Psychotropic drugs during pregnancy and lactation. The effect of antipsychotics on pregnancy and the fetus Who gave birth on antipsychotics

Pregnancy. A number of drugs have embryotoxic and teratogenic effects, which can result in miscarriages, prematurity, postmaturity, malformations, and sometimes death of the fetus and newborn. The consequences of taking medications depend not only on the type of drug, dose and duration of therapy, but also on the duration of pregnancy.

There are three critical periods of embryogenesis, when exposure to unfavorable factors is most dangerous. The first critical period of embryogenesis occurs at the beginning of the 2nd week of pregnancy, when cell differentiation occurs, their regenerative ability decreases and sensitivity to drugs increases. After implantation, a period of organogenesis begins, which lasts until the 3-4th month of intrauterine life. During this period, the most sensitive to the effects of drugs is the 3-8th week (the second critical period of embryogenesis). The third critical period of embryogenesis occurs between the 18th and 22nd weeks. During this period, the most significant changes in the bioelectrical activity of the brain, hematopoiesis, and hormone production occur.

Most psychotropic drugs (neuroleptics, antidepressants, tranquilizers) are biologically highly active substances and can have undesirable effects on the fetus during the mother's pregnancy. In addition, psychotropic drugs and their active metabolites easily penetrate into the milk of a nursing mother and affect the newborn, causing sedation, depression of the central nervous system, respiration, and blood circulation.

It has been established that neuroleptics (representatives of the phenothiazine series and butyrophenones) with long-term use can cause the formation of fetal malformations. In this regard, only their one-time use as antiemetics for severe toxicosis of pregnancy is allowed.

Benzodiazepines can cross the placenta and accumulate in fetal tissues. The toxic effect of benzodiazepines on the central nervous system is caused by their slow metabolism in the fetus. There are reports that chronic use of benzodiazepines (diazepam, nitrazepam, chlordiazepoxide, etc.) can cause congenital anomalies and malformations (for example, “cleft lip” and cleft palate), although this possibility has not been fully proven. Long-term use of benzodiazepines during the last 3 months of pregnancy can lead to the development of “withdrawal syndrome” in the fetus. Usually, only a single prescription of benzodiazepines is allowed for severe toxicosis of pregnancy, eclampsia, or for pain relief during childbirth. Benzodiazepines penetrate into the mammary glands and mother's milk and can have undesirable effects on the newborn, leading to respiratory and circulatory disorders.

During pregnancy and lactation, it is not recommended to treat with antidepressants, including the new class of antidepressants with a predominant inhibition of serotonin reuptake (fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram). There are reports that tricyclic antidepressants may cause developmental abnormalities in newborns. Taking tricyclic antidepressants in the first 3 months of pregnancy is especially undesirable. The use of MAO inhibitors should be avoided during pregnancy due to the existing danger of hypertensive reactions leading to severe vascular damage in the mother and fetus. Experiments on animals have shown the teratogenic effect of MAO inhibitors.

Lithium salt preparations are contraindicated during pregnancy. Taking them can lead to fetal developmental defects. The term "lithium children" implies the presence of such defects as 24 such as abnormal development of the tricuspid valve or Ebstein's anomaly. When taking lithium, there is a tendency to shorten pregnancy, reduce weight and increase mortality in newborns. Carbamazepine (Finlepsin) is not recommended for use in the first 3 months of pregnancy. The use of other psychotropic drugs during pregnancy remains controversial and is the subject of close study.

According to the American classification, all drugs according to the degree of teratogenicity are divided into categories A, B, C, D, X.

Category A includes drugs for which a teratogenic effect has not been identified either in the clinic or in experiments. However, it is not possible to completely eliminate the risk of teratogenic effects. There are no such drugs among psychotropic drugs.

Category B includes drugs that have no teratogenicity in the experiment, but there are no clinical data. This group of drugs includes serotonergic antidepressants (fluoxetine, fluvoxamine, citalopram, paroxetine, sertraline, trazadone), the tranquilizer buspirone, antipsychotics - risperidone, clozapine (cited by D.E. Vybornykh, 1996).

Category C includes drugs that were found to have adverse effects on the fetus in animal studies but were not subject to adequate clinical monitoring. Of the psychotropic drugs, drugs in this group include most neuroleptics, especially phenothiazine derivatives, haloperidol, as well as carbamazepine, tranquilizers (clonazepam, lorazepam, oxazepam) and the antidepressant clomipramine.

Category D includes drugs that have a teratogenic effect, but the need for their use outweighs the potential risk of harm to the fetus. These drugs are prescribed only for health reasons and the woman should be informed about the possible consequences of adverse effects on the fetus. Psychotropic drugs in this group include tranquilizers (chlordiazepoxide, alprazolam, diazepam), lithium salts, antidepressants, irreversible MAO inhibitors.

Category X includes drugs with proven teratogenicity in experiments and clinics. Their use is absolutely contraindicated during pregnancy. There are no similar data for psychotropic drugs.

Taking into account the above, the use of psychotropic drugs during pregnancy and lactation should be strictly limited.

Psychotropic drugs should be prescribed only when the need for their use outweighs the potential risk of adverse effects on the fetus. In any case, you should avoid taking psychotropic drugs during critical periods of pregnancy, when the organs of the unborn child are formed (4-10 weeks of pregnancy). If the situation is such that taking psychotropic drugs is necessary, they should be prescribed for a short period, in lower doses, with their temporary withdrawal 5-10 days before birth.

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Antipsychotic drugs are used to treat mental illness. During pregnancy, a woman is often exposed to stress, depression, and emotional instability, which negatively affects the fetus. Therefore, the use of antipsychotics in some cases is necessary. Neuroleptic drugs have a multifunctional effect on the body, for example, a calming effect, reducing aggressiveness and suppressing hallucinations. The danger of using antipsychotics is that they can cross the placenta and enter the fetus. This is fraught with the occurrence of malignant tumors in newborns. The use of psychotropic drugs can cause congenital abnormalities in the fetus. Clinical studies have shown that fluoxetine is the safest among antidepressants. Before starting treatment, a woman should consult a neurologist and psychiatrist. Based on the data obtained during the examination, the doctor decides on the need for treatment with antipsychotic drugs.

psychotropic drugs

impact

neuroleptics

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1. Belousov Yu.B., Moiseev V.S., Lepakhin V.K. "Clinical pharmacology and pharmacotherapy" Publisher: "Universum Publishing" Year of publication: 1997

2. Kulakov V.I. Serov V.N. “Rational pharmacotherapy in obstetrics and gynecology” Publisher: Litterra Year of publication: 2006

3. Ushkalova E.A. Journal “Pharmateka for Practitioners” Year of publication: 2003 Issue No. 4, “Pharmacotherapy of neuropsychiatric diseases in pregnant women”

4. Gerald Rosenbaum, George Arana “Pharmacotherapy of mental disorders” Publisher: Binom Year of publication: 2006

5. Schatzberg A.F., Cole D.O., DeBattista C. “Manual of Clinical Psychopharmacology” Year of publication: 2013

Neuroleptic drugs - affect the higher mental functions of the brain. This is one of the most important groups of modern psychotropic drugs.

Neurotropic drugs include antidepressants, local irritants, local anesthetics, anesthetics, neuroleptics, general tonics, psychostimulants, sedatives, hypnotics and drugs that affect neuromuscular transmission.

