LETTER TO THE EDITORS
Transfer of Aripiprazole to Breast Milk A Case Report To the Editors: ripiprazole is an atypical antipsychotic drug used in the treatment of schizophrenia, bipolar disorder, and depression. It was approved by the US Food and Drug Administration in 2002 and the European Medicines Agency in 2004. Since then, there have only been 3 published case reports where drug concentrations in breast milk have been measured.1Y3 In the first report, 2 breast milk samples were taken just before administration of the daily dose of 15 mg aripiprazole on 2 consecutive days 2 weeks after medication was initiated.1 Milk concentrations of 13 and 14 ng/mL were detected. In the second report, aripiprazole was not detected in 3 breast milk samples (limit of detection, 10 ng/mL) taken 1 month after delivery from a woman using 15 mg aripiprazole per day since the beginning of pregnancy.2 The authors estimated the relative infant dose to be less than 0.7% and reported that the infant showed normal development up to age 3 months, although it is not explicitly stated that the infant was breast-fed throughout this period. In the third report, a single breast milk sample taken 6 days after delivery from a woman who had been using 18 mg aripiprazole per day since gestational week 34 showed a concentration of 38.7 ng/mL.3 Breast-feeding was stopped the same day because of maternal illness. The authors reported that the mother and child were doing well 2 months after delivery. Since there is still very little information available on the transfer of aripiprazole to breast milk in lactating women, we report a case of successful breast-feeding in a patient using 10 mg aripiprazole per day. Breast milk concentrations were measured throughout the course of 2 days, and the infant was observed for 4 months.
A
CASE REPORT The patient was a 35-year-old woman with a diagnosis of bipolar disorder. After her first delivery 13 years ago, she developed a postpartum psychosis and was hospitalized several times in the years to follow. Thereafter, she had 2 consecutive pregnancies with mild depressive symptoms. Because of treatment with psychotropic drugs during
Journal of Clinical Psychopharmacology
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and after the first 3 pregnancies, she had been advised not to breast-feed these infants. When she became pregnant with her fourth child, she was using 50 mg lamotrigine per day and 10 mg aripiprazole per day. Both drugs were discontinued when her pregnancy was confirmed in gestational week 5. However, 10 mg aripiprazole per day was reintroduced in gestational week 9 because of manic symptoms. She remained mentally stable throughout the rest of her pregnancy and experienced no other complications. Before delivery, she expressed a strong wish to breast-feed because one of her previous infants (who had not been breast-fed) had developed asthma and allergy. She also felt that breast-feeding would promote her bonding to the childVsomething she considered would be positive for her mental health. A healthy girl was delivered at term (week 39 + 4 days), weighing 3395 g. The Apgar scores were 9, 10, and 10 one, five, and ten minutes after delivery. The infant showed good suckling reflexes and thrived normally. No signs of excessive somnolence were observed after delivery or reported by the mother after discharge from the hospital. After 6 weeks of breast-feeding exclusively, a milk substitute was introduced and given regularly because of insufficient breast milk production. At 7 weeks, the infant weighed 4600 g and was breastfed approximately 8 times daily, receiving approximately 40 mL of breast milk per feeding. At the age of 4 months, the still breast-fed infant weighed 5600 g. The mother who had been using 10 mg aripiprazole per day throughout this period gave her consent for publication of this case report. Sampling of breast milk was undertaken 8 and 10 weeks postpartum at the following time intervals: 0 hour (before the morning dose) and 2, 3, 6, 9, 12, and 24 hours after drug intake, respectively. The woman was instructed to express midfeed samples. The samples were stored frozen at j20-C until the day of analysis. Aripiprazole and its metabolite dehydroaripiprazole in breast milk were determined by a liquid chromatographyVa mass spectrometry method developed in our laboratory. Milk samples, spiked standards, and quality controls were extracted as follows: 1 mL sample, 25 KL of the internal standard 2 Kg/mL aripiprazole-d8, 0.2 mL of 1 mol/L Na2CO3, and 4 mL of the organic solvent hexane/butanol/acetonitrile (93:5:2 ratio) were mixed, centrifuged, and frozen
Volume 34, Number 2, April 2014
