Antidepressants alone are not enough

We should reconsider how we use antidepressants more effectively. The latest studies have shown that antidepressants restore the capacity of certain areas of the brain to repair abnormal neural pathways. According to neuroscientist Eero Castrén, the recipient of EUR 2.5 million of ERC funding, recovery requires redirection of these pathways through practice, rehabilitation or therapy.

“Antidepressants are not being used effectively.”

This is a surprisingly blunt view, even for a respected neuroscientist such as Eero Castrén. After all, millions of people throughout the world have been prescribed antidepressants, and pharmaceutical companies have made a billion-dollar business out of selling them. Surely the system cannot be entirely wrong?
Recent studies suggest that this may be the case. Research on animal models demonstrates that antidepressants are not a cure as such. Rather, their role is to restore plasticity in the adult brain. Antidepressants reopen a window of brain plasticity, which allows the formation and adaptation of brain connections through the patient’s own activities and observations, similarly to a young child whose brain and experiences about the world develop in response to environmental stimuli.    

Correcting abnormal pathways

When cerebral plasticity is reopened, problems caused by false connections in the brain can be addressed. Such problems can be manifested, for example, as phobias. Studies conducted on animal models by Professor Eero Castrén’s research group show that therapy helps to reduce fears for a time, but an antidepressant alone provides no relief. By combining the two, however, long-term effects can be achieved.

“Simply taking drugs is not enough. We must also show the brain what the desired connections should be,” Professor Castrén explains.

The need for both therapy and medical treatment may also explain why antidepressants sometimes seem to have no effect. If the patient’s environment and situation remain unchanged, the drug-induced capacity of the brain to change will not make the patient feel better.

Reaching this point is the result of years of research. Scientists discovered as early as the 1960s that antidepressants affect neurotransmitters in the brain, such as serotonin. Later, antidepressants were found to increase neurotrophins and their ability to transmit signals in the brain. Only recently have scientists begun to explore the effects of drugs on plasticity of brain networks.

Enhancing the plasticity of the adult human brain through antidepressants has opened a whole new field of research for Eero Castrén. He has received a five-year grant of EUR 2.5 million from the European Research Council (ERC) to investigate mechanisms related to adult brain plasticity.

A cure for functional amblyopia

Eero Castrén obtained his first results on the impact of antidepressants on brain plasticity by studying the visual brain cortex of an animal model. The results are now being applied to the practical treatment of lazy eye, or amblyopia, in adult humans.

Amblyopia occurs when vision in one eye is impaired in childhood. The brain learns to use only the visual information mediated by the better eye. The vision of the other eye remains weak even if the original reason of the impaired vision is resolved with glasses or an operation.

Amblyopia can be cured by rehabilitating the weaker eye. That is done by wearing a patch over the better eye.  Eero Castrén says that this type of treatment is effective only in small children.
“The visual cortex loses most of its plasticity before children reach school age. After that the patching treatment alone is no longer effective,” Castrén points out.  However, treating adult rats with an antidepressant drug reactivates juvenile-like plasticity in the adult visual cortex and makes patching treatment effective again.

Currently, a double-blind test on adult amblyopia patients is underway to test whether antidepressants have a similar effect in humans, too. To be completed this spring, the study aims to develop an effective treatment for amblyopia. The research is carried out by Hermo Pharma Ltd, a company established in 2008 by Professors Eero Castrén, Heikki Rauvala and Mart Saarma together with Dr Henri Huttunen.

“We aim for a new means of treatment, so we need support from the pharmaceutical industry. Proving the efficacy academically is just not enough. Amblyopia is rather a common disease which is accompanied with a deficiency in depth perception. New treatments are really needed” Eero Castrén says.

Text: Elina Raukko
Translation: Stephen Stalter
Photo: 123rf