- Email: [email protected]
Neonatal Gabapentin Withdrawal Syndrome
Pediatric Neurology xxx (2015) 1e3
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Neonatal Gabapentin Withdrawal Syndrome Melisa Carrasco MD, PhD a, Sanjai C. Rao DO b, Cynthia F. Bearer MD, PhD c, Sripriya Sundararajan MBBS, MD c, * a
Department of Pediatrics, Children’s Hospital, University of Maryland, Baltimore, Maryland Department of Neurology, University of Maryland, Baltimore, Maryland c Division of Neonatology, Children’s Hospital, University of Maryland, Baltimore, Maryland b
abstract INTRODUCTION: Gabapentin, an anticonvulsant, neuroleptic, and pain medication, is widely used in both adults and
children for management of epilepsy, bipolar illness, and neuropathic pain. Gabapentin use has also been recommended for hyperemesis gravidarum and restless leg syndrome in pregnant mothers. OBJECTIVE: Although gabapentin use is deemed safe during pregnancy, no clinical reports of gabapentin withdrawal syndrome in a neonate have been described. RESULTS: We present a newborn who showed signs of withdrawal after prolonged in utero exposure to gabapentin. CLINICAL IMPLICATIONS: Clinicians should be aware of possible withdrawal symptoms from drugs such as gabapentin, administered to mothers during pregnancy. We also encourage the tapering of gabapentin treatment in neonates gradually over weeks to months similar to the adult population. Keywords: gabapentin, withdrawal, newborn, pregnancy
Pediatr Neurol 2015; -: 1-3 Ó 2015 Elsevier Inc. All rights reserved.
Introduction
Neonatal abstinence syndrome associated with opiate withdrawal in newborns is routinely observed in the neonatal intensive care unit and newborn nursery. Neonatal abstinence syndrome is associated with a cluster of signs and symptoms manifested by the newborn while withdrawing from in utero exposure to opioids.1 Readily established protocols are available for treatment of this Funding Source: No funding was secured for this study. Financial Disclosure: Authors have no financial relationships relevant to this article to disclose. Conflict of Interest: Authors have no conflicts of interest to disclose. Clinical trial registration: Not applicable. Contributor’s statement: Dr. Carrasco collected all data, interpreted the data, and wrote the first draft of the manuscript and approved the final manuscript as submitted; Dr. Rao critically reviewed and edited the manuscript and contributed references to the manuscript and approved the final manuscript as submitted; Dr. Bearer reviewed and edited the manuscript and approved the final manuscript as submitted; and Dr. Sundararajan conceptualized the case report, reviewed, and revised the manuscript and approved the final manuscript as submitted.
Article History: Received June 5, 2015; Accepted in final form June 27, 2015 * Communications should be addressed to: Dr. Sundararajan; Division of Neonatology; Department of Pediatrics; University of Maryland; 110 S. Paca Steet; 8th Floor; Baltimore, MD 21201. E-mail address: [email protected] 0887-8994/$ e see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2015.06.023
syndrome. It is possible for children to withdraw from additional medications, including gabapentin. Gabapentin is an anticonvulsant, neuroleptic, and pain medication frequently used in adults and children with epilepsy, neuropathic pain, and neurological impairment.2 Of note, there is no literature available on withdrawal symptoms in infants of gabapentin treated mothers, nor has the treatment of a newborn with signs of drug withdrawal from in utero gabapentin exposure been defined. Here we report a newborn who was successfully treated for withdrawal from in utero exposure to gabapentin. Patient Description A female newborn was born at 35 6/7 weeks of gestation via spontaneous vaginal delivery to a 31-year-old mother with paraplegia. The mother had suffered a motor vehicle accident at age 20 and sustained a C6-7 incomplete transection injury to the spinal cord. Since then, the mother has been on several medications for neuropathic pain and neurogenic urinary bladder. Maternal medications were continued over the course of the entire pregnancy, which included baclofen (30 mg by mouth, four times a day), gabapentin (600 mg by mouth, three times daily), and oxybutynin (10 mg daily). Maternal use of alcohol, tobacco, caffeine, herbal medicines, or other drugs including drugs of abuse was denied during the pregnancy. Urine toxicology screening was negative for drugs of abuse (amphetamine, methamphetamine, barbiturates,
