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deciency anemia, has been reported during pregnancy. Data on pramipexole,
an important drug that is used for the treatment of RLS, both during pregnancy
and breastfeeding, have also remained very limited (Dostal etal. 2013).
This chapter aims to evaluate and synthesize current evidence on the safety proles during pregnancy and lactation of clinically important drugs that are not classied into drug groups such as antidepressants, antipsychotics, benzodiazepines,
and mood stabilizers. The chapter also highlights the well-documented risks along
with areas where the data are insufcient. This chapter can contribute towards
ensuring the best outcomes for both mothers and their babies by providing an evidence-based framework for determining the safest treatment strategy for pregnant
and breastfeeding women.
14.2 Methadone, Buprenorphine, Buprenorphine/Naloxone
Methadone has been the mainstay for the management of opioid use disorder for a
long time. The use of methadone during pregnancy has been associated with neonatal abstinence, decreased head circumference, agitation, movement defects,
decreased interactive behavior, as well as impaired motor and cognitive functions
(Daly etal. 2012; Chen etal. 2015; Kongstorp etal. 2020). Although a few studies
have reported the lack of any signicant increase in the risk of congenital malformations due to methadone use during pregnancy (Ordean and Tubman-Broeren 2023),
there are not enough data in the literature on the long-term consequences of methadone exposure during pregnancy and lactation reported. Daly etal. (2012) reported
that perinatal methadone exposure did not have a signicant effect on the physical
development of the animals. However, their behavioral development was affected
(Daly etal. 2012). In a more recent animal study, methadone exposure in the prenatal and early postnatal period was shown to affect the development of the circadian
rhythm, circadian rhythm-related gene expression, and melatonin levels in newborns (Pačesová etal. 2023). Reports suggest that very low levels of methadone are
excreted into breast milk, which may be conducive to the management of opioid
withdrawal in the newborn (Jansson etal. 2008).
Ordean and Tubman-Broeren (2023) reviewed the safety and efcacy of the use
of buprenorphine by pregnant women, as well as neonatal and maternal outcomes
from 7 different studies. The authors examined birth parameters, congenital anomalies, and neonatal withdrawal symptoms in pregnant women and reported that the
buprenorphine dose ranged from 8 to 20mg/day. Moreover, there was a signicant
reduction in illicit opioid use in pregnant women using buprenorphine. This review
included four different newborn groups: (1) those exposed to buprenorphine/naloxone combination, (2) those exposed to other opiate replacement therapies (buprenorphine monotherapy or methadone), (3) those exposed to illicit opioids, and (4) those
without opioid exposure. No signicant difference was identied in birth parameters and prevalence of congenital anomalies between the four groups. However, a
signicant increase in neonatal opioid withdrawal was observed in the methadoneexposed newborns. Overall, the authors emphasized that buprenorphine/naloxone
14 Miscellaneous Drugs During Pregnancy andLactation
313
combination treatment was a safe and effective treatment option in pregnant women
with opioid use disorder (Ordean and Tubman-Broeren 2023).
Suarez etal. (2022) investigated neonatal and maternal outcomes in a large sample of patients who used methadone and buprenorphine during pregnancy. The
authors reported that 52% of the infants of pregnant women exposed to buprenorphine and 69.2% of the infants exposed to methadone had neonatal withdrawal syndrome. Fewer preterm births (14.4% vs 24.9%), small-for-gestational-age births
(12.1% vs 15.3%), and miscarriages (8.3% vs 14.9%) were reported in infants
exposed to buprenorphine in early pregnancy compared to those exposed to methadone. No signicant difference was identied in the rate of cesarean section delivery or other serious maternal complications between the two groups. The authors
therefore emphasized that buprenorphine use was associated with lower rates of
neonatal complications compared to methadone (Suarez etal. 2022). Similar ndings were shown in another study that also compared maternal and neonatal outcomes related to maternal exposure to buprenorphine and methadone. In addition, it
was reported that the rate of illicit drug use was higher among the methadone users.
