Selective Serotonin Reuptake Inhibitor Induced Neonatal Abstinence Syndrome

By Klinger, Gil; Merlob, Paul | The Israel Journal of Psychiatry and Related Sciences, April 1, 2008 | Go to article overview

Selective Serotonin Reuptake Inhibitor Induced Neonatal Abstinence Syndrome


Klinger, Gil, Merlob, Paul, The Israel Journal of Psychiatry and Related Sciences


Abstract: Depression is common in women of childbearing age and especially during pregnancy and the postpartum period. Selective serotonin reuptake inhibitors (SSRIs) are increasingly being used to treat depression prior to and throughout pregnancy. Up to 30% of the newborn infants exposed to SSRIs may present with clinical signs during the first days after birth. Neonatal abstinence syndrome (NAS) describes this clinical syndrome resulting from prior prolonged exposure to SSRI induced by cessation of the drug. NAS includes a wide spectrum from mild to severe non-specific symptoms which were categorized into four groups of effects: central nervous system (depression followed by excitation), gastrointestinal, autonomie and respiratory. A protocol for observation of SSRI-exposed newborns is presented including an objective method (Finnegan score) to monitor onset, progression and improvement of NAS symptoms.

Introduction

Depression is common in women of childbearing age (1). During pregnancy increased stress may aggravate depression resulting in a prevalence of up to 12.9% of this disorder (2, 3). The prevalence of depression during the postpartum period continues to be high with 19.2% of women experiencing a major depressive episode within the first three months after delivery (2). Because many women experience depression during the postpartum period, it is often dismissed as part of the "normal" physiological changes that are associated with childbirth (4). However, if untreated, perinatal depression can have severe consequences for the fetus and newborn, as well as for the mother. Although psychotherapy is the first-line treatment for depression during pregnancy or after birth, antidepressant treatment is warranted in some patients. Because selective serotonin reuptake inhibitors (SSRIs) are perceived as safer than alternative medications, they are increasingly being used to treat depression prior to and throughout pregnancy. A recent survey has shown that 2.8% of women use SSRIs for the entire duration of pregnancy (5). This figure translates to 92,000 of approximately 4 million annual live births in the United States. Prolonged fetal exposure to SSRIs may be associated with a neonatal abstinence syndrome (NAS) affecting 30% of newborns (6). The widespread use of SSRIs during pregnancy and the resulting occurrence of NAS warrant a thorough review.

Pharmacokinetics

SSRIs are a group of psychotropic drugs that is chemically unrelated to tricyclics, tetracyclics, monoamine oxidase inhibitors or other antidepressants. They are used to treat depression, but also for obsessive-compulsive and other disorders. The action of SSRIs is thought to be linked to their inhibition of prejunctional reuptake of serotonin, but they do not have receptor-blocking effects. The side-effects of tricyclic and tetracyclic antidepressants may be worrisome in pregnancy and their narrow therapeutic range increases the risk of overdose. SSRIs have a safer therapeutic profile because of their relatively benign side-effects and their safety in overdose (4). The SSRI group is comprised of the following drugs:

1. Fluoxetine (Prozac, Prizma, Flutine, Affectine)

2. Paroxetine (Seroxat, Paxet, Paxol, Paroxetine)

3. Sertraline (Lustral, Zoloft)

4. Fluvoxamine (Favoxil, Luvox)

5. Citalopram (Cipramil, Recital)

6. Escitalopram (Ciprodex, Cipralex)

Venlafaxine (Efexor, Venla, Viepax) is a selective norepinephrine-serotonin reuptake inhibitor (SNSRI) that is closely related to the SSRIs.

The pharmacokinetic properties of SSRIs (7) are presented in Table 1. This table lists the most commonly recorded adult drug half-life of SSRIs because there is little or no information regarding the newborn. It is of note that during the newborn period, drug half-life is prolonged for most medications, but this is also dependent on drug metabolism. Of the SSRI half-lives, fluoxetine, sertraline and citalopram have a long one with fluoxetine having the longest, paroxetine and fluvoxamine have an intermediate one and venlafaxine has the shortest. …

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