Important Considerations of Serious Mental Illnesses in Women During Periods of Hormonal Flux
The Pubertal Transition and Menarche
The rate for SMI starts to become higher among girls than boys during menarche. In addition to hormonal factors, girls are more heavily influenced by environmental triggers, such as peer pressure and societal roles. Many girls start using substances or become sexually active around this time. Girls with SMI can be more vulnerable to sexual predators. This is a good opportunity to discuss contraception as up to half of pregnancies in this population are unwanted or unplanned, and there is a high incidence of abortion and custody loss.[28,29] Early identification of symptoms and prompt intervention are important for harm reduc-tion and better long-term outcomes.
Serious Mental Illnesses Associated With the Menstrual Cycle
Psychiatric symptoms associated with the menstrual cycle present in a spectrum that constitutes premenstrual syndrome, premenstrual exacerbation of a depressive disorder, premenstrual dysphoric disorder (PMDD), and premenstrual psychosis. It is believed that approximately two-thirds of women with bipolar disorder have worsening mood symptoms in the days preceding their period and PMDD occurs in about 40% of women with underlying unipolar depression. The prevalence of peri-menstrual psychosis is unclear and many cases go undiagnosed. Allopregnenolone, a GABAA receptor agonist involved in the stress response, has been implicated in psychiatric decompensations during the luteal phase. The diagnosis typically requires prospective mood charting over the course of at least two menstrual cycles. The treatment consists of both pharmacological and nonpharma-cological approaches. Selective serotonin reuptake inhibitors (SSRI) are first-line treatment for PMS and PMDD and have a high response rate (https://www.uptodate.com/contents/treatment-of-pre-menstrual-syndrome-and-premenstrual-dysphoric-disorder?topicRef=2159&source=see_link). They can be prescribed continuously, during the luteal phase only, or at the onset of symptoms. Perimenst-rual psychosis typically requires the use of antipsy-chotic medications (with or without mood stabilizers if the underlying diagnosis is bipolar dis-order). Continuous use of hormonal contraceptives to inhibit ovulation also leads to effective results. Nonpharmacological approaches include lifestyle changes, including good sleep hygiene, physical exercises, mindfulness meditation, and dietary changes.
As stated before, contraception is a very important topic to discuss with women with mental ill ness, especially SMI as they experience a high number of unwanted pregnancies and sexual abuse and are more predisposed to mood and psychotic episodes or exacerbations during the luteal phases of their cycles and in the postpartum period. Contra ceptives containing estrogen are preferred over pro gesterone-only medications because of estrogen's protective effect on psychosis and progester-one's negative effect on mood. This comes, how ever, at the expense of increased cardiovascular risk, especially in older women, smokers, or those with risk factors, including a positive personal or family history for cardiac disease, in which case progester one intrauterine devices may be the preferred choice.
Until relatively recently, pregnancy was perceived as a state of emotional well-being that conferred some protection against the exacerbation of mental illness. We now know that pregnancy is a period of increased vulnerability with regards to psychopathology. Psychiatric issues are the most common complication of pregnancy, with one in seven women having worsening psychiatric symptoms during the perinatal period.[33,34]
Despite the American Council for Obstetricians and Gynecologists' recommendation for universal screening, it still does not happen consistently, especially among minorities and underserved pop ulations. The most widely used screening tools for perinatal depression are the Edinburgh Postnatal Depression Scale (EPDS) and the 9-item Patient Health Questionnaire (PHQ-9) for depression.
Continued treatment with psychotropic medications is recommended to prevent a psychiatric decompensation during pregnancy and in the post-partum period as untreated mental illness during pregnancy increases the risk for adverse obstetrical, maternal, and fetal outcomes[35–39] Untreated depression is also linked with increased risk of depression in adolescence and transgenerational risks. Despite the common hesitation to use medications during pregnancy, two-thirds of preg nant patients take at least one prescription medication and one-third take a psychotropic medication. Thanks to the national registry for antipsychotics, we now have robust data on the reproductive safety of most antipsychotics regarding teratogenicity, obstetrical outcomes, and metabolic side effects, including gestational diabetes.
An individualized risk/benefit assessment should be performed and the potential benefits of antipsychotic treatment generally outweigh the potential risks of its discontinuation. With few exceptions (e.g. valproic acid), the same agent(s) required to stabilize a patient prior to pregnancy should be continued. The lowest effective dose to maintain stability should be used and polypharmacy ideally avoided or minimized. Some agents require periodic adjustments during pregnancy because of the physiological changes of pregnancy (e.g. increased plasma volume, metabolic changes secondary to increases in estrogen, increased renal excretion). Lamotrigine doses, for example, need to be increased as higher estrogen levels increase its metabolism and lithium levels should be periodically monitored and its dose adjusted accordingly.
