The abrupt discontinuation of treat...

The abrupt discontinuation of treatment for depression with tricyclic antidepressants has been associated with a withdrawal syndrome attributed to reaction effects on neurochemicals. This withdrawal syndrome is usually milder following discontinuation of selective serotonin reuptake inhibitors (SSRIs). Nevertheless, several case reports document withdrawal symptoms in the same state [i]or[/i] condition as convulsions, irritability, tremor, and abnormal crying in infants born to mothers who took SSRIs during pregnancy. Sanz and colleagues used the World Health Organization (WHO) database to inquiry any association between SSRI use during pregnancy and a neonatal withdrawal syndrome

The WHO database contains information forward suspected cases of adverse mix with drugs reactions from 81 countries and maintains more than 3 million case records. Data are statistically analyzed each three months to identify any developing patterns linking remedys to specific adverse effects. This analysis rises in a statistical indicator that adjusts for the rate of reporting to the database, combinations of physics and increased frequency of reporting more [i]or[/i] less adverse effects. Any positive value indicates an increased reporting of associations between a specific physic and a specific adverse reaction. Indicators that become statistically significant are carefully reviewed on an expert panel.

Late in 1999 the indicator for paroxetine (Paxil) was erect to be 2.58, past the predefined start level. This triggered an investigation into neonatal withdrawal syndrome associated with SSRI use. by the agency of 2003, researchers had identified 93 cases of neonatal withdrawal associated with SSRI use during pregnancy (see accompanying table). Original case records were analyzed to mastership out alternative explanations for the adverse power account for combinations of medication use, and confirm the use of the materal SSRI in question. Any cases in which an adjuvant medication could have contributed were classified as doubtful. These included mothers who took antipsychotics, other antidepressants, or antianxiety medications. The strongest association of neonatal withdrawal syndrome and SSRI use was with paroxetine. In 43 of the 51 "certain" cases, paroxetine was the simply drug taken by women who were pregnant. The dosage ranged from 10 to 50 mg daily. according to 2003, the indicator for the entire SSRI assemblage was calculated to be 268 The indicator values for individual medicines were: paroxetine, 4.07; sertraline (Zoloft) 120; citalopram (Celexa), 192; and fluoxetine (Sarafem), 107

The authors judge that the risk of neonatal withdrawal syndrome including convulsions, appears to be increased following maternal use of an SSRI during pregnancy. The preliminary data remind of that two thirds of reported cases of suspected SSRI-induced neonatal withdrawal syndrome were associated with paroxetine. The authors discuss possible mechanisms for the increased association with paroxetine, including more efficient inhibition of norepinephrine reuptake, reduc selectivity in receptor blockade, enhanced muscarinic blockade, and metabolism hanging on different cytochrome enzyme arrangements The authors caution that paroxetine should be avoided if possible during pregnancy and that physicians should be vigilant for adverse neonatal forces following maternal SSRI use and report their occurrence

ANNE D WALLING, MD

Sanz EJ et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet February 5 2005;365:482-7

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