In 1967, the first classification of psychotropic drugs was developed and called them “neuroleptics” (neuroleptic drugs). They are used in the treatment of mental disorders such as schizophrenia, psychosis, and neurotic stress. In recent years, some countries have replaced the term “neuroleptics” with the term “antipsychotic drugs.”

Neuroleptic drugs have a multifunctional effect on the body. The pharmacological features of these drugs include a calming effect, which is accompanied by inhibition of the reaction to external irritation, suppression of feelings of fear, reduction of aggressiveness and psychomotor agitation. These drugs are capable of suppressing hallucinations, delusions and other neurotic syndromes and providing a therapeutic effect on patients with mental disorders.

Antipsychotics can cross the placenta and enter the fetus and amniotic fluid. When examining these preparations, no visible signs of congenital anomalies were found. However, given the comparative lack of information, it is better not to use these drugs during pregnancy. At the same time, there are many situations in which the mother cannot do without treatment, since otherwise there is a high risk for the fetus. There is evidence that indicates that the pregnant woman and fetus tolerated treatment with traditional antipsychotic drugs well.

There is much evidence of problems that arise when antipsychotic drugs are prescribed in late pregnancy. Some articles indicated that mothers who were treated with antipsychotic drugs gave birth to children with signs of a malignant tumor. The half-life of antipsychotic drugs in the fetus lasts at least 7-10 days, so pregnant women are advised to discontinue the use of antipsychotic drugs two weeks before delivery. This allows you to avoid the development of a malignant tumor in the newborn.

Women of childbearing age are more susceptible to nervous mental illnesses. Thanks to research in recent years, new data have been obtained on the effect of psychotropic drugs on the fetus, which makes it possible to assess the benefits and risks of using antipsychotics and develop recommendations for rational treatment therapy in pregnant women. Thanks to modern diagnostic methods, it is possible to identify serious congenital anomalies in the early stages of pregnancy and timely resolve the issue of its termination.

The negative effects of psychotropic drugs on the fetus and newborn include: structural disorders (congenital anomalies), intoxication and withdrawal syndrome, intrauterine death, intrauterine growth retardation, and neurobehavioral teratogenicity.

Congenital anomalies are divided into major and minor. Major anomalies are structural defects that form during organogenesis. If left untreated, they lead to severe organ dysfunction, such as congenital heart disease, spina bifida, intestinal atresia and urogenital defects. Minor anomalies include minor structural deviations in the structure of the body that do not lead to negative medical or cosmetic consequences. Such structural abnormalities are disturbances in facial morphology (V-shaped eyebrows, low-set ears, wide mouth) and hypoplasia of the distal phalanges and nails. Neurobehavioral teratogenicity is a disorder in the nervous system that manifests itself in the postpartum period and leads to behavioral and learning impairments.

Typically, the side effects of psychotropic drugs manifest themselves in changes in their pharmacological action during pregnancy, which requires a change in the dose of the drug. Some of them can accumulate in the fetus’s body, causing negative effects for a long time in the postnatal period. A feature of psychotropic drugs is that they can cause withdrawal syndrome in the fetus.

Now let’s look at the effect of antidepressants during pregnancy. Very often, pregnant women are exposed to neuropsychiatric disorders such as depression. Their effect on the child in the womb has not been well studied. But it was revealed that after birth the child has impaired cognitive functions, and he also becomes emotionally unstable. Such consequences are expressed not only in early childhood, but also in adolescence, leading to mental disorders and learning problems. Boys are more susceptible to such disorders than girls.

When you stop taking antidepressants during pregnancy, relapses of the disease are very common. In many cases they have an acute onset and are long-lasting. During this period, a pregnant woman is susceptible to suicidal thoughts that threaten her life, as well as the life of the child. Therefore, when discontinuing such drugs, it is worth considering the possible risk of relapse of the disease and the risk of negative effects on the fetus.

Modern antidepressants have proven to be quite safe during pregnancy. Selective serotonin reuptake inhibitors (SSRIs) are now more commonly prescribed to pregnant women. Among them, fluoxetine has been the best studied.

Scientists conducted clinical studies of fluoxetine. One of them revealed an increase in the occurrence of minor anomalies in newborns whose mothers took this drug in the first or third trimester of pregnancy. It was also noted that in mothers taking fluoxetine in the third trimester of pregnancy, cases of premature birth and difficulty breathing, fearfulness, cyanosis, and weight loss in newborns increased. The cause of weight loss in newborns is fetal hypoxemia.

In the history of medicine, there is only one known case of withdrawal syndrome in a fetus whose mother took fluoxetine at the end of pregnancy.

In studies of children who were exposed to fluoxetine in the first trimester of pregnancy, there were no developmental delays compared with children whose mothers took other antidepressants during pregnancy.

Thus, among antidepressants, fluoxetine is the safest for use during pregnancy, as it does not cause sedative, hypotensive and cardiotoxic effects.

In conclusion, I would like to say that thanks to the data known today, it is possible to make recommendations for the prescription of antipsychotic drugs during pregnancy:

1. Based on the information obtained during the examination of the patient, the issue of continuing to take the medication should be decided. The consequences of discontinuation of antipsychotic drugs can be predicted by knowing the diagnosis and the severity of previous diseases.

2. In cases where it is impossible to do without treatment with antipsychotics, you should choose the drugs that are most suitable for the patient’s condition.

3. The drug should be prescribed in the minimum dose that allows you to control the disease. The dose of the drug can be changed during pregnancy, based on the clinical picture.

4. Before starting treatment, a pregnant woman should consult a neurologist or psychiatrist.

5. The patient should be informed about the benefits, risks and unpredictability of treatment with antipsychotic drugs and give written consent.

Bibliographic link

Bagmanova A.R., Artamonova M.O. EFFECT OF NEUROLEPTIC DRUGS ON THE BODY OF A PREGNANT WOMAN AND FETUS // International Student Scientific Bulletin. – 2014. – No. 4.;
URL: http://eduherald.ru/ru/article/view?id=11926 (date of access: November 25, 2019). We bring to your attention magazines published by the publishing house "Academy of Natural Sciences"

Antipsychotics easily cross the placenta and are quickly detected in fetal tissue and amniotic fluid. However, as a rule, drugs in this group do not cause significant developmental defects in children born to mothers who took them during pregnancy. Reports of congenital anomalies with their use are few and cannot be clearly systematized. This is all the more important because a number of drugs in this group (etaperazine, haloperidol) are sometimes prescribed by obstetricians in small doses in early pregnancy as an antiemetic.

Descriptions of functional disorders when pregnant women use “old” antipsychotics are also few: isolated cases of withdrawal syndrome have been identified in newborns whose mothers received antipsychotic therapy for a long time, as well as respiratory failure when high doses of chlorpromazine were used in late pregnancy. No intellectual impairments were found in preschool children exposed prenatally to antipsychotics.

Reports of the use of atypical antipsychotics during pregnancy are limited. In particular, a possible increase in the risk of spontaneous miscarriages and stillbirths is indicated.

Thus, it is clear that the use of psychotropic drugs during pregnancy should be limited, and women of childbearing potential receiving psychotropic drugs should avoid pregnancy. If there is an urgent need to use these drugs, the potential teratogenic risk must be weighed against the severity of the mental disorder. At the same time, since the effect of new drugs (neuroleptics, antidepressants) on the fetus has not been sufficiently studied at present, it is preferable to prescribe “old” drugs that are more predictable in terms of teratogenic effects.