A comparison of buprenorphine and buprenorphine/naloxone showed no signicant
differences in maternal and neonatal outcomes (Kanervo etal. 2023). In a metaanalysis including 20 studies, Kinsella etal. (2022) reported that buprenorphine was
associated with higher birth weight and less risk of prematurity compared to methadone (Kinsella etal. 2022) and was the safer option during pregnancy.
Breast milk and serum samples of mothers who used buprenorphine were collected on postpartum days 2, 3, 4, 14, and 30, and serum samples of infants were
collected on postpartum day 14. The levels of buprenorphine and its metabolites
were generally low in maternal serum and breast milk samples and were positively
correlated with the daily dose. Additionally, buprenorphine levels were reported to
be low or undetectable in the serum of breastfed infants and undetectable in the
serum of 14-day-old infants. In light of these data, the authors suggested that mothers who were regularly prescribed buprenorphine could continue breastfeeding
(Jansson etal. 2016). In a relatively recent study, buprenorphine and its metabolites
were shown to be at low levels in the serum and milk of breastfeeding mothers who
were using buprenorphine/naloxone, while naloxone levels were very low or undetectable. Moreover, naloxone levels were shown to be very low or undetectable in
the serum of infants (Jansson etal. 2024). However, it should be mentioned that the
relatively small number of participants in these studies is an important limitation.
14.3 Naltrexone
Naltrexone is an opioid receptor antagonist that is prescribed to reduce pleasure in
addiction treatment, particularly in the treatment of alcohol and opioid use disorders
(Antonelli et al. 2018). Newborns exposed to naltrexone were reported to have
decreased body weight and length at birth, increased duration of hospitalization,
increased frequency of congenital urogenital malformations, and susceptibility to
infectious diseases in childhood (Kelty and Hulse 2017a, b). In relatively more
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H. Bakay
recent studies, neonates exposed to naltrexone were reported to have signicantly
lower rates of withdrawal symptoms and hospitalizations compared to those exposed
to methadone and buprenorphine (Wachman et al. 2019; Towers et al. 2020).
Considering the maternal outcomes, ectopic pregnancy and other birth complications were reported to be higher in pregnant women using naltrexone compared to
unexposed women (Kelty and Hulse 2017c). On the contrary, no signicant increase
in maternal risk during pregnancy with naltrexone use has also been reported
(Quintrell etal. 2025).
Animal studies have shown that naltrexone exposure during pregnancy was
associated with weight gain in the body and organs of the offspring (McLaughlin
2002; Youngentob etal. 2012). In another important study, although an increase
in offspring size and a slight decrease in birth weight were reported in subjects
with long-release naltrexone implant, no change in brain morphology was
detected (Farid etal. 2012). However, naltrexone exposure in the middle and
late periods of pregnancy was reported to have a negative effect on testicular
development, although it had no effect on sperm development (Cajú etal. 2011).
Naltrexone exposure was shown to have a dose-dependent effect on locomotor
activity (Quintrell etal. 2025). Some studies have suggested that naltrexone
exposure can increase cortical thickness without changing the number of neurons in the brain, contribute to neuronal maturation, and may even have neuroprotective effects on ethanol-exposed offspring (Youngentob et al. 2012).
Studies also suggest that naltrexone may increase the risk of preterm birth in a
dose-dependent manner (Javadi-Paydar etal. 2009).
In a recent multicenter prospective cohort study, Mantri etal. (2024) compared the 1-year development of infants who were exposed to naltrexone or
buprenorphine/naloxone during pregnancy and reported the lack of any statistically signicant difference (Mantri etal. 2024). It should be noted that the number of participants in the naltrexone arm was very small compared to the
buprenorphine/naloxone arm in this study (n= 7 vs 34). A recent systematic
review and meta-analysis that compared the exposure to naltrexone, methadone,
or buprenorphine in pregnancy reported that the risk of preterm birth did not
increase with naltrexone exposure compared to methadone and buprenorphine
exposure; moreover, neonatal withdrawal symptoms were signicantly less
(Atluru etal. 2024). However, it should be noted that the referred analysis had
important limitations such as the relatively small number of studies as well as
participants, which may signicantly reduce the statistical power of the results
obtained. Thus, it is imperative that the reassuring perinatal results with the use
of naltrexone are conrmed in larger samples.
