Search tips
Search criteria 


Logo of schbulOxford JournalsContact UsMy BasketMy AccountSchizophrenia BulletinAbout this JournalContact this JournalSubscriptionsCurrent IssueArchiveSearch
Schizophr Bull. 2010 May; 36(3): 518–544.
Published online 2008 September 11. doi:  10.1093/schbul/sbn107
PMCID: PMC2879689

Antipsychotic Therapy During Early and Late Pregnancy. A Systematic Review


Objective: Both first- (FGAs) and second-generation antipsychotics (SGAs) are routinely used in treating severe and persistent psychiatric disorders. However, until now no articles have analyzed systematically the safety of both classes of psychotropics during pregnancy. Data sources and search strategy: Medical literature information published in any language since 1950 was identified using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from companies developing drugs. Search terms were pregnancy, psychotropic drugs, (a)typical-first-second-generation antipsychotics, and neuroleptics. A separate search was also conducted to complete the safety profile of each reviewed medication. Searches were last updated on July 2008. Data selection: All articles reporting primary data on the outcome of pregnancies exposed to antipsychotics were acquired, without methodological limitations. Conclusions: Reviewed information was too limited to draw definite conclusions on structural teratogenicity of FGAs and SGAs. Both classes of drugs seem to be associated with an increased risk of neonatal complications. However, most SGAs appear to increase risk of gestational metabolic complications and babies large for gestational age and with mean birth weight significantly heavier as compared with those exposed to FGAs. These risks have been reported rarely with FGAs. Hence, the choice of the less harmful option in pregnancy should be limited to FGAs in drug-naive patients. When pregnancy occurs during antipsychotic treatment, the choice to continue the previous therapy should be preferred.

Keywords: antipsychotics, gestational metabolic complications, neuroleptics, neonatal complications, pregnancy, safety


The fertility rate among women suffering from schizophrenic and other severe and persistent psychiatric disorders (SPPDs) has increased since deinstitutionalization.1,2 This may be as a direct result of availability of sexual partners or concurrent changing attitudes toward conception among those with serious mental illness.3 The growing diffusion of second-generation antipsychotics (SGAs), except for risperidone, less likely than first-generation antipsychotics (FGAs) to induce hyperprolactinemia, may have also contributed to improved fecundity in this population of patients.

Unfortunately, however, unplanned and unwanted pregnancies occur more frequently in women with SPPDs than in the general population.4,5 This may result in delayed or poor antenatal care and unhealthy behavior (such as alcohol and street drug consumption) that may be avoided if the woman is made aware of her status.6

Evidence regarding the impact of pregnancy on the course of schizophrenia is inconclusive: however, McNeil et al7 found that in those women with a history of a psychotic disorder, during pregnancy a worsening rather than an improvement of symptoms was more common.8 Regarding bipolar disorder, there are some peculiar features of bipolar women that set them apart from other patient populations. Women with bipolar disorder are typically in their teens and early 20s at onset of the illness, placing them at risk of mood episodes during childbearing age.9 The female reproductive cycle also introduces multifactorial complexities into the treatment of the disease.10 The course of recurrence is often severe and characterized by a relatively high frequency of rapid-cycling forms, mixed mania, and antidepressant-induced mania.11,12 The issue of whether bipolar disorder improves during pregnancy is controversial1316; however, pregnancy seems not to be protective for all bipolar women. Indeed, during the gestational period, risk of a relapse of the disorder does not decrease.17

Consequently, it is particularly important that the mental health of women with SPPDs is stable if they are about to become parents.

Both FGAs and SGAs are known as indispensable effective medications for SPPDs.18 Until now, however, only one relatively recent systematic review has investigated the safety of SGAs in pregnancy.19 Nonetheless, data on the reproductive safety of both SGAs have gradually accumulated adding further information on the use of such agents to these vulnerable mothers.

The lack of updated articles on FGAs may reflect reduced scientific interest in clinical safety of this class of medications. However, they should not be considered as a forgotten therapy.20 Moreover, almost all previous reviews on this topic show a narrative design.2123 Regrettably, conclusions emerging from narrative reviews of scientific literature may be biased by a study selection based on subjective methodologies, and some of the analyzed studies might have reflected the authors’ personal point of view, rather than reflecting intrinsic scientific validity.24 Furthermore, a single (nonrecent) meta-analysis was able only to provide statistical analysis of pregnancy outcomes following first trimester exposure of low-potency neuroleptics.25

An updated and systematic review of studies focused on investigating safety of both classes of psychotropic agents in pregnancy—the gold standard to obtain evidence, despite lack of randomized controlled trials in pregnant women26—is hence the primary aim of this article. A second (but not secondary) aim is to attempt to identify the less harmful treatment option for the mother-infant pair. Beyond classic reproductive risks, we have also taken into consideration risks associated with possible iatrogenic metabolic complications that may affect the physiological course of pregnancy and that have been associated with the use of both FGAs and (prevalently) SGAs (see box 1).

Box 1.

Potential Risks for the Mother-Child Pair Associated With Early and Late Pregnancy Exposure to Antipsychotic Medications

Fetal major malformations (structural teratogenicity)

Perinatal complications (neonatal toxicity)

Postnatal behavioral sequelae (behavioral toxicity)

Gestational complications

Data Selection


Medical literature information published in any language since 1950 was identified using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from companies developing drugs.

Search Strategy

MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library search terms were pregnancy, psychotropic drugs, (a)typical-first-second generation antipsychotics, and neuroleptics. A separate search was also conducted to complete the safety profile of each reviewed medication. Searches were last updated on July 24, 2008. More than 2000 articles (N = 2189, excluding duplicates) were found through the investigation of such databases.


Selected on the basis of their abstract or the full-text article when the abstract was unavailable, all articles reporting primary data on the outcome of pregnancies exposed to antipsychotic medications were acquired and analyzed, without methodological limitations (N = 110). Data supplied by manufacturers (N = 2) and/or obtained from the manual search performed on the reference lists of electronically identified articles (N = 5) provided 7 additional sources of information not identified in the initial search. The author was the only reviewer who performed selection and data extraction.

Data Synthesis

Second-Generation Antipsychotics


To my knowledge, the drug is not approved in the United States as antipsychotic medication. Thus, its pregnancy category has been established by the Congenital Abnormalities Subcommittee of the Australian Drug Evaluation Committee (ADEC),27 which uses a rating system different to that used by the US Food and Drug Administration (FDA). In accordance with the ADEC system, amisulpride is rated as B3 (drugs which have been taken by only a limited number of pregnant women and women of childbearing age, with no increase in the frequency of malformation).28 Despite there being no evidence of teratogenicity in embryo-fetal developmental studies in mice and rabbits following oral doses up to 4 times the maximum recommended human dose, no published information on human pregnancies is available.


Aripiprazole is rated FDA Pregnancy Category C: this means that there is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (eg, if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). In animal studies, aripiprazole demonstrated teratogenicity and developmental toxicity, as well as decreased fetal weight, at doses of 3–10 times the maximum recommended human dose.29,30 Until now, only 3 case reports have investigated the safety of aripiprazole in human pregnancies (see table 1).3133 In 2 cases, the baby showed neither structural anomalies nor neurodevelopmental impairment; conversely, transient symptoms attributable to poor neonatal adaptation phenomena were observed.31 In the third case, the outcome was fully healthy. However, in 2 of these 3 cases, the fetus was exposed to the drug only after week 20 of gestation.31,33

Table 1.
SGAs and Pregnancy


Clozapine is rated FDA Pregnancy Category B, despite paucity of data. Reproductive studies performed in rats and rabbits at doses of approximately 2–4 times the human dose revealed no harm to the fetus.34 In humans, information on the safety of clozapine in human pregnancies (reassumed in table 1) has been available since the early 1990s.35 Single cases of major malformations, gestational metabolic complications, poor pregnancy outcome, and perinatal adverse reactions associated with exposure to clozapine during various stages of pregnancy have been subsequently reported, though they derive solely from case reports and/or small case series studies.3648 However, clozapine overdose during pregnancy may cause fatal poisoning of the newborn.49 On the other hand, clinical observations suggesting safe use of clozapine in pregnant women are limited.5054


Olanzapine is rated FDA Pregnancy Category C. Reproductive studies show no evidence of fetal harm in animals.55 Unfortunately, however, large, prospective studies in humans are presently unavailable. A postmarketing surveillance study on 8858 patients in England identified a small number of olanzapine-exposed pregnancies. One case of therapeutic abortion was due to a fetal malformation identified prenatally.56 The first report from the Lilly Worldwide Pharmacovigilance Safety Database identified no cases of fetal malformations but some cases of perinatal adverse reaction and complicated pregnancy outcome.57 Conversely, further expansion of this registry has recorded anecdotal cases of major structural anomalies; however, the manufacturer states that the prevalence of such events does not differ from that found in the general population. (Eli Lilly Italia, written communication, December 2006). Nonetheless, sporadic cases of olanzapine-associated fetal major malformations, gestational metabolic complications (such as the onset or worsening of gestational diabetes), neonatal adverse reactions, self-remitted neurodevelopmental impairment are now being recorded.44,5866 Very recently, Newport et al67 investigated the placental passage (defined as the ratio between umbilical cord and maternal plasma concentrations) of different antipsychotic agents. Olanzapine showed a higher amount of placental passage (mean 72.1%, SD = 42.0%) and, also, higher rates of either low birth weight and/or perinatal complications as compared with other antipsychotics. In contrast, there are a number of reports describing healthy outcomes in infants exposed to olanzapine during early, late, and throughout pregnancy.6875 Data on the use of olanzapine in pregnancy are shown in table 1.


