Pharmacologic Factors Associated With Transient Neonatal Symptoms Following Prenatal Psychotropic Medication Exposure

Oberlander, Tim F.; Misri, Shaila; Fitzgerald, Colleen; Kostaras, Xanthoula; Rurak, Dan; Riggs, Wayne

doi:10.4088/jcp.v65n0214

Cited by 215 publications

(217 citation statements)

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“…While a substantial number of reactions were seen at 48 h after birth, it is doubtful whether clomipramine-exposed neonates could be safely discharged from the hospital 48 h after birth. Studies with SSRIs found percentages of 15-30% for neonatal withdrawal symptoms in the first days after delivery [37,38]. However, most data were derived from case reports and not, as in the present study, with structured observations of every clomipramine-complicated pregnancy.…”

Section: Figurecontrasting

confidence: 42%

Clomipramine concentration and withdrawal symptoms in 10 neonates

Horst

Linde

Smit³

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Antidepressants are associated with withdrawal symptoms after in utero exposure.• Half-life of clomipramine in neonates is prolonged compared with that in adults. WHAT THIS STUDY ADDS• We present 10 cases of neonates exposed in utero to clomipramine, with detailed information about withdrawal symptoms and pharmacokinetics.• There is a high and severe complication rate in our cohort regarding the mother and the neonate. AIMAfter in utero exposure to tricyclic antidepressants, neonatal withdrawal symptoms have been reported with an estimated incidence between 20 and 50%; however, few data are available for clomipramine. This could also be the case for neonatal pharmacokinetic clomipramine parameters and so this study was set up. METHODSBabies exposed to clomipramine in utero were included in an observational study, approved by the local ethics committee, after written informed consent. Withdrawal symptoms were scored at 12, 24 and 48 h after birth using the Finnegan score. Plasma concentrations were determined using an in-house-developed, validated liquid chromatography with mass detection (LC-MSMS) method at 0, 12, 24 and 48 h after birth. RESULTSWe found that three of 11 pregnancies were complicated with pre-eclampsia. Ten neonates were observed for clomipramine withdrawal symptoms. The observed withdrawal symptoms were too short a period of sleep after feeding (6), poor feeding (3), mild to severe tremors (6), hyperactive Moro reflex (3) and respiratory rate >60 breaths min -1. Serious withdrawal reactions, such as tachycardia and cyanosis, were seen. We calculated a half-life value of 42 Ϯ 16 h for clomipramine in neonates. Only a weak correlation was found between withdrawal reactions and clomipramine plasma concentration or desmethylclomipramine plasma concentration. CONCLUSIONSIn neonates, clomipramine is eliminated with a half-life value of 42 h, compared with 20 h in adults. In two of 10 neonates, tachycardia and cyanosis were seen as serious withdrawal symptoms after maternal use of clomipramine.

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Section: Figurecontrasting

confidence: 42%

Clomipramine concentration and withdrawal symptoms in 10 neonates

Horst

Linde

Smit³

et al. 2012

Brit J Clinical Pharma

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“…These include pharmacological factors related to varying half lives, pharmacologically active metabolites 31 and possible competitive inhibition with other medications. 11 Paroxetine's high potency for inhibition of 5HT reuptake and affinity for muscarinic receptors may lead to adverse neonatal outcomes once medication exposure ceases, suggesting a 'discontinuity condition' as proposed by Moses-Kolko. 1 Alternatively some of our findings could also represent a condition analogous to the 'serotonin syndromes' observed in adults 32 associated with increased intrasynaptic serotonin (leading to increased postsynaptic serotonin receptor stimulation), resulting in nausea, diarrhea, agitation and insomnia.…”

Section: Discussionmentioning

confidence: 99%

“…Using previously reported outcomes 3,11 neonatal outcomes during two distinct time periods were tabulated. From the immediate newborn period Apgar scores at 1 and 5 min, birth weight, head circumference, length and gestational age at birth were obtained.…”

Section: Neonatal Healthmentioning

confidence: 99%

“…Compounding medication-related effects, adverse neonatal behaviors have also been observed following exposure to maternal depression alone 8 and therefore identifying SRI-related outcomes has been challenged by the difficulty of distinguishing medication effects from the effects of the maternal disease itself. 9 A number of mechanisms have been proposed to explain neonatal adverse outcomes associated with prenatal SRI exposure, including prolonged prenatal central neurotransmitter suppression, 10 pharmacological toxicity, 11 altered pulmonary vasculature, 3 changes in central serotoninergic neurodevelop-ment 12 and effects of exposure to maternal illness itself. 13 Given that SRIs block the reuptake of serotonin (5HT) within the presynaptic cleft via the serotonin transporter (5HTT), this transporter plays a key role as a regulator of serotoninergic neurotransmission and modifier of SRIs effects.…”