A relative infant dose (RID) value of 1.06% was calculated for naltrexone during
breastfeeding and no adverse effects were reported for the infant (Chan etal. 2004).
Thus, the use of naltrexone during breastfeeding appears to be safe; nonetheless,
these data need to be supported by other independent studies.
14 Miscellaneous Drugs During Pregnancy andLactation
315
14.4 Buspirone
Buspirone is an important drug that is frequently used for the treatment of women
of childbearing age for the treatment of anxiety disorders, although its use is generally not prioritized. Freeman etal. (2022) evaluated 68 women who used buspirone
in early pregnancy and evaluated 72 babies of these pregnant women at 12weeks
postpartum. The authors reported the lack of any malformations in these babies
(Freeman etal. 2022). The data obtained from referred study suggest that buspirone
use does not pose an increased risk for neonatal effects; however, the study sample
was small and therefore the data need to be conrmed in larger samples that also
include control groups.
Comprehensive studies on the passage of buspirone into breast milk and its
effects on the infant during breastfeeding have not been reported to date. In a recent
study, buspirone levels were found to be below 1.5ng/mL in milk samples obtained
from 9 mothers who used buspirone at doses of 15–60mg/day (Krutsch etal. 2024).
The levels of 1-pyrimidinylpiperazine, the active metabolite of buspirone, were also
shown to be low. The RID value for buspirone was found to be between 0.21% and
2.17% (mean<1%), which was within the safe range for the infant (10% or less)
and no side effects were observed in infants (Krutsch etal. 2024). In light of these
data, the authors suggest that the use of buspirone during breastfeeding poses minimal risk.
14.5 Gabapentinoids
Pregabalin and gabapentin, which were rst developed as antiepileptics, are now
widely used especially in the treatment of neuropathic pain and certain types of
anxiety disorders. These drugs exert their effects by binding to voltage-coupled calcium channels and reduce presynaptic excitatory neurotransmitter release by inhibiting calcium transport. These drugs also ameliorate neuropathic pain via alpha2
adrenoreceptors (Kremer etal. 2016; Goodman and Brett 2019). A recent review
reported that the prevalence of gabapentinoid use in pregnancy was less than 1%.
However, there has been an increase in its use in recent years (Beau etal. 2024).
14.5.1 Pregabalin
Certain adverse neonatal outcomes such as preterm birth, stillbirth, miscarriage, and
neurodevelopmental disorders were reported to be associated with exposure to pregabalin (Mostacci etal. 2018; Margulis etal. 2019; Bjørk etal. 2022). In a recent
review, Richardson etal. (2023) reported a small increase (approximately 1.5-fold)
in the risk of malformations in the infants of women who were exposed to pregabalin (4% vs 4.8–5.6%). However, the authors concluded that attributing this minimal
increase in risk to pregabalin use could be controversial, emphasizing important
methodological limitations such as concurrent use of other medications among the
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patients included in the study (Richardson et al. 2023). In addition, the authors
examined specic malformations such as central nervous system, eye, urogenital
system, orofacial defects, and craniosynostosis and reported the lack of any association between pregabalin exposure and all other identied anomalies except for nervous system anomalies. In a more recent study from Turkiye, Kaskal etal. (2024)
retrospectively compared women with (n=31) and without (n =93) pregabalin
exposure (Kaskal etal. 2024). In this study, preterm delivery rates and low birth
weight rates in infants were signicantly higher in women who used pregabalin. No
signicant difference was reported in the spontaneous abortion rates. Although a
higher incidence of major malformations was observed in the pregabalin group, no
statistically signicant difference could be identied between the two groups (11%
vs 4.5%, p=0.21). In conclusion, the authors showed that maternal pregabalin use
during pregnancy was associated with increased preterm birth and low birth weight
in infants compared to a control group, along with an increase in the incidence of
additional comorbidities (Kaskal etal. 2024).