Quetiapine is rated FDA Pregnancy Category C. Preclinical safety data from the Summary of Product Characteristic report no teratogenic effects in animals (Astra Zeneca SpA, Medical Science and Communication, Basiglio, Milan, Italy, written communication). In human studies, quetiapine showed the lowest amount of placental passage (mean = 23.8%, SD = 11.0) when compared with both FGAs (haloperidol) and SGAs (risperidone and olanzapine).65 Moreover, drug maternal serum levels and pharmacokinetic properties do not show relevant changes during pregnancy.76 A number of case reports have described healthy outcomes in babies exposed in utero to quetiapine despite the fact that, in some of these occasions, the pregnant mothers had also been treated with other psychotropic medications.44,7785 McKenna et al58 recently reported manufacturer's updated information reassuming spontaneous reports of outcomes of pregnancies exposed to quetiapine. In many cases (N = 295), the outcome was unknown, and there were other medications also taken during pregnancy. Despite some cases of major malformations occurring, no recurrent pattern of anomalies was recorded. The authors also identified prospectively 36 women treated with quetiapine during early pregnancy: these patients were compared with a control group of women exposed to nonteratogenic agents. Primary outcome of interest was the presence or absence of major fetal malformation. Secondary outcome of interest included a range of maternal conditions and neonatal health outcomes. Quetiapine was not associated with an increase of the teratogenic risk, and both maternal and neonatal health was apparently unaffected by this treatment. However, one of the limitations of this study was its small sample size; therefore, it only had an 80% power to detect a 4-fold increase in the rates of fetal malformations, which is an α of .05. Hence, this finding requires large, prospective confirmations.


Risperidone is rated FDA Pregnancy Category C, and the drug has shown no direct teratogenic effects in animal studies.86,87 In humans, the amount of placental passage of risperidone was estimated at 49.2% ± 33.9% (SD).67 The prospective study by McKenna et al58 showed quite reassuring results, which substantially replicated those emerging from a postmarketing safety surveillance study and case reports.8892 In fact, only sporadic clinical observations have described fetal malformations and complicated pregnancy outcomes following in utero exposure to the drug.44,9395 Very recently, a comprehensive review assembled all prospective and retrospective reports of pregnancies exposed to risperidone received by the Benefit Risk Management (a division of Johnson & Johnson Pharmaceutical Research & Development, LLC)96: 201 unpublished cases of risperidone-exposed pregnancies were identified. A number of cases of birth defects and peri- and postnatal complications have been reported, but most reports were confounded by the concomitant use of other psychotropic medications (some of which are known teratogens). The authors concluded that an increased risk of spontaneous abortions and fetal teratogenicity could not be identified in pregnant women administered with risperidone. However, such results did not derive from incidence rates but, rather, from percentages of voluntarily reported prospective cases or retrospectively identified cases where the subsequent outcome was known or reported.


Sertindole is rated FDA Pregnancy Category C, though no human data are available on this drug that, however, has not demonstrated any teratogenic effects in animal reproduction studies.97


Ziprasidone is rated FDA Pregnancy Category C. In animal studies, ziprasidone demonstrated developmental toxicity, including possible teratogenic effects (mainly represented by ventricular septum defects and kidney malformations), at doses similar to the human therapeutic dose.98 At present, no human data are available.

First-Generation Antipsychotics

Butyrophenone, Diphenylbutylpiperidine, and Thioxathene Derivates.


Haloperidol is rated FDA Pregnancy Category C. In animal studies, haloperidol rarely induced fetal malformations.99 In humans, the amount of placental passage shown by the drug is 65.5% ± 40.3% (SD).67 Information describing congenital anomalies (most frequently, limb defects) in neonates born to mothers who took haloperidol while pregnant is available since 1966.100 Such a concern was identified in further clinical observations101103 but remains controversial.44,104,105 In fact, the safety of haloperidol in pregnancy was assessed in a recent, multicenter, prospective, controlled cohort study.106 Babies exposed in utero to haloperidol showed congenital malformation rates within the expected baseline risk for the general population. However, because of the small sample size and the ratio between exposed and unexposed subjects, the study had a detection power of 80% to identify a 2.9-fold increase in the overall rate of major malformations (with 95% confidence interval). On the other hand, warning information is available about the risk of perinatal adverse reactions in newborns,107110 despite a case of drug overdose during pregnancy that induced transient and self-remitted complications in the neonate.111 Data on the safety of haloperidol during pregnancy are summarized in table 2.

Table 2.
Butyrophenone, Diphenylbutylpiperidine, and Thioxathene Derivates and Pregnancy

Penfluridol and Pimozide.

Penfluridol and pimozide are both rated FDA Pregnancy Category C. The study by Diav-Citrin et al106 identified a small number of pregnancies exposed to penfluridol. One case of fetal malformation was recorded, whereas no cases of birth defects have been reported in anecdotal description of human pregnancies exposed to pimozide (see table 2).44,112

Flupenthixol, Chlorprothixene, and Zuclopenthixol

Chlorprothixene and zuclopenthixol are both rated FDA Pregnancy Category C, while to the best of my knowledge FDA Pregnancy Category for flupenthixol has still not been established. Recently, Reis and Källén44 identified retrospectively a number of pregnancies exposed to flupenthixol, chlorprothixene, and zuclopenthixol. Some cases of birth defects and gestational metabolic complications were recorded in both zuclopenthixol- and flupenthixol-exposed pregnancies (see table 2).


Studies Investigating Phenothiazine Agents as a Group.

The teratogenic effect of phenothiazines as a group has been proved in mice and rats.113 The amount of placental passage of these drugs is unknown. In humans, Favre-Tissot and Broussolle114 investigated the outcomes of a relatively large number of phenothiazine-exposed pregnancies, most of them exposed to chlorpromazine. Although some cases of fetal major malformations were recorded, the authors concluded that the rate of these anomalies was not statistically different from that shown by unexposed populations. Rawlings et al115 reported similar findings. However, a relatively high rate (23.4%) of spontaneous abortion was recorded in this study. Quite reassuring results also emerged from a prospective study on the use of phenothiazines as a short-term treatment of nausea and vomiting in pregnancy.116 In contrast, a statistically significant increase in the rate of birth defects associated with first trimester exposure to phenothiazines with 3-carbon aliphatic side chain (specifically, chlorpromazine, methotrimeprazine, trimeprazine, and oxomemazine) was demonstrated in 2 prospective surveys.117,118 However, in the first of these studies, phenothiazines were also used for controlling threat of abortion. Because early pregnancy loss may be due to an embryo affected by chromosomal or structural anomalies,119,120 the reported association between pregnancy exposure to this class of antipsychotics and birth defects seems to be the result rather than the cause of birth defects.117 Scokel and Jones121 also suggested an increased risk of neonatal jaundice in preterm infants whose mothers had been treated with phenothiazines during labor. The long-term behavioral outcome of children exposed in utero to phenothiazines after week 20 of pregnancy was investigated in a single case-control study.122 These children, aged 9–10 years, showed no behavioral anomalies. However, the development of such children was assessed by their teachers using an oversimplified, semistructured formulary; neither specific instruments of evaluation nor qualified intervention by specialized staff was actually provided. Studies investigating phenothiazine agents collectively are shown in table 3.

Table 3.
Phenothiazines and Pregnancy

Studies on Specific Phenothiazine Agents


Chlorpromazine is rated FDA Pregnancy Category C. In animal studies, chlorpromazine has been associated with an increased risk of congenital malformations (involving skeletal and central nervous systems, eye, cleft palate, fetal death, and reduced fetal weight gain) but at doses many times higher than the human-recommended dose.123,124 Regarding human teratogenicity, Rumeau-Rouquette et al117 reported a personal communication by Crombie, who found no case of fetal malformations in a small number of babies born to mothers who had been treated with chlorpromazine during the first trimester of pregnancy. Such reassuring results were confirmed retrospectively by subsequent case reports and case series studies on drug exposure during early and late pregnancy.44,125128 However, it was hypothesized that chlorpromazine might be associated with an increased risk of neonatal respiratory distress if used at daily doses higher than 500 mg.126 Until now, only one case of either fetal malformations or gestational diabetes has been reported,44,129 whereas perinatal complications seem to be relatively common when the drug is used in late pregnancy (see table 3).75,130140


Prochlorperazine is rated FDA Pregnancy Category C. One case of rare and mortal fetal anomaly was described in a woman who needed prochlorperazine during pregnancy because of suffering from a severe form of hyperemesis gravidarum.141 Prospective investigations and case reports also suggested an increased risk of major and minor congenital malformations after exposure to prochlorperazine during the first 20 weeks of gestation.142145 Conversely, Reis and Källén44 found no cases of fetal malformations in a relatively large number of retrospectively identified prochlorperazine-exposed pregnancies. Data on prochlorperazine are shown in table 3.


Trifluoperazine is rated FDA Pregnancy Category C. More than 40 years ago, Smith Kline and French reexamined its database to determine whether there was evidence of a causal relationship between trifluoperazine therapy in pregnancy and an increased risk of fetal malformations.146 No evidences of teratogenicity were found. However, most of these women (87%) received the drug to control nausea and vomiting in pregnancy; only 13% of women had been on long-term treatment because of psychiatric disorders. Nonetheless, in December 1992, the Canadian Food and Drug Directorate stated that trifluoperazine might be associated with sporadic cases of congenital anomalies, including skeletal and multiple internal deformities.147 Indeed, some cases of limb defects and other unspecified malformations following early in utero exposure to trifluoperazine during the first trimester had been observed,148151 although anecdotal clinical reports and one relatively large retrospective investigation (this last study conducted on women who took the drug for nausea and vomiting in pregnancy) did not confirm such observations.132,152 Data on trifluoperazine in pregnancy are summarized in table 3.


