The risk of stopping is a measured risk too

Every stop so far has measured a risk of taking something. This one measures the other side, because a decision made with only half the evidence is not a safer decision - it is an uninformed one.

Significant findings

The most cited study followed 201 pregnant women with a history of major depression through pregnancy with monthly assessments. Among those who discontinued antidepressants, 44 of 65 (68%) relapsed; among those who maintained treatment, 21 of 82 (26%), a hazard ratio of 5.0 (95% CI 2.8-9.1). The limitation is not hidden in a footnote: this was a prospective naturalistic cohort, not a randomised trial. Women who stopped chose to stop, and they may differ systematically from women who continued in illness severity, previous episodes and past treatment response. The headline comparison also rests on 147 of the 201 women enrolled. The paper drew published criticism in JAMA letters at the time (Terao, doi:10.1001/jama.296.2.165-a; Rifkin and Rifkin, doi:10.1001/jama.296.2.165-b; Urato, doi:10.1001/jama.296.2.166-a) with a reply from the authors. The hazard ratio of 5.0 is not a measured causal effect of discontinuation, and treating it as one overstates it.

For bipolar disorder the pattern is consistent across designs. A prospective cohort of 89 women euthymic at conception found recurrence during pregnancy in 85.5% (53 of 62) of those who discontinued a mood stabiliser against 37.0% (10 of 27) of those who continued (Am J Psychiatry 2007, doi:10.1176/appi.ajp.2007.06101639); the paper published no confidence intervals for those proportions. A meta-analysis of 37 studies covering 5,700 deliveries put postpartum relapse at 35% overall (29-41), 66% (57-75) among women who went through pregnancy without medication and 23% (14-37) among those on prophylaxis (Am J Psychiatry 2016, doi:10.1176/appi.ajp.2015.15010124). These are also observational.

Depression during pregnancy is itself associated with obstetric outcomes. A meta-analysis of 29 prospective studies found preterm birth at a relative risk of 1.39 (1.19-1.61) and low birth weight at 1.49 (1.25-1.77) with a categorical depression measure (Arch Gen Psychiatry 2010, doi:10.1001/archgenpsychiatry.2010.111). A later meta-analysis restricted to untreated depression, 23 observational studies and 25,663 women, found preterm birth at an odds ratio of 1.56 (1.25-1.94) and low birth weight at 1.96 (1.24-3.10) (JAMA Psychiatry 2016, doi:10.1001/jamapsychiatry.2016.0934). That paper's own subgroup analysis is worth as much as its headline: the preterm-birth odds ratio was 2.50 (1.70-3.67) in studies that reported conflicts of interest against 1.34 (1.08-1.66) in those that did not.

So the honest state of the field is symmetrical. There is no randomised trial of continuing versus stopping psychiatric medication in pregnancy, in either direction, and there is unlikely ever to be one. Both halves of the decision rest on observational evidence with the same weakness, and the weakness does not favour either answer.

Worth asking

Nothing in this stop is a recommendation to continue anything, any more than the earlier stops were a recommendation to stop. The questions that make the trade-off concrete are for the person who knows your history: what has happened to me before when this medication was reduced or stopped; how quickly did it happen; what would we watch for and who would I call; is a dose change an option where a stop is not; and how does the postpartum period change the answer? Those are questions for a prescriber and an obstetrician together, and they are better asked before a pregnancy than during one.