M. Carrasco et al. / Pediatric Neurology xxx (2015) 1e3
benzodiazepines, cannabinoids, cocaine metabolites, methadone, opiates, and phencyclidine). Upon delivery, Apgar scores at 1 and 5 minutes were 8 and 9, respectively. Her birth weight was 2250 g. Soon after birth, the baby was transferred from the newborn nursery to the neonatal intensive care unit for management of hypoglycemia and apnea with desaturations that required moderate stimulation. Following admission to the neonatal intensive care unit, she was mildly hypotonic with poor respiratory effort that required 2 L/min of air delivered by nasal canula and one dose of caffeine (10 mg/kg of caffeine base). She remained stable on room air, was quickly weaned off nasal canula, and maintained normal oxygen saturations with good respiratory effort. The hypoglycemia resolved with initiation of intravenous fluids and subsequent enteral feeding. Because of an initial concern for neonatal sepsis, she was treated with prophylactic intravenous antibiotics, including ampicillin and gentamicin, for 48 hours with negative blood culture. During the first two days of life, she fed poorly by mouth. She specifically demonstrated poor pacing and coordination of suck with oral feeds that prompted a speech therapy evaluation and subsequent gavage feeding. She began to display signs and symptoms associated with drug withdrawal by 24 hours of life, including sneezing, irritability, jitteriness, and loose stools. There were no signs of clinical seizures or hyperthermia. The overall clinical picture raised initial concerns for possible withdrawal syndrome from prolonged in utero gabapentin exposure. She was initially treated at 36 hours of life with lorazepam for presumed gabapentin withdrawal, at 0.5 mg/kg every 6 hours, after withdrawal scores ranged from 15 to 19 on the Finnegan scoring system, a frequently used neonatal abstinence scoring system to monitor signs of drug withdrawal in the neonatal intensive care unit.3 The Finnegan scores remained elevated (11-19) despite initiation of treatment with lorazepam; subsequently, the lorazepam dosage was increased on day of life 3 to 0.1 mg/kg every 6 hours. She required a dose escalation of lorazepam on day of life 5 to 0.15 mg/kg every 6 hours for Finnegan scores of 7-10. The etiology of withdrawal in this infant was attributed to the placental transfer of maternal gabapentin with the constellation of described symptoms in this infant best fitting the description of gabapentin withdrawal syndrome from in utero gabapentin exposure. She began treatment with gabapentin after other causes of neonatal abstinence syndrome were excluded. Baclofen withdrawal was excluded because signs of neonatal seizures and hyperthermia were absent. Oxybutynin withdrawal was excluded because chronic oxybutynin use does not induce physical dependence. Gabapentin was started at 2.5 mg/kg every 12 hours on day of life 6. The dose was gradually increased on day of life 7 to a maximum dose of 5 mg/kg every 12 hours for continued elevated Finnegan scores. The newborn started showing signs of clinical improvement in withdrawal symptoms and lowering of the Finnegan scores once treatment with gabapentin was initiated, as depicted in the Figure. With continued gabapentin therapy and assistance from speech therapists, she was able to nipple all of her enteral feeds by day of life 24. The improvement in nipple feeds while on gabapentin therapy was further strengthened by the gestational maturation over time of this late preterm infant. Because of the dramatic clinical response after initiation of gabapentin treatment, the lorazepam dose was decreased by half on day of life 8 to 0.15 mg/kg every 12 hours, then to 0.15 mg/kg every 24 hours on day of life 9, and subsequently discontinued on day of life 10. Meanwhile, the gabapentin dose was maintained at 5 mg/kg twice a day until day of life 15 when the weaning from gabapentin drug treatment was started. Gabapentin was gradually weaned to 7.5 mg twice a day (on day of life 27), followed by 5 mg twice a day (on day of life 34). When evaluated on day of life 35 her mother denied any withdrawal symptoms. The baby was next weaned to 2.5 mg twice a day (on day of life 41); finally, gabapentin was discontinued on day of life 48.
