The Mail Online today refers to the UK as a “Prozac Nation,” saying that use of antidepressants “has soared by 500% in the past 20 years”.
The most widely used type of antidepressants are known as selective serotonin reuptake inhibitors (SSRIs). The current study assessed use of antidepressants as a whole, including SSRIs and other antidepressants such as tricyclic antidepressants and serotonin–norepinephrine reuptake inhibitors (SNRIs).
The study found that in almost all countries, greater increases in antidepressant usage were associated with greater reductions in suicide rates.
However, this study only looked at the population level, meaning it cannot conclusively prove that antidepressants are solely responsible for any changes seen. For example, the changes in antidepressant usage may also be paralleled by general improvements in mental health care that could also be influencing suicide rates.
Other factors may also have an influence, such as economic factors. The researchers did try to take some of these into account by adjusting for unemployment, divorce and alcohol consumption in these countries.
As suicide is a relatively uncommon event, it can be difficult to study it as an outcome in randomised controlled trials (RCTs) which generally include relatively small numbers of people followed for a limited period of time.
Therefore, alongside RCTs and individual level studies such as cohort studies, this type of country level research can help to provide useful additional evidence about the potential effect of antidepressants on suicide rates.
Where did the story come from?
The study was carried out by researchers from the New University of Lisbon and other research centres in Europe and the US. The project has received funding from the European Community. One of the authors declared being an advisory board member, consultant or speaker for various drug companies. It was published in the peer-reviewed, open access journal PLoS ONE.
The Mail Online’s headline takes a sensationalist approach – highlighting the “bad news” (countries’ antidepressant usage) while ignoring the “good news” (drop in suicide rates).
However the main body of the story does include both aspects of the findings. It also includes appropriate notes of caution on the findings from a study author. He said that “other factors should not be discounted – such as a country’s economic state, cultural mores and access to psychological services”.
He also notes that “a decline in suicide rates cannot be linked directly to antidepressants, but the evidence in support of them – when used appropriately – is pretty compelling”.
What kind of research was this?
This was an ecological study looking at changes in use of antidepressants and in suicide rates in Europe. The researchers say that a review of ecological studies showed mixed findings about the relationship between antidepressant use and suicide rates.
This type of study looks at information at a population level. That is, how many people take antidepressants in the population and how many people in the population have committed suicide. They then look at whether the patterns are consistent with one having an effect on the other.
However, it does not follow individual people and assess their antidepressant use and whether they commit suicide. This means that while it can provide evidence that the two factors may be related, it cannot conclusively prove that one factor is directly causing the other.
The researchers argue that there are three reasons for these studies being useful:
- there is a need to assess the long term effectiveness of antidepressants at the population level, especially due to increasing spending on these drugs – an increasingly important issue as most, if not all, countries are still recovering from the financial crisis of 2007 to 2008
- to detect an effect on the relatively rare event of suicide, they estimate that an RCT would need to have 20,000 participants, which may be difficult to achieve in practice
- they suggest that using suicide as an outcome in a RCT would be unethical
While these points are reasonable, the limitations of this type of study do still need to be borne in mind when interpreting the study’s findings.
What did the research involve?
The researchers collected data on use of antidepressants and suicide rates for 29 European countries between 1980 and 2009. They used various statistical methods to test whether and how these were related to each other.
The researchers used three sources for antidepressant drug use:
- wholesale drug figures from a database called IMS Health and OECD pharmacy
- sales data
- data from national statistical offices
- published literature
The researchers used a standardised measure of antidepressant use between countries so they could be compared.
This involved converting prescriptions to a measure called Defined Daily Dosage (DDD). DDD gives a rough estimate of use of antidepressants and the proportion of the population receiving treatment with a particular antidepressant on a daily basis. Some countries had data available for longer periods, and some for shorter periods.
The researchers obtained data on suicide rates from the World Health Organization’s (WHO) Health for All European Mortality Database (WHO-MDB). They assumed that countries’ data collection methods had stayed the same over time. The measure they used was a standardised measure called the Standardised Death Rate (SDR), which takes into account differences in the populations being compared.
They collected data on alcohol consumption, unemployment and divorce rates from the WHO Global Information System on Alcohol and Health, WHO European Region Health For All Database, and OECD Social Indicators databases.
They also looked at the relationship between alcohol consumption, unemployment and divorce rates and suicide rates. They also took these potential confounding factors into account when looking at the relationship between use of antidepressants and suicide rates.
What were the basic results?
The researchers found that over an average of 15 years, the use of antidepressants increased on average by 19.83% each year for the 29 countries included in the study. Over an average of 28 years, the standardised death rate for suicide reduced on average by 0.81% annually.
In all countries, except Portugal, there was what is called an “inverse correlation” between antidepressant use and suicide rates. This means that countries with greater increases in antidepressant usage tended to have greater reductions in suicide rates. This was true in the periods 1980 to 1994 and 1995 to 2009. However, the relationship was stronger in the earlier period.
The relationship with alcohol consumption, divorce, and unemployment rates varied between countries, with some countries showing higher rates of these factors being associated with higher suicide rates and some countries showing the opposite.
How did the researchers interpret the results?
The researchers concluded that “suicide rates have tended to decrease more in European countries where there has been a greater increase in the use of antidepressants”. They say that this “underlines the importance of the appropriate use of antidepressants as part of routine care for people diagnosed with depression, therefore reducing the risk of suicide”.
This study has shown that in most European countries, the increase in use of antidepressants over the years has been paralleled by a reduction in suicide rates. This suggests that one could be contributing to the other. The fact that there is the same pattern across 28 European countries does support a relationship between the factors.
However, as this study only looked at the population level, that is, did not find out whether the individuals taking antidepressants were less likely to commit suicide, it cannot by itself conclusively prove that antidepressants are solely responsible for the change seen. For example, the changes in antidepressant usage may also be paralleled by general improvements in mental health care, which could be influencing suicide rates.
There are also other limitations, which the authors acknowledge, such as the fact that the figures for antidepressant prescriptions may not fully represent antidepressant usage by patients, and that antidepressants may be prescribed for causes other than depression. The study also cannot look at unsuccessful suicide attempts.
As suicide is a relatively uncommon event, it can be difficult to study it in RCTs, which generally include small numbers of people followed for a limited period of time. Therefore, alongside RCTs and individual level studies such as cohort studies, this type of country level research can help to provide additional evidence about the potential effect of antidepressants on suicide rates.