In addition to pharmacological treatment, psychotherapy, lifestyle modifications (e.g. smoking cessation, physical exercises, sleep hygiene), increased psychosocial support, and control of medical comorbidities are very important aspects of treatment.
The most widely prescribed class of medications in pregnancy are the SSRIs, usually well tolerated and benign during pregnancy and lactation. The most common adverse outcome associated with their use is neonatal adaptation syndrome, characterized by respiratory distress, tremor, irrita bility, sleep disturbance, and feeding difficulties. It is typically mild and self-limited, does not require specific treatment and is not associated with lasting sequelae.
Persistent pulmonary hypertension of the new born (PPHN) is another complication linked to the use of SSRIs in pregnancy. Nevertheless, recent studies are reassuring, with one recent review reporting lower rates of PPHN than expected (2–3 cases/1000, compared with baseline rate of 1–2/1000), with an even lower risk when controlling for maternal depression. There have been studies correlating SSRIs and autism spectrum disorders (ASD). Many of those studies, however, did not control for important variants, such as severity of maternal symp toms, medication compliance, heritability, and behavioral factors.
Most of the safety data of mood stabilizers in pregnancy comes from epilepsy registries rather randomized controlled trials. Valproic acid should be avoided throughout the entire pregnancy because of high risk of teratogenicity, neurocogni-tive impairment, and adverse obstetrical outcomes. It is crucial to discuss contraception options if one chooses to prescribe it to a woman of reproductive age, which ideally should not happen. Data on lamotrigine in pregnancy is reassuring with recent studies finding no increase in the risk for major malformations or neurocognitive deficits.
Lithium is an effective mood stabilizer with antisuicidal properties that helps prevent postpartum psychosis when used prophylactically in the third trimester. Important considerations include the risk of Ebstein's cardiac malformation, which affects 1–2 per 1000 infants with first-trimester exposure to lithium. Lithium levels should be periodically checked and the dose adjusted because of physiological changes that occur throughout the pregnancy that can affect lithium levels. Holding lithium 24 – 48 h prior to delivery can prevent lith ium toxicity. Folate supplementation is recom mended for women taking mood stabilizers during pregnancy.
The postpartum is a period ofhigher vulnerability in a woman's life, postpartum depression (PPD) being a public health concern that affects between 10 and 20% of women within 1 year of delivery. Untreated PPD is associated with adverse maternal and neonatal outcomes. Despite the high prevalence and the recommendation for universal screen ing, screening does not happen consistently and a large percentage of women report not being asked about depression during prenatal visits (one in five) or postpartum visits (one in eight).
Risk factors for PPD include untreated depres sion during pregnancy, history of pregnancy complications, belonging to a racial minority or lower socioeconomic status, substance use, and history of trauma. Treatment is similar to treatment of major depression outside of pregnancy (i.e. medications, psychotherapy, behavioral modifications). In 2019, the Food and Drug Administration (FDA) approved the first drug specifically for PPD. Brexanolone, an allosteric modulator on the synaptic and extrasynaptic gamma-aminobutyric acid GABAA receptors, is given as an intravenous infusion over the course of a few days and significantly reduces depressive scores in a relatively short period of time.
Rapid hormonal changes and psychosocial factors put women at increased risk for developing postpartum psychosis, a true psychiatric emergency that affects 1 in 1000 to 1 in 2000 women.[48,49] Untreated mental illness during pregnancy, particularly bipolar disorder, is another important risk factor. With a quick onset and rapidly fluctuating course, it is imperative that clinicians closely monitor those women and have good familiarity with this entity as it is associated with severe morbidity and a 4% risk of infanticide. Immediate psychiatric hospitalization with treatment with antipsychotic medications is required. Additionally, medications to suppress lactation should not be used in women at risk as they are usually D2 agonists and may increase the risk of postpartum psychosis.
Breastfeeding has numerous benefits for the mother and the baby, including promoting a health ier bonding/attachment, and should be encouraged in women with SMI according to individual prefer ence with closely monitoring of the infants. The amount of psychotropic medications excreted into the breastmilk is relatively too low to cause neonatal harm.
Curr Opin Psychiatry. 2022;35(3):157-164. © 2022 Lippincott Williams & Wilkins