Clinical application and safety of common psychotropic drugs in pregnancy

Psychotropic drugs can produce adverse reactions to the fetus through the placenta, the common occurrence of perinatal syndrome, severe case


Psychotropic drugs can produce adverse reactions to the fetus through the placenta, the common occurrence of perinatal syndrome, severe cases can cause fetal malformations, may also have an impact on long-term neurological behavior. It is very important for pregnant women with mental disorders to carry out effective psychotropic drug treatment and reduce the adverse effects on mother and baby as much as possible. The United States Food and Drug Administration (Food and Drug Administration, FDA) of drugs during pregnancy were graded - grade A: control study found no adverse reaction; B: there is no evidence of any adverse reactions to the human beings; class C: you can not exclude the presence of adverse reaction; D: the existing evidence of adverse effects; X grade: pregnancy. In this paper, the classification of the risk of drug use during pregnancy is taken as the clue, and the application and safety of the 4 kinds of psychotropic drugs in pregnancy are discussed in order to provide reference for the clinical application of FDA.

1 antipsychotic drugs

1.1 in the application of maternal and fetal effects of antipsychotic drugs in addition to clozapine for the B class, the others were C. The typical antipsychotics: phenothiazine drugs such as chlorpromazine, perphenazine, pipothiazine, in late pregnancy use can cause neonatal withdrawal syndrome, such as extrapyramidal symptoms, reflex enhancement, irritability, usually lasts a few days away. The study of chlorpromazine, treatment group (315 cases) of the fetal abnormality rate than the treatment group (11099 cases) increased slightly (3.5% vs. 1.6%), but still based on abnormality rate (2% ~ 4%) range; studies show that early pregnancy taking perphenazine 12mg/d, had no harmful effects on fetal and maternal. The atypical antipsychotics: reports of clozapine and olanzapine, risperidone, quetiapine, ziprasidone and other reported adverse effects on the fetus. The existing aripiprazole 2 cases of neonatal neural tube defects report; late pregnancy taking clozapine can cause neonatal hypotonia and seizures; clozapine and olanzapine can cause maternal weight gain, insulin resistance, diabetes increased the risk of pregnancy period, and the maternal metabolic syndrome not only for the early development of fetal risks. But also can cause adverse effects on the long-term growth of children.

1.2 pregnant women with schizophrenia to guide the treatment of estrogen has an anti dopaminergic effect, the increase in estrogen during pregnancy can prevent the recurrence of schizophrenia, endocrine changes during pregnancy can stabilize the condition. Therefore, if the patients with psychiatric symptoms disappeared completely and stable for more than 2 years, stopping pregnancy or in pregnancy after 12 weeks of medication; stable condition should not stop, but may be appropriate to reduce the dose of the drug; and the psychotic symptoms of severe or chronic recession, and the use of large doses of antipsychotic drugs patients should not be pregnant. As in pregnancy can not discontinuation of antipsychotic drugs, then use the minimum effective dose, can implement weekend withdrawal; at the end of pregnancy should reduce the dose of the drug, in order to avoid neonatal withdrawal syndrome after childbirth; schizophrenia relapse or exacerbation, it should be appropriate to increase postpartum drug dose. Typical antipsychotics with perphenazine on the fetal safety and atypical antipsychotic to clozapine or olanzapine in more safety but teratogenic, monitoring of pregnant women body weight and blood glucose level etc..

2 antidepressants

2.1 effect of pregnancy on maternal and child most antidepressants C, bupropion and maprotiline for grade B, while imipramine and nortriptyline and Pa Rossi Dean D. A large study of tricyclic antidepressants, early pregnancy does not increase the weight of taking fetal abnormality rate and fetal mortality, but in the 7~9 month of pregnancy taking occasional neonatal seizures, intestinal obstruction and urinary retention. The selective serotonin reuptake inhibitors (5- selective serotoninreuptake inhibitors, SSRIs): epidemiological data show that Pa Rossi Dean used in early pregnancy, fetal cardiac malformation incidence increased by 1.5~2.0 times, so the United States will have its FDA from level C to level D; the study found, taking fluoxetine in early pregnancy, the risk of neonatal cardiovascular malformation increased, and citalopram can make neonatal spina bifida increased risk; SSRIs may cause miscarriage or premature delivery in pregnancy, the use of SSRIs after the first 20 weeks of pregnancy may increase the risk of neonatal pulmonary hypertension, the incidence rate of about 1%, 6 times for the user. In the later period of pregnancy, antidepressants were taken out, and the withdrawal syndrome occurred in about 1/3 newborns.

2.2 treatment of depression during pregnancy is pregnancy guide female depression peak period, the recurrence rate was 2/5 pregnancy depression history, can cause serious harm to the pregnant women themselves depression during pregnancy, but also harmful to fetal growth and development, which should be timely and effective treatment. Mild to moderate depressive symptoms can be treated with interpersonal psychotherapy, cognitive behavioral therapy, and so on, and for severe depression, recurrent depression, should be promptly treated with antidepressants. Can choose SSRIs (except Pa Rossi Dean), Vin Rafa Sin, and so on, and so on, the relative safety of the fetus, and so on, and so on, and so on, and so on, and so on. In order to avoid the occurrence of neonatal withdrawal syndrome and adverse reactions of pregnant women during pregnancy, 2 weeks before the slow reduction of 25%~50% dose. There is a strong trend of drug therapy or electroconvulsive therapy, effective and relatively safe. Studies have shown that low-frequency repetitive transcranial magnetic stimulation (repetitive transcranial magnetic stimulation, rTMS) has a good effect on depression during pregnancy, and no adverse reaction to pregnant women and fetuses.

