Prenatal exposure to selective serotonin reuptake inhibitors may cause withdrawal syndrome in newborns, according to an article in the February 5th issue of the Lancet.

This class of antidepressants was introduced in 1988, and these medications are becoming the gold standard treatment for depression and a wide spectrum of other mood and behavioral disorders. The presence of a withdrawal reaction to selective serotonin reuptake inhibitors is now widely recognized and several cases of neonatal withdrawal syndrome associated with the drugs - characterized by seizures, irritability, abnormal crying, and tremor - have been reported.

Dr. Emilio Sanz and his Spanish colleagues screened the World Health Organization database of adverse drug reactions for cases of neonatal seizures and neonatal withdrawal syndrome associated with maternal use of these antidepressants. The database contains information from 72 countries and holds over 3 million records dating from 1968. Use of other medications and symptoms were carefully reviewed in the original reports to rule out alternative causes of withdrawal syndrome.

The investigators found that by November 2003, a total of 94 cases of selective serotonin reuptake inhibitor (SSRI) use associated with either neonatal seizures or withdrawal syndrome had been reported, suggesting a possible causal relationship. Of these cases, 64 were associated with paroxetine, 14 with fluoxetine, 9 with sertraline, and 7 with citalopram.

The dose was only reported in 13 cases associated with paroxetine (range, 10 mg to 50 mg per day). The duration of treatment was reported only in eight cases, and in all of them the drug was used for 4 to 60 months before delivery and stopped at delivery.

Professor Sanz concluded: “Within the limits of spontaneous reports on these drugs, the results suggest that symptoms of withdrawal might be a greater problem for paroxetine than for other drugs. Paroxetine should not be used in pregnancy, or if used, it should be given at the lowest effective dose. With the other SSRIs, especially citalopram and venlafaxine, their use should be carefully monitored and new cases promptly communicated to drug vigilance systems.”

In an accompanying commentary Vladislav Ruchkin and Andres Martin (Yale University School of Medicine, USA) stated that it would be unwise to assume that neonatal withdrawal syndrome was only associated with paroxetine use.

Dr Ruchkin commented: “It remains to be seen whether Sanz and colleagues' report ultimately reflects a minor problem for a particular antidepressant, or further evidence of a larger set of serious problems for SSRI use in young people. From a pessimistic extreme, these reports might jointly herald the beginning of the end for the uncontested SSRI hegemony of the past decade. For now, and before others replicate or refute these findings, we should make better use of empirically grounded non-pharmacological interventions, question and perhaps recalibrate our personal prescription thresholds, especially during pregnancy, lactation, or early childhood, and hope that the next wave of revolutionary new compounds is right around the corner.”