To the best of my knowledge, fluphenazine has not been formally assigned to a pregnancy category by the FDA. The effects of fluphenazine on pregnancy outcomes were studied extensively only in women who took the drug for treating hyperemesis gravidarum.153 Delivery and neonatal records revealed that the rates of spontaneous abortions, perinatal mortality, premature delivery, and fetal malformations were similar between the fluphenazine group and a control group of women treated with placebo.153 Sporadic case reports and information from retrospective investigation of birth registers have also suggested that maternal fluphenazine treatment may be relatively safe for the developing fetus and rarely induce gestational metabolic complications but may induce neonatal adverse reactions.44,154 These studies are summarized in table 3.

Thioridazine and Thiethylperazine.

Thioridazine and thiethylperazine have not, as yet, been assigned a formal FDA Pregnancy Category. A small number of women who have needed low doses of thioridazine during pregnancy have showed uncomplicated deliveries.137,155 Conversely, late in utero exposure to the drug might be associated with an increased risk of extrapyramidal symptoms in neonates.133 Until now, only one case of fetal malformations following placental exposure to the drug has been reported.44 One study suggested an increased risk of fetal major malformations associated with early in utero exposure to thiethylperazine.156 Very recently, a relatively large, observational, case-control study has also hypothesized that the drug might be associated with a statistically significant increase (odds ratio: 1.7; 95% confidence interval: 1.1–2.5) in the risk of cleft and lip palate if used during early pregnancy (see table 3).157 Data on thioridazine and thiethylperazine are shown in table 3.

Promethazine, Perphenazine, and Levomepromazine.

Promethazine, perphenazine, and levomepromazine are all rated FDA Pregnancy Category C. In the case of promethazine, a relatively large number of women exposed early in pregnancy were prospectively and retrospectively identified. Despite some cases of birth defects being observed in babies born to these mothers, the rate of major structural malformations (4.3%) did not differ from that expected (see table 3).150 Two case reports described fetal malformations in infants whose mothers took perphenazine (but amitriptyline too) during early pregnancy (see table 3).158 Sporadic cases of both fetal malformations and gestational metabolic complications also emerged from a recent retrospective study investigating the use of perphenazine during pregnancy.44 Anecdotal cases of birth defects and gestational metabolic complications have been reported among a relatively small number of women who had taken levomepromazine during early pregnancy.44 Data on these 3 antipsychotic medications are shown in table 3.


Previously published guidelines, editorials, and narrative reviews have rightly highlighted the necessity to start or continue antipsychotic therapy in vulnerable mothers because either the relapse or the recurrence of psychotic symptoms represents medical and obstetrical emergencies.25 However, these studies provided no information about the best treatment option for the mother-infant pair because they frequently concluded that, when available, reassuring findings on structural teratogenicity of all antipsychotics, either of first or second generation, were preliminary and too limited for recommending safe use in pregnancy.25,159162 Moreover, the majority of studies on the reproductive safety of antipsychotic medications are also characterized by single-dimension experimental design, which is unable to individuate all the factors that, in pregnant women with SPPD, may lead to increase in the risk of birth defects and poor pregnancy outcomes independent of the drugs (malnutrition, poor antenatal cares, episodes of domestic and/or sexual violence, gynecological infectious diseases, and unhealthy behaviors).163 This situation is not surprising: it is indeed unethical to include pregnant women in randomized controlled trials because this would involve deliberate exposure of the fetus to a potential teratogen.164 As a result, the best available data on antipsychotic drug usage in pregnant women that can be used to support clinical decisions come from nonrandomized, prospective, and observational studies, and, more often, single case reports or small case series studies thus also suffer from being methodologically poor. It must be stressed, however, that the lack of data on the use of psychotropic medications in women is not limited to this specific phase of the female reproductive cycle: despite the urgent need to identify major gaps in our knowledge of how gender may influence psychiatric diagnoses and treatment outcomes,165 it was not until 1990 that the National Institute of Health in the United States issued guidelines mandating the inclusion of women in clinical trials.166 Nevertheless, in the absence of more controlled researches, reviewed studies provide the only information source potentially useful in clinical practice, and it is reassumed below.


When investigated collectively, antipsychotic medications have been associated with a statistically significant increase in the risk of birth defects as a whole, with no significant differences in malformation risk between classes and/or single medications44; thus, it is possible that underlying pathology or unidentified confounding factors may explain the increased risk.44 In addiction, the use of both SGAs and FGAs during late pregnancy has been associated with increased rates of perinatal complications. However, the following findings (including specific comments on the specificity of iatrogenic metabolic complications in this phase of the female reproductive cycle) need to be highlighted.

SGAs and Structural/Behavioral Teratogenicity

Because of the lack of any human data, the teratogenic risk of amisulpride, ziprasidone, and sertindole should be considered unknown. Only 3 case reports are available on aripiprazole: in one of these cases, transient unwanted effects on the neonatal cardiac rhythm were observed.31 Hence, these drugs should be avoided in pregnant women because either no or limited anecdotal data are available about their own structural and behavioral teratogenicity.

Approximately, 200 babies exposed in utero to clozapine have been investigated. Fifteen cases of fetal malformations have been reported, as well as cases of poor pregnancy outcomes and perinatal complications (including transient floppy infant syndrome, retinopathy, and severe neonatal hypoxemic encephalopathy).3638,42,4448,56,57 However, in most of these cases no information was available about the kind of the malformation; hence, possible recurrent patterns of anomalies cannot be ascertained. Moreover, on some occasions the mothers took concomitant medications. In addiction, Pinkofsky et al167 have raised the issue of potential clozapine-induced fetal agranulocytosis. Thus, white blood cell counts of all newborn infants whose mothers have received clozapine during pregnancy should be monitored weekly for the first 6 months to detect agranulocytosis that may result in life-threatening infectious diseases.168

Olanzapine is the SGA with the highest number of reports regarding its use during pregnancy (n = 419), but the attempt to analyze the possible teratogenicity of the drug is impaired by the fact that these mothers were exposed concomitantly to other psychotropic medications. Twenty-six cases of congenital malformations have been reported (fully described in all cases). Neural tube defects were diagnosed in 4 of these cases.56,58,59 Thus, some signals seem to exist suggesting that the drug may increase the risk of this specific anomaly.59,169 63 cases of perinatal complications following inuter exposure to olanzapine have been reported. However, clinical information on these untoward events was rarely available (Eli Lilly Italia, wriiten communication47,57)

At the time of writing, 227 reports of pregnancies exposed to quetiapine are available, in 8 cases complicated by the occurrence of fetal malformations of unknown typology. For this reason, no conclusions can be drawn about the safety of this drug in early pregnancy. Moreover, the first reports of perinatal complications are now being released.67

Three hundred twenty-one cases of pregnancy exposure to risperidone are available. Fifteen cases of fetal malformations (all with known typology) have been observed, with no recurrent patterns of anomalies. Perinatal complications of various degrees of severity may also occur, ranging from withdrawal reactions to seizures.58,92,95,96 Finally, sporadic cases of poor pregnancy outcome and neonatal complications have been recorded.92,9496

SGAs and Gestational Metabolic Complications

Most SGAs (with the possible exception of aripiprazole and ziprasidone) are likely to induce obesity and other metabolic complications, especially during long-term treatments.170,171 This risk seems to be higher in women with childbearing potential.19,21 It must be stressed that women who become obese prior to pregnancy are more likely to deliver malformed babies than nonobese women (see table 4); the mechanism underlying such an association may be related to an undiagnosed diabetes.172 Gestational diabetes has also been associated with an increased risk of developing breast cancer later in the mother's life.173 In addition, a recent prospective study has demonstrated that infants exposed in utero to SGAs might show a significantly higher incidence of being large for gestational age and a mean birth weight significantly heavier than those exposed to FGAs.174 Besides neonatal hypoglycemia, infants who are born large for gestational age show increased lipolysis and a propensity for decreased insulin sensitivity already at birth; such infants are also at risk of developing obesity, cardiovascular disease, and diabetes later in life.175 Among SGAs, clozapine3941,43,45,51,57 and olanzapine44,57,6264 should definitively be considered as drugs associated with an increase in the risk of metabolic complications in pregnancy (prevalently gestational diabetes). Until now, amisulpride, aripiprazole, quetiapine, sertindole, and ziprasidone have not been associated with occurrence of gestational metabolic complications, whereas a single case of gestational diabetes has been reported during therapy with risperidone.44

Table 4.
Fetal Malformations Related to Prepregnancy Obesity With Statistical Significance172

FGAs and Fetal/Behavioral Teratogenicity

Despite approximately 40 years of clinical use and a safety database recently defined as “reasonably extensive,”66 we have found only 411 published cases of pregnancies exposed to haloperidol. Overall, 14 cases of fetal anomalies were reported (3 were limb malformations100102). Thus, the risk of limb anomalies associated with early in utero exposure to haloperidol cannot be excluded. One case of limb deformity has also been detected among 27 penfluridol-exposed babies.106 Finally, the risk of perinatal complications associated with late in utero exposure to haloperidol (ranging from withdrawal symptoms to instability of body temperature) should be stressed.

