Short-Term Safety of Paroxetine Plus Low-Dose Mirtazapine During Lactation

Introduction

It has been well documented that postpartum women frequently experience depression and anxiety disorders.^1,2 Many women with depression or anxiety disorders require pharmacological treatment that includes antidepressants. A major challenge in the pharmacological treatment of postpartum women with these disorders is the safety profile of the pharmacological agents in the breastfed infant.

The selective serotonin reuptake inhibitors (SSRIs), venlafaxine, duloxetine, and mirtazapine, are the antidepressants that are most commonly used in clinical practice. In the past two decades, data on the safety of SSRIs during lactation have been extensively published in the literature. Paroxetine is one of the SSRIs that is recommended as first line due to its good safety profile in breastfeeding women. ³ However, psychiatrists sometimes need to administer additional antidepressants to alleviate symptoms such as severe insomnia and dramatic reduction in appetite in women with depression and anxiety disorders. A meta-analysis suggested that compared with SSRIs, mirtazapine was significantly more likely to cause weight gain or increased appetite. ⁴ Nonetheless, data on the safety of combined antidepressants in breastfeeding women are very limited. This report presents data on the safety of short-term use of paroxetine plus low-dose mirtazapine in eight breastfeeding women.

Cases

The eight breastfeeding women were recruited from patients who were admitted to the perinatal psychiatry outpatient clinic of a University hospital and their data were retrospectively obtained from clinical registers. Informed patient consent to the usage of scientific data was obtained. In addition, the local ethics committee approved the methodology of the data. Major depression and anxiety disorders were diagnosed by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (SCID-I). ⁵ According to SCID-I, three patients had major depression, three patients had generalized anxiety disorder plus major depression, whereas two patients had panic disorder plus major depression.

The mean age of the eight patients was 28.1 ± 5.3 years. Six (75%) of the patients had completed primary or secondary school, and two (250%) were employed. The mean number of children was 1.1 ± 0.9. The mean age of infants at the initiation of treatment was 4.3 ± 3.1 weeks. The present report includes results from a follow-up period of 3 to 6 weeks as mirtazapine was stopped due to significantly decreased depressive and anxiety symptoms, including disturbances in sleep and appetite. The patients did not receive any psychotropic medication other than paroxetine and mirtazapine during the follow-up period. Daily dose of paroxetine and mirtazapine in each patient was 20 and 15 mg, respectively. One patient (12.5%) reported restlessness in her baby that developed 5 days after initiation of treatment. When paroxetine but not mirtazapine was stopped, the infant showed complete recovery from these symptoms within 48 hours. No further adverse events were observed in the infants.

Discussion

The present case series appears to be the first report examining short-term safety of combined usage of paroxetine and mirtazapine in breastfed infants. We have limited scientific data on the use of mirtazapine during lactation. Kristensen et al. ⁶ reported that the mean relative infant dose for mirtazapine was 1.5% with no adverse events in the eight infants. In their study, the daily dose of mirtazapine (30–120 mg) was much higher than the current cases. A recent systematic review ⁷ has supported that despite limited data the use of mirtazapine may be safe during lactation.

In the present cases, adverse events were observed in only one infant. The most frequently reported adverse events in infants exposed to antidepressants through breastfeeding are irritability, feeding and sleep disturbances, agitation, and sedation.^8,9 In a recent retrospective cohort study,^5,10 similar adverse events were reported in 11.9% of infants exposed to paroxetine. In this case series, restlessness was observed in one infant that was ameliorated after the withdrawal of paroxetine; therefore, it appears that this adverse event was associated with paroxetine rather than mirtazapine.

In conclusion, the present case series suggests that the addition of mirtazapine at 15 mg/day to paroxetine in breastfeeding women may be well tolerated by breastfed infants for a short-term period. However, long-term follow-up studies with larger sample size including infants exposed to SSRI plus mirtazapine are needed.