To study the potential association of antidepressant use and suicide at a population level, we analyzed the associations between suicide rates and dispensing of the prototypic SSRI antidepressant fluoxetine in the United States during the period 1960–2002.
Methods and Findings
Sources of data included Centers of Disease Control and US Census Bureau age-adjusted suicide rates since 1960 and numbers of fluoxetine sales in the US, since its introduction in 1988. We conducted statistical analysis of age-adjusted population data and prescription numbers. Suicide rates fluctuated between 12.2 and 13.7 per 100,000 for the entire population from the early 1960s until 1988. Since then, suicide rates have gradually declined, with the lowest value of 10.4 per 100,000 in 2000. This steady decline is significantly associated with increased numbers of fluoxetine prescriptions dispensed from 2,469,000 in 1988 to 33,320,000 in 2002 (rs = −0.92; p < 0.001). Mathematical modeling of what suicide rates would have been during the 1988–2002 period based on pre-1988 data indicates that since the introduction of fluoxetine in 1988 through 2002 there has been a cumulative decrease in expected suicide mortality of 33,600 individuals (posterior median, 95% Bayesian credible interval 22,400–45,000).
The introduction of SSRIs in 1988 has been temporally associated with a substantial reduction in the number of suicides. This effect may have been more apparent in the female population, whom we postulate might have particularly benefited from SSRI treatment. While these types of data cannot lead to conclusions on causality, we suggest here that in the context of untreated depression being the major cause of suicide, antidepressant treatment could have had a contributory role in the reduction of suicide rates in the period 1988–2002.
An association has been shown between the introduction of the antidepressant fluoxetine in the USA in 1988 and a reduction in the number of suicides.
Depression is very common. For example, in the US, an estimated 10% of men and 20% of women will suffer from major depression at some stage in their lives. One way of treating the condition is with drugs. Several types of antidepressant drugs are available, and in many countries they are among the most commonly prescribed medicines. However, all antidepressants have side effects.
One family of antidepressants, called selective serotonin uptake inhibitors (SSRIs), was introduced in the late 1980s. The name of these drugs comes from their effect, which is to prevent the removal (reuptake) from the nerve endings of one type of chemical (serotonin) that is important for transmitting nerve impulses between brain cells. SSRIs are claimed to be more effective and to have fewer side effects than older antidepressants, and many brands of SSRI are now on the market. However, in recent years there have been claims that some people taking SSRIs have committed suicide as a result of the drugs. Whether the SSRIs are the cause of the suicide is hard to know, because people who are depressed do sometimes feel like killing themselves; so if a depressed person taking an SSRI commits suicide, it is hard to tell whether this is a result of the depression or a side effect of the treatment (the SSRI). The drug regulatory authorities in some countries are now carefully studying the issue of suicides and antidepressant use, both in adults and in children. The US Federal Drug Administration has issued what it calls a “black box warning” on the use of these drugs.
Why Was This Study Done?
The researchers wanted to discover whether the number of suicides in the US had increased or decreased since treatment with the first widely used SSRI (fluoxetine, also known as Prozac) began in 1988. Any difference in the number of suicides found before and after that date would not necessarily be the result of the introduction of this antidepressant, or other SSRIs, but the information would provide helpful information about the effects of these drugs.
What Did the Researchers Do and Find?
They looked at annual suicide rates between 1960 and 1988 and compared them with annual rates in the period 1988 to 2002. They used several sources of data, including the Centers of Disease Control and the US Census Bureau. The researchers found that from the early 1960s until 1988, in the entire US population, between 12.2 and 13.7 people in every 100,000 committed suicide each year. After that time, the numbers of suicides gradually declined, with the lowest figure (10.4 people per 100,000) reached in 2000. The researchers did mathematical tests, which demonstrated that the steady decline was statistically associated with the increased number of fluoxetine prescriptions—that is, the more prescriptions there were, the fewer suicides there were. (There were around two-and-a-half million prescriptions of the drug in 1988, increasing to over 33 million in 2002.)
What Do These Findings Mean?
In all scientific research, it is an important principle that finding an association between two events does not prove that one caused the other to occur. However, the authors of this paper suggest that the use of this drug could have contributed to the reduction of suicide rates in the US in the period 1988 to 2002. Several other SSRIs are also now in common use, but they were not considered in this study, nor were other antidepressants, or other treatments for depression.
As depression is such a common condition—and because there are so many ways of treating it, including counseling and psychotherapy—there are many Web sites devoted to the subject. We have given a small selection below. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030190.
• From the American Academy of Family Physicians (AAFP), general advice on depression
• Also from the AAFP, advice specifically about antidepressant drugs
• MedlinePlus brings together authoritative information about depression from the US National Library of Medicine, National Institutes of Health, and other government agencies and health-related organizations
• Health pages of the BBC on depression
• Information about depression from other UK health advice sites: Patient UK and NetDoctor.co.uk