Taking into account the above information, a number of recommendations are offered for the use of psychotropic drugs during pregnancy:

• · the use of psychotropic drugs should be avoided in the first trimester of pregnancy;
• · if a pregnant woman develops mental disorders of the psychotic level, hospitalization is indicated to resolve the issue of prescribing therapy;
• · it is recommended to obtain consent to treatment not only from the patient, but also from her husband;
• · if there is an urgent need for psychotropic treatment, “old”, well-studied drugs should be given preference, since the teratogenic risk of new ones has not yet been studied;
• · it is advisable to use minimally effective doses of drugs; at the same time, the goal should not be to completely stop the symptoms at any cost, since this may require high doses of medications that increase the risk of complications for the fetus;
• · it is undesirable to use combinations of psychotropic drugs;
• · reduction and discontinuation of medications should be carried out as quickly as possible, with the exception of cases of drug remission, when discontinuation of treatment can lead to exacerbation of the disease;
• · it is necessary to carry out careful clinical and instrumental monitoring of the fetus, especially in the early stages, for the timely detection of pathology;
• · throughout pregnancy there should be close interaction between psychiatrists and obstetricians;
• · patients need observation during the postpartum period, since at this time the risk of occurrence (exacerbation) of mental disorders increases;
• · an important element in working with pregnant women, especially those suffering from mental disorders, is the creation of a favorable psychotherapeutic environment and preparation for childbirth.

mental schizophrenia depression pregnancy

The complexity of medical care during pregnancy and subsequent lactation is associated with changes in the pharmacokinetics of most drugs. At the same time, in women of reproductive age there is an increase in the incidence of extragenital pathology, requiring therapeutic interventions for the normal course of pregnancy and the postpartum period.

Factors that determine the pharmacokinetics of drugs during pregnancy

Speaking about the peculiarities of using drugs during pregnancy, it should be taken into account that during this period the pharmacokinetic parameters of almost all known drugs change. Features of the pharmacokinetics of drugs during pregnancy are determined by several factors:

• Almost all pregnant women experience some kind of renal dysfunction, often provoked by the pregnancy itself. This results in an increase in the half-life of those drugs that are primarily excreted by the kidneys;
• progesterone and pregnanediol, the concentration of which increases during pregnancy, block glucoronyltransferase, which leads to a slowdown in phase II drug metabolism. A particularly pronounced decrease in the activity of this process is observed in the third trimester of pregnancy;
• progesterone and pregnanediol activate the sulfation of a number of drugs;
• hormonal changes during pregnancy lead to a slowdown in the oxidation of a number of xenobiotics;
• hepatic hemodynamics changes. During pregnancy, cardiac output increases, but hepatic blood flow does not change, so the relative hepatic clearance in pregnant women decreases;
• during a normal pregnancy, the renal clearance of the drug decreases; there is an increase in the volume of drug distribution, especially pronounced during gestosis (due to fluid retention in the extracellular space);
• during pregnancy, the content of blood plasma proteins gradually decreases, which leads to an increase in the free fraction of drugs;
• almost all drugs pass through the placenta, which leads to a change in the apparent volume of distribution of the drug and, in turn, to the retention of drugs in the body;
• additional depots for medicinal substances appear - amniotic fluid and fetal adipose tissue;
• the placenta may participate in the metabolism of certain drugs, which leads to significant variations in their half-life;
• drugs can be distributed and metabolized in the fetus.
• The pharmacokinetic model that describes the distribution of drugs in the body of a pregnant woman contains a larger number of chambers than that of a non-pregnant woman. Typically, four-compartment pharmacokinetic models are used to describe the pharmacokinetics of drugs during pregnancy. They are characterized by longer retention of low drug concentrations in the mother's body and longer circulation of drugs.
• with long-term use of the drug, the listed factors can lead to its accumulation.

Mechanisms of changes in the pharmacokinetics of drugs:

1. Transport of drugs across the placenta .Most drugs pass through the placenta by diffusion, active transport and pinocytosis.
1. Low molecular weight substances pass freely through the placenta.
2. The transplacental transfer of most low-molecular-weight drugs occurs through the mechanism of simple diffusion. This process follows a concentration gradient. The penetration of drugs through the placenta is influenced by various physicochemical factors:
3. lipophilicity - an increase in lipophilicity leads to an increase in diffusion;
4. ionization of drugs - non-ionized drugs pass through the placenta better;
5. chemical structure of drug molecules;
6. degree of binding to blood proteins: the smaller the free fraction of the drug, the slower it passes through the placenta. Usually, by the third trimester of pregnancy, the mother experiences hypoalbuminemia, which leads to an increase in the free fraction of drugs and increases their entry through the placenta;
7. placental blood flow - with an increase in blood flow, the concentration of drugs reaching the fetus increases. At the same time, many drugs can directly (aminophylline, dibazole, papaverine, caffeine, cordiamine) or indirectly (aspirin, magnesium sulfate) increase placental blood flow;
2. degree of development of the placenta - thinning of the placenta and an increase in its area as it matures facilitates the flow of drugs to the fetus. With normal development of the placenta, maximum permeability is observed at 32-35 weeks of pregnancy; number of villi - the more villi, the more intensely the drugs diffuse across the placenta.
3. Metabolism of drugs in the placenta Quite often, drugs can be absorbed from amniotic fluid through the skin. At the same time, the fetus secretes urine containing medicinal substances into the amniotic fluid. Thus, the drug can remain in the amniotic fluid for a long time. Amniotic fluid can be swallowed by the fetus, as a result of which the drugs dissolved in it enter the fetal intestine. In this case, the drugs, before entering the systemic circulation, pass through the liver, where they can undergo chemical modification. A different distribution pattern of drugs is observed during their diffusion through the placenta. Blood from the placenta collects in the umbilical vein, from which 60-80% of the blood enters the portal vein, and 20-40% of the blood, bypassing the liver, immediately enters the inferior vena cava and from it into the systemic circulation.
4. Therefore, a significant part of drugs reaches the heart and brain, bypassing the liver. With fetal hypoxia, the percentage of blood that immediately enters the systemic circulation from the umbilical vein increases, which increases the likelihood of damage to vital organs. Metabolism in the fetus.

LV in the fetus is carried out by the liver, adrenal glands, skin, lungs and intestines, and the mechanisms of biotransformation in the fetus may differ from those in the mother.

Examples of drugs that are metabolized more slowly or differently in the fetus than in adults:	A drug
Metabolism mechanism	Aminazine
Ndemethylation	Hexobarbital
Hydroxylation	Desmethylimipramine
Aromatic hydroxylation	Diazepam
Oxidation	Carbamazepine

Epoxidation

1. Enzyme systems involved in the metabolism of drugs are detected in the fetus starting from the middle of the first trimester, but even by the end of pregnancy their activity is 20-80% of the activity of similar systems in an adult. While in an adult the main organ that metabolizes drugs is the liver, in the fetus this organ is the adrenal glands. It is often discovered that drugs selectively accumulate in certain organs and tissues of the fetus. :
1. Factors determining the pharmacokinetics of drugs during lactation
2. most drugs diffuse from the blood into breast milk, which, on the one hand, also leads to an increase in the rate of their elimination, and on the other, to their entry into the newborn’s body;
3. an increase in the lipophilicity of a drug molecule is accompanied by an increase in the concentration of the drug in milk;
4. The greater the free fraction of the drug in the blood, the greater its filtration into milk.