Discussion
We present a newborn who was actively treated for gabapentin withdrawal with gabapentin administration.
20 18 16 Finnegan Score
2
2.5mg/kg q12h
5.0mg/kg q12h
14 12 10 8 6 4 2 0 0
100
200 300 Time, hours
400
500
FIGURE. Neonatal abstinence scores were monitored using the Finnegan scoring system in the neonatal intensive care unit starting at 24 hours of life. Gabapentin treatment was initiated at approximately 124 hours of life (day of life 6) and the gabapentin dose was further escalated within the next 24 hours, as depicted by black arrows. The decline in Finnegan scores following gabapentin treatment is presented as a moving average over the period of hours of postnatal life. (The color version of this figure is available in the online edition.)
Previous research has shown that gabapentin can be easily transmitted from to a child in utero through active transplacental transport of gabapentin via the placental L-type amino acid transporter.4 Gabapentin has been used in pregnancy for treatment of hyperemesis gravidarum and restless leg syndrome.5,6 Gabapentin use throughout pregnancy does not seem to increase the risk of congenital malformations7 nor is it associated with increased rates of maternal adverse events, Cesarean section, miscarriage, or low birth weight.5 Thus, data from published pregnancy registries and cohorts that included gabapentin use during pregnancy support the safety of gabapentin use in pregnancy.6 However, the number of exposures to date remains relatively small. Additionally, data on the long-term effects of gabapentin withdrawal from in utero exposure on neonates are not available. Gabapentin has been recommended for the treatment of recurrent irritability and neuropathic pain in children with neurological impairment.8 The mechanism of action of gabapentin for treating neuropathic pain depends on its binding to the alpha-2/delta subunit of neuronal voltagegated calcium channels and possibly on its interference with neuronal Ca influx.9 In the neonatal intensive care unit, alternative uses for gabapentin are sparse. Our review of the literature revealed two case reports that document the use of gabapentin for the treatment of pain in newborns who were unresponsive to other medications.2,10 Gabapentin has also been used as an analgesic in a neonate with amyoplasia congenita.11 A few reports document the resolution of apnea following treatment with gabapentin in neurologically impaired neonates.12 Gabapentin has been used in adults with epilepsy, pain syndromes, migraine, and bipolar illness.13 This medication is not protein bound, is not metabolized in the liver, and is excreted unchanged by the kidneys. Examples of gabapentin withdrawal syndrome in adults have been described; they clinically resemble alcohol or benzodiazepine withdrawal.14
M. Carrasco et al. / Pediatric Neurology xxx (2015) 1e3
Resolution of withdrawal symptoms from prolonged gabapentin use has been reported with resumption of gabapentin treatment and gradual taper rather than abrupt discontinuance.15 It has been proposed that a gabapentin taper should follow a course similar to that of a benzodiazepine taperdslowly and over a period of weeks to monthsdsuch as in our neonatal patient. Although gabapentin offers an advantage as an alternative medication for management of pain and chronic symptoms in neurologically impaired children, there are no published reports of gabapentin withdrawal in a newborn from maternal exposure. Therefore, there are no available safety and pharmacokinetic data in newborns to further support the use of gabapentin for the treatment of gabapentin withdrawal. This constitutes a significant gap in the literature that could be addressed with future research. Our patient highlights the importance of withdrawal syndrome developing in a neonate especially in situations where pregnant mothers have been taking large doses of gabapentin over a prolonged period. Conclusion
Physicians should be alert for the possibility of withdrawal syndrome developing from abrupt discontinuance of any prolonged drug exposure. Our report documents gabapentin withdrawal in a newborn and management of gabapentin withdrawal within the neonatal intensive care unit setting. References 1. Hudak ML, Tan RC. Neonatal drug withdrawal. Pediatrics. 2012;129: e540-e560.