According to data reported in a recently published and methodologically strong
meta-analysis, exposure to pregabalin in the rst trimester was associated with an
increased risk of major congenital anomalies in the newborn (Dudukina etal. 2023).
Using various sensitivity analyses, the authors reported that this association persisted even when confounding factors such as polypharmacy were controlled.
Although an increase in the incidence of minor congenital anomalies such as orofacial clefts and urogenital anomalies has been reported, these data came from a relatively small number of studies and were interpreted as statistically weak data. The
existing literature does not provide a clear conclusion regarding specic (minor)
congenital anomalies (Blotière etal. 2019; Dudukina etal. 2023). In the context of
pregnancy outcomes, exposure to pregabalin was reported to increase the risk of
stillbirth, miscarriage, low birth weight, and small for gestational age (Beau
etal. 2024).
Lockwood etal. (2016) reported in a case study that the amount of pregabalin
measured from the breastmilk corresponded to about 7% of the dose consumed by
the mother (Lockwood etal. 2016). Humerickhouse etal. (2024) determined the
pregabalin levels in breast milk by using a physiologically based pharmacokinetic
model simulation in which the physicochemical properties of a specic drug can be
integrated with existing lactation data to predict its passage into breast milk and
infant exposure. Using this method, the authors calculated a RID value of 7% in the
milk of mothers receiving 300mg/day (2×150 mg) of pregabalin. The simulation
experiment predicted a peak level of 0.44μg/mL in the rst 2weeks followed by a
gradual decrease over time (Humerickhouse etal. 2024). Although the RID values
obtained from these reports appear to be in the safe range, an animal study reported
a higher risk of tumor development in the offspring exposed to pregabalin through
breast milk; therefore, the use of this drug is not recommended during breastfeeding
(Sauberan 2025).
14 Miscellaneous Drugs During Pregnancy andLactation
317
14.5.2 Gabapentin
Exposure of the fetus to gabapentin due to maternal use was shown to increase the
risk of preterm birth, low birth weight, and the need for neonatal intensive care (Fujii
etal. 2013; Mostacci etal. 2018; Patorno etal. 2020). The risk of major congenital
anomalies was found to increase by 49–77%; however, when evaluated with confounding factors, no signicant increase in the risk of major malformations was identied (Patorno etal. 2020). After post-hoc analysis, the authors noted only an increase
in the risk of conotruncal defect that did not reach statistical signicance. A partial
increase in preterm birth, small for gestational age, and the need for neonatal intensive care with exposure to gabapentin were also reported. However, based on the
overall data, it was concluded that gabapentin has a safe prole for use in pregnancy.
Recent studies with relatively smaller number of patients also support the lack of any
signicant increase in the risk of anomalies associated with gabapentin exposure in
pregnancy (Vajda etal. 2018; Blotière etal. 2019; Quintrell etal. 2025). In addition,
gabapentin exposure during pregnancy has not been reported to adversely affect neurodevelopment in children (Blotière etal. 2020; Bjørk etal. 2022).
Unlike clinical research, several animal studies have shown that gabapentin
exposure is indeed associated with signicant anomalies. These include brachygnathia, pointed nose, cataracts, limb deformities, vertebral deformities, trunk malformations, and neural tube defects (Prakash etal. 2008; Afshar and Golalipour
2008; Afshar etal. 2009; Cetinkal and Cakir 2021). However, other animal studies
have also reported that exposure to low doses of gabapentin during pregnancy did
not cause any neurotoxic effects in the offspring (Erisgin etal. 2019). The ndings
obtained from animal studies suggest that gabapentin may increase the risk of
adverse effects in a dose-dependent manner.