in liquid nitrogen. The organic phases were evaporated and the extracts acidified and washed with hexane containing 10% formic acid. The samples were then mixed and centrifuged, and the inorganic phases were evaporated and dissolved in methanol. Chromatographic separations were achieved with a Zobrax Stable Bond Cyano (SB-CN) column (150 4.6 mm, 5 Km; Agilent, Palo Alto, CA), with a mobile phase consisting of 75% acetonitrile and 25% 50 mmol/L ammonium acetate at a flow rate of 1 mL/min. The injection volume was 5 KL, and the retention time was approximately 3 minutes. Analysis was performed on an Agilent LCMS-1100 series (Agilent, Palo Alto, CA), applying atmospheric pressure chemical ionization. The quantification ions were mass/ charge (m/z) 448 and 285 for aripiprazole, 464 and 285 for dehydroaripiprazole, and 456 for aripiprazole-d8. Within-assay coefficients of variation were 4.0% for aripiprazole and 5.0% for dehydroaripiprazole, and recoveries were 84% and 73%, respectively. The method was found to be accurate irrespective of the triglyceride content of the sample. The limits of quantification were 5 ng/mL for both analytes, and the method was linear at least up to 1000 ng/mL. Triglyceride concentrations were analyzed using a commercial kit based on enzymatic hydrolysis with subsequent determination of glycerol (Triglycerides GPO-PAP; Roche Diagnostics, Mannheim, Germany). The absolute dose to the breast-fed infant was calculated in nanogram per kilogram per day by multiplying the drug milk concentration (in nanogram per milliliter) by the daily milk intake, assumed to be 150 mL/kg per day. In this calculation, the mean 24-hour milk concentration was used, calculated as the area under the time-concentration curve during a dose interval of 24 hours divided by 24. The relative infant dose was calculated as the infant daily dose in milligram per kilogram body weight 100% divided by the maternal daily dose in milligram per kilogram body weight. The maternal body weight at the time of breast milk sampling was 87 kg. The concentrations of aripiprazole and dehydroaripiprazole in breast milk are shown in Figure 1. Based on area under timeconcentration curve calculation, the mean concentrations were 52.6 and 8.8 ng/mL, respectively (first sampling day), and 53.6 and 6.3 ng/mL, respectively (second sampling day). This infant, who was receiving approximately 320 mL of milk per day, would thus ingest close to 20 Kg of aripiprazole www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1
Letter to the Editors
Journal of Clinical Psychopharmacology
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Volume 34, Number 2, April 2014
FIGURE 1. Concentrations of aripiprazole and its metabolite dehydroaripiprazole in breast milk obtained 8 and 10 weeks postpartum, respectively, from a lactating woman treated with a dose of 10 mg aripiprazole per day.
daily through breast milk. Using average milk concentration values and based on a maternal dose of 10 mg/d, the absolute dose of aripiprazole ingested by an exclusively breast-fed infant weighing 5 kg would be 47 Kg/d. The relative infant dose was calculated to 8.3%. At the age of 4 months, the still breast-fed infant showed normal psychomotor and behavioral development and had reached the expected milestones for her age. The dehydroaripiprazole/aripiprazole ratio in milk was 0.12 to 0.17, which is lower than what has been found in serum (approximately 0.44). The reason may be poorer transfer of the metabolite into breast milk because of lower lipophilicity than the parent drug. The maternal serum concentration in a sample obtained some weeks later, while she still used a dose of 10 mg aripiprazole per day, was 114 ng/mL for aripiprazole and 44 ng/mL for dehydroaripiprazole (7 hours after intake of her daily dose). The milk triglyceride content in the samples varied between 44 and 63 mmol/L (3.9Y5.5 g/dL). We found a statistically significant relationship between the triglyceride content and the aripiprazole concentration in breast milk (r = 0.68; P = 0.029). Based on the regression line, every 10-mmol/L change in the triglyceride levels would cause a change in the aripiprazole concentration of 6.7 ng/mL (corresponds to a change of 7.5 ng/mL in the aripiprazole concentration per gram per deciliter change in the triglyceride levels). Treatment with aripiprazole might have been the cause of the mother’s insufficient milk production, as previously reported,5
2
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because her serum levels of prolactin were 35 to 40 ng/mL, which is lower than the values of 50 to 100 ng/mL that are usually seen in lactating women with sufficient production of milk.