3
2. Haney AL, Garner SS, Cox TH. Gabapentin therapy for pain and irritability in a neurologically impaired infant. Pharmacotherapy. 2009;29:997-1001. 3. Finnegan LP, Connaughton JF, Kron RE, Emich JP. Neonatal abstinence syndrome: assessment and management. Addict Dis. 1975;2: 141-158. 4. Ohman I, Vitols S, Tomson T. Pharmacokinetics of gabapentin during delivery, in the neonatal period, and lactation: does a fetal accumulation occur during pregnancy? Epilepsia. 2005;46: 1621-1624. 5. Montouris G. Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy Registry. Epilepsy Behav. 2003;4: 310-317. 6. Guttuso T, Shaman M, Thornburg LL. Potential maternal symptomatic benefit of gabapentin and review of its safety in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2014;181:280-283. 7. Fujii H, Goel A, Bernard N, et al. Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. Neurology. 2013;80:1565-1570. 8. Hauer JM, Wical BS, Charnas L. Gabapentin successfully manages chronic unexplained irritability in children with severe neurologic impairment. Pediatrics. 2007;119:e519-e522. 9. Sutton KG, Martin DJ, Pinnock RD, Lee K, Scott RH. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol. 2002;135: 257-265. 10. Allegaert K, Naulaers G. Gabapentin as part of multimodal analgesia in a newborn with epidermolysis bullosa. Paediatr Anaesth. 2010; 20:972-973. 11. Behm MO, Kearns GL. Treatment of pain with gabapentin in a neonate. Pediatrics. 2001;108:482-484. 12. Hauer J, Mackey D. Treatment with gabapentin associated with resolution of apnea in two infants with neurologic impairment. J Palliat Med. 2013;16:455-458. 13. Letterman L, Markowitz JS. Gabapentin: a review of published experience in the treatment of bipolar disorder and other psychiatric conditions. Pharmacotherapy. 1999;19:565-572. 14. Myrick H, Malcolm R, Brady KT. Gabapentin treatment of alcohol withdrawal. Am J Psychiatry. 1998;155:1632. 15. Tran KT, Hranicky D, Lark T, Jacob NJ. Gabapentin withdrawal syndrome in the presence of a taper. Bipolar Disord. 2005;7: 302-304.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Neonatal Gabapentin Withdrawal Syndrome Melisa Carrasco MD, PhD a, Sanjai C. Rao DO b, Cynthia F. Bearer MD, PhD c, Sripriya Sundararajan MBBS, MD c, * a
Department of Pediatrics, Children’s Hospital, University of Maryland, Baltimore, Maryland Department of Neurology, University of Maryland, Baltimore, Maryland c Division of Neonatology, Children’s Hospital, University of Maryland, Baltimore, Maryland b
abstract INTRODUCTION: Gabapentin, an anticonvulsant, neuroleptic, and pain medication, is widely used in both adults and
children for management of epilepsy, bipolar illness, and neuropathic pain. Gabapentin use has also been recommended for hyperemesis gravidarum and restless leg syndrome in pregnant mothers. OBJECTIVE: Although gabapentin use is deemed safe during pregnancy, no clinical reports of gabapentin withdrawal syndrome in a neonate have been described. RESULTS: We present a newborn who showed signs of withdrawal after prolonged in utero exposure to gabapentin. CLINICAL IMPLICATIONS: Clinicians should be aware of possible withdrawal symptoms from drugs such as gabapentin, administered to mothers during pregnancy. We also encourage the tapering of gabapentin treatment in neonates gradually over weeks to months similar to the adult population. Keywords: gabapentin, withdrawal, newborn, pregnancy
Pediatr Neurol 2015; -: 1-3 Ó 2015 Elsevier Inc. All rights reserved.