Overall, gabapentin appears to have a safer prole compared to pregabalin;
nonetheless, when evaluated together with the ndings from animal studies, the current literature raises concerns about the safety of gabapentinoids in pregnancy. It is
suggested that the use of gabapentinoids should be assessed in a case-by-case basis
taking into account the balance of benet and harm for both the mother and the fetus
and should only be used when appropriate alternative medications are not available
(Richardson etal. 2023; Beau etal. 2024).
A gabapentin level of approximately 11.1mg/L was reported in the breast milk
of a mother taking 1800mg/day gabapentin after a 600mg intake. The milk/plasma
ratio was 0.86 and the RID value was calculated as 2.3%. In addition, no side effects
were observed in the infant (Kristensen etal. 2006). Another study reported RID
values of 1.3% to 3.8% in samples from 5 mothers with no adverse effects (Ohman
etal. 2005). In a recently published study, Ozalp Horsanalı etal. (2024) concluded
that gabapentin use may be safe for breastfeeding women (Ozalp Horsanalı etal.
2024). Although the use of gabapentin during breastfeeding is not recommended,
the current literature does not report any adverse effects upon infant exposure
through breastfeeding and the RID values are in the safe range.
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14.6 Pramipexole
The existing literature provides very limited data on the use of pramipexole during
pregnancy and breastfeeding. Benbir etal. (2014) reported the successful use of
pramipexole in a 35-year-old pregnant woman with Parkinson’s disease where the
pregnancy was completed with a healthy baby (Benbir etal. 2014). Dostal et al.
(2013) examined the safety proles of the use of dopamine agonists during pregnancy in patients diagnosed with RLS (n=59) (Dostal etal. 2013). These authors
reported that spontaneous abortion occurred in only three of the 12 pregnant subjects who received treatment exclusively with pramipexole. In addition, nine pregnancies were successfully completed without complications, and no malformations
were observed. No congenital complications or malformations were reported in
three pregnant women who received a combined treatment with pramipexole and
levodopa. Although these preliminary data on the safety of pramipexole in pregnancy seem promising, more studies are needed to form a denitive opinion.
Pramipexole, a dopamine agonist, is currently not recommended for use during lactation as it may decrease lactation by suppressing prolactin (Benbir etal. 2014;
Picchietti etal. 2015).
14.7 Methylphenidate
The prevalence of ADHD among women of childbearing age is approximately 3%.
Methylphenidate is one of the most commonly used drugs in the treatment of ADHD
(Koren etal. 2020; Szpunar etal. 2023; Scoten etal. 2024). One study reported that
23.3% of women diagnosed with ADHD and prescribed medication before pregnancy continued their treatment during pregnancy, while 41.8% discontinued their
treatment (Bang Madsen etal. 2024). Among the latter patients, 17.7% resumed
medication in the postpartum period. Methylphenidate was the most commonly prescribed medication for ADHD treatment in this study, emphasizing the signicance
of investigating its safety during pregnancy and breastfeeding.
Although some studies have reported a slight increase in the risk of cardiac
defects (1.07% vs 1.7%, a 59% increase) with methylphenidate use during pregnancy (Koren etal. 2020; Kolding etal. 2021), the majority of studies have not
shown any signicant increase in the risk of congenital malformations (BoleaAlamanac etal. 2014; Ornoy 2018; Jiang etal. 2019; Damer etal. 2021). In a recent
study, 45 women who used methylphenidate during the rst trimester of pregnancy
were followed longitudinally. No major malformations were observed in these
infants at 6months after birth (Szpunar etal. 2023). Considering other pregnancy
outcomes, some studies reported preeclampsia, preterm delivery, low birth weight,
and increased need for neonatal intensive care; however, these adverse effects could
not be attributed unequivocally to the drug (Scoten etal. 2024). Untreated ADHD in
pregnancy may have greater adverse effects on the mother’s quality of life and the
developing fetus by increasing the rates of spontaneous abortion and preterm birth
(Baker etal. 2022; Scoten etal. 2024). A meta-analysis of nearly 30,000 women
14 Miscellaneous Drugs During Pregnancy andLactation
319
with ADHD from 10 large studies showed no signicant increase in congenital
anomalies and miscarriages in the infants of mothers who received treatment with
methylphenidate and atomoxetine during pregnancy compared to control groups (di
Giacomo etal. 2024). The evidence from this large-sample meta-analysis provides
important insights into the safety of methylphenidate during pregnancy.
