patient care, and clinical drug development.
Major depressive disorder (MDD) is the most common mood disorder, with life-changing impact on people such as decreased quality of life, functional impairment, and increased mortality rate. In fact, suicide related to depression is a major cause of death in industrialized countries.
While we have had antidepressants since the 1950s, in many cases people with depression still are not correctly diagnosed and treated. This can be due to stigma as well as perceived efficacy.
Biopharmaceutical research continues to improve care by developing novel antidepressants but periodically their benefits in daily practice are questioned. Skeptics sometimes argue that new medicines provide only limited additional efficacy over current therapies. These challenges can complicate biopharmaceutical research in psychiatric disorders but also provide me and others encouragement to take R&D to new levels.
We’ve long known the pathophysiology of these conditions involves many biological aspects such as mono-aminergic neurotransmitter changes, stress circuits dysregulation, and many other related disturbances. New approaches and new targets are needed. Innovation is not only associated with testing new targets but also with developing new ways to test. We need to identify clinical signals earlier, with more certainty, and in the right populations.
That is what we, at Lilly, are doing – investigating new targets related to those fundamental changes associated with depression. We have discovered molecules which target new mechanisms of action and might lead to treatment advancements for patients with mood disorders and other psychiatric diseases.
Our development work is still early, but current clinical data for one target are exciting enough that we hope to translate some of our preclinical findings and outcomes from animal models into practical clinical knowledge. To understand the potential benefits of this compound, we applied established technologies such as PET and fMRI. These helped us understand our target receptor and functional implication. Moreover, we used behavioral assessments and neurophysiological tools (clinical biomarkers) –new research tools for us – to identify treatment responses earlier.
The basis for the latter approach is that patients suffering from MDD often have cognitive negative biases. That is, they are more likely to remember negative information and pay attention to negative stimuli than to non-depressed subjects. To identify these markers early, we use behavioral paradigms based on psychological testing, and neuroimaging techniques such as fMRI. Using these experimental tools allowed for more effective signal detection and gave new insights in the mechanism of our compound.
Besides such clinical tools, genetics may help us in the next round of discovery and development to identify new targets in psychiatry and overcome the stagnation in the field.
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