ArticlesSelective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis
Introduction
Since 1990, the British National Formulary1 has included a warning of a possible withdrawal syndrome associated with antidepressants. Discontinuation of treatment with tricyclic antidepressants has been linked to withdrawal syndrome for almost 20 years.2 The main symptoms—influenza-like syndrome and sleep disturbances—are mostly in agreement with a cholinergic rebound as the underlying mechanism, with a connection with noradrenergic and dopaminergic pathways.2, 3, 4, 5
Since the introduction of selective serotonin reuptake inhibitors (SSRIs) in clinical practice in 1988, they have become the drugs of choice in the treatment of depression and are becoming the gold standard of treatment for a wide spectrum of other mood and behavioural disorders, such as obsessive-compulsive disorder, panic disorder, social phobia, post-traumatic stress disorder, premenstrual dysphoric disorder, and generalised anxiety disorder. SSRIs do not affect α adrenergic receptors so intensively, but withdrawal syndromes have been described with these compounds, and the presence of withdrawal reaction to SSRIs is now widely acknowledged.6 Neonatal withdrawal syndrome associated with SSRIs—characterised by convulsions, irritability, abnormal crying, and tremor—has been reported in several cases.7, 8, 9, 10 This database study was done to analyse a large series of reports of neonatal withdrawal syndrome associated with SSRIs and the possible differences between them.
Section snippets
Methods
Spontaneously reported cases of suspected adverse drug reactions (ADRs) are forwarded from national centres (appointed by national governments) in 72 countries (plus nine associated countries) to the WHO Collaborating Centre for International Drug Monitoring, Uppsala Monitoring Centre, Sweden. The case reports, recorded in a common format, are processed and stored in the ADR database. Over 3 000 000 case records are maintained by the centre, which provides a unique source of international ADR
Results
A total of 102 cases (reported up to the second quarter of 2003, from 11 different countries) of SSRI use associated with either neonatal convulsions or withdrawal syndrome were identified. Paroxetine was the most commonly reported SSRI with these ADRs. Cases were also reported for fluoxetine, sertraline, and citalopram, but not for any of the other drugs included in the N06AB group (table 1). Copies of the original reports were obtained from the national centres for 66 cases and, after careful
Discussion
Risks of neonatal convulsions and neonatal withdrawal syndrome seem to be increased with all SSRIs. Nearly two-thirds of reported cases of suspected SSRI-induced neonatal withdrawal syndrome were associated with paroxetine. The withdrawal syndrome is related to the mechanism of action of the compounds. With tricyclic antidepressants, withdrawal syndrome in the adult has been associated with the suspension of the effect on cholinergic muscarinic receptors, cholinergic rebound syndrome,
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