The more you know

Antidepressant drugs work

The authoritative British scientific journal Lancet has published an article which – comparing data from 522 different studies – concludes that the 21 most popular antidepressant drugs are more effective than placebos for treating depression. It was not a foregone conclusion, given that the effectiveness of antidepressants is at the center of a debate in the scientific community. In recent decades, the idea has spread that in clinical trials on these drugs the number of patients who notice an improvement after taking a placebo (i.e. a pill that does not contain any active ingredients, even if those who take it do not know it) is increased. The problem is that large studies like these on the subject had never been done: and for this reason the idea has spread that pharmaceutical companies would modify the results of the studies in the way that suits them most and a certain conspiracy around psychiatric drugs.

The study published in the Lancet was done over the course of six years taking into consideration not only the data of all the studies on the main antidepressants published in the world, but also a series of unpublished data provided to researchers by pharmaceutical companies. All together, the data collected concern a sample of 120 thousand people with a diagnosis of depression. A team of 18 international experts led by Andrea Cipriani, an Italian psychiatrist who teaches at the University of Oxford, worked on the firm. Most of the drugs considered are selective serotonin reuptake inhibitors (SSRIs): they are used against depression because they increase the body’s levels of serotonin, a chemical that within the brain is involved in regulating mood, sleep and appetite, among other things.

In addition to demonstrating that antidepressants work better than placebos, the study compared the effectiveness of the different drugs with each other and their side effects. According to the effectiveness scale, the most famous of the antidepressants, that is Prozac or fluoxetine according to the generic name, is in 16th place, but it is one of the most tolerated by the participants in the studies: it is one of the drugs for which fewer side effects are reported and for which there is a low dropout rate from tests before they finish. The drug that according to the Lancet study is the most effective is amitriptyline, which in Italy is found as Adepril, Laroxyl and Triptizol; as far as tolerance is concerned, it is sixth.

The three drugs that, combining efficacy and tolerance, are the best in the study are agomelatine (marketed in Italy as Valdoxan and Thymanax), escitalopram (Cipralex, Entact) and vortioxetine (Brintellix). The three that are worst are fluvoxamine (Maveral, Fevarin, Dumirox), reboxetine (Davedax, Edronax) and trazodone (Triptych). Sagar Parikh of the University of Michigan and Sidney Kennedy of the University of Toronto, two doctors who did not participate in the study, commented on the study saying that doctors can consider the first three drugs as the “first choice” for prescriptions. although in cases of more severe depression it may be advisable to prescribe some of the more effective drugs, such as agomelatine and venlafaxine.

That said, the study does not indicate that certain drugs should never be prescribed: it is possible that even those that have been less effective in the studies done so far are the most suitable for some people, as Cipriani himself pointed out.

About 80 percent of people who are prescribed antidepressant drugs stop taking them after a month, which tends to be too early for them to have any real effect. However, antidepressants have a similar success rate to that of cognitive-behavioral psychological therapies. About 60 percent of people who take them experience a 50 percent decrease in symptoms within two months – in practice, they have a better mood, sleep better, and so on. There is no doubt that they are not the best possible drugs: there are still many things that psychiatrists do not know about the treatment of depression, which cannot simply be considered as the consequence of an imbalance of some chemical compounds in the brain. Unfortunately, for how the pharmaceutical industry works, there is not a lot of research in this field.

All the articles published so far in the general journals about the Lancet study are very enthusiastic. An article by New Scientist, however, invites us to carefully consider the data of the study: the studies that in the past had questioned the effectiveness of antidepressants concerned people with mild or moderate depression, while most of the 120,000 people whose data merged in the last study they had severe depressions. Because of this, says Clare Wilson of New Scientist, the enthusiastic headlines hold true for those with severe depression, but not for everyone else. This is no small thing, considering that the less intense forms of depression are the most common. We do not know what the effects of antidepressants are on these people and many think that psychiatrists prescribe them too easily, often without informing patients well of the side effects, including loss of sexual desire and the onset of agitation.

Another criticism that Wilson makes of the Lancet study concerns the reliability of the initial studies, those whose data were compared. “Experience has shown that pharmaceutical companies can cut and play with data to make their results look better than they are,” writes Wilson. An example: A 2001 study of paroxetine (not considered in the Lancet study) said the drug had a similar rate of side effects to placebo. In 2015, however, a group of researchers reviewed the original data from the study and found that paroxetine was linked to more cases of self-harm and suicide threats.

Wilson also points out that the study says nothing about the effectiveness of antidepressants in treating other ailments they are prescribed for, such as anxiety and certain phobias, nor that it is difficult for many people to stop antidepressant therapy, given that there are specific side effects when the dosage is reduced. It is generally recommended to reduce it gradually, but it is not always possible to do so, because some antidepressants are not produced in small enough dosages. The study also says nothing about therapies lasting more than eight weeks, the data of which were not considered. For this reason it is right to consider this study important, but not definitive.

The reason there are so many doubts about antidepressants is that they have different effects depending on the person they are prescribed to: many patients say they blunt emotions, some people hate them and say they make them feel like zombies, others that they are in able to lift them from the bad mood. There are also different experiences for side effects. According to Wilson, this confusion is the reason why there is a very polarized and often ideological debate on antidepressants but “as is often the case with science, the reality may lie somewhere in between.”


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