Risk of developing generational psychosis period in the general population is 0.1–0.25%. At the same time, postpartum psychoses account for 45%–86% of all psychoses of the generation period, lactation psychoses account for 10%–42% and psychoses period pregnancy– 3%–15%. It is believed that the level of severe mental disorders during pregnancy the same or even lower compared to the level of pain outside childbirth, but it increases sharply after childbirth. Postpartum psychoses occur with an incidence of 1–2 per 1000 births.

The problem of the safety of using psychotropic drugs during the gestational period has different aspects: on the one hand, the degree of risk of their pathogenic effect on the fetus is taken into account, on the other hand, the severity of pathological disorders in the expectant mother, which determines the need for their use. The general rule here is to use medications only when the risk of complications for the mother or fetus if the medications are not used exceeds the risk of their side effects.

To date, objective evidence has supported both the impact of untreated mental illness on fetal development and the unhealthy lifestyle of women with untreated mental illness, including factors such as poor nutrition, heavy smoking, alcohol and substance abuse, lack of exercise, self-care, unsanitary living conditions and irregular visits to antenatal clinics. During the perinatal period, women with mental disorders face a serious risk of committing suicide.

On the other hand, neonatal toxicity, prematurity and stillbirth, congenital malformations and deformities, and behavioral disturbances are potential consequences of the use of psychotropic drugs. The modern direction of medicine is “behavioral teratology,” showing that prenatal exposure of the fetus to psychotropic drugs can lead to brain changes manifested not by anatomical, but by behavioral abnormalities.

NEUROLEPTICS.

Antipsychotics easily cross the placenta and are quickly detected in fetal tissue and amniotic fluid. However, as a rule, drugs in this group do not cause significant developmental defects in children born to mothers who took them during pregnancy. Reports of congenital anomalies with their use are few and cannot be clearly systematized. This is all the more important because a number of drugs in this group (etaperazine, haloperidol) are sometimes prescribed by obstetricians in the early stages of pregnancy as an antiemetic.

Typical antipsychotics:

Descriptions of functional disorders when pregnant women use “old” antipsychotics are few: isolated cases of withdrawal syndrome in newborns have been identified, as well as respiratory failure when using high doses of chlorpromazine in late pregnancy. No intellectual impairments were found in preschool children exposed to prenatal antipsychotics. Chlorpromazine increases the risk of neonatal jaundice.

Low dose haloperidol in the first trimester of pregnancy had no harmful effects on fetal weight, length of pregnancy, fetal or neonatal mortality, or the incidence of malformations and malformations. Neither oral nor depot conventional antipsychotic drugs have been associated with fetal malformations and malformations, and it has been concluded that these drugs are safe in pregnancy. Complications in an infant can be observed directly in the postnatal period. Transient perinatal syndrome, a lethargic (hypotonic) child, withdrawal symptoms, such as increased irritability, decreased and increased muscle tone, and insufficiently formed reflexes are observed in infants exposed to various doses of antipsychotic drugs during fetal development.

Atypical antipsychotics.

Increasingly, cases are being described in which women taking clozapine, olanzapine, risperidone or quetiapine ended their pregnancy without any harmful effects on the newborn.

From the available data it follows that relatively safe antipsychotic drugs include sulpiride, perphenazine, clozapine, trifluoroperazine. After childbirth, there is a high risk of exacerbation (relapse) of schizophrenia, so it is necessary to use antipsychotic drugs in the full dose that is previously effective for the patient. Antipsychotic drugs used in women who are breastfeeding can adversely affect the development of the infant and cause poisoning. Therefore, until at least 10 weeks of age, an infant should not be breastfed if the mother is taking antipsychotic medications.

Clozapine can be considered potentially dangerous in relation to the development of agranulocytosis not only in the mother, but also in the fetus. Agranulocytosis can develop either acutely or gradually in the first 6 months of life, leading to death in a third of children.

Adequate clinical studies of risperidone have not been conducted; animal experiments revealed the fetotoxic effect of the drug.

The drug of first choice is sulpiride, since its safety in humans has already been proven.

During breastfeeding, sulpiride can be given. Sulpiride enhances lactation, and its use has not established any side effects in a child. Moderate-risk agents include haloperidol and phenothiazines. They pass into mother's milk and in high doses can cause drowsiness in the baby. Clozapine is contraindicated during breastfeeding due to the risk of agranulocytosis. Risperidone and olanzapine are not recommended during breastfeeding.

Data on the use of antipsychotics during pregnancy can be summarized as follows:

· Despite the risk of developing extrapyramidal disorders in newborns, preference during pregnancy is recommended to be given to neuroleptics with high antipsychotic activity (fluphenazine, haloperidol, perphenazine, thiothixene and trifluoperazine), which do not cause anticholinergic, hypotensive and pronounced sedative effects in the mother.

· Data on the use of chlorprothixene, clozapine, loxapine, mesoridazine, molindone, olanzapine, pimozide and resperidone in pregnant women are extremely limited, therefore recommendations regarding them are not formulated.

· The use of long-acting (depot) drugs with high antipsychotic activity (fluphenzine enanthate, fluphenazine decanoate, haloperidol decanoate) should be avoided in order to limit the duration of possible toxic effects in newborns.

· Maternal-fetal withdrawal syndrome does not appear to be a serious problem with antipsychotic treatment, but chlorpromazine should be avoided if possible before delivery as it may cause hypotension.

· In children whose mothers received clozapine during pregnancy, the white blood cell count should be carefully monitored for 6 months to detect agranulocytosis.

ANTIDEPRESSANTS.

Antenatal depression and anxiety are associated with low birth weight and smaller head circumference. Depression increases the risk of premature birth. Untreated mental illness that continues into the postnatal period affects the well-being of the infant, leading to impaired attachment, cognitive functioning and worsening behavioral disorders.

Antidepressants for pregnant women are prescribed:

- with pronounced affective manifestations with anxiety, agitation, sleep and appetite disorders, aggravating the somatic condition of pregnant women and women in labor;

- with suicidal thoughts and tendencies.

When starting treatment for pregnant women with depression:

· start treatment with the lowest possible dose and monitor regularly; evaluate the possibility of postponing the drug until the second or even third trimester of pregnancy;

· consider alternative treatment options

· P The TCAs nortriptyline and desimpramine should be considered the drugs of choice; the SSRI fluoxetine should be considered an alternative.

· treatment with nortriptyline and desimpramine should be carried out under the control of drug concentrations in the blood (at least once per trimester). Their doses should be adjusted as pregnancy progresses; in the third trimester, a significant increase in doses may be necessary.

· the use of antidepressants in late pregnancy to prevent withdrawal syndrome in the newborn requires more detailed study. To date, there are no clear recommendations on this issue. If the decision is made to discontinue antidepressants, their dose should be reduced gradually (approximately 25% per week).

