Babies exposed to anti-depressants called Selective Serotonin Reuptake Inhibitors (SSRIs) in the womb may be born with withdrawal syndrome, suggests a study published in this week's issue of The Lancet. The authors of the study conclude that doctors should avoid or cautiously manage the prescribing of these drugs to pregnant women with psychiatric disorders. SSRIs were introduced in 1988 and are becoming the gold standard treatment for depression and a wide spectrum of other mood and behavioural disorders. The presence of a withdrawal reaction to SSRIs is now widely recognised and several cases of neonatal withdrawal syndrome associated with the drugs-characterised by convulsions, irritability, abnormal crying and tremor- have been reported.

Emilio Sanz (University of La Laguna, Spain) and colleagues screened the WHO database of adverse drug reactions for cases of neonatal convulsions and neonatal withdrawal syndrome associated with the use of SSRIs. 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 93 cases of SSRI use associated with either neonatal convulsions or withdrawal syndrome had been reported, suggesting a possible causal relationship. Of these cases 64 were associated with paroxetine, 14 with fluoxetine, nine with sertraline and seven with citalopram.

The dose was only reported in 13 cases associated with paroxetine and ranged from 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 concludes: ?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 Andr?s Martin (Yale University School of Medicine, USA) state that it would be unwise to assume that neonatal withdrawal syndrome was only associated with paroxetine use.

Dr Ruchkin comments: ?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.?

Contact: Professor EJ Sanz, Department of Pharmacology, School of Medicine, University of Laguna, 38071 La Laguna, Tenerife, Spain. T) +34 922 319347

Comment Dr Vladislav Ruchkin, Yale Child Study Center, Yale University School of Medicine, 230 South Frontage Road, New Haven, CT 06520-7900, USA. T) + 1 203 785 6973

This is a press release from THE LANCET