DISCUSSION To our knowledge, this is the only case report on the transfer of aripiprazole to breast milk where several daily measurements have been performed, enabling us to estimate a more representative infant intake of aripiprazole than what was previously reported. Moreover, in this case, the woman was still breast-feeding her infant, thus mirroring ‘‘a real life’’ situation. Interestingly, although the patient used a lower aripiprazole dose than in the 3 previously published reports (15Y18 mg/d), we found higher milk concentrations, most likely illustrating individual differences in maternal pharmacokinetics. The estimated absolute daily dose ingested by a 5-kg infant would still be low (0.5 mgVie, one twentieth to one sixtieth of an adult therapeutic dose of 10Y30 mg/d), but nevertheless, there might be a risk of adverse effects. Although the elimination half-life of aripiprazole in adults is approximately 75 hours and it could be expected to be even longer in neonates and infants because of a reduced metabolic capacity, accumulation over several weeks may occur in the infant if still exposed through breast milk. In fact, in the textbook Medications and Mother’s Milk, Dr Hale6 reports that he has received several calls on somnolence in infants exposed to aripiprazole through
breast milk. As the infant showed no signs of adverse drug reactions, we did not insist on taking a blood sample from the infant. This would have provided additional information about the potential of causing pharmacologic effects in breast-fed infants. Analyzing the triglyceride content in milk enabled us to demonstrate how aripiprazole is concentrated in the fat fraction of the milk. As hindmilk contains 1.5 to 3 times more triglycerides than foremilk, it will also have a higher concentration of aripiprazole. However, stopping lactation before the breast is empty is not considered recommended because fat is an essential source of nutrition for the infant. Moreover, avoiding breast-feeding the first hours after drug intake is of little value because the drug concentration in the milk is fairly stable throughout the dose interval (Fig. 1). This case illustrates the importance of an individualized risk-benefit approach in the counseling of mothers treated with aripiprazole in the postpartum period. Some women will have a strong wish to breastfeed, whereas others may not. The severity of the mental illness, the risk of nonadherence to needed pharmacologic treatment, the woman’s personal preferences related to breast-feeding, and the benefits of mother’s milk to the infant must all be balanced against potential risks of adverse pharmacologic effects to the breastfed infant. Moreover, factors such as infant age and health, severity of the maternal mental illness, and maternal polypharmacy may vary and cause different risk/ benefit evaluations. The answer on whether * 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology
&
Volume 34, Number 2, April 2014
to recommend (or accept a desire of) breastfeeding or not may therefore be ‘‘yes’’ for some women and ‘‘no’’ for others. The woman’s decision should in any case be an informed one. If a woman decides to breast-feed her infant while using aripiprazole, we recommend that the infant is monitored for potential adverse effects such as drowsiness, poor feeding, and sleeping pattern changes. As long as information about breast milk transfer of aripiprazole is limited, we also recommend that breast feeding should be supported by determination of drug concentrations in breast milk, if possible. Including our case, only 4 cases of breast-feeding while using aripiprazole have been published. Consequently, there is an urgent need for more studies of the safety of this drug during breast-feeding.
AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest.
* 2014 Lippincott Williams & Wilkins
Hedvig Nordeng, MScPharm, PhD School of Pharmacy University of Oslo and Division of Mental Health Norwegian Institute of Public Health Oslo, Norway [email protected] Guri Gjerdalen, MD Department of Obstetrics and Gynecology Drammen Hospital VVHF Drammen, Norway Wenche Rødseth Brede, MSc Lisbeth Solem Michelsen, BSc Department of Clinical Pharmacology St Olav’s University Hospital Trondheim, Norway Olav Spigset, MD, PhD Department of Clinical Pharmacology St Olav’s University Hospital and Department of Laboratory Medicine Children’s and Women’s Health Norwegian University of Science and Technology Trondheim, Norway
Letter to the Editors
REFERENCES 1. Schlotterbeck P, Leube D, Kircher T, et al. Aripiprazole in human milk. Int J Neuropsychopharmacol. 2007;10:433. 2. Lutz UC, Hiemke C, Wiatr G, et al. Aripiprazole in pregnancy and lactation: a case report. J Clin Psychopharmacol. 2010;30:204Y205. 3. Watanabe N, Kasahara M, Sugibayashi R, et al. Perinatal use of aripiprazole: a case report. J Clin Psychopharmacol. 2011;31: 377Y379. 4. Sparshatt A, Taylor D, Patel MX, et al. A systematic review of aripiprazoleVdose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. J Clin Psychiatry. 2010;71: 1447Y1456. 5. Mendhekar DN, Sunder KR, Andrade C. Aripiprazole use in a pregnant schizoaffective woman. Bipolar Disord. 2006;8:299Y300. 6. Hale T. Medication and Mother’s Milk. 16th ed. Amarillo, TX: Hale Publishing; 2012.
