The brain is a highly complex organ from which the mind – with its diverse array of thoughts, feelings, and behaviors – emerges. Our mental life makes us uniquely human, and provides a richness of experience that is awe-inspiring. Our complex mental functioning can go awry at times, and when problems are idiosyncratic, sustained, pervasive, and/or interfere with functioning, they may rise to the level of a diagnosable mental health condition. Some of these disorders – like schizophrenia or bipolar affective disorder – can come out of the blue, unbidden, much like nonpsychiatric diseases such as cancer or diabetes. Other mental conditions begin only after exposure to an extraordinarily adverse event or – in someone with personality vulnerabilities – to more routine stressful events. Some mental conditions are more behavioral in nature, such as eating disorders (ED), sexual disorders (e.g., pedophilia, voyeurism) and substance use disorders (SUD), which typically begin with an initial choice to engage in the behavior, followed by a pleasurable effect that leads to the behavior happening repeatedly as the drive becomes stronger and the choice more difficult to resist . Women with opioid use disorders (OUD) in pregnancy are – by definition – suffering from at least one mental health condition. However, the likelihood that they have another co-occurring disorder is quite high.
Pregnant and postpartum women – compared to nonpregnant women – seem to have significantly lower rates of most mental health conditions, including SUD. (The main exception is found among postpartum women who may have significantly higher rates of major depressive disorder [MDD]) . Suggested risk factors for increased rates of mental health conditions among pregnant and postpartum women include SUD, personal history of other mental illness, young adult age, lack of social support, a negative attitude toward pregnancy, current or previous pregnancy complications, stressors, and a history of trauma [2–6].
How do prevalence rates of mental health conditions compare between pregnant women with SUD and those without SUD? Not surprisingly, pregnant women with SUD tend to have higher rates of co-morbid mental health conditions than pregnant women without SUD. For example, one study reported women with an SUD had 3 times the odds of having a psychiatric illness than women without SUD . Opioid-dependent pregnant women are at increased risk for personality disorders, post-traumatic stress disorder (PTSD), anxiety, depression, and bipolar affective disorder .
A large, multisite study of opioid-dependent pregnant women found 65 percent who endorsed symptoms consistent with one or more mental health condition (49 percent mood disorder; 40 percent anxiety disorder). Compared to the opioid-dependent women without psychiatric symptoms, they had more impairment on the Addiction Severity Scale, especially in the domains of Family/Social Functioning, and Psychological Functioning. Those who reported symptoms of MDD, dysthymia, hypomania, generalized anxiety disorder (GAD), PTSD and suicidality had significantly higher scores in substance use severity .
These and other epidemiologic findings suggesting high prevalence of mental health conditions among pregnant/postpartum women with SUD highlight the importance of screening for such disorders in this population. Pregnant women are an especially important population to screen for these illnesses, as they not only affect the health of the mother, but also can adversely impact the pregnancy and the baby. Additionally, due to the effects of psychiatric symptoms on substance use (and vice versa) and psychosocial functioning, evaluation and effective treatment should be a routine part of managing pregnant women with SUD.
Although psychiatrists are the only physicians trained exclusively in the evaluation and treatment of disordered thoughts, feelings, and behaviors, patients with mental health concerns usually seek and receive treatment from nonpsychiatric primary care providers. The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM) provides a common language by which clinicians – regardless of specialty training – and researchers can more reliably diagnose patients, and the DSM has led to some modest advancements in treatment. However, the DSM must not be the sole basis of a patient’s evaluation. The DSM is meant only “to assist trained clinicians in the diagnosis of their patients’ mental disorders as part of a case formulation assessment [emphasis ours] that leads to a fully informed treatment plan for each individual.”  Clinicians are meant to not rely on the DSM’s helpful checklist of signs and symptoms as the sole means to formulate a patient’s condition. Instead clinicians are advised to use the DSM as just one part of the assessment and to take into consideration the multiple and complex aspects of each individual who comes to them for help .
For the primary care clinician who is first evaluating a pregnant woman with OUD or co-occurring mental health conditions, the following streamlined approach (Box 4.1) is recommended.
1. Gather a family history of psychiatric illness including depression, mania, schizophrenia, attempted/completed suicides, and attention problems.
2. Inquire about any childhood illnesses and behavioral symptoms (e.g., fire setting, animal cruelty, fighting, truancy). Ask about potential attention disorder symptoms (e.g., inattention, hyperactivity, impulsivity) and any special education requirements.
3. Take an educational and occupational history.
4. Obtain a sexual history (including any sexual abuse) and marital/relationship history (e.g., partner substance use, supportiveness, interpersonal violence). Ask where she is currently living and any recent history of homelessness. Also inquire about religious affiliations.
5. Document legal history and, if available, conduct an online state judiciary case search (each state maintains its own website for which one can search online).
