Fluoxetine Prescriptions and Suicide Rates in the United States

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.

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.

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.)

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.

Because of evidence made available in recent months, US and UK regulatory agencies have been critically examining suicidality and antidepressant use in children and adults. The crucial point is whether antidepressants increase suicidality over and above what is caused by the underlying disorders, such as major depression. With such recent scrutiny of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and the US Food and Drug Administration-recommended “black box warning,” it becomes timely to examine temporal trends in suicide and to study the potential impact of antidepressants on mortality caused by self-harm.

This is a complex task because while on the one hand acute antidepressant use has been associated with suicidality, but untreated depression is also the major cause of suicide . Therefore, two competing hypothesis exist. The first is that the acute effects of antidepressants can induce suicidality, and the second is that by effectively treating depression, antidepressants can reduce the rates of suicide.

Major depressive disorder is a common and complex disorder of gene-environment interactions, for which there is no curative treatment [2–4]. The disorder afflicts approximately 10% of American men and 20% of American women over their lifetimes. The point prevalence is in the range of 3% (2% in men, 4% in women) [5,6], but increases up to 10% in the elderly [7,8]. Because the prevalence of depression is so high, and treatment lasts several months to years, antidepressant pharmacotherapy is among the most frequently used treatments in all of medical therapeutics.

Depression is itself the most prevalent cause of suicides [1], and suicide is, in turn, still among the major causes of death. According to the latest figures from the Centers for Disease Control and Prevention (CDC), in the United States in 2002, suicide was the eleventh leading cause of death (in 1998 it was the eighth leading cause of death). When the data are analyzed by age cohort, suicide is the fifth leading cause of death in the age group 5–14, the third leading cause of death in the age group 15–24, and the fourth cause of death in the age group 25–44 (Table 1) [9]. It has been estimated that 60%–70% of acutely depressed patients experience suicide ideations [10]. It is universally agreed that depression increases the risk for suicide. However, the extent of the risk has been a subject of debate. The figure of lifetime risk for suicide in patients with major depression had been commonly quoted as in the range of 10%–20% [10–12], based on the study of hospitalized patients. However, recent studies have examined other types of samples and found a much lower risk, reported as 6% by Inskip et al. [13] based on a meta-analysis, 3.4%–3.5% (7% in males and 1% in women) based on gender and age-stratified calculations made on the entire population [14,15], and 2.4% based on analysis of a community sample in England [16]. An interesting meta-analysis in which papers were stratified by type of presentation revealed that in patients hospitalized for suicidality the lifetime prevalence of suicide was 8.6%; for affective disorder patients hospitalized without specification of suicidality, the lifetime risk of suicide was 4.0%, and for mixed inpatient/outpatient populations it was 2.2%; for the nonaffectively ill population, it was less than 0.5% [17]. Depression appears to be present in at least 50% of all suicides in adults [18,19]; in children that rate has been reported to be in the range of 62%–76% [20,21].