What is SSRI (Selective Serotonin Reuptake Inhibitor) sensitization?

SSRI Sensitization: Neonatal Serotonin Syndrome

SSRI sensitization refers to a neonatal syndrome occurring in infants exposed to selective serotonin reuptake inhibitors during the third trimester of pregnancy, characterized by excessive serotonergic activity manifesting as continuous crying, irritability, tremors, hypertonia, feeding difficulties, and respiratory distress. 1

Clinical Presentation

The syndrome presents with a constellation of signs resulting from elevated serotonin concentrations in the central nervous system:

Neurological and Behavioral Signs 1

• Continuous crying and marked irritability
• Jitteriness, restlessness, and tremors
• Hypertonia or muscle rigidity
• Hyperreflexia and myoclonic jerks
• Seizures (in severe cases)

Autonomic and Systemic Signs 1

• Tachypnea or respiratory distress
• Hyperthermia and shivering
• Hypersalivation
• Feeding difficulty and poor suck
• Sleep disturbances
• Hypoglycemia

Timing and Duration

• Onset occurs within hours to several days after birth 1
• Symptoms typically resolve within 1-2 weeks, though cases have been documented lasting up to 4 weeks (particularly with paroxetine exposure) 1
• The timing reflects the infant's clearance of maternal SSRI and active metabolites after delivery 1

Pathophysiology: Two Competing Mechanisms

The medical literature debates whether this represents true "sensitization" or withdrawal:

Serotonin Syndrome Hypothesis 1

• Results from excessive serotonin in the intersynaptic cleft
• Characterized by the classic triad seen in adults: mental status changes (agitation, confusion), autonomic hyperactivity (fever, tachycardia, tachypnea), and neuromuscular abnormalities (tremor, hyperreflexia, hypertonia) 1
• In adults, severe serotonin syndrome typically requires combination of multiple serotonergic agents, though single SSRIs can cause mild-to-moderate symptoms 1

SSRI Withdrawal Hypothesis 1

• Attributes symptoms to a relative hypo-serotonergic state following abrupt cessation of in utero SSRI exposure
• In adults, serotonin withdrawal manifests as anxiety, headache, nausea, fatigue, and rarely extrapyramidal signs 1

The clinical presentation in neonates more closely resembles serotonin excess rather than withdrawal, given the predominance of hyperactivity, hypertonia, and autonomic instability 1

Clinical Management

Acute Treatment 1

• Most infants respond to supportive care alone with symptom resolution within 1-2 weeks
• In severely affected infants, chlorpromazine provides measurable relief of symptoms through its antiserotonergic properties 1
• Treatment goals include preventing further drug absorption (not applicable postnatally), supporting the central nervous system, controlling hyperthermia, and managing seizures if present 2

Monitoring Considerations 1

• Close observation for respiratory distress and feeding difficulties
• Blood glucose monitoring due to risk of hypoglycemia
• Assessment of muscle tone and neurological status
• Evaluation for seizure activity in severe cases

Risk Factors and Prevention

All SSRIs carry this risk when used in the third trimester, including fluoxetine, paroxetine, sertraline, citalopram, escitalopram, and fluvoxamine 1. The syndrome occurs regardless of which specific SSRI is used, though paroxetine has been associated with more prolonged symptoms 1.

Prognosis

The prognosis is excellent with appropriate supportive care 2. In documented case series, symptoms are self-limited and resolve without long-term sequelae when recognized and managed appropriately 1. The key is distinguishing this syndrome from other neonatal conditions requiring different interventions.

Differential Diagnosis

This presentation must be distinguished from:

• Neonatal abstinence syndrome from other substances 1
• Sepsis or meningitis
• Metabolic disorders causing hypoglycemia
• Primary seizure disorders
• Other drug withdrawal syndromes (benzodiazepines, opioids) 1

The clustering of signs, their severity, and temporal relationship to maternal SSRI use distinguish SSRI sensitization from isolated adverse effects or other neonatal conditions 3.