Early pregnancy exposure to thioxathenes have been sporadically associated with birth defects,44 whereas only anecdotal, despite reassuring, descriptions of human pregnancies exposed to pimozide are available.44

A relatively large number of babies exposed in utero to phenothiazine agents (as a group) have been investigated (4060 cases). However, most of these babies were exposed to such agents for only a short period; indeed, their mothers were not psychiatric patients but needed such drugs for treating hyperemesis gravidarum. In addition, because these studies lump together different neuroleptics, their results provide no significant information about the teratogenicity of specific drugs.118,176 In any case, the overall rate of birth defects was about 10% (N = 406). The suggested risk of fetal cardiac malformations cannot be confirmed118 also because published data are impaired by incomplete reporting.116

More than 400 cases of pregnancies exposed to chlorpromazine have been published. Only 5 cases of fetal malformations have been described.117,129 Conversely, the use of this drug during late pregnancy seems to be inevitably associated with an increased risk of perinatal complications (including extrapyramidal signs, which may persist up to 1 year of age; respiratory distress; seizures; and transient neurodevelopmental delay).132140

Whereas reports on pregnancies exposed to prochlorperazine show contradictory findings,44,141145 more than 1000 cases of pregnancy exposed to trifluoperazine are known. Nineteen cases of major malformations have been described. The poor methodology of such reports makes it impossible to confirm or exclude the doubtful finding that the drug may be associated with an increased risk of fetal skeletal and internal anomalies if used during early pregnancy.146152

The theoretical risk of increased rates of cleft lip palate associated with the use of thiethylperazine early in pregnancy has been hypothesized in only one study, based however on a very small sample size.157

Further, no conclusions can be drawn about the teratogenicity of fluphenazine, thioridazine, and promethazine, despite the first 2 drugs being definitively associated with an increased incidence of neonatal extrapyramidal reactions.

FGAs and Gestational Metabolic Complications

Although recent researches suggest that FGAs may also induce clinically relevant weight gain during long-term therapy,177 until now the number of reports describing FGA-induced gestational metabolic complications is limited. Early pregnancy exposure to thioxathenes and chlorpromazine have been sporadically associated with the onset or worsening of gestational diabetes.44

Treatment Guidelines

Despite both the lack of methodologically valid safety data and the presence of possible reproductive safety concerns specified above, antipsychotic therapy must be considered mandatory in women with SPPDs even during pregnancy because the risks associated with pharmacological intervention may outweigh the risks of an untreated mental illness for the mother-infant pair.178,179 Independent of any safety considerations, it should be stressed that most of these pregnant women require admission to psychiatric emergency services for pharmacological management of psychotic breakdown episodes: in such conditions, antipsychotics are the more frequently administered drugs.180 Moreover, some SPPDs seem to be an independent risk factor for adverse pregnancy outcomes (higher rates of prenatal hospitalization due to maternal medical problems, placental anomalies, eclampsia, antepartum hemorrhages, premature delivery, lower birth weight and Apgar scores, shorter length at delivery, fetal distress, stillbirth, perinatal mortality, and congenital anomalies).181184 The existing correlation between unfavorable perinatal circumstances (such as low birth weight) and increased rates of suicide of offspring as young adults should also be highlighted.185 This seems to be especially true for schizophrenia, which has also been specifically associated with an increase in risk of major neurological malformations, preterm delivery, low birth weight, and small-for-gestational age babies.186,187 In contrast, these findings remain controversial for affective psychosis.188 It has been recently confirmed that increased risk of obstetrical complications in schizophrenic patients seems to be due to engagement in health risk behaviors during pregnancy, whereas genetic susceptibility to the disorder, by itself, does not appear to influence the natural course of pregnancy.189

In any case, maternal SPPDs may have a devastating impact on the quality of the mother-infant bonding and on the infant's neurodevelopment. Mothers with schizophrenia are likely to have their attachment to the baby compromised by the maternal psychopathology and the reality of their psychosocial situation.190 These women are also more likely to experience difficulties with parenting and thus to lose custody of their children.8 Maternal bipolar disorder is associated with increased rates of memory and attention disturbances, impaired social functioning, behavioral and emotional problems, and even severe psychiatric disorders in the offspring.191194

Managing SPPDs in Pregnant, Drug-Naïve Women

Given this background, when clinicians have to manage psychotic symptoms in pregnant, drug-naïve women, the less harmful pharmacological option should be selected within FGAs. In contrast with Trixler et al22 who suggest to privilege high-potency agents (such as haloperidol) as first-line management of psychotic disorders during pregnancy,23 in our opinion chlorpromazine should be considered as a possible first-line option because the drug evidences less-worrying teratogenic data. In fact, the association between first trimester exposure to phenothiazines and congenital anomalies reported in other narrative reviews and a single meta-analysis25,195197 seem to be unconfirmed for chlorpromazine.24 Moreover, among both FGAs and SGAs, phenothiazines are the only medications that show some, albeit preliminary and methodologically not impeccable, findings suggesting no impact on later infants’ school behavior.122 Moreover, only anecdotal reports have described an increased risk of clinically significant episodes of orthostatic hypotension in pregnant women on chlorpromazine treatment,75 a clinical concern previously emphasized.23 Further, the reported increased height in children born to mothers on FGA therapy during pregnancy compared with those born to untreated mentally impaired mothers (this difference, however, disappeared at 7 years of age)198 seems to have no clinical relevance; this finding might be simply due to the improvement of maternal mental conditions secondary to antipsychotic treatment. Restoration of patient sound contact with reality and the pharmacological control of other positive symptoms might have facilitated a good adherence to antenatal care and reduced unhealthy lifestyle and behaviors, with obvious favorable effects on infant development. It must be stressed, however, that chlorpromazine may induce neonatal extrapyramidal reactions, respiratory distress, and transient neurodevelopmental delay (see box 2). However, use of central acting anticholinergic drugs for controlling extrapyramidal adverse events should be avoided whenever possible. Information on the safety of such medications is available neither in animal nor in human pregnancies.

Box 2.

Managing Psychotic Symptoms During Pregnancy

Antipsychotic therapy should be considered mandatory in pregnant patients with psychotic features

When a planned or unplanned pregnancy occurs during antipsychotic treatment, privilege the choice to continue the previous therapy, if known as effective Pregnancy is not the best period to experiment the effectiveness of drugs

In the case of occurrence of psychotic symptoms in drug-naïve pregnant patients, privilege the drug showing the highest number of reassuring reports and the lowest reported number of fetal anomalies (eg, chlorpromazine)

Provide strict gynecological surveillance (tritest, regular clinical follow-up, and ultrasound monitoring) during therapy with both first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs)

Provide strict endocrinological surveillance (Hb1Ac, glycemia, cholesterol and triglycerides serum levels, bodyweight gain) during therapy with FGAs but, especially, with SGAs

Take into consideration the possibility to taper both FGAs and SGAs during the last trimester in order to reduce the risk of neonatal extrapyramidal reactions and seizures Match this decision with the risk of a relapse of psychotic symptoms

Provide strict cooperation between gynecologists, neonatologists, and pediatricians in order to warrant optimal maternal antenatal cares and promptly diagnose and manage eventual perinatal complications during the first hours after delivery

Provide regular follow-up of children exposed in utero to either FGAS and SGAs in order to diagnose and manage possible signs of neurodevelopmental delay

Managing SPPDs in Patients Who Incur in an Unplanned Pregnancy During Antipsychotic Treatment

Given the increasing use of SGAs in clinical practice, most of these women could be on SGA treatment at the time of conception; unfortunately, no evidence-based information allows to individuate the safest SGA in pregnancy. However, the risk of polypharmacotherapy, either concomitant and/or consecutive, has not been established in pregnancy, despite nearly one-third of women with SPPDs filled prescriptions for up to 10 medications during their pregnancy.199 Thus, when an unplanned pregnancy occurs during antipsychotic treatment, the choice to continue the previous therapy (if known as effective, even when based on SGAs) should be preferred. Pregnancy is not the best period to attempt pharmacological shifts and experiment on the effectiveness of drugs. However, such women should be carefully monitored to prevent or manage metabolic complications (such as excessive weight gain, increased serum triglyceride and cholesterol levels, glucose intolerance, and/or gestational diabetes—see box 2).

Managing SPPDs in Patients on Antipsychotic Treatment Who Wish to Become Mothers

In the light of these considerations, in this situation clinicians should evaluate the general reproductive safety of the current antipsychotic treatment. If the patient is already prescribed chlorpromazine, no changes are needed. Conversely, these patients and their partners should be carefully counseled to plan effective anticonception measures until pharmacological shift from previously prescribed antipsychotic drug to the lowest effective dose of chlorpromazine is complete.


The desire of women with SPPD to have a child should be taken into great consideration, for as many as 50% of them are mothers, which almost equals the figure for the general population.200 Hence, in these women pharmacological management of the underlying illness is only part of an integrated multidisciplinary approach. Other indispensable tools must include the implementation, before conception, of educational programs finalized to reduce unhealthy behaviors that may contribute to increase in risk of fetal malformations independently of drug use (alcohol, nicotine, and street drug) and unprotected sexual practices (which amplify risk of sexually transmitted diseases).

