7 June 2019

All benzos are risky in pregnancy

Drugs O&G Women

Benzos increase the risk of having a miscarriage in early pregnancy, regardless of whether you’re taking a short-acting one for insomnia or a longer-acting one for anxiety, Canadian researchers say.

According to their large case-controlled study involving almost 450,000 pregnancies, benzodiazepine exposure in early pregnancy was associated with an 85% higher risk of spontaneous abortion compared with pregnancies where that class of drugs were not taken. And this increased risk remained the same, after a whole range of possible confounders had been adjusted for, including maternal mood and anxiety disorders.

But this isn’t the new bit. Previous research, including both a UK population-based study and an Israeli prospective study had confirmed the link between benzos and spontaneous abortion. And, in Australia benzodiazepines have been given a Category C rating in terms of safety in pregnancy. (Drugs owing to their pharmacological effects have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations.)

“Benzodiazepines cross the placental barrier and accumulate in the fetal circulation at levels that are one to three times higher than the maternal serum levels,” the researchers explained.

What hasn’t been known, to date, is whether this is a class effect or are some benzos worse than others.

Well, according to this study in JAMA Psychiatry, “the risk was similar among pregnancies exposed to short-acting …and long-acting benzodiazepines during early pregnancy”.

So it didn’t matter if you were prescribed long-acting clonazepam or short-acting lorazepam, (interestingly, the two most frequently prescribed benzos) the risk was more or less the same.

“All benzodiazepine agents were independently associated with an increased risk of [spontaneous abortion],” the study authors said.

In addition, the study found the risk increased as the daily dose of benzodiazepines increased, suggesting a dose-response effect. So basically the more doses of benzos a pregnant woman takes, either in terms of strength or duration, the greater the risk she will miscarry.

Overall, the researchers concluded that pregnant women should avoid taking benzodiazepines, and if they have to take them only take the lowest dose possible for shortest duration possible.

“Alternative nonpharmacologic treatments exist and are recommended, but if benzodiazepines are needed, they should be prescribed for short durations,” the authors concluded.

JAMA Psychiatry. 2019; doi: 10.1001/jamapsychiatry.2019.0963