Tricyclic antidepressants . Experimental (animal) studies of various tricyclic (eg, imipramine, amitriptyline) and tetracyclic (eg, maprotiline) antidepressants using supramaximal doses have shown that they do not increase the risk of birth defects in the first trimester of pregnancy. Single case studies of women treated with imipramine and amitriptyline throughout pregnancy showed that tricyclic antidepressants do not increase the risk of malformations. Only the use of ultra-high doses leads to multiple severe developmental anomalies in the fetus. However, since they easily cross the placenta, the developing fetus is vulnerable to their anticholinergic side effects, manifested in the form of tachyarrhythmias, urinary retention, tremor, and increased muscle tone. After birth, the newborn may experience toxic effects of tricyclic antidepressants in the form of suppressed respiratory function, cyanosis, hypertension, irritability and seizures. A withdrawal syndrome is possible, which is manifested by colic, irritability, difficulty feeding and tachypnea. Nortriptyline and desipramine cause fewer maternal side effects than other TCAs. They have the least pronounced sedative effect, influence on the gastrointestinal tract, heart and blood pressure, and therefore can be considered as the drugs of choice during pregnancy.

To maintain a therapeutic level of concentrations of tricyclic antidepressants in the blood, especially in the third trimester of pregnancy, their dose must be increased by 1.6 times.

MAO inhibitors. Preclinical studies confirm the existence of a teratogenic effect in humans. The risk of developing a hypertensive crisis, characteristic of MAO inhibitors, in the presence of significantly safer alternative groups of antidepressants, leads to the conclusion that contraindications prescribing MAO inhibitors during pregnancy.

SSRIs. The safety of fluoxetine in pregnant women has been studied in several prospective and retrospective studies involving a total of more than 2000 women. The results of all studies show that any complications in the postnatal period when using fluoxetine in the third trimester of pregnancy are unlikely. Moreover, another study demonstrated normal development of cognitive abilities, speech and behavioral skills in children whose mothers received fluoxetine during pregnancy. Similar data exist for sertraline. Fluoxetine, paroxetine, sertraline, fluvoxamine and citalopramne increased the incidence of severe malformations and deformities in newborns compared with a control group not taking antidepressants.

A withdrawal syndrome was described in 4 newborns whose mothers received paroxetine at a dose of 20-120 mg/day during pregnancy. It was manifested by nervousness, vomiting, increased excitability and hypoglycemia. Necrotizing enterocolitis was observed in 2 out of 4 children. The authors suggest that it may be a manifestation of withdrawal syndrome. SSRIs reduce the penetration of serotonin into platelets, which leads to disruption of their aggregation. It is likely that their withdrawal leads to platelet reactivation, predisposing to bleeding disorders and subsequent necrotic changes. Other authors have described 3 cases of withdrawal syndrome in newborns whose mothers took paroxetine at a dose of 10-40 mg/day. Another study assessed pregnancy outcomes when paroxetine was used in the third trimester. In the experimental group, premature births were more often observed, complications requiring prolonged hospitalization and intensive therapeutic measures developed in a larger number of newborns exposed to paroxetine in utero compared to the control group. In the paroxetine group, respiratory distress syndrome was observed, followed by the development of jaundice and hypoglycemia. In some cases, intubation was required. Symptoms persisted for 1-2 weeks. It is believed that the severe withdrawal symptoms associated with paroxetine are due to its shorter half-life (26 hours) compared to most SSRIs.

The effect of another SSRI, citalopram, was studied in doses of 20-40 mg/day. The level of citalopram in the blood of newborns was 64% of that in the blood of mothers. The drug was determined in children during the first two months of life. No deviations in the physical and neurological status of the children were observed either at birth or during follow-up for 1 year. A case of withdrawal syndrome in a newborn was described when using citalopram in the third trimester of pregnancy. According to prospective studies, the use of citalopram during pregnancy was not associated with an increased risk of teratogenicity. In particular, the incidence of congenital anomalies in children whose mothers received citalopram was no different from that in the general population.

A retrospective study analyzed 185 cases of use of SSRIs (fluoxetine, fluvoxamine, paroxetine and sertraline) and 209 cases of use of tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine, nortriptyline, protriptyline) in the third trimester of pregnancy. In women receiving SSRIs, the risk of preterm birth was 10% and approximately 2 times higher than that in women not taking any medications. Infants exposed to SSRIs in utero had significantly lower gestational age, weight, and Apgar scores than control infants. Normalization of body weight occurred only by the 6th month of life. In contrast, children of mothers receiving TCAs did not differ in all assessed parameters (gestational age, weight, head circumference, Apgar status, number of congenital anomalies) from children of the control group

There are few published studies examining the incidence of malformations or side effects with trazodone, nefazodone, and mirtazapine in humans. The experiment noted postnatal disturbances in behavioral reactions under their influence. Venlafaxine was used in 150 pregnant women, with no increase in the incidence of severe malformations and deformities compared with the baseline figure of 1–3%. When maprotiline was used during pregnancy, seizures were observed significantly more often than when using TCAs, so its use should be avoided, especially in women with hypertension and seizure disorders. Although anecdotal published cases indicate no side effects, precautions should be taken when prescribing new antidepressants to pregnant women.

TRANQUILIZERS.

Benzodiazepines,prescribed in the first trimester of pregnancy, increase the risk of oral clefts and congenital malformations of the central nervous system and urinary tract to 0.06%. K. L. Wisner, J. M. Perel (1988) in a review of studies show that these drugs in the neonatal period cause in infants symptoms of intoxication, withdrawal symptoms, respiratory depression, muscle hypotension, and, therefore, a possible diagnosis of “flaccid (hypotonic) child " However, dosage, duration of treatment, drug class, and the effects of other concomitant medications must be taken into account. The main recommendation is to avoid high doses and long-term treatment. Data on the neurobehavioral teratogenicity of benzodiazepines are limited. There are several reports of developmental delays in children aged 7-8 years whose mothers used these drugs during pregnancy.

It was revealed that when using diazepam In the first trimester of pregnancy, the likelihood of non-fusion of the hard palate, upper lip and the development of an inguinal hernia in newborns increases. Long-term use of the drug during pregnancy can lead to its accumulation in fetal tissues (especially in adipose tissue and liver) and thereby cause toxic effects. Newborns may experience muscle hypotonia, hypothermia, and hyperbilirubinemia. Possible respiratory depression until it stops and the sucking reflex is impaired. The use of diazepam in low doses during childbirth, as a rule, does not have any adverse effect on the fetus, however, high doses can lead to attacks of suffocation, decreased muscle tone, and pathological metabolic reactions to a decrease in temperature in newborns.

Anxiolytics of other groups have been studied much less well during pregnancy. In a large epidemiological study, comparing the pregnancy outcomes of women treated with meprobamate or chlordiazepoxide with the pregnancy outcomes of women not treated with these drugs, there were no differences in the incidence of preterm birth, intrauterine fetal death, congenital anomalies, or other neonatal complications. Assessment of physical and mental development at the age of 8 months and the results of IQ testing at the age of 4 years did not reveal developmental abnormalities in children exposed in utero to meprobamate or chlordiazepoxide at different stages of gestation.

There is virtually no information on the use of the non-benzodiazepine anxiolytic buspirone in pregnant women.

Thus, to improve fetal safety, the following recommendations must be adhered to:

· Women of childbearing age when treated with benzodiazepines should be warned about the potential danger of these drugs to the fetus and the need to use effective contraception.

· If pregnancy occurs during treatment with benzodiazepines, the issue of discontinuing them or replacing them with other drugs should be considered. In many cases, benzodiazepines can be replaced by safer SSRIs, which have, along with an antidepressant effect, an anxiolytic effect.