Introduction
Neonatal abstinence syndrome associated with opiate withdrawal in newborns is routinely observed in the neonatal intensive care unit and newborn nursery. Neonatal abstinence syndrome is associated with a cluster of signs and symptoms manifested by the newborn while withdrawing from in utero exposure to opioids.1 Readily established protocols are available for treatment of this Funding Source: No funding was secured for this study. Financial Disclosure: Authors have no financial relationships relevant to this article to disclose. Conflict of Interest: Authors have no conflicts of interest to disclose. Clinical trial registration: Not applicable. Contributor’s statement: Dr. Carrasco collected all data, interpreted the data, and wrote the first draft of the manuscript and approved the final manuscript as submitted; Dr. Rao critically reviewed and edited the manuscript and contributed references to the manuscript and approved the final manuscript as submitted; Dr. Bearer reviewed and edited the manuscript and approved the final manuscript as submitted; and Dr. Sundararajan conceptualized the case report, reviewed, and revised the manuscript and approved the final manuscript as submitted.
Article History: Received June 5, 2015; Accepted in final form June 27, 2015 * Communications should be addressed to: Dr. Sundararajan; Division of Neonatology; Department of Pediatrics; University of Maryland; 110 S. Paca Steet; 8th Floor; Baltimore, MD 21201. E-mail address: [email protected] 0887-8994/$ e see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2015.06.023
syndrome. It is possible for children to withdraw from additional medications, including gabapentin. Gabapentin is an anticonvulsant, neuroleptic, and pain medication frequently used in adults and children with epilepsy, neuropathic pain, and neurological impairment.2 Of note, there is no literature available on withdrawal symptoms in infants of gabapentin treated mothers, nor has the treatment of a newborn with signs of drug withdrawal from in utero gabapentin exposure been defined. Here we report a newborn who was successfully treated for withdrawal from in utero exposure to gabapentin. Patient Description A female newborn was born at 35 6/7 weeks of gestation via spontaneous vaginal delivery to a 31-year-old mother with paraplegia. The mother had suffered a motor vehicle accident at age 20 and sustained a C6-7 incomplete transection injury to the spinal cord. Since then, the mother has been on several medications for neuropathic pain and neurogenic urinary bladder. Maternal medications were continued over the course of the entire pregnancy, which included baclofen (30 mg by mouth, four times a day), gabapentin (600 mg by mouth, three times daily), and oxybutynin (10 mg daily). Maternal use of alcohol, tobacco, caffeine, herbal medicines, or other drugs including drugs of abuse was denied during the pregnancy. Urine toxicology screening was negative for drugs of abuse (amphetamine, methamphetamine, barbiturates,
M. Carrasco et al. / Pediatric Neurology xxx (2015) 1e3
benzodiazepines, cannabinoids, cocaine metabolites, methadone, opiates, and phencyclidine). Upon delivery, Apgar scores at 1 and 5 minutes were 8 and 9, respectively. Her birth weight was 2250 g. Soon after birth, the baby was transferred from the newborn nursery to the neonatal intensive care unit for management of hypoglycemia and apnea with desaturations that required moderate stimulation. Following admission to the neonatal intensive care unit, she was mildly hypotonic with poor respiratory effort that required 2 L/min of air delivered by nasal canula and one dose of caffeine (10 mg/kg of caffeine base). She remained stable on room air, was quickly weaned off nasal canula, and maintained normal oxygen saturations with good respiratory effort. The hypoglycemia resolved with initiation of intravenous fluids and subsequent enteral feeding. Because of an initial concern for neonatal sepsis, she was treated with prophylactic intravenous antibiotics, including ampicillin and gentamicin, for 48 hours with negative blood culture. During the first two days of life, she fed poorly by mouth. She specifically demonstrated poor pacing and coordination of suck with oral feeds that prompted a speech therapy evaluation and subsequent gavage feeding. She began to display signs and symptoms associated with drug withdrawal by 24 hours of life, including sneezing, irritability, jitteriness, and loose stools. There were no signs of clinical seizures or hyperthermia. The overall