Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature

I n the United States, selective serotonin reuptake inhibitor (SSRI) antidepressants are advertised directly to consumers [1]. These highly successful direct-to-consumer advertising (DTCA) campaigns have largely revolved around the claim that SSRIs correct a chemical imbalance caused by a lack of serotonin (see Tables 1 and 2). For instance, sertraline (Zoloft) was the sixth best-selling medication in the US in 2004, with over $3 billion in sales [2] likely due, at least in part, to the widely disseminated advertising campaign starring Zoloft's miserably depressed ovoid creature. Research has demonstrated that class-wide SSRI advertising has expanded the size of the antidepressant market [3], and SSRIs are now among the best-selling drugs in medical practice [2]. Given the multifactorial nature of depression and anxiety, and the ambiguities inherent in psychiatric diagnosis and treatment, some have questioned whether the mass provision of SSRIs is the result of an over-medicalized society. These sentiments were voiced by Lord Warner, United Kingdom Health Minister, at a recent hearing: " …I have some concerns that sometimes we do, as a society, wish to put labels on things which are just part and parcel of the human condition " [4]. He went on to say, " Particularly in the area of depression we did ask the National Institute for Clinical Excellence [an independent health organisation that provides national guidance on treatment and prevention] to look into this particular area and their guideline on depression did advise non-pharmacological treatment for mild depression " [4]. Sentiments such as Lord Warner's, about over-medicalization, are exactly what some pharmaceutical companies have sought to overcome with their advertising campaigns. For example, Pfi zer's television advertisement for the antidepressant sertraline (Zoloft) stated that depression is a serious medical condition that may be due to a chemical imbalance, and that " Zoloft works to correct this imbalance " [5]. Other SSRI advertising campaigns have also claimed that depression is linked with an imbalance of the neurotransmitter serotonin, and that SSRIs can correct this imbalance (see Table 2). The pertinent question is: are the claims made in SSRI advertising congruent with the scientifi c evidence? In 1965, Joseph Schildkraut put forth the hypothesis that depression was associated with low levels of norepinephrine [6], and later researchers theorized that serotonin was the neurotransmitter of interest [7]. In subsequent years, there were numerous attempts to identify reproducible neurochemical alterations in the nervous systems of patients diagnosed with depression. …