A gentleman just called to consult me about medication for his wife who has bipolar disorder and is preparing to get pregnant.
The prevalence of bipolar disorder is among the second most prevalent conditions in our department’s outpatient clinics. The treatment of bipolar disorder in pregnant and lactating women, especially with regard to the effects of medications on the fetus, is a concern for many patients and their families.
Therefore, I am going to present some information here, but what I say here may not be correct and is for reference only.
Knowledge in this area is still being updated and accumulated, and what I say today may be updated with evidence-based medicine tomorrow.
I. Medication ideas for physicians
1. Discuss with the patient and the patient’s partner the risks and benefits (both to the patient and to the fetus) of continuing medication and discontinuing treatment during pregnancy. The physician is not the decider of treatment or not; the physician is the provider and articulator of knowledge and information, and in most cases, it is the physician’s responsibility to
① to provide the patient and her partner with up-to-date, non-personally biased information and information about the possible risks of medication and the possible consequences of not treating; the advantages and disadvantages of the various options should be communicated in most cases as well as from the patient’s individual situation (medical history, current status, previous reactions to medication, etc.), respectively
(ii) Help the patient or patient couple to choose the best decision for themselves, but the physician must recognize that the final decision on the option is up to them.
③ Once the decision has been made, the physician should verbally support their final choice.
2. Inform the patient of the increased risk of relapse of bipolar disorder during pregnancy and postpartum, suggest additional psychiatric visits, and also consider combined psychotherapy.
3. Develop a written plan for pregnancy, perinatal and postpartum as soon as possible; and inform the obstetrician, ribbed midwife and internist of the plan (note: we are not currently in a position to do this in China).
4.If the patient is taking antipsychotic medication and is stable, but discontinuing the medication will likely result in relapse, it is usually recommended to continue taking antipsychotic medication and monitor liver function, weight and blood sugar.
5. Try to avoid the following drugs: valproic acid, carbamazepine, lithium, lamotrigine, and prolonged use of benzodiazepines (Note: Suhagra is a class X).
6.For all women of childbearing age, doctors have the obligation to inform and record accordingly, and should check before using the medication if they are not sure whether they are pregnant or not (Note: At present, the conditions in our country have not reached this requirement).
7. If the physician has performed a clinical evaluation of the patient, including questions about pregnancy, uncomplicated periods, any pregnancy plans, etc., these should be recorded in the medical record (Note: at present, our domestic conditions have not met this requirement).
II. Planned Pregnancy
Theoretically, pregnancies should be planned whenever possible, as unplanned pregnancies often make treatment and related management very reactive.
2. During the pre-treatment evaluation, for patients with significant psychiatric symptoms who are actively preparing for pregnancy, the physician should advise the patient to postpone the pregnancy plan until her psychiatric status is effectively controlled.
3. Advise to stop taking valproic acid, carbamazepine, lithium, lamotrigine, and switch to other less risky drugs such as antipsychotics if necessary (a comparison of the risks and efficacy of olanzapine during pregnancy showed that its efficacy (prevention of disease relapse during pregnancy and delivery) outweighed the risks to the mother and fetus, but the results of such individual studies should only be used as a reference and should still be consulted).
4. Inform the patient that antipsychotic medications may cause an increase in prolactin levels, which may lead to a decrease in the chances of conception, and if the increase in prolactin levels is significant, consider switching to other medications that have less impact.
5.If the patient is considering pregnancy, it is recommended to reduce the dose appropriately under the guidance of the doctor.
6.If the patient becomes depressed after stopping the medication, cognitive behavioral therapy or other patient-appropriate psychotherapy techniques can be considered. If antidepressants must be used, SSRIs other than paroxetine are recommended.