However, the main clinical concern of pregnant women with SPPDs is probably psychotic relapse due to nonadherence to neuroleptic medications, which may lead to poor outcomes such as termination of pregnancy, obliged cesarean section, and institutionalization of their offspring due to reduced child-care capabilities.201,202 Hence, clinicians should make all possible effort to inform these vulnerable mothers about the advantage of accepting a possible, modest increase in teratogenic risk in comparison with the need to maintain stable mental health during pregnancy.21 These women should be made aware that fetal malformation is a relatively common pregnancy complication even in general health population.203 Approximately, 150 000 children with malformations are born annually in the United States.204 Ethical and legal concerns regarding the validity of informed consent from severely mental ill patients are beyond the scopes of this article (see resource documents issued by American Psychiatry Association205 and Royal Pharmaceutical Society206): however, it should be stressed that most patients with serious mental illness have abilities similar to healthy persons when making treatment decision, and deficits in their decision-making performance may be temporary and may improve with treatment.207 Nonetheless, the decision to start or continue antipsychotic therapy during pregnancy should be shared with partners and/or other family members because evidence is that women usually involve (or are influenced by) these people in their reproductive decisions.178,179 Indeed, expectant fathers and patient relatives may also have prejudices about teratogenic risks of those medications deemed indispensable by clinicians for maintaining stable mental conditions or obtaining satisfactory recovery after a psychotic storm.178,179 Thus, the second tool consists of implementing specific consultation services for parents and clinicians, finalized to empower the quality of information about the reproductive safety profile risks of any psychotropic medications. Indeed, pharmacological treatment also remains an indispensable tool for acquiring maternal adherence to alternative interventions.208

The third tool is enhancement of all other non–drug-related support programs (which must include psychological support to maternity, implementation of the number of psychiatric mother-baby units for preventing attachment-turmoil and mother-baby division during postpartum period,209 social support finalized to facilitate community reintegration, and identification of potential alternative caregivers to the children) that may contribute to the maintenance of good, stable mental status210 and may facilitate construction of sound mother-child bonding.


Dr Gentile acknowledges Medical Information Service (Annamaria Desiati, Lucia Fantini, Cristina Mari, Stefania Metafonti, and Luana Salvati), a free-access service of Eli Lilly SpA, Sesto Fiorentino, Italy, for the kind and professional support in providing full-text articles. He dedicates this article to his father. No source of funding was used.