Section: Introductionmentioning

confidence: 99%

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Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications

et al. 2007

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Reduced Apgar scores and birth weight, increased risk of respiratory distress, jitteriness and increased tone have been reported in up to 30% of neonates with prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressant medications. In adults, effects of these medications may be related to the genotype for the serotonin transporter (SLC6A4) promoter. In this study we investigated whether SLC6A4 genotype influences the risk for adverse outcomes in neonates with prenatal SRI exposure. Neonatal outcomes including Apgar scores, birth weight, gestational age at birth, symptoms of poor neonatal adaptation and genotype for SLC6A4 were determined in 37 prenatally SRI exposed neonates and compared with 47 nonexposed neonates. Reduced 5 min Apgar scores were observed in exposed neonates and this was moderated by the ss genotype (P < 0.001). Birth weight was lower in exposed ls neonates (P = 0.008). Risk for respiratory symptoms (respiratory distress and rapid breathing) was higher in exposed neonates with the ll genotype compared to non-exposed neonates (P < 0.05) and risk for neuromotor symptoms increased in exposed ss neonates (P < 0.026). These relationships remained when controlling for maternal mood during pregnancy, length of gestational medication exposure and gestational age at birth and cesarean section rate. Prenatal SRI exposure was associated with adverse neonatal outcomes and these effects were moderated by infant SLC6A4 genotype. Relationships between polymorphisms and specific outcomes varied during the neonatal period, suggesting that beyond apparent gene-medication interactions, multiple mechanisms contribute to adverse neonatal outcomes following prenatal SRI exposure.

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“…These withdrawal effects are common, appearing in 30% of infants exposed to SSRIs, but they are generally mild, transient, and self-limiting. 64 They appear to be particularly associated with the use of paroxetine. 65 It is worth noting that in many cases, these correlations between SSRI/SNRI usage and adverse effects are confounded by underlying maternal depression, thereby precluding any firm causal conclusions from being drawn.…”

Section: Antidepressantsmentioning

confidence: 99%

Perinatal Generalized Anxiety Disorder: Assessment and Treatment

Misri

Abizadeh

Sanders

et al. 2015

Journal of Women's Health

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113

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Perinatal generalized anxiety disorder (GAD) has a high prevalence of 8.5%-10.5% during pregnancy and 4.4%-10.8% postpartum. Despite its attendant dysfunction in the patient, this potentially debilitating mental health condition is often underdiagnosed. This overview will provide guidance for clinicians in making timely diagnosis and managing symptoms appropriately. A significant barrier to the diagnosis of GAD in the perinatal population is difficulty in distinguishing normal versus pathological worry. Because a perinatal-specific screening tool for GAD is nonexistent, early identification, diagnosis and treatment is often compromised. The resultant maternal dysfunction can potentially impact mother-infant bonding and influence neurodevelopmental outcomes in the children. Comorbid occurrence of GAD and major depressive disorder changes the illness course and its treatment outcome. Psychoeducation is a key component in overcoming denial/stigma and facilitating successful intervention. Treatment strategies are contingent upon illness severity. Cognitive behavior therapy (CBT), relaxation, and mindfulness therapy are indicated for mild GAD. Moderate/severe illness requires pharmacotherapy and CBT, individually or in combination. No psychotropic medications are approved by the FDA or Health Canada in pregnancy or the postpartum; off-label pharmacological treatment is instituted only if the benefit of therapy outweighs its risk. SSRIs/SNRIs are the first-line treatment for anxiety disorders due to data supporting their efficacy and overall favorable side effect profile. Benzodiazepines are an option for short-term treatment. While research on atypical antipsychotics is evolving, some can be considered for severe manifestations where the response to antidepressants or benzodiazepines has been insufficient. A case example will illustrate the onset, clinical course, and treatment strategies of GAD through pregnancy and the postpartum.

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Pharmacologic Factors Associated With Transient Neonatal Symptoms Following Prenatal Psychotropic Medication Exposure

Cited by 215 publications

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Clomipramine concentration and withdrawal symptoms in 10 neonates

Clomipramine concentration and withdrawal symptoms in 10 neonates

Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications

Perinatal Generalized Anxiety Disorder: Assessment and Treatment

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