As many as 1.2 million Dutch people take antidepressants. The drugs are known to take a number of weeks to have an effect. Only now is it really clear why this is the case: antidepressants increase the number of connections in the brain.
Most antidepressants are so-called selective serotonin reuptake inhibitors (SSRIs). They prevent the reuptake of serotonin, leaving more of the neurotransmitter active in the brain. In this way, the medications suppress anxiety symptoms and make people feel better. However, that will take a while. The drugs only have an effect a few weeks after starting use.
More synapses
It is important to understand this delayed response so that doctors and psychologists can explain to patients why they should continue treatment. In the first ever human study, researchers therefore looked at changes in synapses – the connections between nerve cells – after treatment with antidepressants in otherwise healthy adults. “We found that over time, those who took SSRIs experienced a gradual increase in synapses in the neocortex and hippocampus in the brain,” explains neuroscientist Gitte Knudsen of the Copenhagen University Hospital.
Besides the fact that it takes a while for the drugs to have an effect, they also do not work equally well for everyone. It is also unclear why this happens, because the precise mechanism behind the effect is not well known. The theory is that SSRIs cause an increase in synaptic plasticity in the brain. This ability of synapses to grow stronger or weaker over time is likely important for learning, memory, and mood regulation.
Placebo or not
To test this, the Danish researchers a double-blind study conducted on 32 adults without depression. The participants either received a daily dose of 20 milligrams of escitalopram (an SSRI) or a placebo for five weeks. A PET scan measured the level of a protein called SV2A in the brain. Higher levels of this protein in a specific brain region indicate a greater density of synapses. There appeared to be considerable differences between the two groups. People who took escitalopram had more SV2A in their neocortex and to a lesser extent in the hippocampus than those who received a placebo.
Afbeelding: Marc Dingman, Neuroscientifically Challenged
The neocortex, which accounts for about half of our brain volume, is responsible for higher mental processes, such as emotions, sensory perception and cognition. The hippocampus plays a role in learning and memory. “The results indicate that SSRIs increase the density of synapses in the brain areas involved in depression,” Knudsen responds. “It appears that synaptic density in the brain is involved in how these antidepressants function. That gives us a target for the development of new drugs for depression.”
29 days
It also became clear that the antidepressants needed some time before the differences emerged. During the first 29 days of the study, there was no difference in SV2A density between the escitalopram group and the placebo group. It also appeared that the density of the number of synapses was greater in people who took the antidepressant for a longer period of time, compared to short-term use. “Our data shows that synapses increase over a period of weeks, which explains why it takes time for these drugs to take effect,” the neuroscientist said. “We didn’t see any effect in the people who took a placebo.”
The researchers deliberately chose people who did not have depression, because this way the effect of SSRIs on synaptic plasticity could be studied without the disruption of psychological complaints. But that also means that more research is needed to see whether the same thing happens in people with depression and whether an increase in synapses also leads to an improvement in psychological health.
Puzzle solved
“The delayed action of antidepressants has long been a puzzle to psychiatrists, in fact since their discovery fifty years ago,” says neuroscientist David Nutt of the Imperial College London, who was not involved in the study. “So this new data from brain scans in humans, showing that there is a gradual increase in the number of brain connections, is very interesting.”
2023-10-18 11:02:01
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