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Why do antidepressants work for some people but not others?

By Meghan Masotti


Living with depression may feel like you’re underwater. The depth and turbulence of the water can vary day by day, or person to person. No matter where they are in the turbulent seas, many search for a life vest only to find very little to grab on to. Sometimes, the life vest offers a respite. Other times, we may be thrown back underwater. What life vests are available to us depend on current treatments for depression, which are complicated and on-going, with stumbles and setbacks along the way. Most of us are familiar with the experience described, either our own or our loved ones with depression. Depression is a unique and personal experience. Symptoms vary, and how they affect people are as distinct as the people themselves. For some, the drug treatments helped. For others, they may have done more harm than good. But drugs are supposed to work, right? Then why do so many people suffering with depression disagree?


For years scientists have believed that depression, like other mental illnesses, is caused by an imbalance in certain chemicals important for your brain to work. These chemicals, called neurotransmitters, help your brain communicate with itself and your body. A few neurotransmitters have been linked to depression. One of these neurotransmitters, serotonin, has been shown to be decreased in the brains of people with depression. While there are many types of antidepressants out there, the most common ones affect serotonin levels. Emerging as the leading treatment for depression, selective-serotonin reuptake inhibitors (SSRIs) work by blocking the breakdown of serotonin in your brain. Less breakdown of serotonin results in an additive effect- non-broken down serotonin plus any newly released are now available for the brain to work with.

While research suggests these treatments are able to successfully boost serotonin, not everyone feels better taking them. But why? Recent studies have looked into how many people are helped with standard courses of antidepressants. One study estimates that 40-60% of people are helped by antidepressants. Of these 40-60%, only a 20% decrease in depression symptoms are observed on average. If the treatment worked, why didn’t the symptoms go away? SSRIs also come with a host of side effects. While research suggests SSRIs act on the brain to do their job, they also can have unwanted effects. People who take SSRIs describe feelings of anxiousness, weight gain, sleep disturbances, and sexual dysfunction. These effects could be the result of serotonin in other parts of the body. 95% of serotonin is found in the gut, and it's known to have effects on digestion. Nerves and muscles also respond to serotonin, and the heart uses it to coordinate beating.


Image Credit: Shutterstock 2022544571


Scientists don’t currently have concrete answers to why antidepressants have varied effects. Some believe that people don’t respond to antidepressants in the same way because each person is a little different. Some people are better at breaking down drugs when they enter the body, leaving less to work in the brain. Others have lower levels of neurotransmitters, and any boost can cause noticeable differences. Each of us is unique in how our brains and emotions work and it's possible drug treatments for depression just can't keep up.


Perhaps future drug therapies lie in the complexity of the brain. Our brains use many neurotransmitters, not just serotonin. Future treatments may look at other neurotransmitters linked to depression. For example, some scientists are looking at glutamate, another neurotransmitter recently linked to depression, as a new potential target. Similarly, some researchers acknowledge that every person’s depression may be caused by unique changes in brain chemistry, and are hunting down ways to identify the cause and tailor treatment. Identification of these “bio-markers”, or bodily clues, would allow for better selection of therapeutics earlier in depression. Other researchers are taking a different approach entirely, instead wondering how we can make our brains more adaptive. Their goals are to increase our brain's ability to change, and with that change help move away from depressive symptoms.


The only way to know if therapeutic treatments for depression will ever be the life vest we're looking for is through continued understanding of how the brain works. Scientists are invested in understanding the billions of connections in the brain and using that knowledge to create new treatments. This push to dive into the depths of the human brain is transforming the way we understand depression. Scientists continue to seek new therapeutics targeting different chemicals, different parts of the brain, and different parts of the body. These combined efforts just might help more people escape the turbulent seas of depression.

 

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If you're interested in reading more check out these evidence-based sources I used in researching this answer!












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