Depression Drug Development: Researching New Mechanisms to Source Novel Antidepressants

depression drug development
Millions of people suffer from depression, but some patients remain unresponsive to current treatment options. Does the key rest with depression drug development based on new mechanistic approaches?
Image source: Flickr CC user Carsten Schertzer

Major depressive disorder, or simply depression as it’s often referred colloquially, is one of the most common forms of mental illness today. Due to the number of people afflicted, many pharmaceutical companies have dedicated a large amount of resources to develop medications that can treat and manage the mood disorder. In fact, there are over 20 types of antidepressants currently available on the market.

Despite the variety of approved medications, many people with depression—especially those with the chronic form of the disorder—continue without relief as existing drugs fail to help their condition. As a result, some patients have turned toward alternative methods such as repeated exposure to near-infrared light1 and infusions of a staple anesthetic popular among veterinarians and burn centers. And while the latter treatment, in particular, has caused some excitement within the psychiatric community due to its fast-acting effects and high efficacy among patients, the fact is that its results are only temporary. Patients can relapse only one week after an infusion.2 Such a treatment may function well as a stopgap in cases of people with serious symptoms of depression, but we cannot consider this viable in the long-term. The costs and dosing schedule necessary to administer the infusions could be untenable to the patient.

New Approaches to Depression Drug Development

The antidepressants currently available on the market target the neurotransmitters responsible for encoding emotion in our brains. But because each of these drugs helps only about a third of depression patients, it’s become increasingly obvious that we must consider other biological mechanisms when it comes to depression drug development. In other words, we must shift our way of thinking. Rather than looking at the neurotransmitters, we need to see if we can exploit other disease mechanisms.

Some researchers are already doing this. One project involves a drug that utilizes a completely different mode of treatment. Instead of interacting with neurotransmitters, the drug stimulates neurogenesis, or the production of new brain cells. In this specific case, the new growth takes place in the hippocampus. We typically associate the hippocampus with learning and memory, but loss of nerve cells located in this region has been linked to depression. Early clinical trials of the drug confirm this connection by demonstrating a profound antidepressant effect. Not only did patients taking the drug show marked improvement, the results lasted for several months after they stopped treatment.3 Its oral administration route is also more convenient than other novel options that require invasive infusions.

The drug candidate is still in early clinical trials, but these results suggest that other companies should focus on depression drug development based on new biological mechanisms. Given this specific drug candidate’s ability to induce neurogenesis, further plans to test its efficacy in treating other neurological conditions such as Alzheimer’s disease, strokes and traumatic brain injuries are currently in the works. In today’s competitive pharmaceutical market, a product that can address a variety of diseases and conditions would offer a boon to any life sciences firm’s catalogue.

What other biological mechanisms are implicated in depression beyond neurotransmitters and loss of nerve cells? Life sciences organizations can use the neurogenesis-stimulating drug as an example and develop novel depression medications based on similar strategies. Can other drugs encouraging nerve cell growth be created? What about ones that improve neuroplasticity? Poor neuroplasticity has also been implicated in major depressive disorder.

No matter the mechanism studied, we’ve reached the point where new approaches to depression drug development must be adopted. In addition to the patients who remain unserved by currently approved medications, there is also the matter that sometimes these medications lose their efficacy after long-term use, requiring that depression sufferers find other alternatives. Wouldn’t a drug that is well-tolerated and has long-lasting effects due to the mechanism behind its efficacy be more attractive? Even then, considering the complicated biological processes involved in depression, it’s doubtful that one drug will be able to help everyone. Multiple drugs are necessary. We just have to discover and develop them.

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  1. “New depression treatment using low-level light showing promise, needs more study,” March 10, 2016,
  2. “Ketamine offers new hope for drug-resistant depression,” February 22, 2016,
  3. “New Type of Antidepressant Shows Promise in Early Trial,” December 8, 2015,