1. Odegard O. Fertility of psychiatric first admission in Norway 1936-1975. Acta Psychiatr Scand. 1980;62:212–220. [PubMed]
2. Miller WH, Bloom JD, Resnick MP. Prenatal care for pregnant chronic mental ill patients. Hosp Community Psychiatry. 1992;43:942–943. [PubMed]
3. Castle DJ, McGrath J, Kulkarni J. Women and Schizophrenia. Cambridge, UK: Cambridge University Press; 2000. Reproductive, preconceptual and antenatal needs of women with schizophrenia.
4. Coverdale JH, Bayer TL, McCullough LB, Chervenak FA. Respecting the autonomy of chronic mentally ill women in decision about contraception. Hosp Community Psychiatry. 1993;44:671–674. [PubMed]
5. Miller LJ, Finnrerty M. Sexuality, pregnancy, and childbearing among women with schizophrenia-spectrum disorders. Hosp Community Psychiatry. 1996;47:502–506. [PubMed]
6. Gentile S. Special care-needs for schizoaffective women in childbearing age [abstract] Turk J Psychiatry. 2006;2(suppl 1):271.
7. McNeil TF, Kaij L, Malmquiat-Larsson A. Women with nonorganic psychosis: pregnancy's effect on mental health during pregnancy. Obstetric complications in schizophrenic patients. Acta Psychiatr Scand. 1984;70:140–148. [PubMed]
8. Coverdale JH, Turbort SH, Roberts H. Family planning needs and STD risk behaviours of female psychiatric outpatients. Br J Psychiatry. 1997;171:69–72. [PubMed]
9. Yonkers KA, Wisner KL, Stowe Z, et al. Management of bipolar disorder during pregnancy and postpartum period. Am J Psychiatry. 2004;161:608–620. [PubMed]
10. Freeman MP, Gelenberg AJ. Bipolar disorder in women: reproductive events and treatment considerations. Acta Psychiatr Scand. 2005;112:88–96. [PubMed]
11. Swann AC. Special needs of women with bipolar disorder. Intellyst™ Medical Communication. International Congress on Women's Mental Health; 17–20 March 2004; Washington, DC. pp 4–18.
12. Burt VK, Rasgon N. Special considerations in treating bipolar disorder in women. Bipolar Disord. 2004;6:2–13. [PubMed]
13. Grof P. Protective effect of pregnancy with lithium-responsive bipolar disorder. J Affect Disord. 2000;61:31–39. [PubMed]
14. Kendell RE, Chalmers JC, Plaz C. Epidemiology of puerperal psychosis. Br J Psychiatry. 1987;150:622–673. [PubMed]
15. Pugh TF, Jerath BK, Schmidt WM, Reed RB. Rates of mental disease related to childbearing. N Engl J Med. 1963;268:1224–1228. [PubMed]
16. Terp IM, Mortensen PB. Postpartum psychosis: clinical diagnosis and relative risk of admission after parturition. Br J Psychiatry. 1998;172:521–526. [PubMed]
17. Freeman M, Smith K, Freeman S, et al. The impact of reproductive events on the course of bipolar disorder in women. J Clin Psychiatry. 2002;63:284–287. [PubMed]
18. Gentile S. Atypical antipsychotics in the treatment of bipolar disorder. More shadows than lights. CNS Drugs. 2007;21:367–387. [PubMed]
19. Gentile S. The clinical utilization of atypical antipsychotics in pregnancy and lactation. Ann Pharmacother. 2004;38:1265–1271. [PubMed]
20. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DD. for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353:209–223. [PubMed]
21. Ernst CL, Goldberg JF. The reproductive safety profile of mood stabilizers, atypical antipsychotics, and broad-spectrum psychotropics. J Clin Psychiatry. 2002;63(suppl 4):42–55. [PubMed]
22. Trixler M, Gáti A, Fekete S, Tényi T. Use of antipsychotics in the management of schizophrenia during pregnancy. Drugs. 2005;65:1193–1206. [PubMed]
23. Nurnberg GH, Prudic J. Guidelines for treatment of psychosis during pregnancy. Hosp Community Psychiatry. 1984;35:67–71. [PubMed]
24. Collins JA, Fauser BCJM. Balancing the strengths of systematic and narrative reviews. Hum Reprod Update. 2005;11:103–104. [PubMed]
25. Altshuler L, Cohen L, Martin S, Burt VK, Gitlin M, Mintz J. Pharmacological management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry. 1996;153:592–596. [PubMed]
26. Starfield B. Quality of care-research: internal elegance and external relevance. JAMA. 1998;280:1006–1008. [PubMed]
27. Australian Drug Evaluation Committee (ADEC) ADEC Pregnancy Category. Accessed June 19, 2008.
28. Solian. Product information. Accessed June 19, 2008.
29. Product Information. Abilify (aripiprazole) Princeton, NJ: Bristol-Myers Squibb; 2003.
30. Aripiprazole. Drugdex drug evaluations, 1974-2003. Thomson Micromedex, Healthcare Series Vol 117.
31. Mendhekar DN, Sunder KR, Andrade C. Aripiprazole use in a pregnant schizoaffective woman. Bipolar Disord. 2006;8:299–300. [PubMed]
32. Mervak B, Collins J, Valenstein M. Case report of aripiprazole usage during pregnancy. Arch Womens Ment Health. [published online ahead of print June 26, 2008] [PubMed]
33. Mendhekar DN, Sharma JB, Srilakshmi P. Use of aripiprazole during late pregnancy in a woman with psychotic illness [letter] Ann Pharmacother. 2006;40:575. [PubMed]
34. Clozaril.® Prescribing information. Accessed March 20, 2007.
35. Lieberman J, Safferman AZ. Clinical profile of clozapine: adverse reactions and agranulocytosis. In: Lapierre Y, Jones B, editors. Clozapine in Treatment Resistant Schizophrenia: A Scientific Update. London, UK: Royal Society of Medicine; 1992.
36. Bazire S. Psychotropic Drug Directory. Salisbury, UK: Fivepin Limited; 2005. p. 239.
37. Dev VJ, Krupp P. Adverse event profile and safety of clozapine. Rev Contemp Pharmacother. 1995;6:197–208.
38. Vavrusova L, Konikova M. Clozapine administration during pregnancy [in Czechoslovakian] Ceska Slov Psychiatr. 1998;94:282–285.
39. Nguyen HN, Lalonde P. Clozapine and pregnancy [in French] Encephale. 2003;29:119–124. [PubMed]
40. Dickson RA, Hogg L. Pregnancy of a patient treated with clozapine. Psychiatr Serv. 1998;49:1081–1083. [PubMed]
41. Waldman MD, Safferman A. Pregnancy and clozapine [letter] Am J Psychiatry. 1993;150:168–169. [PubMed]
42. Mendhekar DN, Sharma JB, Srivastava PK, et al. Clozapine and pregnancy [letter] J Clin Psychiatry. 2003;64:850. [PubMed]
43. Rzewuska M. Leczenie zaburzeá psychicznych (in Polish) Warszawa, Poland: PZWL; 2000.
44. Reis M, Källén B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol. 2008;28:279–288. [PubMed]
45. Karakula H, Szajer K, Śpila B, Gryza A, Guy A, Przywara G. Clozapine and pregnancy. A case history. Pharmacopsychiatry. 2004;37:303–304. [PubMed]
46. Stoner SC, Sommi RW, Jr, Marken PA, Anya L, Vaughn J. Clozapine use in two full-term pregnancies [letter] J Clin Psychiatry. 1997;58:364–365. [PubMed]
47. Di Michele V, Ramenghi LA, Sabatino G. Clozapine and lorazepam administration in pregnancy [letter] Eur Psychiatry. 1996;11:214. [PubMed]
48. Yogev Y, Bem-Haroush A, Kaplan B. Maternal clozapine treatment and decreased fetal hearth rate variability. Int J Gynaecol Obstet. 2002;79:259–260. [PubMed]
49. Klys M, Rojek S, Rzepecka-Woźniak E. Neonatal death following clozapine self-poisoning in late pregnancy. An unusual case-report. Forensic Sci Int. 2007;171:e5–e10. [PubMed]
50. Barnas C, Bergant A, Hummer M, Saria A, Fleischhacker WW. Clozapine concentrations in maternal and fetal plasma, amniotic fluid, and breast milk [letter] Am J Psychiatry. 1994;151:945. [PubMed]
51. Gupta N, Grover S. Safety of clozapine in 2 successive pregnancies [letter] Can J Psychiatry. 2004;49:863. [PubMed]
52. Tényi T, Trixler M. Clozapine in the treatment of pregnant schizophrenic women [in Hungarian] Psychiatr Danub. 1998;10:15–18.
53. Mendhekar DN. Possible delayed speech acquisition with clozapine therapy during pregnancy and lactation [letter] J Neuropsychiatry Clin Neurosci. 2007;19:196–197. [PubMed]
54. Duran A, Ugur MM, Turan S, Emuk M. Clozapine use in two women with schizophrenia during pregnancy. J Psychopharmacol. 2008;22:111–113. [PubMed]
55. Zyprexa. Prescribing information Accessed May 8, 2005.
56. Biswas PN, BR, Wilton LV, Pearce GL, Freehahtle S, Shakir SA. The pharmacovigilance of olanzapine: results of a post-marketing surveillance study on 8858 patients in England. J Psychopharmacol. 2001;15:265–271. [PubMed]
57. Goldstein DJ, Corbis LA, Fung MC. Olanzapine-exposed pregnancies and lactation: early experience. J Clin Psychopharmacol. 2000;20:399–403. [PubMed]
58. McKenna K, Koren G, Tetelbaum M. Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. J Clin Psychiatry. 2005;66:444–449. [PubMed]
59. Arora M, Praharaj SK. Meningocele and ankyloblepharon following in utero exposure to olanzapine. Eur Psychiatry. 2006;21:341–346. [PubMed]
60. Spryropoulou AC, Zrvas IM, Soldatos CR. Hip dysplasia following a case of olanzapine exposed pregnancy: a questionable association. Arch Womens Ment Health. 2006;9:219–222. [PubMed]
61. Yeshayahu Y. The use of olanzapine in pregnancy and congenital cardiac and musculoskeletal abnormalities [letter] Am J Psychiatry. 2007;164:1759–1769. [PubMed]
62. Littrell KH, Johnson CG, Peabody BA, Hilligoss N. Antipsychotics during pregnancy [letter] Am J Psychiatry. 2000;157:1342. [PubMed]
63. Vemuri MP, Rasgon NL. A case of olanzapine-induced gestational diabetes mellitus in the absence of weight gain [letter] J Clin Psychiatry. 2007;68:1989. [PubMed]
64. Aichhorn W, Yadzi K, Kralovec K, et al. Olanzapine plasma concentration in a newborn. J Psychopharmacol. [published online ahead of print February 28, 2008] [PubMed]
65. Friedman SH, Rosenthal MB. Treatment of perinatal delusional disorder: a case report. Int J Psychiatry Med. 2003;33:391–394. [PubMed]
66. Kirchheiner J, Berghöfer A, Bolk-Weischedel D. Healthy outcome under olanzapine treatment in a pregnant woman. Pharmacopsychiatry. 2000;33:78–80. [PubMed]
67. Newport J, Calamaras MR, DeVane CL, et al. Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcome. Am J Psychiatry. 2007;164:1214–1220. [PubMed]
68. Nagy A, Tenyi T, Lenard K, Herold R, Wilhelm F, Trixler M. Olanzapine and pregnancy [in Hungarian] Orv Hetil. 2001;142:137–138. [PubMed]
69. Neumann NU, Frasch K. Olanzapine and pregnancy [in German]. 2 case reports. Nevernatz. 2001;72:876–878. [PubMed]
70. Mendhekar DN, War L, Sharma JB, Jiloha RC. Olanzapine and pregnancy. Pharmacopsychiatry. 2002;35:122–123. [PubMed]
71. Malek-Ahmadi PM. Olanzapine in pregnancy [letter] Ann Pharmacother. 2001;35:1294–1295. [PubMed]
72. Lim LM. Olanzapine and pregnancy. Aust N Z J Psychiatry. 2001;35:856–857. [PubMed]
73. Sharma V, Smith A, Mazmanian D. Olanzapine in the prevention of postpartum psychosis and mood episodes in bipolar disorder. Bipolar Disord. 2006;8:400–404. [PubMed]
74. Dervaux A, Ichou P, Pierrot F, Devianne F, Bavoux F. Olanzapine and pregnancy [abstract] Eur Psychiatry. 2007;22:S110.
