Neonatal signs following exposure to ssris

Hum Psychopharmacol Clin Exp 2005; 20: 522.
Neonatal signs following exposure to SSRIs Moses-Kolko et al. (2005) reported that late (final tri- acetylcholine (e.g., anti-muscarinic drugs)-related def- mester of pregnancy) exposure of serotonin reuptake icits such as memory and cognition in rodent models, inhibitor (SRI) carries an overall risk ratio of 3.0 for and are also effective in animal models of depression a neonatal behavioral syndrome as compared with (Hayashi and Su, 2004; Hashimoto and Ishiwata, early gestational SRI exposure or no exposure. Eleven 2005). Additionally, fluvoxamine acts as an agonist at (61%) of the 18 cases of SRI-related neonatal signs sigma-1 receptors although it is unknown whether were associated with paroxetine exposure. Further- other SRIs are agonists at sigma-1 receptors (Hayashi more, neonatal behavioral signs across the cohort stu- and Su, 2004; Hashimoto and Ishiwata, 2005). Taken dies and the case series were similar to those reported together, it seems that agonistic activity of fluvoxamine in the single case reports (Moses-Kolko et al., 2005).
at sigma-1 receptors might, in part, play a role in the Furthermore, Sanz et al. (2005) reported recently the lack of these side effects of fluvoxamine although association between neonatal withdrawal syndrome further studies using selective sigma-1 receptor ago- and maternal use of SRIs, especially paroxetine. They nists would be necessary. Therefore, it is likely that identified a total of 102 cases of SRI use associated SRIs (e.g., fluvoxamine) with high affinity at sigma-1 with either neonatal convulsions or withdrawal syn- receptors might be useful for the treatment of perina- drome. Paroxetine was the most commonly reported SRI with these adverse side effects. Cases were alsoreported for fluoxetine, sertraline, and citalopram, butnot for any of the other SRIs including fluvoxamine (Sanz et al., 2005). They conclude that paroxetine Moses-Kolko EL, Bogen D, Perel J, et al. 2005. Neonatal signs after should not be used in pregnancy or, if used, should late in utero exposure to serotonin reuptake inhibitors-literature be given at the lowest effective dose (Sanz et al., review and implications for clinical applications. JAMA 293: 2005). These two authors suggested that a moderate affi- Narita N, Hashimoto K, Tomitaka S, et al. 1996. Interactions of nity of paroxetine at muscarinic acetylcholine receptors selective serotonin reuptake inhibitors with subtypes of sigma could contribute to neonatal behavioral syndromes and receptors in rat brain. Eur J Pharmacol 307: 117–119.
withdrawal syndrome associated with paroxetine use Hashimoto K, Ishiwata K. 2005. Sigma receptor ligands: possible (Moses-Kolko et al., 2005; Sanz et al., 2005).
application as therapeutic drugs and as radiopharmaceuticals.
Sigma-1 receptors are brain-enriched endoplasmic Hayashi T, Su TP. 2004. Sigma-1 receptor ligands: potential in the reticulum proteins that are implicated in certain psy- treatment of neuropsychiatric disorders. CNS Drugs 18: 269– chiatric disorders including depression and anxiety (Hayashi and Su, 2004; Hashimoto and Ishiwata, Sanz EJ, De-las-Cuevas C, Kiuru A, et al. 2005. Selective serotonin 2005). Sigma-1 receptors modulate a number of neu- reuptake inhibitors in pregnant women and neonatal withdrawalsyndrome: a database analysis. Lancet 365: 482–487.
rotransmitter systems, including noradrenergic, gluta-matergic, and cholinergic systems (Hayashi and Su,2004; Hashimoto and Ishiwata, 2005). We reported that SRIs possessed high to moderate affinities at sigma-1 receptors in the brain (Narita et al., 1996).
Chiba University Center for Forensic Mental Health The rank order of potency of drugs for sigma-1 recep- tors was as follows: fluvoxamine (Ki ¼ 36 nmol/L) > sertraline> fluoxetine> citalopram > paroxetine (Ki ¼ l893 nmol/L). Sigma-1 receptor agonists can improve Copyright # 2005 John Wiley & Sons, Ltd.

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