Depression affects millions of men and women and is one of the most commonly diagnosed mental disorders globally. The often stigmatised and sinister affliction is the leading catalyst of suicide in teenagers and young adults.
Individuals suffering from the disease or symptoms associated with it, have a life expectancy of up to a decade shorter than those without it, according to the World Health Organisation.
However, new research conducted by the Chinese Academy of Sciences (CAS) could provide a glimmer of hope to those battling the disease.
A medical research unit from the Interdisciplinary Research Centre on Biology and Chemistry (IRCBC) at CAS says it has developed a method to remove the unwanted side effects of Esketamine, a recently approved yet highly controversial antidepressant synthesised from the potent anaesthetic, Ketamine.
Esketamine, also referred to as S-ketamine, and its chemical variants have been widely used in medicine for nearly half a century. The compound was first patented in 1963 by Belgian chemists looking to develop safe and efficacious veterinary anaesthesia.
At high doses, the drug provides pain relief and sedation, with the subject having little to no memory of the experience. At lower doses, Ketamine is effective for pain relief and treatment-resistant depression.
However, the drug has developed a reputation for some of its adverse side effects, including hallucinations, hypertension and dysphoria. Prolonged use and abuse have also been associated with liver toxicity and urinary issues.
The team, in their research paper published in a September issue of Nature Neuroscience, claims to have isolated the previously understudied mechanism that induces the compound’s adverse side effects.
Esketamine works by directly targeting regions of the brain called NMMDA-type glutamate receptors, a neurotransmitter whose function is hypothesised to be the formation of memories, says the co-author of the study, Geng Yang. However, identifying the pathway that the drug uses to trigger its antidepressant effect has eluded scientists thus far.
In 2015, IRCBC-founder, Chen Yelin, set about solving the problem for good by isolating the target genes in lab mice and inactivating them to observe the results.
Two years later, he and his team identified the crucial receptor protein called, GluN2A which, when deactivated, removed Esketamine’s antidepressant properties while keeping its hallucinogenic effects.
The research unit found the discovery might assist them in the development of a “perfect” ketamine therapy that eliminated all of the compound’s undesirable side effects.
Chen and the IRCBC team are hopeful their work will be picked up by drug development firms and are confident clinical trials can begin as early as 2024.
While the breakthrough is promising, Zhejiang-based psychiatrist, Huang Manli, cautioned that even if all goes according to plan, it may take upwards of a decade for the potential wonder drug to be made available to the public.