Suicide Rates and Antidepressant Prescribing: A Casual or Causal Relationship?

I n an ecological study in this issue of PLoS Medicine , Milane and colleagues found a temporal association between prescription of specifi c serotonin reuptake inhibitor (SSRI) antidepressants and suicide rates in the United States [1]. Their study addresses a subject of great public health importance and clinical interest. The researchers asked the question: was the use of antidepressants associated with a change in suicide rates in the general population of the United States between 1988 and 2002? There were two underlying hypotheses: (1) antidepressants can trigger suicide and subsequently increase suicide rates, and (2) through the treatment of depression with antidepressants, suicide rates decline over time. Methodology To address these hypotheses, the researchers conducted an ecological study drawing on aggregated data on suicide in the US general population between 1960 and 2002. These data were collected from the annual statistical fi les of the National Vital Statistics System compiled by the US Centers for Disease Control. Data on fl uoxetine prescription were obtained from IMS Health, a company that provides data on drug use to the pharmaceutical and health-care industries. The authors estimated a potential effect of fl uoxetine on suicide rates by the use of a time-series regression model. They assumed a predicted suicide mortality in 1988–2002 based on maintained pre-1988 suicide trends, and considering fl uoxetine as a covariate for a potential effect on change of suicide rates between 1988 and 2002. The authors reported that suicide rates were most prominent in the following two age groups: 15–24 and 25–44 years of age (the upper age limit of the study population was 65 years of age). The authors found that suicide rates fl uctuated between 12.2 and 13.7 per 100,000 people for the entire population from the early 1960s until 1988, but then the rates gradually declined (in men and women), with the lowest value of 10.4 per 100,000 people in the year 2000. They also found that the prescription of fl uoxetine inversely increased in relation to the trend in suicide rates from 1988 to 2002. This inverse relationship was highly correlated (r s = −0.92, p < 0.001). Milane and colleagues then modeled suicide rates in 1988–2002 based on pre-1988 suicide trends, and their modeling suggested that fl uoxetine prescription decreases suicides, both in women and in men. Further modeling analysis showed that if pre-1988 trends (i.e., trends in the pre-SSRI era) were extrapolated …