About half of all pregnancies are unplanned.  In this situation, many women who conceive while on psychotropic medications decide to abruptly stop their medications when they discover they are pregnant.  While this may seem like the safest option, in terms of protecting the developing fetus, we have data demonstrating high rates of relapse in women who discontinue antidepressant medications or mood stabilizers proximate to conception.  We now have data (from several studies in non-pregnant populations) to indicate that the rate of medication discontinuation (abrupt vs. gradual) may also affect risk of relapse.

In a recent study, Baldessarini and colleagues compared relapse rates in patients who discontinued antidepressant rapidly (in 1–7 days) versus slowly (14 days).  Over half of the patients in this study had recurrent major depressive disorder (n=224); the remainder had panic disorder (n=75), bipolar II disorder (n=62), or bipolar I disorder (n=37).  This was an observational study; the researchers did not determine who discontinued treatment rapidly (n=188) or gradually (n=210).  The patients were followed for at least 1 year (mean, 2.8 years; mean length of antidepressant treatment, 8.5 months).

Over a period of one year, relapse rate were high: 59% in those who discontinued gradually and 78% in those who discontinued rapidly.  In addition, the time to relapse was shorter (median, 3.6 vs. 8.4 months) in those who discontinued rapidly.  The findings were most pronounced for those with bipolar I and panic disorders.

Among patients who gradually tapered, it was found that the type of antidepressant also affected relapse risk.  Time to relapse was substantially longer in those taking tricyclic antidepressants versus those treated with newer antidepressants (median, 11.4 vs. 6.27 months). Time to relapse was also longer in those taking antidepressants with longer half-lives (such as fluoxetine): antidepressant dose, duration of illness or treatment, or concurrent treatment did not appear to affect time to relapse.

These findings parallel work done earlier in patients with bipolar disorder who discontinued lithium.  Compared to those who discontinued lithium gradually, those who discontinued rapidly were about three times as likely to relapse into mania and five times as likely to relapse into depression.

These data indicate that psychotropic medications should not be abruptly discontinued when a woman inadvertently conceives.  Rapid discontinuation of antidepressants or mood stabilizers not only increases the risk of relapse but also shortens the time to relapse.  If a pregnant woman decides to discontinue treatment, a gradual taper of the drug may result in somewhat greater exposure of the fetus to medication but it may substantially diminish her risk of relapse during pregnancy.  All patients, especially women of child-bearing age, should be informed of the risks associated with abrupt discontinuation of medications.  These data also highlight the importance of pre-conception planning.  Before conceiving or even attempting to conceive, women with recurrent illness should meet with their treaters to discuss treatment options during pregnancy, taking both the baby’s and the mother’s well-being into consideration.

Ruta Nonacs, MD PhD

Baldessarini RJ et al. Illness risk following rapid versus gradual discontinuation of antidepressants. Am J Psychiatry 2010; 167:934.