Which drug is better than ketamine

depressionLooking for alternatives to ketamine

Most antidepressants take two to three weeks to show their effects. It's too long for severely affected patients, says psychiatrist Roland Duman of the American Yale School of Medicine.

"Ketamine has great potential here; it could revolutionize the treatment of depression, especially in suicidal patients who can't wait that long."

Researchers at the Berlin Charité are not that euphoric after their first treatment experiences. They tried ketamine on patients who did not respond to some other drugs. After all, a third of these severely depressed people reported a rapid improvement in mood. Not a miracle cure, but very promising. Side effects such as hallucinations did occur, but hardly affect the patient. This generated great interest not only among the sick, but also among users of party drugs. Some of them even tried to sneak into the study. No wonder there is great interest in safe alternatives to ketamine. But they are difficult to construct because the drug's mechanism of action is still in the dark. Ketamine influences the neurotransmitter glutamate, but also a whole range of other signaling systems. Roland Duman is therefore trying to at least narrow down the drug's site of action in the brain in experiments with rats. The experiments focus on part of the anterior cerebral cortex.

"This region controls the mood and the emotions. With depression and under constant stress it shrinks, the connections to the emotional centers wither."

Here in the infralimbic cortex, ketamine is said to attack. If Roland Duman blocks the nerve cells at this point, the drug no longer works. If, on the other hand, he injects ketamine into precisely this region of the brain, his test rats appear less depressed. Now you cannot ask a rat about its mood, but the animals approach food in an open area without cover more courageously, they do not give up so quickly in an endurance swim test and are also more receptive to sugar water. And all of this directly after the treatment and not after weeks as with other antidepressants. Duman:

"Ketamine stops the loss of nerve cells and even leads to the creation of new connections."

In a further experiment, Roland Duman was able to achieve the effect entirely without drugs by first making the nerve cells in the intralimbic cortex sensitive to light using genetic tricks and then activating them specifically with a laser.

"There was a controversy as to whether ketamine achieves its effect against depression by activating or inhibiting the nerves. It is now clear that activation in this very region of the cerebral cortex is central. This will help us decisively in the future."

Roland Duman is in the process of finding out which receptor ketamine binds to on this particular nerve. Once that is clear, it should be possible to find variants of the molecule that work quickly against depression without causing hallucinations or addiction problems. Until then, psychiatrists at Yale, Berlin and other clinics are continuing to explore the real potential of ketamine, albeit under strict medical supervision.