6. Obtain a detailed substance use history, including any tobacco, alcohol, marijuana, and cocaine use, as well as use of other illicit drugs (e.g., LSD, MDMA, PCP, methamphetamine, synthetic marijuana, solvents, inhalants, caffeine) and prescription drug abuse (e.g., amphetamines, benzodiazepines). For each drug, include route (e.g., intranasal, intravenous, inhalation), age at first use, age at first daily use, current use and duration, maximum use, last use, longest abstinence (date/length/context), and withdrawal symptoms. Also include any prior substance abuse treatment, including medically supervised withdrawal, rehabilitation programs and pharmacologic treatment (e.g., methadone, buprenorphine, disulfiram, naltrexone).
7. Document other medical and surgical history, outpatient providers (primary care provider, psychiatrist, therapist, case manager), and the patient’s current medications and drug allergies.
8. A complete review of systems is needed.
9. Clarify any past history of mental health concerns, identifying time of first onset (e.g., childhood), without regard to treatment-seeking. Symptoms during periods of abstinence from opioids and/or other substances should be noted. Include all suicide attempts with age, description of method, circumstances, and any medical consequences to best understand both the intent and potential lethality of each attempt. Include all psychotropic medication trials with dose, duration, side effects, and efficacy.
10. Outline a description of the events leading to the current presentation, including a detailed history of substance use, recurrence of symptoms, medication nonadherence, and life stressors. Again, inquire about the temporal relationship between opioid and/or other substance use and any change in the patient’s thoughts, feelings, and behaviors.
11. Conduct a thorough mental status examination, including assessments of affect (mood, sleep, appetite, energy, concentration, and view of self/future (including suicidal thoughts, plans, intentions)), hallucinations, delusions, orientation, and memory.
12. Conduct a thorough physical examination.
13. Obtain laboratory testing including toxicology screens.
14. Electrocardiogram for QT interval monitoring may be indicated. This is especially important for patients who are receiving or may receive methadone-assisted treatment, which is associated with prolongation of the QT interval and possible cardiac arrhythmia (Torsade des Pointes).
Behavioral Treatments and Mental Hygiene
Women who use opioids in pregnancy and also have co-occurring mental health conditions need specialized services designed to optimize treatment outcomes for both their opioid use and their co-occurring disorders. Normal mental life relies on healthy biological and psychological functioning, which can be influenced by a variety of factors. When normal mental functioning goes awry, treatments based in the sciences of biology and psychology – and even sociology – are often necessary. For example, both biological treatments – such as methadone, buprenorphine, naltrexone – and psychological treatments – such as motivational interviewing, cognitive behavioral therapy, contingency management – are effective for OUD, and are often most effective in combination.
When opioid-using pregnant women have co-occurring mental health conditions, both pharmacologic and behavioral treatments – along with social supports – are usually necessary for successful outcomes. In addition to prescribing medications to remedy any obvious mental diseases like manias or severe depressions, clinicians need to engage patients in individual talk therapy. One goal of psychotherapy is to help women make sense of the losses they have encountered because of their opioid use and other mental health condition(s) and to offer hope that they can overcome these and any future challenges. Clinicians can also help women better understand their individual personalities, help them set goals, and guide them through all of life’s provocations, steering a steady course toward wellness. Couples and family therapy can also be helpful, even for patients with brain-based diseases like schizophrenia and manic depressive illness. It is helpful to talk directly with patients and their families about how pharmacologic and behavioral treatments can be enhanced by social supports based in the domains of family, community, education, and employment. For example, less expressed emotion in families improves treatment outcomes in schizophrenia  and regular religious service attendance can lower the risk of suicide .
Introduction to Medication in Pregnancy
When evaluation of an opioid-dependent pregnant woman indicates that pharmacologic treatment is appropriate (likely in addition to psychotherapy), the available options must be weighed for each individual patient and situation. We will review what is currently known about the use of psychotropic medications in pregnancy, though this is not an exhaustive list including all risks and benefits (please see  for a more detailed discussion). When deciding whether to prescribe a psychotropic medication to a pregnant woman, there are several key factors to consider (Figure 4.1). Not only should the risks and benefits of treating the mother be considered, but one must also contemplate the potential risk of medication exposure to the fetus. The risks of untreated illness for the mother and fetus should also be taken into account, as some conditions have life-threatening consequences when untreated, including suicide, and can also serve as an exposure to the fetus that can affect subsequent development of the child.
Figure 4.1 General factors to consider when forming a treatment plan for a pregnant woman with OUD, and their potential effects on the health of the mother and fetus
Given the risks that maternal mental health conditions pose for both mother and child, restoring a pregnant woman to mental health is a high priority. Each woman’s past psychiatric history, severity of symptoms, medication response and wishes regarding pharmacologic treatment during pregnancy must be explored prior to developing an individualized treatment plan . Each plan should include a combination of pharmacologic and behavioral treatment strategies.