7. If a patient taking lithium salts plans to become pregnant, it is recommended that
a. If the patient’s condition is stable and the risk of relapse is not high, then it is recommended to gradually stop or change the medication under close observation and guidance of the physician.
b. If the patient is still unstable or at high risk of relapse, it is recommended to gradually switch to an antipsychotic drug; or gradually discontinue lithium and reintroduce it after 3 months of pregnancy (if the patient is not planning to breastfeed and previous treatment suggests that lithium is more effective than other drugs), but this is a riskier medication and requires the physician to discuss with the patient and the patient’s family and fully weigh the pros and cons before deciding.
c. If the patient has had manic episodes during pregnancy, and the previous treatment is only good for lithium, after detailed risk discussion, lithium can be considered to continue to take lithium, but this is a risky medication, and the doctor must discuss with the patient and the patient’s family and fully weigh the pros and cons before deciding.
d. If the patient continues to take lithium salts during pregnancy, it is recommended that the blood lithium concentration (0.6-1 mmol/L) be monitored every 4 weeks and weekly after 36 weeks of pregnancy until 24 hours after delivery, and the drug dose will always be adjusted according to the blood concentration.
III. Unplanned pregnancy
1.Quickly confirm whether pregnancy.
2. stop taking valproic acid, carbamazepine, lamotrigine under medical supervision.
3. if it is within the third trimester of pregnancy and the condition is stable, it is recommended to gradually discontinue lithium salts over a period of >4 weeks and inform the patient of the risk of congenital malformations in the fetus (ebstein malformation 0.005 % → 0.01 to 0.005 %), but the treatment plan specific to each patient needs to be interviewed by the physician.
4. if the patient continues to take lithium salts during pregnancy, it is recommended that blood lithium concentrations be monitored every 4 weeks and weekly after 36 weeks of gestation until 24 hours after delivery, and the drug dose will always be adjusted according to the blood concentration.
5. medication preference for antipsychotic medication.
6. appropriate screening and counseling on whether to continue the pregnancy and testing for fetal risk, and the newborn needs to undergo a full pediatric evaluation.
7. For those who have greater difficulty in adjusting or changing medication, hospitalization is recommended.
IV. Acute manic episode during pregnancy
1.If you are taking antipsychotic drugs, consider increasing the dose, combining or switching to other antipsychotic drugs with more powerful antimanic effects.
2.If not currently taking antipsychotic drugs, consider adding or switching to antipsychotic drugs.
3.If the patient has poor efficacy of antipsychotic drugs and has severe manic episodes, consider switching or co-using ECT, lithium salt, valproic acid, and inform the patient and the patient’s family in detail and comprehensively of the possible risks of the drugs to the fetus.
4. If valproic acid is used, it is recommended to use the lowest effective dose possible, and the combination of drugs (except carbamazepine) may be considered, and the maximum dose should not exceed 1g/day.
5.Because of the risk to the fetus, try not to choose items 3 and 4. In my personal experience, items 1 and 2 are chosen, i.e., almost all cases can be controlled with antipsychotic drugs.
6. For those with severe manic symptoms and difficult to control condition, hospitalization is recommended.
V. Acute depressive episode during pregnancy
1.Mild and moderate depression is usually treated mainly with non-pharmacological treatment, such as active self-adjustment of patients under the guidance of doctors, family support and cooperation, psychotherapy, phototherapy, sleep deprivation therapy, etc., and enhanced psychiatric follow-up, and antidepressant medication can be used when necessary.
2.Severe depression is recommended to be treated with medication combined with psychotherapy, according to the characteristics of the patient’s condition and previous medication selection, usually SSRI alone (except paroxetine), or combined with other drugs, or combined with electroconvulsive therapy, and inform the potential risks of treatment, closely observe the changes in the condition, prevent accidents, if necessary, consider hospitalization, and if it turns manic, discontinue antidepressants under the guidance of the doctor.
Sixth, prenatal examination
1. If you are taking drugs such as valproic acid, carbamazepine, lithium salt, etc., you need to do tests on neural tube developmental malformations, such as serum and amniotic fluid alpha-fetoglobulin levels, high-resolution ultrasound, etc. before 20 weeks of pregnancy; and fetal echocardiography is recommended from 16 to 18 weeks of pregnancy to detect cardiovascular developmental abnormalities, and folic acid supplementation.
2. Due to changes in hepatic metabolism, renal excretion, blood volume, and plasma protein binding rate during pregnancy and perinatal period, the patient’s medications need to be adjusted during pregnancy and blood levels monitored. During labor and delivery, a significant decrease in maternal blood volume occurs, which usually requires a reduction in the dose of the drug.