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
3
Transfer of Aripiprazole to Breast Milk A Case Report To the Editors: ripiprazole is an atypical antipsychotic drug used in the treatment of schizophrenia, bipolar disorder, and depression. It was approved by the US Food and Drug Administration in 2002 and the European Medicines Agency in 2004. Since then, there have only been 3 published case reports where drug concentrations in breast milk have been measured.1Y3 In the first report, 2 breast milk samples were taken just before administration of the daily dose of 15 mg aripiprazole on 2 consecutive days 2 weeks after medication was initiated.1 Milk concentrations of 13 and 14 ng/mL were detected. In the second report, aripiprazole was not detected in 3 breast milk samples (limit of detection, 10 ng/mL) taken 1 month after delivery from a woman using 15 mg aripiprazole per day since the beginning of pregnancy.2 The authors estimated the relative infant dose to be less than 0.7% and reported that the infant showed normal development up to age 3 months, although it is not explicitly stated that the infant was breast-fed throughout this period. In the third report, a single breast milk sample taken 6 days after delivery from a woman who had been using 18 mg aripiprazole per day since gestational week 34 showed a concentration of 38.7 ng/mL.3 Breast-feeding was stopped the same day because of maternal illness. The authors reported that the mother and child were doing well 2 months after delivery. Since there is still very little information available on the transfer of aripiprazole to breast milk in lactating women, we report a case of successful breast-feeding in a patient using 10 mg aripiprazole per day. Breast milk concentrations were measured throughout the course of 2 days, and the infant was observed for 4 months.
A
CASE REPORT The patient was a 35-year-old woman with a diagnosis of bipolar disorder. After her first delivery 13 years ago, she developed a postpartum psychosis and was hospitalized several times in the years to follow. Thereafter, she had 2 consecutive pregnancies with mild depressive symptoms. Because of treatment with psychotropic drugs during
Journal of Clinical Psychopharmacology
&
and after the first 3 pregnancies, she had been advised not to breast-feed these infants. When she became pregnant with her fourth child, she was using 50 mg lamotrigine per day and 10 mg aripiprazole per day. Both drugs were discontinued when her pregnancy was confirmed in gestational week 5. However, 10 mg aripiprazole per day was reintroduced in gestational week 9 because of manic symptoms. She remained mentally stable throughout the rest of her pregnancy and experienced no other complications. Before delivery, she expressed a strong wish to breast-feed because one of her previous infants (who had not been breast-fed) had developed asthma and allergy. She also felt that breast-feeding would promote her bonding to the childVsomething she considered would be positive for her mental health. A healthy girl was delivered at term (week 39 + 4 days), weighing 3395 g. The Apgar scores were 9, 10, and 10 one, five, and ten minutes after delivery. The infant showed good suckling reflexes and thrived normally. No signs of excessive somnolence were observed after delivery or reported by the mother after discharge from the hospital. After 6 weeks of breast-feeding exclusively, a milk substitute was introduced and given regularly because of insufficient breast milk production. At 7 weeks, the infant weighed 4600 g and was breastfed approximately 8 times daily, receiving approximately 40 mL of breast milk per feeding. At the age of 4 months, the still breast-fed infant weighed 5600 g. The mother who had been using 10 mg aripiprazole per day throughout this period gave her consent for publication of this case report. Sampling of breast milk was undertaken 8 and 10 weeks postpartum at the following time intervals: 0 hour (before the morning dose) and 2, 3, 6, 9, 12, and 24 hours after drug intake, respectively. The woman was instructed to express midfeed samples. The samples were stored frozen at j20-C until the day of analysis. Aripiprazole and its metabolite dehydroaripiprazole in breast milk were determined by a liquid chromatographyVa mass spectrometry method developed in our laboratory. Milk samples, spiked standards, and quality controls were extracted as follows: 1 mL sample, 25 KL of the internal standard 2 Kg/mL aripiprazole-d8, 0.2 mL of 1 mol/L Na2CO3, and 4 mL of the organic solvent hexane/butanol/acetonitrile (93:5:2 ratio) were mixed, centrifuged, and frozen
Volume 34, Number 2, April 2014