clinical picture raised initial concerns for possible withdrawal syndrome from prolonged in utero gabapentin exposure. She was initially treated at 36 hours of life with lorazepam for presumed gabapentin withdrawal, at 0.5 mg/kg every 6 hours, after withdrawal scores ranged from 15 to 19 on the Finnegan scoring system, a frequently used neonatal abstinence scoring system to monitor signs of drug withdrawal in the neonatal intensive care unit.3 The Finnegan scores remained elevated (11-19) despite initiation of treatment with lorazepam; subsequently, the lorazepam dosage was increased on day of life 3 to 0.1 mg/kg every 6 hours. She required a dose escalation of lorazepam on day of life 5 to 0.15 mg/kg every 6 hours for Finnegan scores of 7-10. The etiology of withdrawal in this infant was attributed to the placental transfer of maternal gabapentin with the constellation of described symptoms in this infant best fitting the description of gabapentin withdrawal syndrome from in utero gabapentin exposure. She began treatment with gabapentin after other causes of neonatal abstinence syndrome were excluded. Baclofen withdrawal was excluded because signs of neonatal seizures and hyperthermia were absent. Oxybutynin withdrawal was excluded because chronic oxybutynin use does not induce physical dependence. Gabapentin was started at 2.5 mg/kg every 12 hours on day of life 6. The dose was gradually increased on day of life 7 to a maximum dose of 5 mg/kg every 12 hours for continued elevated Finnegan scores. The newborn started showing signs of clinical improvement in withdrawal symptoms and lowering of the Finnegan scores once treatment with gabapentin was initiated, as depicted in the Figure. With continued gabapentin therapy and assistance from speech therapists, she was able to nipple all of her enteral feeds by day of life 24. The improvement in nipple feeds while on gabapentin therapy was further strengthened by the gestational maturation over time of this late preterm infant. Because of the dramatic clinical response after initiation of gabapentin treatment, the lorazepam dose was decreased by half on day of life 8 to 0.15 mg/kg every 12 hours, then to 0.15 mg/kg every 24 hours on day of life 9, and subsequently discontinued on day of life 10. Meanwhile, the gabapentin dose was maintained at 5 mg/kg twice a day until day of life 15 when the weaning from gabapentin drug treatment was started. Gabapentin was gradually weaned to 7.5 mg twice a day (on day of life 27), followed by 5 mg twice a day (on day of life 34). When evaluated on day of life 35 her mother denied any withdrawal symptoms. The baby was next weaned to 2.5 mg twice a day (on day of life 41); finally, gabapentin was discontinued on day of life 48.
Discussion
We present a newborn who was actively treated for gabapentin withdrawal with gabapentin administration.
20 18 16 Finnegan Score
2
2.5mg/kg q12h
5.0mg/kg q12h
14 12 10 8 6 4 2 0 0
100
200 300 Time, hours
400
500
FIGURE. Neonatal abstinence scores were monitored using the Finnegan scoring system in the neonatal intensive care unit starting at 24 hours of life. Gabapentin treatment was initiated at approximately 124 hours of life (day of life 6) and the gabapentin dose was further escalated within the next 24 hours, as depicted by black arrows. The decline in Finnegan scores following gabapentin treatment is presented as a moving average over the period of hours of postnatal life. (The color version of this figure is available in the online edition.)
Previous research has shown that gabapentin can be easily transmitted from to a child in utero through active transplacental transport of gabapentin via the placental L-type amino acid transporter.4 Gabapentin has been used in pregnancy for treatment of hyperemesis gravidarum and restless leg syndrome.5,6 Gabapentin use throughout pregnancy does not seem to increase the risk of congenital malformations7 nor is it associated with increased rates of maternal adverse events, Cesarean section, miscarriage, or low birth weight.5 Thus, data from published pregnancy registries and cohorts that included gabapentin use during pregnancy support the safety of gabapentin use in pregnancy.6 However, the number of exposures to date remains relatively small. Additionally, data on the long-term effects of gabapentin withdrawal from in utero exposure on neonates are not available. Gabapentin has been recommended for the treatment of recurrent irritability and neuropathic pain in children with neurological impairment.8 The mechanism of action of gabapentin