Regarding the breastfeeding period, methylphenidate was reported to have very
limited excretion into milk, with a RID value of less than 1% and undetectable levels in the serum of breastfed infants (Collin-Lévesque etal. 2018). No adverse
effects were observed in the infants and therefore it is considered to be generally
safe during breastfeeding (Bolea-Alamanac et al. 2014; Kittel-Schneider et al.
2021). Methylphenidate may lead to a decrease in prolactin levels by increasing
dopamine levels; however, this decrease was not found to exert any adverse effects
on lactation (Scoten etal. 2024). Consequently, clinicians should take into consideration the potential impact of treatment on lactation when prescribing medications
to breastfeeding women or to women who have not yet initiated breastfeeding.
The extant literature suggests that the use of methylphenidate during both pregnancy and breastfeeding is associated with low risks. In cases where patients’ functionality is signicantly affected, use of the drug in the lowest possible doses and in
an intermittent manner according to the patient’s condition could be more
appropriate.
14.8 Acamprosate
Acamprosate is a pharmaceutical agent that is commonly prescribed for the treatment of alcohol use disorder. Its mechanism of action involves the modulation of
N-methyl-d-aspartic acid receptors and calcium channels (Antonelli etal. 2018).
However, data available on the safety of acamprosate use during pregnancy remain
limited. A study conducted on 54 women who used acamprosate during pregnancy
reported no association with adverse effects in the newborn or the mother (Kelty
etal. 2019). A comparison of pregnant women who used or did not use acamprosate
revealed no signicant differences in the rates of low birth weight, preterm birth, or
congenital anomalies between the two groups. However, other studies have identied a potential association between rst-trimester exposure to acamprosate and
adverse outcomes, including miscarriage, premature birth, and minor facial anomalies (Quintrell etal. 2025).
Animal studies have shown that acamprosate exposure during pregnancy did not
result in adverse maternal and neonatal outcomes; in fact, a neuroprotective effect
against alcohol-induced neurodegeneration was observed (Quintrell etal. 2023).
There is a paucity of data on the use of acamprosate during lactation, and no scientic data on its excretion into milk. Nevertheless, considering the chemical structure
of acamprosate, it is likely to be excreted into breast milk. However, given its oral
bioavailability of 11% (Luo etal. 2015), the excretion of acamprosate into breast
milk may not be signicant enough to cause systemic side effects in the infant.
However, this view has yet to be substantiated by scientic data.
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14.9 Disulfiram
Disulram exerts its pharmacodynamic effect through the inhibition of aldehyde
dehydrogenase, resulting in the accumulation of acetaldehyde. In conjunction with
alcohol, the accumulation of acetaldehyde can manifest in a clinical spectrum ranging from aversive reactions to life-threatening consequences, contingent on the
quantity of alcohol consumed (Mutschler etal. 2016). Following the initial observations that use of dilsuram in conjunction with alcohol use disorder exhibited teratogenic properties, the compound was subsequently deemed to be teratogenic
(Mutschler etal. 2016) and no further research was conducted on it. A later study by
Briggs etal. (2017) reported a high rate (28.9%) of teratogenicity associated with
disulram. However, it is also important to note that the limited number of studies
on the teratogenicity of disulram contained signicant methodological limitations.
Some animal studies reported that disulram exposure could lead to severe limb
deformities (Johnson et al. 2007), while others reported no effects other than a
decrease in brain size in the female offspring (Harding and Edwards 1993). A recent
study reported that disulram increased reproductive capacity in mice by increasing
uterine vascularization (Teng et al. 2023). However, no record of pregnancy and
fetal safety is available for this study, and no data on the safety of disulram use
during breastfeeding are currently available.