in liquid nitrogen. The organic phases were evaporated and the extracts acidified and washed with hexane containing 10% formic acid. The samples were then mixed and centrifuged, and the inorganic phases were evaporated and dissolved in methanol. Chromatographic separations were achieved with a Zobrax Stable Bond Cyano (SB-CN) column (150 4.6 mm, 5 Km; Agilent, Palo Alto, CA), with a mobile phase consisting of 75% acetonitrile and 25% 50 mmol/L ammonium acetate at a flow rate of 1 mL/min. The injection volume was 5 KL, and the retention time was approximately 3 minutes. Analysis was performed on an Agilent LCMS-1100 series (Agilent, Palo Alto, CA), applying atmospheric pressure chemical ionization. The quantification ions were mass/ charge (m/z) 448 and 285 for aripiprazole, 464 and 285 for dehydroaripiprazole, and 456 for aripiprazole-d8. Within-assay coefficients of variation were 4.0% for aripiprazole and 5.0% for dehydroaripiprazole, and recoveries were 84% and 73%, respectively. The method was found to be accurate irrespective of the triglyceride content of the sample. The limits of quantification were 5 ng/mL for both analytes, and the method was linear at least up to 1000 ng/mL. Triglyceride concentrations were analyzed using a commercial kit based on enzymatic hydrolysis with subsequent determination of glycerol (Triglycerides GPO-PAP; Roche Diagnostics, Mannheim, Germany). The absolute dose to the breast-fed infant was calculated in nanogram per kilogram per day by multiplying the drug milk concentration (in nanogram per milliliter) by the daily milk intake, assumed to be 150 mL/kg per day. In this calculation, the mean 24-hour milk concentration was used, calculated as the area under the time-concentration curve during a dose interval of 24 hours divided by 24. The relative infant dose was calculated as the infant daily dose in milligram per kilogram body weight 100% divided by the maternal daily dose in milligram per kilogram body weight. The maternal body weight at the time of breast milk sampling was 87 kg. The concentrations of aripiprazole and dehydroaripiprazole in breast milk are shown in Figure 1. Based on area under timeconcentration curve calculation, the mean concentrations were 52.6 and 8.8 ng/mL, respectively (first sampling day), and 53.6 and 6.3 ng/mL, respectively (second sampling day). This infant, who was receiving approximately 320 mL of milk per day, would thus ingest close to 20 Kg of aripiprazole www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1
Letter to the Editors
Journal of Clinical Psychopharmacology
&
Volume 34, Number 2, April 2014
FIGURE 1. Concentrations of aripiprazole and its metabolite dehydroaripiprazole in breast milk obtained 8 and 10 weeks postpartum, respectively, from a lactating woman treated with a dose of 10 mg aripiprazole per day.
daily through breast milk. Using average milk concentration values and based on a maternal dose of 10 mg/d, the absolute dose of aripiprazole ingested by an exclusively breast-fed infant weighing 5 kg would be 47 Kg/d. The relative infant dose was calculated to 8.3%. At the age of 4 months, the still breast-fed infant showed normal psychomotor and behavioral development and had reached the expected milestones for her age. The dehydroaripiprazole/aripiprazole ratio in milk was 0.12 to 0.17, which is lower than what has been found in serum (approximately 0.44). The reason may be poorer transfer of the metabolite into breast milk because of lower lipophilicity than the parent drug. The maternal serum concentration in a sample obtained some weeks later, while she still used a dose of 10 mg aripiprazole per day, was 114 ng/mL for aripiprazole and 44 ng/mL for dehydroaripiprazole (7 hours after intake of her daily dose). The milk triglyceride content in the samples varied between 44 and 63 mmol/L (3.9Y5.5 g/dL). We found a statistically significant relationship between the triglyceride content and the aripiprazole concentration in breast milk (r = 0.68; P = 0.029). Based on the regression line, every 10-mmol/L change in the triglyceride levels would cause a change in the aripiprazole concentration of 6.7 ng/mL (corresponds to a change of 7.5 ng/mL in the aripiprazole concentration per gram per deciliter change in the triglyceride levels). Treatment with aripiprazole might have been the cause of the mother’s insufficient milk production, as previously reported,5
2
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because her serum levels of prolactin were 35 to 40 ng/mL, which is lower than the values of 50 to 100 ng/mL that are usually seen in lactating women with sufficient production of milk.
