Suicide Risk and the SSRIs

Abstract

THE SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) were a welcome innovation in the treatment of depression. Although these drugs are no more efficacious than their predecessors, they are safer in overdose and more acceptable in terms of adverse effects. The popularity of the SSRIs in general, and of fluoxetine (Prozac) in particular, created its own problems. For instance, Prozac achieved a recognition normally given to household items in which the brand name has become identified with the generic product. Selective serotonin reuptake inhibitors can cause agitation and activation, particularly at the start of treatment (eg, such sensations are not pleasant and resemble the akathisia associated with the neuroleptics). In the setting of lowered mood, developing new aversive symptoms might further depress mood and increase the risk of suicide. Also, paradoxical reactions (ie, very occasionally causing agitation) are potential adverse effects of the benzodiazepines, and it is possible that something similar might be observed with SSRIs The current debate about the SSRIs and either self or externally directed aggression initially concerned adult patients, but recently the controversy has extended to children receiving the same drugs, with similar claims being made concerning both increased suicidality and psychological dependence resulting from SSRI use. These concerns have found a receptive media audience. For instance, 2 investigative programs by the British Broadcasting Corp Panorama team generated the largest television audience response they have ever known, receiving several hundred e-mails from the public, nearly all describing adverse effects due to the SSRIs. Unfortunately, evidence on the role of SSRIs in treating adolescent depression, which is indisputably an important problem, is far from perfect. Selective serotonin reuptake inhibitors are certainly frequently prescribed in this age group, few formal studies have been performed, and not all of them are published. Only in the last few weeks has one company, GlaxoSmithKline, agreed to publish all the data it has on paroxetine, possibly stimulated by the lawsuit filed by New York State’s attorney general. Sensitivities about research involving children mean that both academics and industry are increasingly wary about carrying out randomized trials in this age group. The paradox, however, is that it is in these vulnerable populations that high-quality evidence is most needed, yet most difficult to obtain. Relying on evidence from studies of adult populations is far from ideal. The regulatory authorities are faced with a dilemma. The distant specter of thalidomide and the enormous impact of other perceived failures of regulation, such as the bovine spongiform encephalopathy crisis in the United Kingdom, linked to the general precautionary climate has increased the pressures on many regulatory institutions. Fear of being blamed if subsequent evidence of harm emerges means that the regulatory bodies have to operate in an increasingly nervous environment. Hence both the US Food and Drug Administration and the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom have recently issued warnings concerning the use of the SSRIs in children. This is not a “ban” as some media have reported, since SSRI use in children has always been off label, except for fluoxetine. Perusal of any of the summaries of product characteristics for the SSRIs confirms that use in children is not recommended by the manufacturers (again with the exception of fluoxetine) but remains widespread in those younger than 18 years, presumably because of the continuing need to do something to help the serious problem of depression in adolescents. The only drug for which the UK MHRA Committee on Safety of Medicines concluded that there is adequate evidence to support use in those younger than 18 years is fluoxetine. Although it is reasonable to ask questions about the SSRIs and suicide, it is more difficult to answer them. The problem is that depression is unequivocally and substantially associated with suicide and deliberate self-harm. Depression