· Due to potential teratogenicity, benzodiazepines should be avoided if possible during the first trimester of pregnancy. It is also advisable to cancel them before childbirth due to the risk of developing perinatal syndrome. Benzodiazepines should be discontinued gradually (no more than 10-25% of the dose per week).

· During pregnancy, concentrations of benzodiazepines in the blood should be monitored and drug doses adjusted based on the results obtained.

· In neonates whose mothers received benzodiazepines, symptoms of central nervous system and respiratory depression should be monitored.

NORMOTIMICS.

Lithium. Lithium passes relatively easily through the placenta and is found in the fetal blood.The revised risk of teratogenicity of lithium in pregnancy based on the results of a meta-analysis is 0.05%, a relative risk 10–20 times higher than that for the general population. In the first trimester of pregnancy, lithium can lead to malformations and deformities in the fetus. Congenital cardiovascular defects and various heart defects increased in fetuses exposed to lithium in the first trimester of pregnancy mothers. Lithium can cause shortened gestation, weight loss, and increased neonatal mortality.Thus, lithium is contraindicated in the first trimester of pregnancy, but its use during this dangerous period cannot serve as an absolute indication for abortion. Intoxication of a newborn with lithium can manifest itself in the form of so-called floppy baby syndrome. Children experience decreased muscle tone, drowsiness, shallow breathing, cyanosis, suppressed sucking and grasping reflexes, and the absence of the Moro reflex.These disorders are reversible and do not lead to any complications in the future.The observed phenomena can persist up to 10 days after birth.A relationship has been identified between stillbirth, Down syndrome and lithium intake in the first 12 weeks of pregnancy, as well as between goiter in a newborn and lithium intake in the last trimester of pregnancy.

Lithium withdrawal is a complex issue. There is strong evidence that anyone receiving lithium treatment may relapse after abrupt withdrawal of lithium. Average relapse rates reach 50% within six months of stopping this drug, and rapid discontinuation appears to increase the risk of relapse even further, regardless of whether the patient is pregnant or not; The risk of disease relapse in pregnant women who stop taking the drug for more than four weeks is unknown.

A feature of lithium preparations is that they are not metabolized in the body. Their pharmacokinetics is determined by the intensity of excretion by the kidneys, the level of which changes during pregnancy. This leads to the need to modify the regimen of drug use in pregnant women. Thus, an increase in the clearance of lithium by the kidneys requires an increase in the dose of the drug to maintain its optimal concentration in the blood. At the same time, a sharp drop in the level of glomerular filtration and lithium clearance after childbirth can lead to intoxication.

It is believed that a single dose of lithium for pregnant women should not exceed 300 mg, and the level of therapeutic concentration in the blood should be maintained through the frequency of administration.

Lithium treatment program:

1. The concentration of the drug in the blood should be monitored weekly.

2. The dose of lithium should correspond to the lower limit of the therapeutic window.

3. Do not suddenly stop taking lithium; Before delivery, the dose should be gradually reduced to 60–70% of the initial maintenance dose.

4. Lower doses and frequent blood tests should be the norm for pregnant women starting lithium in the first trimester of pregnancy.

5. Lithium started in the second and third trimester of pregnancy or during the perinatal period may reduce the risk of postpartum psychosis.

6. Breastfeeding an infant is not compatible with taking lithium, and women should be aware of this before giving birth.

Can be used as an alternative drug for the prevention of affective phases carbamazepine. This drug is considered quite reliable when used alone, but the risk of congenital deformities increases significantly when it is combined with other anticonvulsants.In particular, carbamazepine can lead to craniofacial deformities (11%), developmental delay (20%) and digital hypoplasia (26%). Exposure to carbamazepine in the first trimester is associated with the occurrence of spina bifida (risk approximately 0.5–1%). A decrease in mean head circumference was noted.

Impact valproate in the prenatal period is associated with congenital anomalies, growth retardation, manifestations of hepatotoxicity and intrauterine distress. There is an increased risk of developing spina bifida, craniofacial anomalies, finger and limb defects, heart defects, abnormal development of organs and the genitourinary system, psychomotor retardation and low body weight. The risk of medullary tube defect is 1–2%; a tenfold increase in the risk of spina bifida has been reported. The relationship between maternal use of anticonvulsant therapy, neonatal behavior, and later neurological functioning was studied. It was found that children exposed to sodium valproate during fetal life had impaired nervous system function and increased excitability in infancy and later in life. It was also found that the concentration of valproate in the blood serum of a newborn correlates with the degree of increased excitability in the neonatal period and dysfunction of the nervous system at the age of six. Thus, valproate clearly causes brain dysfunction in addition to malformations and deformities. The risk of heart defects has been reported to increase fourfold. Fetal valproate syndrome has been described. The use of these anticonvulsants during pregnancy is highly discouraged, except in cases of resistance to other types of therapy and in the case of a life-threatening condition for the woman. If these drugs are still used, they must be combined with taking folic acid supplements.

Lamotrigine is the drug of choice for the treatment of pregnant women with bipolar disorder due to its prevention of bipolar depression, good tolerability, and reasonable reproductive safety profile compared with alternative mood stabilizers.

ANTICHOLINERGIC DRUGS.

There have been reports of possible teratogenic properties associated with their use in combination with antipsychotic drugs. It is generally accepted that these drugs should be avoided whenever possible and the lowest doses should be used if necessary. No studies have been conducted to help differentiate the effects of the most commonly prescribed anticholinergic drugs.

BETA BLOCKERS.

Used during pregnancy for akathisia, does not lead to an increase in cases of congenital birthssignificant developmental defects and deformities.

· the use of psychotropic drugs should be avoided in the first trimester of pregnancy;

· if a pregnant woman develops mental disorders of the psychotic level, hospitalization is indicated to decide on the prescription of therapy;

· if there is an urgent need for psychotropic treatment, “old”, well-studied drugs should be given preference, since the teratogenic risk of new ones has not yet been studied;

· it is advisable to use minimally effective doses of drugs; at the same time, the goal should not be to completely stop the symptoms at any cost, since this may require high doses of medications that increase the risk of complications for the fetus;

· it is undesirable to use combinations of psychotropic drugs; high doses of a single drug are preferable to polypharmacy;

· reduction and discontinuation of medications should be carried out as quickly as possible, with the exception of cases of drug remission, when discontinuation of treatment can lead to exacerbation of the disease;

· it is necessary to carry out careful clinical and instrumental monitoring of the fetus, especially in the early stages, for the timely detection of pathology;

· patients also need observation in the postpartum period, since at this time the risk of occurrence (exacerbation) of mental disorders increases;

· The presence of a mental illness during pregnancy with inadequate treatment or its absence can be the reasons for insufficient compliance in the prenatal period, inadequate nutrition of the mother, uncontrolled use of medications and homeopathic drugs, increase the risk of drinking alcohol and smoking, disrupt direct mother-child contact, and aggravate intrafamily relationships.

· drugs should be prescribed for the shortest possible period and reduce in dose during the last days before childbirth.

· if there is a need to resume taking medications, then you should use those drugs that helped in the past. In this case, preference should be given to such relatively safe antipsychotic drugs as sulpiride, perphenazine, clozapine, trifluoroperazine.

· Medicines should be recommended in divided minimal doses throughout the day.

