Adverse Events in a Breastfed Infant Exposed to Risperidone and Haloperidol

Introduction

Although less frequently observed in the general population, schizophrenia is a more severe psychiatric disorder compared with depression and anxiety disorders. It has been well documented that childbirth may trigger episodes of mood disorders or psychoses. ¹ Antipsychotic medications are the primary treatment regimen for schizophrenia and related psychotic disorders. Owing to the severity of the disorder, most patients with schizophrenia require prophylactic treatment with these medications. In contrast, lactation is a considerable factor in deciding which type of antipsychotics should be used during the postpartum period. When long-term medical and psychological benefits of breastfeeding on infants are considered, one of the important goals in postpartum psychiatric patients is the continuation of breastfeeding. Therefore, safety data on psychotropic drugs during lactation are essential.

It is well known that all antipsychotic drugs are excreted into the breast milk to some extent. Case reports, case series, and studies with small sample sizes examining the safety of antipsychotics during lactation have been published in the literature. ² Olanzapine is an antipsychotic medication with the most extensive safety data. Despite their long history, scientific data on the use of haloperidol and risperidone in the lactation period are very limited.^2,3 In addition, the effects of the use of combined antipsychotics on infant safety are currently unknown. This report presents the adverse events observed in an infant exposed concurrently to haloperidol and risperidone during the lactation period.

Case

A 24-year-old woman was admitted to the perinatal psychiatry outpatient clinic during the 26th week of gestation. The patient was diagnosed 4 years previously with schizophrenia according to the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (SCID-I). ⁴ The patient described a significant decrease in psychiatric symptoms after using risperidone at 1 mg/day plus aripiprazole at 10 mg/day. The patient reported that 1 year after initiation, risperidone was gradually withdrawn and the daily dose of aripiprazole was reduced to 5 mg/day due to a remission in symptoms. The patient reported the subsequent discontinuation of treatment by herself owing to her plans for pregnancy. At her first admission to the perinatal outpatient clinic, the patient presented a history of psychotic symptoms such as reference and persecution delusions, irritability, and dysphoric affect. When the clinical status was explained to the patient and her family and a written informed consent form was obtained, risperidone at 1.5 mg/day was started. Three weeks later, a considerable alleviation in symptoms was observed. The patient gave birth to a healthy baby at the 40th gestational week.

Prophylactic treatment with risperidone at 1.5 mg/day was continued during the lactation period. The patient and her relatives described reference and persecution delusions, anxiety, and irritability at 2 weeks postpartum. Owing to a gradual increase in the severity of these symptoms and a history of positive effects of low-dose haloperidol in the patient, haloperidol at 0.8 mg/day was added to the treatment regimen. Two weeks later, a continuation of the symptoms was observed despite some alleviation in symptom severity. No adverse events in the breastfed infant was reported while the mother was on risperidone at 1.5 mg/day plus haloperidol at 0.8 mg/day. The daily dose of haloperidol was raised to 1.5 mg/day. Three days later, the patient and her relatives reported hypersomnia, poor feeding, and slowing in motor movements in the infant, although maternal psychotic symptoms significantly alleviated. Physical and laboratory evaluations by a pediatrician did not establish any medical condition associated with these symptoms in the infant. The score of the Naranjo Adverse Drug Reaction Probability Scale was 7. This score suggests a probable association. ⁵ The patient and her relatives decided to discontinue breastfeeding. The symptoms observed in the infants were completely resolved within 5 days after the discontinuation of breastfeeding.

Discussion

The available data suggest that there is no a clear contraindication in the use of antipsychotics during lactation.^3,6 Although using a single psychotropic medication at a dose as low as possible is the general recommendation in breastfeeding women, the concurrent use of more than one antipsychotic medication is frequently seen in clinical practice. The safest antipsychotic for use in breastfeeding women appears to be olanzapine. ² Nevertheless, efficacy data on individual medications previously used in patients are an important factor in deciding pharmacological options during lactation. Therefore, prophylactic treatment with risperidone was administered in the current patient.

To date, several case reports have presented data on breastfed infants exposed to combined antipsychotic through breast milk. Aydin et al. ⁷ observed no adverse events in an infant of a breastfeeding mother using olanzapine at 15 mg/day and quetiapine at 200 mg/day. In addition, there are two published case reports presenting the combined use of haloperidol at 5 mg/day with olanzapine at 10 mg/day or amisulpride at 400 mg/day with no reports of any adverse events in breastfed infants. ⁸ In the current case, when haloperidol at a daily dose of much <5 mg was added to risperidone at 1.5 mg/day, adverse events in the infant were observed. The mean overall relative infant dose (RID) for risperidone has been reported to be 3.59%. ³ This value is well below the acceptable limit of <10%. Haloperidol has a wide RID range from 0.2% to 12.0%. ⁹ The adverse events observed in the infant in the current report may be associated with haloperidol, since they were identified after the haloperidol dose was increased to 1.5 mg/day in the mother. This finding may suggest relatively high transfer of haloperidol into breast milk in the current case. However, the lack of any laboratory measurements of the drug concentration in the breast milk or infant plasma is a major limitation for this assumption.

In conclusion, the current report suggests that maternal use of combinations of haloperidol and risperidone during lactation even at low doses may be associated with adverse events in some infants. Further data including studies or case reports on the safety of these combinations in breastfed infants are needed.