 Why do antidepressants take so long to work? Anyone who has been prescribed an antidepressant has likely heard the same warning. Don't expect to feel the difference right away. It may take six to eight weeks for this medication to have its effect. However, the reasons why antidepressants don't work right away are not well known. This is more than just a matter of academic curiosity. For someone struggling with depression, being told that the light at the end of the tunnel is potentially still months away can fight against the sense of hope that is so necessary for recovering from depression. The answers to the question of why antidepressants take so long to work are complex, but let's start with what we know. Most antidepressants work by increasing the amount of serotonin and neurotransmitter that is active and available in the brain. While there is no evidence that depression results from any sort of inherent chemical imbalance per se, the fact remains that medications that increase serotonin are effective at reducing the symptoms of depression in the majority of people who take them. What is perplexing about these medications is that the increase in serotonin happens within minutes of taking the drug, but the effect on depression isn't seen until weeks or months later. This is not what we might expect. After all, many other psychoactive medications have noticeable effects that precisely coincide with their biological action in the brain. Why are antidepressants different? One theory suggests that it has to do with the way that depressed people process information. To put it simply, people with depression see the world differently. Depression causes a tendency to focus on negative rather than positive stimuli. When presented with a list of words, for example, people with depression are more likely to focus on words like hate or pain rather than love or comfort. When shown a variety of faces, a depressed person will fixate on people with negative facial expressions while blocking out those with positive expressions. This phenomenon is referred to as a negative affective bias, negative for being sad or pessimistic, affective referring to one's current emotional state, and bias for being drawn to certain stimuli over others. Take a look at this painting and notice what your eye is drawn to. Is it the bright colors? The friends enjoying each other's company? The girl playing with her dog? These are the first things that jump out to many people. However, for someone in a state of depression, something else may stand out instead. Look at the girl towards the middle of the scene. She isn't talking with anyone else and instead quietly sips her glass of wine. Her face betrays a sense of loneliness, distinct from the sea of happy expressions around her. Someone with a negative affective bias is more likely to focus on this girl, drawn as if by an invisible magnet to her melancholic disposition. This will likely make people with depression think of their own sense of loneliness or isolation, pulling them back into a depressive mindset from just looking at a painting that, for most people, brings a sense of joy. In this way, negative affective biases trap people in a vicious cycle. By automatically focusing only on the sadder aspects of life, the thought patterns of depression are constantly reinforced. So how do antidepressants play into this? Studies have found that, while antidepressants don't instantly cure depression, they do cause an immediate decrease in negative affective biases. Tellingly, this change in perception perfectly coincides with the drug's serotonin boosting effect in the brain. Within minutes of taking an antidepressant, people with depression are more able to remember positive words and are less fixated on sad parts of images. When shown neutral facial expressions, they are more likely to register the face as happy or, at the very least, not sad. These effects are seen even when people without depression are given these medications, suggesting a primary drug effect. By targeting the negative affective biases found in depression, antidepressants set the stage for a gradual unlearning of depressive thought patterns. Like any form of learning, this process will not happen overnight. Rather, it will take days, weeks, months, or, in severe cases of depression, even years, to learn to see the world as a more hopeful, less threatening place. The involvement of negative affective biases explains much of what we see with depression treatment. Some studies have found that the extent to which an antidepressant will ultimately help someone can be predicted by how much it changes their emotional processing within even the first few days of treatment. It also explains why certain forms of therapy, such as cognitive behavioral therapy or CBT, are just as effective as drugs for depression and in roughly the same amount of time. While CBT uses therapy rather than medications to target negative affective biases, the result is the same. Someone with depression is encouraged to establish new thought patterns and learn different ways of interpreting the world. On a biological level, a protein called brain-derived neurotrophic factor, or BDNF, is believed to underlie many of these changes. BDNF plays a major role in forming new connections between nerve cells in the brain. Studies have found that antidepressants ramp up the production of BDNF over time in a way that coincides with the gradual learning of new thought patterns. This could potentially provide a biological explanation for the patterns we see during antidepressant treatment, but more research is needed to make a definitive conclusion. There are newer treatments on the way that could change the way we approach depression. One drug that is making waves in the world of mental health is ketamine, an anesthetic which has been shown to result in immediate reductions in depressive symptoms within minutes or hours of administration. However, the flip side is that these changes rarely last more than a few days or weeks. While the exact mechanisms are still being uncovered, it is likely that rapid-acting antidepressants like ketamine are simply not capable of engaging the learning processes that underlie existing antidepressant treatments. As they say, easy come, easy go. Like any theory, the idea that negative affective biases are involved in depression is not without its detractors. Some have pointed out that some antidepressants do not involve serotonin at all, yet still work in a delayed fashion, an area that deserves further study. Others have argued that what we call a negative affective bias is, in fact, a more accurate way of looking at the world than the happy-go-lucky state of mind that non-depressed people live in, a theory known as depressive realism. This topic is complex enough to warrant another discussion entirely, but it's an interesting idea that some people might want to look into. Ultimately, there's no getting around the fact that antidepressants are not simple, one-shot drugs that target depression like a silver bullet. They don't work in the way that many people think, leading to dashed hopes and unmet expectations. While this can be frustrating, there is a silver lining in knowing that, by catalyzing the process of learning new ways of thinking and interpreting the world, antidepressants can create lasting changes in a way that one-shot drugs rarely can. Thank you so much for watching this latest video. Sorry it's taken a while for it to come out. If you're interested in learning more about this topic, I suggest reading the articles that inspired this talk. The links are down in the description. If you're wanting to learn more about psychopharmacology in general, consider getting my book, Memorable Psychopharmacology from Amazon. You can also check out my other videos and subscribe to my channel to be notified when new ones are posted. Until next time, take care.