· after childbirth, due to the high risk of exacerbation or relapse of schizophrenia, antipsychotic drugs should be taken in the full dose that is previously effective for the patient.

· Before 10 weeks of age, an infant should not be breastfed if the mother is taking antipsychotic medications.

· In most cases, women who become pregnant while using medications should continue treatment.

Zemsky Doctor magazine No. 2-2011

Safety of the use of peichotropic drugs during pregnancy

O.L. Romanova, N.V. Sturov RUDN

117198, Moscow, st. Miklouho-Maklaya, 6

Mental disorders in pregnant women are quite common. The key problem when using psychotropic drugs in this case is the risk of developing congenital pathology in the fetus. The article provides information about the experience of using psychotropic drugs of different groups during pregnancy.

Key words: drug safety, pregnancy, mental disorders, psychotropic drugs.

Treatment of mental illness in pregnant women is a fairly common and pressing problem. If they appear or worsen, pharmacological correction is required to avoid possible complications. It has been proven that the lack of therapy in this case adversely affects pregnancy outcomes.

Untreated depression in pregnant women is a prerequisite for the development of postpartum depression in the mother. Children born to such women are more likely to experience antisocial behavior in adolescence.

If medications are abruptly discontinued in pregnant patients with bipolar disorders, the risk of exacerbations of the disease is high; in this case, there is also a high probability of adverse pregnancy outcomes (premature birth, reduced weight of newborns, intrauterine growth retardation). However, in almost 70% of cases, patients are discontinued psychotropic medications due to fear of their adverse effects on the child.

Obviously, there is a need to assess the safety of the most commonly used drugs for the correction of mental disorders (antidepressants, mood stabilizers, atypical antipsychotics) in pregnant women. In recent years, quite a lot of information, often quite contradictory, has appeared in available sources on this issue.

Antidepressants

Antidepressants are most often used to correct behavior in pregnant women.

Selective neuronal reuptake inhibitors

The effect of drugs in this group on pregnancy outcomes has been studied most fully.

Possible teratogenic effects. Until 2005, neuronal reuptake inhibitors were widely used in pregnant women. In children whose mothers took drugs of this group during pregnancy, the occurrence of congenital anomalies was no more common compared to children who were not exposed to drugs of this group in utero.

In 2005, due to reports of congenital anomalies when taking paroxetine during pregnancy, its FDA safety category was changed from C to D (see table). Presumably, the use of this drug during pregnancy is associated with the appearance of cardiovascular abnormalities in children. Two years later, the results of a retrospective analysis of a large US database were published, also confirming this connection. Similar results were obtained in an analysis of the Swedish Health Register. Nevertheless, there are also research results showing the absence of significant teratogenic effects of paroxetine.

It has been proven that taking other drugs from the group of neuronal reuptake inhibitors during pregnancy, such as fluoxetine (FDA category C), sertraline (FDA category C), citalopram (FDA category C), is associated with the risk of cardiovascular abnormalities. systems. Data on escitopram are mixed.

AC SAFETY

Analysis of the results of a large prospective controlled study assessing the effect of taking venlafaxine in early pregnancy on the occurrence of congenital anomalies confirms the risk of teratogenic effects when taking this drug.

Opposite results were obtained when studying the use of venflaxin in combination with other serotonergic antidepressants.

There are currently no data on the safety of duloxetine in early pregnancy.

When mothers used neuronal reuptake inhibitors in late pregnancy, a wide range of congenital anomalies were observed in newborns (disorders of the cardiovascular, respiratory, nervous, gastrointestinal systems, metabolic disorders). In addition, these children may develop withdrawal syndrome (Prenatal Antidepressant Exposure Syndrome).

Tricyclic antidepressants

There are no studies examining the use of tricyclic antidepressants in pregnant women.

Possible teratogenic effects. A review of the literature on the use of tricyclic antidepressants in early pregnancy shows a possible connection between taking clomipramine and the occurrence of cardiovascular abnormalities in children, while it is impossible to draw clear conclusions regarding other tricyclic antidepressants.

When taking tricyclic antidepressants in late pregnancy, it is possible to develop

withdrawal syndrome (Prenatal Antidepressant Exposure Syndrome) in a child.

Other antidepressants

Data on the use of other antidepressants (bupropion, mirtazepine, nefazodone, reboxetine and tradozone) during pregnancy are sparse, possibly due to the less frequent use of these drugs in psychiatric practice. To date, there is no evidence that the use of these drugs during pregnancy increases the risk of congenital anomalies. However, there may be an association between the use of mirtazapine (FDA category C) and reboxetine in late pregnancy and the occurrence of perinatal complications.

Classic mood stabilizers

The safety of classic mood stabilizers has been studied in several studies.

Lithium salts

Lithium salts are the first class of drugs for which a normothimic effect has been proven.

Possible teratogenic effects. When reviewing the available information on the use of lithium salts in pregnant women, it was shown that when used in early pregnancy, these drugs do not have significant teratogenic effects. Similar conclusions were drawn based on the following data:

Reports of 24 children describe only one case of Ebstein's anomaly;

Retrospective studies (n = 500) showed 8 cases of cardiovascular abnormalities;

A Controlled studies in women have shown no risk to the fetus in the first trimester (and no evidence of risk in other trimesters). The possibility of harm to the fetus seems unlikely

B Animal reproduction studies have shown no risk to the fetus and no controlled studies have been conducted in pregnant women, or adverse effects (other than decreased fertility) have been shown in animal experiments but have not been confirmed in controlled studies in women in the first trimester of pregnancy (and no evidence of risk in other trimesters)

C Animal reproduction studies have shown adverse effects on the fetus, and adequate and strictly controlled studies have not been conducted in pregnant women, but the potential benefits of the drug for pregnant women may justify its use. Or animal studies and adequate well-controlled studies in pregnant women have not been conducted

D There is evidence of a risk to the human fetus, but the benefit of use in pregnant women may outweigh the risk (for example, if the drug is needed in a life-threatening situation or to treat a serious illness for which safer drugs cannot be used or are ineffective)

X Studies in animals or humans have revealed fetal developmental abnormalities and/or there is evidence of a risk to the fetus based on experience with the drug in humans. The risk of use in pregnant women outweighs any possible benefit. Contraindicated in pregnant women and women who may become pregnant

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magazine "Zemsky Doctor" No. 2-2011

In case-control studies, only one of 266 children with congenital anomalies was exposed to lithium salts in utero.

The main problem with the need to use lithium salts during pregnancy is the need for frequent monitoring of the concentration of the drug in the mother’s blood serum and constant adjustment of the dose of the drug, since when, for example, nausea and vomiting of pregnant women occur, dehydration is possible and, as a result, a rapid increase in the concentration of the corresponding drug in blood serum.

In a study by Newport et al. It has been shown that when using lithium salts in late pregnancy, an increased risk of complications such as lower Apgar scores, central nervous system damage, and neuromuscular side effects cannot be excluded. In addition, the risk of such complications directly depends on the concentration of the drug in the mother’s blood serum. Other complications in children whose mothers took lithium salts during late pregnancy include preterm birth, macrosomia, diabetes insipidus, cardiac and renal dysfunction, and thyroid dysfunction.

Taking into account the occurrence of possible adverse reactions for lithium salts, the FDA classification category is D.