for treating neuropathic pain depends on its binding to the alpha-2/delta subunit of neuronal voltagegated calcium channels and possibly on its interference with neuronal Ca influx.9 In the neonatal intensive care unit, alternative uses for gabapentin are sparse. Our review of the literature revealed two case reports that document the use of gabapentin for the treatment of pain in newborns who were unresponsive to other medications.2,10 Gabapentin has also been used as an analgesic in a neonate with amyoplasia congenita.11 A few reports document the resolution of apnea following treatment with gabapentin in neurologically impaired neonates.12 Gabapentin has been used in adults with epilepsy, pain syndromes, migraine, and bipolar illness.13 This medication is not protein bound, is not metabolized in the liver, and is excreted unchanged by the kidneys. Examples of gabapentin withdrawal syndrome in adults have been described; they clinically resemble alcohol or benzodiazepine withdrawal.14
M. Carrasco et al. / Pediatric Neurology xxx (2015) 1e3
Resolution of withdrawal symptoms from prolonged gabapentin use has been reported with resumption of gabapentin treatment and gradual taper rather than abrupt discontinuance.15 It has been proposed that a gabapentin taper should follow a course similar to that of a benzodiazepine taperdslowly and over a period of weeks to monthsdsuch as in our neonatal patient. Although gabapentin offers an advantage as an alternative medication for management of pain and chronic symptoms in neurologically impaired children, there are no published reports of gabapentin withdrawal in a newborn from maternal exposure. Therefore, there are no available safety and pharmacokinetic data in newborns to further support the use of gabapentin for the treatment of gabapentin withdrawal. This constitutes a significant gap in the literature that could be addressed with future research. Our patient highlights the importance of withdrawal syndrome developing in a neonate especially in situations where pregnant mothers have been taking large doses of gabapentin over a prolonged period. Conclusion
Physicians should be alert for the possibility of withdrawal syndrome developing from abrupt discontinuance of any prolonged drug exposure. Our report documents gabapentin withdrawal in a newborn and management of gabapentin withdrawal within the neonatal intensive care unit setting. References 1. Hudak ML, Tan RC. Neonatal drug withdrawal. Pediatrics. 2012;129: e540-e560.
3
2. Haney AL, Garner SS, Cox TH. Gabapentin therapy for pain and irritability in a neurologically impaired infant. Pharmacotherapy. 2009;29:997-1001. 3. Finnegan LP, Connaughton JF, Kron RE, Emich JP. Neonatal abstinence syndrome: assessment and management. Addict Dis. 1975;2: 141-158. 4. Ohman I, Vitols S, Tomson T. Pharmacokinetics of gabapentin during delivery, in the neonatal period, and lactation: does a fetal accumulation occur during pregnancy? Epilepsia. 2005;46: 1621-1624. 5. Montouris G. Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy Registry. Epilepsy Behav. 2003;4: 310-317. 6. Guttuso T, Shaman M, Thornburg LL. Potential maternal symptomatic benefit of gabapentin and review of its safety in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2014;181:280-283. 7. Fujii H, Goel A, Bernard N, et al. Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. Neurology. 2013;80:1565-1570. 8. Hauer JM, Wical BS, Charnas L. Gabapentin successfully manages chronic unexplained irritability in children with severe neurologic impairment. Pediatrics. 2007;119:e519-e522. 9. Sutton KG, Martin DJ, Pinnock RD, Lee K, Scott RH. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol. 2002;135: 257-265. 10. Allegaert K, Naulaers G. Gabapentin as part of multimodal analgesia in a newborn with epidermolysis bullosa. Paediatr Anaesth. 2010; 20:972-973. 11. Behm MO, Kearns GL. Treatment of pain with gabapentin in a neonate. Pediatrics. 2001;108:482-484. 12. Hauer J, Mackey D. Treatment with gabapentin associated with resolution of apnea in two infants with neurologic impairment. J Palliat Med. 2013;16:455-458. 13. Letterman L, Markowitz JS. Gabapentin: a review of published experience in the treatment of bipolar disorder and other psychiatric conditions. Pharmacotherapy. 1999;19:565-572. 14. Myrick H, Malcolm R, Brady KT. Gabapentin treatment of alcohol withdrawal. Am J Psychiatry. 1998;155:1632. 15. Tran KT, Hranicky D, Lark T, Jacob NJ. Gabapentin withdrawal syndrome in the presence of a taper. Bipolar Disord. 2005;7: 302-304.