DISCUSSION To our knowledge, this is the only case report on the transfer of aripiprazole to breast milk where several daily measurements have been performed, enabling us to estimate a more representative infant intake of aripiprazole than what was previously reported. Moreover, in this case, the woman was still breast-feeding her infant, thus mirroring ‘‘a real life’’ situation. Interestingly, although the patient used a lower aripiprazole dose than in the 3 previously published reports (15Y18 mg/d), we found higher milk concentrations, most likely illustrating individual differences in maternal pharmacokinetics. The estimated absolute daily dose ingested by a 5-kg infant would still be low (0.5 mgVie, one twentieth to one sixtieth of an adult therapeutic dose of 10Y30 mg/d), but nevertheless, there might be a risk of adverse effects. Although the elimination half-life of aripiprazole in adults is approximately 75 hours and it could be expected to be even longer in neonates and infants because of a reduced metabolic capacity, accumulation over several weeks may occur in the infant if still exposed through breast milk. In fact, in the textbook Medications and Mother’s Milk, Dr Hale6 reports that he has received several calls on somnolence in infants exposed to aripiprazole through
breast milk. As the infant showed no signs of adverse drug reactions, we did not insist on taking a blood sample from the infant. This would have provided additional information about the potential of causing pharmacologic effects in breast-fed infants. Analyzing the triglyceride content in milk enabled us to demonstrate how aripiprazole is concentrated in the fat fraction of the milk. As hindmilk contains 1.5 to 3 times more triglycerides than foremilk, it will also have a higher concentration of aripiprazole. However, stopping lactation before the breast is empty is not considered recommended because fat is an essential source of nutrition for the infant. Moreover, avoiding breast-feeding the first hours after drug intake is of little value because the drug concentration in the milk is fairly stable throughout the dose interval (Fig. 1). This case illustrates the importance of an individualized risk-benefit approach in the counseling of mothers treated with aripiprazole in the postpartum period. Some women will have a strong wish to breastfeed, whereas others may not. The severity of the mental illness, the risk of nonadherence to needed pharmacologic treatment, the woman’s personal preferences related to breast-feeding, and the benefits of mother’s milk to the infant must all be balanced against potential risks of adverse pharmacologic effects to the breastfed infant. Moreover, factors such as infant age and health, severity of the maternal mental illness, and maternal polypharmacy may vary and cause different risk/ benefit evaluations. The answer on whether * 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology
&
Volume 34, Number 2, April 2014
to recommend (or accept a desire of) breastfeeding or not may therefore be ‘‘yes’’ for some women and ‘‘no’’ for others. The woman’s decision should in any case be an informed one. If a woman decides to breast-feed her infant while using aripiprazole, we recommend that the infant is monitored for potential adverse effects such as drowsiness, poor feeding, and sleeping pattern changes. As long as information about breast milk transfer of aripiprazole is limited, we also recommend that breast feeding should be supported by determination of drug concentrations in breast milk, if possible. Including our case, only 4 cases of breast-feeding while using aripiprazole have been published. Consequently, there is an urgent need for more studies of the safety of this drug during breast-feeding.
AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest.
* 2014 Lippincott Williams & Wilkins
Hedvig Nordeng, MScPharm, PhD School of Pharmacy University of Oslo and Division of Mental Health Norwegian Institute of Public Health Oslo, Norway [email protected] Guri Gjerdalen, MD Department of Obstetrics and Gynecology Drammen Hospital VVHF Drammen, Norway Wenche Rødseth Brede, MSc Lisbeth Solem Michelsen, BSc Department of Clinical Pharmacology St Olav’s University Hospital Trondheim, Norway Olav Spigset, MD, PhD Department of Clinical Pharmacology St Olav’s University Hospital and Department of Laboratory Medicine Children’s and Women’s Health Norwegian University of Science and Technology Trondheim, Norway
Letter to the Editors
REFERENCES 1. Schlotterbeck P, Leube D, Kircher T, et al. Aripiprazole in human milk. Int J Neuropsychopharmacol. 2007;10:433. 2. Lutz UC, Hiemke C, Wiatr G, et al. Aripiprazole in pregnancy and lactation: a case report. J Clin Psychopharmacol. 2010;30:204Y205. 3. Watanabe N, Kasahara M, Sugibayashi R, et al. Perinatal use of aripiprazole: a case report. J Clin Psychopharmacol. 2011;31: 377Y379. 4. Sparshatt A, Taylor D, Patel MX, et al. A systematic review of aripiprazoleVdose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. J Clin Psychiatry. 2010;71: 1447Y1456. 5. Mendhekar DN, Sunder KR, Andrade C. Aripiprazole use in a pregnant schizoaffective woman. Bipolar Disord. 2006;8:299Y300. 6. Hale T. Medication and Mother’s Milk. 16th ed. Amarillo, TX: Hale Publishing; 2012.
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
3
