最強の抗うつ薬はなにか？精神科医がぶっちゃけます。

Good evening. I'm Takahiro Haga, a psychiatrist. Today, I'd like to discuss the topic of "What is the most effective antidepressant?" as evidence-based as possible. This isn't just based on my clinical experience. Of course, in my daily practice, I sometimes feel that "this drug is strong" or "this drug is easy to use." However, this time, instead of relying on such personal impressions, I want to look at the effects of antidepressants based on data that integrates clinical studies conducted around the world. Antidepressants and the treatment of depression have been studied as a very important topic worldwide. Across national, cultural, and racial differences, many researchers have investigated whether antidepressants truly work and which drugs are more effective. A study that collects many such studies and re-analyzes them statistically is called a "meta-analysis." This time, I will organize the effects of antidepressants based on such a meta-analysis. A study that remains very important in considering the effects of antidepressants is the study by Cipriani et al., published in the medical journal The Lancet in 2018. This is a very large-scale meta-analysis of antidepressant clinical trials conducted between 1979 and 2016 as part of an international collaborative study involving institutions such as Oxford University in the UK and Kyoto University in Japan. The study included 21 types of antidepressants, 522 double-blind randomized controlled trials, and 116,477 adult patients with depression. A double-blind randomized controlled trial is a study in which patients are randomly divided into a drug group and a placebo group, and neither the patients nor the treating physicians know which group is receiving the real drug. This method aims to neutrally investigate the effects of a drug by minimizing biases such as physician expectations and patient expectations. This study uses an indicator called "response rate." That is, the percentage of people whose depressive symptoms improved by a certain amount or more compared to before treatment. The "odds ratio" is used as an indicator of the drug's effectiveness. This odds ratio is a somewhat difficult concept to understand. For example, let's say 30% of people improve with the placebo. An odds ratio of 2 for a particular drug doesn't mean that "30% will improve to 60%." This is a very common misconception. Roughly speaking, an odds ratio of 2 means that while a placebo group might improve by 30%, the antidepressant group might see an improvement in the mid-40% range. In other words, antidepressants are not "drugs that dramatically cure everyone." Depression has a natural course, and improvement also comes from seeking medical attention, adjusting one's lifestyle, receiving support, and simply having hope. Even in clinical trials, the placebo group isn't doing nothing. They receive medical attention, have their progress monitored, and receive support. Within that context, a certain percentage of people do improve. Therefore, it's more realistic to understand the effect of antidepressants as "raising the improvement rate from around 30% without any intervention to the 40% range." This is by no means a small difference. In actual clinical practice, that 10% to 15% difference can be very significant. However, having too much of an image of "dramatic improvement immediately after taking the drug" can lead to a large gap between expectations and reality. Antidepressants act on neurotransmitters such as serotonin and norepinephrine, increasing neuronal plasticity via BDNF and gradually aiding brain recovery. I often explain it like taking vitamins for skin problems. Vitamins alone won't instantly improve your skin. They only work after sleep, diet, stress levels, and lifestyle habits are in order; they gradually enhance the effects. Antidepressants are somewhat similar. So, which is the most effective among them? In a 2018 meta-analysis by Cipriani et al., amitriptyline had the highest odds ratio for response to placebo. Its brand name is Tryptanol. This is a tricyclic antidepressant, a fairly old drug. Currently, it's less frequently used as a first-line antidepressant. The reason is its numerous side effects. Compared to SSRIs and SNRIs, it's more difficult to manage, with side effects including dry mouth, constipation, drowsiness, dizziness, anticholinergic effects, and effects on electrocardiograms. However, in terms of effectiveness alone, it is strong. The odds ratio for amitriptyline is approximately 2.13, the highest result in this analysis. In other words, if we consider only its "ability to lift depression," Tryptanol is a very strong drug. I myself, from a clinical perspective, also believe that Tryptanol is a strong drug. However, due to the problem of side effects, it is not a drug that can be used casually for everyone. Currently, it is often used for purposes other than antidepressant effects, such as refractory insomnia, chronic pain, migr...