A team in the Netherlands is currently investigating the effects of tapering off of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) during pregnancy. In this randomized controlled trial, one group of women will be guided in tapering off of SSRIs (STOP condition) while also receiving psychological support in the form of online preventive cognitive therapy (PCT). The other group will serve as the control group (GO condition) and will continue taking the SSRI as usual. The study is designed to compare the rates of relapse or recurrence of depression in both groups.
A previous study found that pregnant women experienced higher rates of relapse when an antidepressant medication was discontinued compared to when it was continued. The researchers in this study hope that adding PCT will offset this risk. They explain:
“The expectation is that tapering of SSRIs with added PCT does not increase the risk of clinically relevant maternal relapse or recurrence of depression or onset of anxiety disorders during pregnancy up to three months postpartum in excess of [absolute] 15 % compared to continuation of SSRIs. If so, discontinuation is deemed non-inferior with regard to relapse/recurrence risk. Furthermore, we expect that tapering of SSRIs is better than continuation of SSRIs with respect to child development. Finally, but not unimportantly, we hypothesize that discontinuation will decrease total costs per woman and child on a 3 month and projected long-term base, assuming no relevant effects of discontinuation on the mother and no effects on the child are found.”
This study is important given earlier studies that have found that prenatal exposure to SSRIs is associated with higher rates of depression in early adolescence, fetal and developmental complications as well as autism and other pregnancy complications. The addition of a psychological intervention as women are coming off the medication is a choice that is in line with patient preferences around wanting management strategies from their physicians as they make the decision to come off SSRIs and begin experiencing withdrawal symptoms.
“At present, there are no suitable data available to guide evidence-based decisions on SSRI continuation or discontinuation during pregnancy,” the researchers write. They aim to recruit 200 women who will be divided into the STOP and GO groups and assessed for depression symptoms at 34 and 36 weeks of pregnancy and 4 and 12 weeks after delivery.
Tapering off of SSRIs has been a contentious topic because of the high rates of withdrawal reactions experienced by patients when they stop taking antidepressant drugs. Repeated findings in the literature reiterate that stopping or tapering SSRIs causes withdrawal symptoms much like other substances or drugs, like alcohol, benzodiazepines, barbiturates, opioids, and stimulants. In fact, Giovanni Fava and his colleagues conducted a review of the literature on SSRIs and concluded that clinicians “need to add SSRI to the list of drugs potentially inducing withdrawal phenomena. The term ‘discontinuation syndrome’ minimizes the vulnerabilities induced by SSRI and should be replaced with ‘withdrawal syndrome.’”
There is not a lot of robust evidence or controlled studies on how best to taper off SSRIs even among non-pregnant adults, although there are some researchers who are investigating this question presently. What we do know, however, based on Fava’s et al., findings is that withdrawal symptoms are a likely outcome upon stopping ADM irrespective of whether the medication is stopped abruptly or gradually tapered.
In this study, the authors will assess for withdrawal symptoms using the Discontinuation-Emergent Signs and Symptoms Checklist (DESS) and will follow a tapering protocol – “the aim is to taper the use of SSRIs within four weeks, depending on patient preferences and drug characteristics (e.g., half-life in the body).” The participants in the tapering will be monitored weekly through telephone interviews for signs of withdrawal symptoms.
The researchers are also interested in monitoring and comparing child development up to 24 months post delivery and associated health care costs between the two groups. They conclude, “results of this study will be published and will contribute to further development of (international) guidelines. The results will provide a first step in giving pregnant women an answer to the question whether it is better to stop or to continue the use of SSRIs during pregnancy.”
****
Molenaar, N. M., Brouwer, M. E., Bockting, C. L. H., Bonsel, G. J., van der Veere, C. N., Torij, H. W., . . . Lambregtse-van den Berg, M. P. (2016). Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial. BMC Psychiatry, 16(1), 1-10. doi:10.1186/s12888-016-0752-6 (Article)