75. Kulkarni J, McCauley-Elsom K, Marston N, et al. Preliminary findings from the National Register of Antipsychotic Medication in Pregnancy. Aust N Z J Psychiatry. 2007;42:38–44. [PubMed]
76. Klier CM, Mossaheb N, Saria A, Schloegelhofer M, Zernig G. Pharmacokinetics and elimination of quetiapine, venlafaxine, and trazodone during pregnancy and postpartum [letter] J Clin Psychopharmacol. 2007;27:720–721. [PubMed]
77. Twaites BR, Wilton LV, Shakir SAW. The safety of quetiapine: results of a post-marketing surveillance study on 1728 patients in England. J Psychopharmacol. 2007;21:392–399. [PubMed]
78. Balke LD. Quetiapine is effective in the treatment of bipolar affective disorder during pregnancy. Poster session presented at: 7th World Congress of Biological Psychiatry; July 1–6, 2001; Berlin, Germany.
79. Tényi T, Trixler M, Kerestes Z. Quetiapine and pregnancy [letter] Am J Psychiatry. 2002;159:674. [PubMed]
80. Pace A, D'Agostino F. Quetiapine in pregnancy: a case report [in Italian] Giorn It Ost Ginecol. 2003;XXV:381–385.
81. Taylor TM, O'Toole MS, Ohlsen RI, Walters J, Pilousley CS. Safety of quetiapine during pregnancy [letter] Am J Psychiatry. 2003;160:588–589. [PubMed]
82. Lee A, Giesbrecht E, Dunn E, Ho S. Excretion of quetiapine in breast milk [letter] Am J Psychiatry. 2004;161:1715–1716. [PubMed]
83. Gentile S. Quetiapine-fluvoxamine combination during pregnancy and while breastfeeding [letter] Arch Womens Ment Health. 2006;9:158–159. [PubMed]
84. Kruninger U, Meltzer V, Hiemke C, Herpich S. Pregnancy and lactation under treatment with quetiapine. Psychiatr Prax. 2007;34(suppl):75–76.
85. Cabuk D, Sayin A, Derinöz O, Biri A. Quetiapine use for the treatment of manic episode during pregnancy. Arch Womens Ment Health. 2007;10:235–236. [PubMed]
86. Risperdal (risperidone) Janssen, LP prescribing information. Accessed December 1, 2005.
87. Reilly T, Heylen SLE. Guidelines for the practical use of risperidone. In: Kane JM, Moller HJ, Awouters F, editors. Serotonin in Antipsychotic Treatment. New York, NY: Dekker Inc; 1996. pp. 357–368.
88. MacKay FJ, Wilton GL, Pearce SN, Freemantle SH, Mann RD. The safety of risperidone: a post-marketing study on 7684 patients. Hum Psychopharmacol Clin Exp. 1998;13:423–428.
89. Ratnayake T, Libretto SE. No complications with risperidone treatment before and throughout pregnancy and during the nursing period [letter] J Clin Psychiatry. 2002;63:76–77. [PubMed]
90. Kato S, Sato J, Suzuki H. Anesthesia for caesarean section in a parturient taking risperidone and haloperidol. Masui. 2005;54:301–303. [PubMed]
91. Kim SW, Kim KM, Kim JM, et al. Use of long-acting injectable risperidone before and throughout pregnancy in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:543–545. [PubMed]
92. Dabbert D, Heinze M. Follow-up of a pregnancy with risperidone microspheres [letter] Pharmacopsychiatry. 2006;39:235. [PubMed]
93. Physician's Desk Reference. 55th ed. Montale, NJ: Medical Economics; 2001.
94. Grover S, Avasthi A. Risperidone in pregnancy: a case of oligohydramnios [in German] J Psychiatry. 2004;7:56–57.
95. McCauley-Elsom K, Kulkarni J. Managing psychosis in pregnancy. Aust N Z J Psychiatry. 2007;41:289–292. [PubMed]
96. Coppola D, Russo LJ, Kwarta RF, Jr, Varughese S, Schmider J. Evaluating the postmarketing experience of risperidone use during pregnancy. Pregnancy and neonatal outcomes. Drug Saf. 2007;30:247–64. [PubMed]
97. Sertindole. Supportive material. Accessed June 19, 2008.
98. Geodon. Warning and precautions. Accessed April 30, 2007.
99. Seay PH, Field WE. Toxicological studies on haloperidol. Int J Neuropsychiatry. 1968;3(suppl):1–4. [PubMed]
100. Dieulangard P, Coignet J, Vical JC. Sur un cas d'ectro-phocomelia peut-être d'origine médicamenteuse [in French] Bull Fed Soc Gynecol Obstet Lang Fr. 1966;18:85–87.
101. Kopelman AE, Mc Cullar FW, Heggeness L. Limb malformations following maternal use of haloperidol. JAMA. 1975;231:62–64. [PubMed]
102. Council on drugs. Evaluation of a new antipsychotic agent. Haloperidol (Haldol) JAMA. 1968;205:105–106. [PubMed]
103. Godet PF, Marie-Cardine M. Neuroleptics, schizophrenia, and pregnancy. Epidemiological and teratologic study [in French] Encéphale. 1991;7:543–547. [PubMed]
104. Hanson JW, Oakley GP. Haloperidol and limb deformity [letter] JAMA. 1975;321:26. [PubMed]
105. Van Waes A, Van de Velde E. Safety evaluation of haloperidol in the treatment of hyperemesis gravidarum. J Clin Pharmacol. 1969;9:224–227.
106. Diav-Citrin O, Shechtman S, Ornoy S, et al. Safety of haloperidol and penfluridol in pregnancy: a multicenter, prospective, controlled study. J Clin Psychiatry. 2005;66:317–322. [PubMed]
107. Sexson WR, Barak Y. Withdrawal emergent syndrome in an infant associated with maternal haloperidol therapy. J Perinatol. 1989;9:170–172. [PubMed]
108. Mohan MS, Patole SK, Whitehall JS. Severe hypothermia in a neonate following antenatal exposure to haloperidol [letter] J Paediatr Child Health. 2000;36:412. [PubMed]
109. O'Collins K, Comer JB. Maternal haloperidol therapy associated with dyskinesia in a newborn. Am J Health Syst Pharm. 2003;60:2253–2255. [PubMed]
110. Walloch JE, Klauwer C, Lanczik M, Brockington JE, Kornhuber J. Delusional denial of pregnancy as a special form of Cotard's Syndrome. Psychopathology. 2007;40:61–64. [PubMed]
111. Hansen LM, Megerian G, Donnenfeld AE. Haloperidol overdose during pregnancy. Obstet Gynecol. 1997;90:659–661. [PubMed]
112. Bjarnason NH, Rode L, Dalhoff K. Fetal exposure to pimozide: a case-report. J Reprod Med. 2006;51:443–444. [PubMed]
113. Szabo KT, Brent RL. Species differences in experimental teratogenesis by tranquillising agents [letter] Lancet. 1974;1:565. [PubMed]
114. Favre-Tissot M, Broussolle P. Du pouvoir teratogene éventuel des produits psychopharmacologique. In: Brill A, editor. Neuropsychopharmacology. Proceedings of the Fifth International Congress of the Collegium Internationale Neuro-psychopharmacologicum. Amsterdam, The Netherlands: Excepta Medica Foundation; 1967. pp. 583–596.
115. Rawlings WJ, Ferguson R, Madison TG. Phenmetrazine and trifluoperazine [letter] Med J Aust. 1963;1:370.
116. Milkovich L, van den Berg BJ. An evaluation of the teratogenicity of certain antinauseant drugs. Am J Obstet Gynecol. 1976;125:244–248. [PubMed]
117. Rumeau-Roquette C, Goujard J, Huel G. Possible teratogenic effect of phenotiazines in humans beings. Teratology. 1975;15:57–64. [PubMed]
118. Slone D, Siskind V, Heinonen OP, Monson RR, Kauffman DW, Shapiro S. Antenatal exposure to phenothiazines in relation to congenital malformations, perinatal mortality rate, birth weight, and intelligence quotient score. Am J Obstet Gynecol. 1977;128:486–488. [PubMed]
119. Haxton MJ, Bell J. Fetal anatomical abnormalities and other associated factors in middle-trimester abortion and their relevance to patient counselling. Br J Obstet Gynaecol. 1983;90:501–506. [PubMed]
120. Royal College of Obstetricians and Gynaecologists. The investigation and treatment of couples with recurrent miscarriage. Guidelines No. 17. Accessed June 22, 2008.
121. Scokel PW, Jones WN. Infant jaundice after phenothiazine drugs for labor: an enigma. Obstet Gynecol. 1962;20:124–127. [PubMed]
122. Štika L, Elisova K, Honzáková H, et al. Effects of drug administration in pregnancy on children's school behaviour. Pharm Weekbl Sci. 1990;12:252–255. [PubMed]
123. Singh S, Padmanabhan R. Teratogenic effects of chlorpromazine hydrochloride in rat fetuses. Indian J Med Res. 1978;67:300–309. [PubMed]
124. Hannah RS, Roth SH, Spira AW. The effects of chlorpromazine and phenobarbital on cerebellar Purkinje cells. Teratology. 1982;26:21–25. [PubMed]
125. Kris BE, Carmichael DM. Chlorpromazine maintenance therapy during pregnancy and confinement. Psychiatr Q. 1957;31:690–695. [PubMed]
126. Ayd FJ., Jr Children born to mothers treated with chlorpromazine during pregnancy. Clin Med. 1964;71:1758–1763.
127. Kris BE. Children of mothers maintained on pharmacotherapy during pregnancy and postpartum. Curr Ther Res. 1965;7:785–789. [PubMed]
128. Sobel DE. Fetal damage due to ECT, insulin coma, chlorpromazine, or reserpine. Arch Gen Psychiatry. 1960;2:606–611. [PubMed]
129. O'Leary JL, O'Leary JA. Non-thalidomide ectromelia. Obstet Gynecol. 1964;23:17–20. [PubMed]
130. Falterman CG, Richardson CJ. Small left colon syndrome associated with maternal ingestion of psychotropic drugs. J Pediatr. 1980;97:308–310. [PubMed]
131. Ben-Amital D, Merlob P. Neonatal fever and cyanotic spells from maternal chlorpromazine [letter] DICP. 1991;25:1009–1010. [PubMed]
132. Ergenkon E, Atalay Y, Tunaoglu S, Koc E. Transient heart block in a newborn due to maternal antipsychotic treatment during pregnancy. Eur J Pediatr. 2000;159:137–138. [PubMed]
133. Auerbach JG, Hans SL, Marcus J, Naeir S. Maternal psychotropic medication and neonatal behavior. Neurotoxicol Teratol. 1992;14:399–406. [PubMed]
134. Levy W, Wisniewski K. Chlorpromazine causing extrapyramidal dysfunction in newborn infant of psychotic mother. N Y State J Med. 1974;74:684–685. [PubMed]
135. Nielsen HC, Wiriyathian S, Rosenfeld CR, Levenko K, Garriott JC. Chlorpromazine excretion by the neonate following chronic in utero exposure. Pediatr Pharmacol. 1983;3:1–5. [PubMed]
136. Meut C, Bavoux F, Cynober E, LeBrun F. Necrotizing enterocolitis in a newborn: maternal psychotropic drugs suspected [letter] Can J Psychiatry. 1994;39:127. [PubMed]
137. Hill RM, Desmond MM, Kay JL. Extrapyramidal dysfunction in an infant of a schizophrenic mother. J Pediatr. 1966;69:589–595. [PubMed]
138. O'Connor M, Johnson GH, James DI. Intrauterine effects of phenotiazines. Med J Aust. 1981;1:416–417. [PubMed]
139. Tamer A, McKey R, Arias D, Worley L, Foggl BJ. Phenothiazine-induced extrapyramidal dysfunction in the neonate. J Pediatr. 1969;75:479–480. [PubMed]
140. Falterman CG, Richardson CJ. Small left colon syndrome associated with maternal ingestion of psychotropic drugs. J Pediatr. 1880;97:308–310. [PubMed]
141. Farag RA, Ananth J. Thanatrophic dwarfism associated with prochlorperazine administration. N Y State J Med. 1978;78:279–282.
142. Mellin GW. Report of prochlorperazine utilization during pregnancy from Fetal Life Study Data Bank [abstract] Teratology. 1975;11:28A.
143. Rafla N. Limb deformities associated with prochlorperazine [letter] Am J Obstet Gynecol. 1987;156:1557. [PubMed]