14.10 Baclofen
Baclofen, a GABA-B receptor agonist, has been approved for the treatment of alcohol use disorder for the last 20years. However, its use for this specic disorder is
not yet widespread due to questionable effectiveness (Addolorato etal. 2006; Müller
etal. 2015; Reynaud etal. 2017). A case series of 4 patients associated with baclofen
exposure during pregnancy reported incidents of preeclampsia in the mother and
small for gestational age in the infants (Morton etal. 2009). However, no teratogenicity was reported in this patient population, although the number of patients was
very low (n=4). A recent case report also found no congenital anomaly in the baby
of a pregnant woman who received intrathecal baclofen (Yang etal. 2024). Thus,
although case reports suggest that the use of baclofen is safe during pregnancy and
breastfeeding (Hara etal. 2018), the current body of research is insufcient to provide a denitive conclusion on this matter.
14.11 Other Medicines
14.11.1 Nalmefene
Nalmefene is known to be particularly effective in reducing excessive consumption
in alcohol use disorder and shows an effect on opioid receptors. However, its safety
during pregnancy and breastfeeding has not been reported yet.
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321
14.11.2 Biperiden
Biperiden has been prescribed to patients during pregnancy and lactation for conditions such as neuroleptic malignant syndrome and Parkinsonism. However, there is
no record of its safety during pregnancy and lactation (Tüfekçioğlu etal. 2018;
Escobar-Vidarte etal. 2019).
14.12 Conclusions
Pregnancy and lactation are critical periods when cautious and careful decisions regarding treatment strategies need to be made because of exposure-related adverse effects on
maternal and infant health. This chapter summarized the current evidence on the safety
of the use of a number of psychopharmaceuticals other than antidepressants, antipsychotics, benzodiazepines and mood stabilizers during this period. While some medications such as buprenorphine, methadone, and methylphenidate have been studied
extensively during pregnancy and lactation, others such as buspirone, gabapentinoids,
biperiden, pramipexole, acamprosate, baclofen, disulram, and naltrexone require further research to make a denitive statement about their safety (Table14.1).
Table 14.1 Expert recommendations based on scientic evidence and clinical experience
Strong evidence is currently lacking on the safety of prescribed psychopharmaceuticals that
are not included in the category of antidepressant, antipsychotic, benzodiazepine, and mood
stabilizer drugs during pregnancy and lactation
Although no signicant adverse events related to methadone exposure during pregnancy have
been reported, buprenorphine and buprenorphine/naloxone have a more favorable safety
prole during pregnancy and lactation as they prevent possible opioid withdrawal symptoms in
the newborn
Buprenorphine and buprenorphine/naloxone can be used with low risk during pregnancy and
breastfeeding. Since this treatment may reduce illicit drug use, clinicians can take the initiative
to start treatment. However, use of the lowest possible dose and close monitoring for possible
side effects are always necessary
Although meta-analyses have reported that use of naltrexone is associated with less
withdrawal symptoms as well as a low risk of anomalies in the infant, studies have indeed
reported congenital urogenital anomalies upon exposure in utero. Therefore, the use of
naltrexone during pregnancy is associated with moderate risk. Alternative options should be
considered, especially in the rst trimester if possible. Although low RID values have been
reported for naltrexone, the current literature is insufcient to conclude safety during lactation
Buspirone appears to be safe during breastfeeding due to its low RID values. There are no
adverse reports associated with exposure during pregnancy suggesting that drug exposure may
not pose any serious risks to the mother or baby. However, further studies are needed to
substantiate this claim
Gabapentinoids, which are frequently used in the treatment of neuropathic pain, are generally
not associated with any serious increase in risk during pregnancy. In this regard, gabapentin
can be considered to have a better safety prole than pregabalin. However, the results obtained
from animal studies suggest the presence of adverse effects, which should be considered when
making treatment decisions
(continued)