ON PRESENT AND NOVEL TREATMENTS FOR DEPRESSION

We aim to shed further light on established antidepressants and to pursue a possible new treatment for difficult-to-treat cases.

Subproject 1: In item-based, patient-level analyses of placebo-controlled clinical trials, 3 issues will be addressed. 1) Are there differences between antidepressants in terms of efficacy? 2) How often does discontinuation of an SSRIs/SNRIs cause psychiatric withdrawal symptoms and for how long do such symptoms last? 3) Are there other predictors of relapse in subjects having recovered during with an SSRI/SNRI and then continued with active drug or placebo.

Subproject 2: (-)-OSU6162 is a silent dopamine D2 receptor antagonist named a dopamine stabiliser since it – unlike other drugs targetting the dopamine synapse – enhances psychomotor activation in inactive animals while dampening it in active animals.

There are several reasons why this molecule may be expected to exert antipressant properties, and we are currently exploring if this is the case and also assess possible predictors for response.

We also try to shed further light on the yet unresolved mechanisms of action of this highly intriguing compound with respect to its impact on psychomotor activity, which appears even more complex than previously understood.

Finally, we are assessing similarities and dissimilarities between different established or putative antidepressants, including (-)-OSU6162, ketamine, psilocybine, and elctroconvuslive treatment, with respect to the BDNF/mTOR pathway.