Safety first, efficacy second? Fear and the need for treatment in the absence of controlled data

In clinical practice, physicians are routinely asked to make decisions about whether to initiate or continue antidepressant treatment in a situation where no safety data are available. Pregnancy and breast-feeding can serve as an example, where controlled clinical trials provide little guidance. Females of fertile age are rarely included in the early phases of clinical testing, indeed, Phase IIb and III trials have a standard provision to use a reliable method of contraception. Pregnancy during a drug trial is considered as a 'serious adverse event' with subsequent study discontinuation. The reasons are not just ethical and legal but also marketing, including the drug manufacturers' fear of having their products associated with potentially grave side effects, such as malformations. Drug treatment in pregnancy and lactation thus pose a highly relevant clinical problem that cannot be addressed in controlled trials. Excessive concerns of negative consequences could erroneously result in a generalized recommendation to not get pregnant or to abort an existing pregnancy. However, the fetus may already have been exposed to drugs early in the first trimester during frequently unplanned pregnancies; in addition, recent epidemiological data indicate increasing consumption of psychotropics, including antidepressants, by pregnant women. Psychiatrists have to weigh the known risks of treatment discontinuation versus the potential risks for the fetus and infant. They should also consider whether alternative non-pharmacological interventions (psychotherapy, ECT, rTMS) are accessible or effective. The only available safety data on antidepressants come from animal studies, epidemiological trials, drug registries, case series, anecdotal case vignettes and clinical observations.

Moreover, published findings have to be viewed with caution and interpreted correctly. For example, recent data suggested an increased teratogenic risk for the antidepressant paroxetine. While it is true that a meta-analysis confirmed an increased relative incidence of malformations, the absolute risk was raised from 3% to 4% for all congenital malformations and from 1% to 2% for cardiac malformations. In 2005 the Prague Psychiatric Center established a specialized consultation outpatient center for pharmacotherapy in pregnancy and breastfeeding. The center provides services and information on safety and treatment recommendations directly to patients, their treating psychiatrists and other physicians as well. The database consists of patients records, data on their illness, treatment and pregnancy outcome. Currently, a prospective study for the longitudinal follow-up of offspring exposed in utero to psychotropics has been designed. The focus is on their developmental milestones, physical health, neuropsychological performance and general well-being.