3 mood stabilizers

Effect of pregnancy on maternal and child 3.1 major mood stabilizers such as lithium, valproate and Kamasi average D grade, C grade and lamotrigine, oxcarbazepine. The lithium: recent studies show that, the abnormality rate is 4%~12%, is 2~3 times the general population, including Abu Stan malformation (three tricuspid valve prolapse with atrial septal defect) was 1 per thousand to 2 per thousand, is 20~40 times that of the general population. The salt of valproic acid: Meta analysis showed that in the antiepileptic drug valproic acid, and the occurrence of congenital malformations are most relevant, in early pregnancy use can increase fetal neural tube defects (5%), atrial septal defect, cleft lip and cranial suture risk early closure of pregnancy; North American antiepileptic drugs registration information, teratogenicity of valproic acid the rate is 10.7%, is 4 times that of other antiepileptic drugs, the teratogenic rate and dose related. C Masi Bing: the teratogenic rate was 5.7%, of which the neural tube defects accounted for (1%). The lamotrigine: Although this drug has C, but early pregnancy taking can increase the risk of fetal cleft lip and palate, the international lamotrigine registration rate of 2.9% of teratogenicity during pregnancy, are taking in early pregnancy; the severe abnormality rate were also dose related.

The 3.2 trimester bipolar disorder treatment guidelines for bipolar disorder in a higher rate of recurrence of pregnancy, intermittent period of mania or bipolar type II patients can be reduced or withdrawn in the early period of lithium salt; frequent seizures or remission in patients with bipolar disorder should not be completely disabled or lithium, fast tendency reactivation; as in early pregnancy has been taking lithium, should be performed at 16~18 weeks of gestation fetal heart examination. Teratogenic mechanism of valproate and lamotrigine, C Masi Bing may be related to drug induced by folic acid deficiency, in early pregnancy folic acid and 2~4mg/d can reduce the risk of neural tube defects. Valproic acid has a high rate of teratogenicity and is contraindicated in pregnancy. In the choice of drugs, lamotrigine for maintenance treatment of patients with bipolar disorder during pregnancy. Some scholars believe that antipsychotic drugs can replace mood stabilizers, especially atypical antipsychotic drugs can be used alone or in combination with mood stabilizers. Postpartum bipolar high recurrence rate, began taking lithium within 48h after delivery, the recurrence rate can be significantly reduced, but not breastfeeding.

4 anti anxiety drugs

Effect of 4.1 pregnancy on maternal benzene two nitrogen (䓬 benzodiaze⁃ pinge, BZD class of drugs), estazolam, flurazepam, midazolam, quazepam, three hydroxy diazepam X, alprazolam, clonazepam and diazepam, oxazepam, Laura Si, midazolam midazolam D; non BZD anti anxiety drugs such as zolpidem, zaleplon, Sahiki Kotaka C, only buspirone is B. The use of BZD during pregnancy can increase the risk of birth defects, most studies have found that early pregnancy taking BZD induced fetal cleft lip and palate than other abnormalities, including low titer drugs than the high titer teratogenic drug. There have also been reports that taking BZD during early pregnancy can cause fetal inguinal hernia, pyloric stenosis, congenital heart defects, etc.. The use of BZD during pregnancy has an effect on the long-term neurological behavior, which may indicate the presence of fetal growth restriction, mental retardation, and the risk of down syndrome. The late pregnancy BZD exposure, caused by neonatal withdrawal, and sustainable period; also appears to inhibit the symptoms of central nervous system, such as hypotonia, sleepiness and so on; can also damage the baby's body temperature regulation, or by a decrease in Apgar score and the incidence of hypoglycemia.

Treatment of 4.2 pregnancy anxiety disorder and sleep disorder and anxiety disorder appear guidance during pregnancy in patients with sleep disorders, usually BZD therapy is not recommended, belongs to X BZD during pregnancy disabled, should choose more safe treatments. Anxiety disorders in pregnancy is the first choice to have a positive effect of psychotherapy, cognitive behavioral therapy, supportive psychotherapy, etc.. The choice of drugs, recommend the use of antidepressants, such as sertraline, Vin Rafa Sin etc.; on antidepressants associated with insomnia by trazodone, mirtazapine has sedative effects, can also be used zolpidem, zaleplon and other non BZD anti anxiety drugs for short-term treatment, when necessary to consider olanzapine, quetiapine sulfur equal atypical antipsychotics. Such as early pregnancy has taken BZD, B - type ultrasonic examination should be at 16~18 weeks pregnant; such as taking BZD, in the 1 month before delivery should be gradual reduction or withdrawal, in order to avoid neonatal withdrawal symptoms occur, but the withdrawal speed must be slow, or pregnant women withdrawal or withdrawal symptoms can be preterm birth.

5 Conclusion

The United States FDA has not yet formally approved any psychotropic drugs can be used in pregnancy and lactation, there is no one kind of psychotropic drugs for fetal development is absolutely safe. Therefore, in principle does not advocate the use of psychotropic drugs during pregnancy. But can give patients and their families to risk benefit analysis, including the potential impact assessment of disease of the mother, fetus and family, to help patients and their families and to weigh the pros and cons. In view of this, the use of psychoactive drugs during pregnancy must be cautious, we should consider the following: as much as possible without drugs in early pregnancy, the sensitive period to avoid the teratogenic and teratogenic effect; the drug dose and drug combination, so as a single drug, and use the lowest effective dose; according to the classification of drugs in the United States FDA, as far as possible the use of the low level of risk, small drug effects on the fetus; should pay attention to regular follow-up and medication, strengthen the blood concentration and monitoring of the fetus in late pregnancy; as far as possible to reduce the dose or withdrawal, in order to avoid the emergence of neonatal withdrawal syndrome or withdrawal symptoms.

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