Resilience-Boosters : A New Class of Antidepressants?

Sunayana Sibal

For the Exam Bonus

Resilience can be understood as the ability to persist in the face of life challenges that evoke distress. Although resilience has been conventionally thought of as a skill that can be developed over time with effort, recent research suggests that resilience may in fact be determined by certain neurobiological factors which manifest early in life.

It is fascinating to know that neuroscientists have developed a drug which can boost the amount of resilience individuals displays. Currently this drug is being tested before approval. Many neuroscientists have argued that this resilience-boosting drug could be a key force to reversing depression amongst clients. A resilience boosting drug would be particularly significant in today’s time when depression is prevalent and the current treatment for depression seems to provide only transient relief.

To test the relationship between depression and resilience, experimenters first explored the neuro-biology underlying resilience. In resilient mice, there was a significantly larger number of genes underwent regulation as compared to mice that exhibited distress. Ming Hu-Han and his associates observed that the neurons in the ventral tegmental area for distressed mice were hyper-excitable. Excessive stimulation of neurons in this situation has been linked to lack of motivation and depression. It was found that in resilient mice the hyper-excitability was significantly higher than it was for non-resilient mice. Following the higher hyper-excitability in resilient mice, Han and his associates observed an offsetting effect wherein the rapid firing of neurons reduced. This offsetting effect was not observed in non-resilient mice.

Han then tested if the drug Lamotrigine could be used to induce the offsetting effect in the non-resilient mice and thus reverse depression. Lamotrigine is generally used to treat Bipolar Disorder but can induce the desired offsetting effect and hence was an appropriate choice in this case. 

Based on Han’s research with the rats, a pilot study was conducted using the anti-epileptic drug Ezogabine. Eighteen people were subjects in the pilot study. The results indicated that Ezogabine did reduce the depressive signs displayed by participants and thus induced resilience.  One salient limitation of this study that must be noted is that there was no control for placebo effects, without which it becomes difficult to draw accurate conclusions.

It is evident that drugs to boost reliance and decrease depression would be very beneficial. However, caution must be exerted. One must consider the applicability of findings gathered from animal research to human clients. Further, preliminary trials for drug effectiveness may provide misleading results. 

David Nutt from the Imperial College of London argue that drugs like Fludac do in fact work on the same principle of reducing hyper-excitability in the neurons however they target different cells than drugs such as Ezogabine. Nonetheless, it would be fruitful to see which of these drugs is more effective.

Neurological screening illustrated that the same reward neuro-circuit involving the Vental Tegmental Area was stimulated for the same drug in the case of both human beings and animals. 

To test against baseline effects, a bigger placebo control study is now being conducted. Although the production of Ezogabine had to be put to a stop, different and new drugs that boost resilience by moderating the quantity of potassium in neurons could be produced. Resilience-boosting drugs could add a new category of medication altogether to the list of treatment measures for depression - MAOs, SSRIs and Anxiolytic amongst others.

While resilience-boosting drugs do seem to be promising, the effect of this class of drugs must be very carefully examined in conjunction to various mental health disorders other than depression as well, since depression is often comorbid with other disorders. A mental health disorder ‘x’ distinct from depression may be attributable to hyper-excitability of neurons. If a patient has both mental disorder ‘x’ and depression, then could resilience-boosting drugs help reduce depression but act as an agonist, increasing the incidence of mental disorder ‘x’. This calls for careful examination of the effects resilience-boosting drugs have on all mental health issues that tend to exist in comorbidity with depression. Similarly, the effect of resilience boosting medication on patients suffering from epilepsy – which has been linked to the hyper-excitability of neurons, must be cautiously tested. 

There are a multitude of neural pathways and circuits in the human brain. The findings of resilience-boosting drugs indicate that there is much to explore in the field of neuropsychology and the potential to develop new drugs which target a number of mental health disorders is promising. This opens up exciting avenues for research and treatment of mental health disorders.