Serotonin Toxicity Versus Withdrawal: Clonidine One Size Fits All?

Serotonin discontinuation syndrome (SDS) can result in a constellation of symptoms exhibited by infants exposed to selective serotonin reuptake inhibitors or other psychotropic drugs during pregnancy. Currently, there is no consensus regarding the pharmacologic management of SDS. We report our experience with clonidine for the management of a term infant with poor neonatal adaption. The infant exhibited biphasic symptoms of acute toxicity at birth and a plateauing of symptoms, followed by subsequent withdrawal symptomatology requiring the use of clonidine in doses up to 4 mcg/kg/dose every 3 hours for control of symptoms. The 38-week gestation Caucasian male infant was born to a mother with major depressive disorder, which was managed with sertraline, trazodone, venlafaxine, and buspirone throughout her pregnancy. The infant exhibited severe hypertonia at delivery and continued to have hypertonia, tremors, hypoglycemia, and feeding issues upon admission to the NICU. The initial Modified Finnegan Neonatal Abstinence scores were extremely elevated, and clonidine was started at 1 mcg/kg/dose every 3 hours and then the dose was titrated up to 4 mcg/kg/dose. This is the first report documenting the use of clonidine to manage serotonin toxicity at birth followed by subsequent neonatal withdrawal associated with maternal antidepressant drug use during pregnancy.

Effect of SSRI discontinuation on anxiety-like behaviours in mice

Background: Abrupt cessation of therapy with a selective serotonin reuptake inhibitor (SSRI) is often associated with a discontinuation syndrome, typified by numerous disabling symptoms including elevated anxiety, which is of unknown cause. Aim: Here, the effect of SSRI discontinuation on anxiety-like behaviour was investigated in mice. Methods: Mice were treated repeatedly with paroxetine, citalopram or saline using a 3-arm experimental design comprising saline, continued SSRI and discontinued SSRI. Mice were assessed over 5 days after SSRI discontinuation using the elevated plus maze (EPM) and other anxiety tests. Results: In an exploratory experiment mice discontinued (2 days) from paroxetine (12 days) showed evidence of increased anxiety on the EPM, although this effect was observed in male and not female mice. Follow-up studies confirmed the EPM findings in male mice discontinued (2 days) from paroxetine (12 or 28 days) or citalopram (12 days) compared to saline controls. Continued treatment with paroxetine was also anxiogenic on the EPM but this was not the case for citalopram. Paroxetine exposure for more than a week was required to elicit evidence of a discontinuation response, which did not obviously strengthen with increased frequency or duration of dose. Finally, SSRI discontinuation effects were not resolvable from continued treatment in other anxiety tests applied between 3 and 5 days post-discontinuation. Conclusion: Overall, the current study provides evidence for a short-lasting increase in anxiety-like behaviour in mice following SSRI discontinuation, and offers a means for the investigation of the neurobiological mechanisms involved.