144. Freeman R. Limb deformities: possible association with drugs [letter] Med J Aust. 1972;3:606–607. [PubMed]
145. Ho CK, Kaufman RL, McAlister WH. Congenital malformations. Cleft palate, congenital hearth disease, absent tibiae, and polydactyly. Am J Dis Child. 1975;129:714–715. [PubMed]
146. Moriarty AJ, Nance MR. Trifluoperazine and pregnancy [letter] Can Med Assoc J. 1963;88:375–376. [PMC free article] [PubMed]
147. Canadian Department of National Health and Welfare, Food and Drug Directorate. Letter of notification to Canadian physicians. 1962. Ottawa, ON.
148. Hall G. A case of phocomelia of the upper limbs [letter] Med J Aust. 1963;1:449–450.
149. Corner BD. Congenital malformations. Clinical considerations. Med J Southwest. 1962;77:46–52. [PubMed]
150. Vince DJ. Congenital malformations following phenothiazine administration during pregnancy [letter] Can Med Assoc J. 1969;100:223. [PMC free article] [PubMed]
151. Wheatley D. Drugs and embryo [letter] Br Med J. 1964;1:631.
152. Schrire I. Trifluoperazine and foetal abnormalities [letter] Lancet. 1963;1:174. [PubMed]
153. King JT, Barry MC, Neary ER. Perinatal findings in women treated during pregnancy with oral fluphenazine. J New Drugs. 1963;3:21–25. [PubMed]
154. Clearly MF. Fluphenazine decanoate during pregnancy. Am J Psychiatry. 1977;134:815–816. [PubMed]
155. Brougher JC. The treatment of emotional disorders in obstetrics and gynecology with thioridazine. Q Rev Surg Obstet Gynecol. 1960;3:44–47. [PubMed]
156. New Zealand Committee on Drug Reactions. Fourth Annual Report. N Z Med J. 1969;70:118–122. [PubMed]
157. Puhó EH, Szunyogh M, Métneki J, Ceizel AE. Drug treatment during pregnancy and isolated orofacial clefts in Hungary. Cleft Palate Craniofac J. 2007;44:194–202. [PubMed]
158. Idänpään-Heikkilä J, Saxen L. Possible teratogenicity of imipramine/chloropyramine. Lancet. 1973;8:282–284. [PubMed]
159. Iqbal MM, Aneja A, Rahman A, et al. Evidence-based pharmacology: the potential risks of commonly prescribed antipsychotics during pregnancy and lactation. Psychiatry. 2005;2:36–44. [PubMed]
160. Menon SJ. Psychotropic medication during pregnancy and lactation. Arch Gynecol Obstet. 2008;277:1–13. [PubMed]
161. Jain AE, Lacy T. Psychotropic drugs in pregnancy and lactation. J Psychiatr Pract. 2005;11:177–191. [PubMed]
162. Howard L, Webb R, Abel K. Safety of antipsychotic drugs for pregnant and breastfeeding women with non-affective psychosis. Br Med J. 2004;329:933–934. [PMC free article] [PubMed]
163. Mental Health Determinants and Populations Department of Mental Health and Substance Dependence. World Health Organization Geneva, 2000. Women's Mental Health: an evidence based review. http://www.WHO_MSD_00.1.pdf. Accessed June 23, 2007.
164. Paton C. Prescribing in pregnancy. Br J Psychiatry. 2008;192:321–322. [PubMed]
165. Narrow WE, First MB, Paul J, Sirovatka PJ, Regier DA. Age and gender Considerations in Psychiatric Diagnosis. A Research Agenda for DSM-V. Arlington, Va: American Psychiatric Pub; 2007.
166. Mastroianni AC, Faden R, Federman S. Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies. Washington, DC: Institute of Medicine, National Academy Press; 1994.
167. Pinkofsky HB, Fitzgerald MJ, Reeves RR. Psychotropic treatment during pregnancy [letter] Am J Psychiatry. 1997;154:718–719. [PubMed]
168. Iqbal MM, Rahman A, Husain Z, Mahmud SZ, Ryan WG, Feldman JM. Clozapine: a clinical review of adverse effects and management. Ann Clin Psychiatry. 2003;15:33–41. [PubMed]
169. Edward IR, Biriell C. Harmonization in pharmacovigilance. Drug Saf. 1994;10:93–102. [PubMed]
170. Allison DB, Mentore JL, Moonseong H, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156:1686–1696. [PubMed]
171. Gentile S. Long term atypical antipsychotics treatment and risk of weight gain. A literature analysis. Drug Saf. 2006;29:303–319. [PubMed]
172. Waller DK, Shaw GM, Rasmussen AS, et al. Prepregnancy obesity as a risk factor for structural birth defects. Arch Pediatr Adolesc Med. 2007;161:745–750. [PubMed]
173. Davson SI. Long-term risk of malignant neoplasm associated with gestational glucose intolerance. Cancer. 2004;100:149–155. [PubMed]
174. Newham JJ, Thomas SH, MacRitchie K, McElhatton P, McAllister-Williams RH. Birth weight of infants after maternal exposure to typical and atypical antipsychotics: prospective comparison study. Br J Psychiatry. 2008;192:333–337. [PubMed]
175. Ahlsson FS, Diderholm B, Ewald U, Gustafson J. Lipolysis and insulin sensitivity at birth in infants who are large for gestational age. Pediatrics. 2007;120:958–965. [PubMed]
176. Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. Br Med J. 1971;3:523–527. [PMC free article] [PubMed]
177. Perez-Iglesias R, Crespo-Facorro B, Martinez-Garcia O, et al. Weight gain induced by haloperidol, risperidone and olanzapine after 1 year: findings of a randomized clinical trial in a drug-naïve population. Schizophr Res. 2008;99:3–22. [PubMed]
178. Gentile S. Schizoaffective disorder in women with childbearing potential. In: Murray WH, editor. Schizoaffective Disorders. New Researches. New York, NY: 2006. pp. 187–220.
179. Gentile S. Managing suicidal risk in pregnant schizoaffective women. In: Murray WH, editor. Schizoaffective Disorder: New Research. 2nd ed. In press.
180. Ladavac AS, Dubin WR, Ning A, Stuckerman PA. Emergency management of agitation in pregnancy. Gen Hosp Psychiatry. 2007;29:39–41. [PubMed]
181. Schneid-Kofman N, Sheier E, Levy A. Psychiatric illness and adverse pregnancy outcome. Int J Gynecol Obstet. 2008;101:53–56. [PubMed]
182. Schneid-Kofman N, Sheiner E, Levy A. Psychiatric illness and adverse pregnancy outcome. Int J Gynaecol Obstet. 2008;101:53–56. [PubMed]
183. Jablensky AV, Morgan V, Zubrick SR, Bower C, Yellachich LA. Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders. Am J Psychiatry. 2005;162:79–91. [PubMed]
184. Niemi LT, Suvisaari JM, Haukka JK, Lönnquist JK. Childhood growth and future development pf psychotic disorder among Helsinki high-risk children. Schizophr Res. 2005;76:105–112. [PubMed]
185. Riordan DV, Selvaraj S, Stark C, Gilbert JS. Perinatal circumstances and risk of offspring suicide. Br J Psychiatry. 2006;189:502–507. [PubMed]
186. Rieder RO, Rosenthal D, Wender D, Blumenthal H. The offspring of schizophrenia. Fetal and neonatal deaths. Arch Gen Psychiatry. 1975;32:200–211. [PubMed]
187. Nilsson E, Lichtenstein P, Cnattingius S, Murray RM, Hultman CM. Women with schizophrenia: pregnancy outcome and infant death among their offspring. Schizophr Res. 2002;58:221–229. [PubMed]
188. Bain M, Juszczak E, McInney K, Kendell RE. Obstetric complications and affective psychosis. Two case-control studies based on structured obstetric records. Br J Psychiatry. 2000;176:523–526. [PubMed]
189. Ellman LM, Huttunen M, Lönqvist J, Cannon D. The effects of genetic liability for schizophrenia and maternal smoking during pregnancy on obstetric complications. Schizophr Res. 2007;93:229–236. [PubMed]
190. Miller LJ. Psychotic denial of pregnancy: phenomenology and clinical management. Hosp Community Psychiatry. 1990;41:1233–1237. [PubMed]
191. Henin A, Biederman J, Mick E, et al. Psychopathology in the offsprings of parents with bipolar disorder: a controlled study. Biol Psychiatry. 2005;58:554–561. [PubMed]
192. Klimes-Dougan B, Ronsaville D, Wiggs EA, Martinez PE. Neuropsychological functioning in adolescent children of mothers with a history of bipolar or major depressive disorders. Biol Psychiatry. 2006;60:957–965. [PubMed]
193. Wais M, Reichart CG, Hillegers MHJ. Prediction of change in level of problem behavior among children of bipolar parents. Acta Psychiatr Scand. 2006;113:23–30. [PubMed]
194. Reichart CG, van der Ende J, Wals M, et al. Social functioning of bipolar offsprings. J Affect Disord. 2007;98:207–213. [PubMed]
195. Patton SW, Misri S, Corral MR, Perry KF, Kuan AJ. Antipsychotic medication during pregnancy and lactation in women with schizophrenia: evaluating the risk. Can J Psychiatry. 2002;47:959–965. [PubMed]
196. Jain AE, Lacy T. Psychotropic drugs in pregnancy and lactation. J Psychiatr Pract. 2005;11:177–191. [PubMed]
197. Pinkofsky HB. Effects of antipsychotics on the unborn child: what is known and how should this influence prescribing? Paediatr Drugs. 2000;2:83–90. [PubMed]
198. Platt JE, Friedhoff AJ, Broman SH, Bond RN, Laska E, Lin SP. Effects of prenatal exposure to neuroleptic drugs on children's growth. Neuropsychopharm. 1988;1:205–212. [PubMed]
199. Peindl KS, Masand P, Mannelli P, Narasimhan M, Patkar A. Polypharmacy in pregnant women with major psychiatric illness: a pilot study. J Psychiatr Pract. 2007;13:385–392. [PubMed]
200. Seeman MV. Schizophrenia and motherhood. In: Gopfert M, Webster J, Seeman MV, editors. Parental Psychiatric Disorder. 2nd ed. Cambridge, Mass: Cambrige University Press; 2004.
201. Howard LM, Kumar R, Thornicroft G. Psychosocial characteristics and needs of mothers with psychotic disorders. Br J Psychiatry. 2001;178:427–432. [PubMed]
202. Howard LM, Goss C, Leese M, Appleby L, Thornicroft G. The psychosocial outcome of pregnancy with psychotic disorders. Schizophr Res. 2004;71:49–90. [PubMed]
203. Heinonen OP, Sloane D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, Mass: PSG Publishing; 1977.
204. Hill LM, Breckle R, Gehrking WC. The prenatal detection of congenital malformations by ultrasonography. Mayo Clin Proc. 1983;58:805–826. [PubMed]
205. The American Psychiatric Association. Principle of informed consent in psychiatry. Resource document. Accessed June 22, 2008.
206. Royal Pharmaceutical Society. Professional Guidance. Accessed February 2, 2008.
207. Appelbaum PS, Grisso T. The MacArthur Treatment Competence Study: I, mental illness and competence to consent to treatment. Law Hum Behav. 2005;19:105–26. [PubMed]
208. Gentile S. More than half of women with a history of psychosis have a psychiatric episode in the first year after childbirth [commentary] Evid Based Ment Health. 2005;32:33. [PubMed]
209. Gentile S. Managing the suicidal risk in pregnant women with severe and persistent psychiatric disorder. Focus on antisuicidal drugs and somatic interventions. Curr Psychiatry Rev. In press.
210. Nishizawa O, Sakumoto K, Hiramatsu KI, Kondo T. Effectiveness of comprehensive supports for schizophrenic women durino pregnancy and puerperium. Preliminary study. Psychiatr Clin Neurosci. 2007;61:665–71. [PubMed]

Articles from Schizophrenia Bulletin are provided here courtesy of Oxford University Press