Antiepileptic drugs

Possible teratogenic effects. The teratogenic effects of valproic acid have been confirmed in numerous studies (FDA category D). The proportion of congenital anomalies when taking valproic acid during pregnancy increases by 2-3 times compared to carbamazepine and lamotrigine. A recent controlled study showed that the risk of congenital anomalies increased by 11.3% with valproic acid monotherapy.

The risk of congenital anomalies when taking valproate is dose-dependent; in particular, when taken at a dose above 800-1000 mg/day, the risk of congenital anomalies doubles.

Even more dangerous is taking valproic acid in combination with other drugs (presumably the most unfavorable is the combination of valproic acid with lamotrigine). However, this assumption is controversial. In the Australian Register of Antiepileptic Drugs in Pregnancy

nancy) showed that when using this combination of drugs, the risk of congenital anomalies (7.26%) is lower than with valproic acid monotherapy (17.9%), regardless of its dose.

On the other hand, for many years carbamazepine was considered highly teratogenic, but recent studies have shown that its safety profile is similar to that of lamotrigine (relatively safe for pregnant women, but with its use there is an increased risk of pathologies such as clefts palate - “cleft palate” and lips - “cleft lip”).

Recent studies have confirmed that the elimination of lamotrigine and the active metabolite of carbamazepine increases during pregnancy, and this must be taken into account when selecting doses of these drugs for pregnant women.

Studies have shown that when taking antiepileptic drugs in late pregnancy, the risk of premature birth increases, the weight of newborns is significantly lower, and the head circumference of newborns is on average 2.5% lower.

Atypical antipsychotics

Possible teratogenic effects. Studies have shown that taking drugs in this group during pregnancy increases the risk of congenital anomalies.

Reis and Kallen in their work showed that when taking antipsychotics (typical or atypical) during pregnancy, there is a slight increase in the proportion of congenital anomalies. The results of other prospective and retrospective studies confirm that the use of atypical antipsychotics is not associated with the occurrence of serious congenital anomalies.

The only atypical antipsychotic for which teratogenicity studies have been conducted is risperidone (n = 700). The results of this study did not show an increased risk of congenital anomalies. However, the FDA category for this drug is C.

Recent studies have also shown that newborns taking olanzapine during pregnancy had significantly higher birth weights compared to babies whose mothers took other antipsychotics during pregnancy. In general, the risk of having low-weight children when taking antipsychotics is significantly higher.

Conclusion

On the one hand, it is obvious that none of the drugs discussed above is ideally safe during pregnancy; on the other hand, women with mental disorders should not be left without treatment during pregnancy.

AC SAFETY

In each case, therapy should be selected individually, taking into account the criteria of “efficacy - safety” not only for the child, but also for the mother.

Paroxetine should not be prescribed to pregnant women due to the risk of teratogenic effects. When prescribing antidepressants, even a new generation, it is necessary to take into account the possibility of withdrawal syndrome in newborns (Prenatal Antidepressant Exposure Syndrome); the risk of its development depends to a greater extent on the duration of taking the drug than on the duration of pregnancy.

It should also be taken into account that when using fluoxetine, symptoms such as nausea and vomiting appear relatively often; when using a combination of citalopram and paroxetine, an increase in fetal weight is possible. Relatively often, changes in body weight are caused by the use of mir-tazapine.

Thus, inhibitors of neuronal serotonin reuptake - fluoxetine, sertraline, escitalopram - are the drugs of choice in pregnant women; If there are contraindications to the use of these drugs, bupropion may be prescribed. This drug has a relatively favorable safety profile (dry mouth, insomnia, hyperhidrosis). A recent study suggests a link between taking this drug during pregnancy and hyperactivity in children, but these findings require further confirmation.

In addition to the above side effects, there is evidence supporting a possible connection between the use of antidepressants in late pregnancy and the development of persistent pulmonary hypertension in infants.

If it is necessary to prescribe classic normotropics, preference should be given to Lamotrigine (the most favorable safety profile); In pregnant women with bipolar I disorder, lithium salts are the drugs of choice. When prescribing lithium drugs, it is necessary to take into account that their use is associated with weight gain.

Valproic acid or carbamazepine should not be prescribed to pregnant women due to their unfavorable safety profile. If pregnancy occurs while taking these drugs, the possibility of prolonging it is considered taking into account the results of additional examinations.

Of the atypical antipsychotics, the most studied are olanzapine, quetiapine and risperidone. When taking these drugs, it is possible to increase the mother's body weight, increase appetite, and even develop

tion of gestational diabetes, so their use during pregnancy should be avoided.

If antipsychotic therapy is necessary during pregnancy, preference should be given to typical antipsychotics due to their more favorable safety profile. Against the background of neuroleptics, both typical and atypical, prescribed in late pregnancy, extrapyramidal disorders may develop in newborns (can manifest before the age of one year), respiratory depression, and transient mental retardation.

Literature.

1. Gentile S. Drug Treatment for Mood Disorders in Pregnancy // Curr Opin Psychiatry. 2011. Vol. 24. No. 1. P. 34-40.

2. Stowe Z.N., Nemeroff C.B. Women at Risk for Postpartum Depression // Amer-ic. Journal Obst. Gynec. 1995. No. 173. P. 639-645.

3. Somerset W., Newport D. J., Ragan K. et al. Mood disorders in women. In: Keyes C., Goodman S.H. et al. Women and Depression: A Handbook for the Social, Behavioral, and Biomedical Sciences. 2006. P. 62-88.

4. Newport D.J., Wilcox M.M., Stowe Z.N. Antidepressants during pregnancy and lactation: defining exposure and treatment issues // Seminars in Perinatology 2001. No. 3. P. 177-190.

5. Loughhead A., Stowe Z.N., Newport D.J. et al. Placental Passage of Tricyclic Antidepressants // Biol. Psych. 2006. No. 3. P. 287-90.

6. Devane C.L., Stowe Z.N., Donovan J.L. et al. Therapeutic drug monitoring of psychoactive drugs during pregnancy in the genomic era: challenges & opportunities // J of Psychopharm. 2006. Vol. 4. No. 20. P 54-61.

7. Llewellyn A., Stowe Z.N., Nemeroff C.B. The Use of Lithium and Management of Women with Bipolar Disorder During Pregnancy and Lactation // Journal Clin. Psych. 1998. No. 59. P. 57-64.

8. Owens M.J., Nemeroff C.B. Pharmacology of Valproate // Psychopharmacol. Bull. 2004. No. 37. P. 17-24.

9. Pennell P.B., Newport D.J., Stowe Z.N. et al. The Impact of Pregnancy and Childbirth on the Metabolism of Lamotrigine // Neurology. 2004. Vol. 62. No. 2. P. 292-295.

10. Stowe Z.N., Newport D.J. Guidelines for the treatment of schizophrenia during pregnancy and the postpartum period. In: IPAP Schizophrenia Algorithm Project. International Psychopharmacology Algorithm Project. 2004. P 1-3.

Safety of psychoactive drugs in pregnancy

O.L. Romanova, N.V. Sturov

Peoples" Friendship University of Russia, Moscow

MikLukho-MakLaya st. 6, Moscow, 117198

Mental disorders are rather common among pregnant women. The key problem in case of psychoactive drugs usage is the risk of congenital abnormalities development. The article provides the information on the experience of psychoactive drugs usage among pregnant women.

Keywords: drug safety, mental disorders, pregnancy, psychoactive drugs.

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