The prevalence of ADHD is greater among individuals with substance use – including opioid-using women – than in the general population. At its core, ADHD is a condition in which an individual is less able to inhibit impulses – to move, to act, to pay attention to less salient stimuli, resulting in the classic ADHD triad of hyperactivity, impulsivity, and inattention. Pharmacologic treatments include stimulant (e.g., methylphenidate, dextroamphetamine) and nonstimulant (atomoxetine, guanfacine) medications. The best studied of these in pregnancy are methylphenidate and atomoxetine [15–18]. Pharmacologic treatments for ADHD are unlikely to be initiated during pregnancy, as the benefits of medication use during pregnancy – given that ADHD is rarely a life-threatening condition – are unlikely to outweigh the risks. Also, because most stimulant medications can be misused and carry with them the risk of addiction, these are especially unlikely to be initiated in opioid-using women during pregnancy. However, pharmacologic treatments are just one component of ADHD care. Behavioral treatments are critically important in the long-term treatment of these disorders, as well. Although a discussion of these is beyond the scope of this review, the interested reader is referred to several recent reviews on this topic [19, 20].
Major Depressive Disorder (MDD)
Hallmark symptoms of MDD include pervasive and sustained changes in mood – irritability and/or sadness – and a change in one’s outlook toward self or the future, manifest often as guilt or hopelessness. An episode of MDD may also be heralded by a change in one’s sleep, appetite, concentration, energy level, ability to experience pleasure, and/or social engagement. Careful screening for MDD among women of reproductive age is imperative, as this condition is relatively common during pregnancy with a prevalence of about 8–13 percent, and depressive symptoms during pregnancy have been associated with poor outcomes such as low birth weight and preterm birth . Depression has also been found to be associated with risk factors that would affect pregnancy outcomes such as substance use (including smoking), hypertension, gestational diabetes, and preeclampsia . Among pregnant women with SUD, about 40–73 percent have comorbid depression and about 50 percent have postpartum depression 6 weeks after delivery . Studies of pregnant women with OUD who were maintained on methadone and had co-occurring depression suggest poor outcomes, such as lower clinic attendance, and more drug-positive urine samples  (Figure 4.1).
The most commonly studied class of antidepressant medication includes selective serotonin reuptake inhibitors (SSRIs), which have been found to be safe in pregnancy among most studies [23–26]. Similarly, most studies have not associated use of tricyclic antidepressants (TCA) [27–30], or other antidepressants [31, 32] with major malformations. There are several conditions that have been discussed in relation to newborns who were exposed to antidepressants in utero, including poor neonatal adaptation syndrome, persistent pulmonary hypertension of the newborn, and autism spectrum disorder. Most of the studies showing these effects are retrospective, introducing recall bias, and suffer from poor design, not controlling for the effects of the maternal mental illness itself [14, 33].
In addition to medication, there are particular modalities of psychotherapy that are helpful for MDD. When considering using psychotherapy alone, or in combination with medication, severity of illness and efficacy of the particular psychotherapy should be considered. A particular modality with known efficacy for both MDD and SUD is cognitive-behavioral therapy (CBT). CBT for depression in pregnancy has been found to be effective, and the combination of CBT and medication for depression during pregnancy and the postpartum period has been found to be more helpful than medication alone or CBT alone .
Bipolar Affective Disorder (BPAD)
Symptoms of BPAD included mood lability, with irritability, anger or euphoric/expansive mood, impulsivity, lack of need for sleep, pressured speech, high self-attitude and increased goal-directed activity. There is a high rate of disease recurrence (81–85.5 percent) among pregnant women who stopped taking their mood stabilizers versus relapse rates (29–37 percent) of women who maintained their pharmacotherapy during pregnancy [35, 36]. The use of CBT is effective for BPAD in combination with pharmacotherapy, but there is little evidence for its efficacy as monotherapy . Thus, medication is the preferred method of treatment of BPAD and prevention of relapse.
Mood stabilizers are commonly used for treatment of BPAD. Lamotrigine is an effective and relatively safe  medication for treatment of BPAD, though levels may need to be followed for dose adjustments during pregnancy . Use of valproic acid and carbamazepine during pregnancy is not generally recommended due to safety concerns for the fetus . Lithium use during pregnancy has been associated with an increased risk of the serious, but very rare, congenital heart defect known as Ebstein’s anomaly . Again, the severity of maternal illness should be considered when weighing the risks of taking lithium, and, if used, blood levels should be followed, as higher doses may be required, with a reduction or discontinuation at the time of labor to avoid toxicity . Neuroleptic medications with indications for BPAD such as lurasidone have also been used in pregnancy and are discussed in the section on schizophrenia.
Delirium and Dementia
A temporarily altered level of consciousness is often a desired effect of substance use, and is often associated with a temporary but global decline in cognitive functioning called delirium. Delirium can result from substance use/intoxication, as well as withdrawal from certain substances (alcohol, benzodiazepines). Additionally, it can be caused by systemic or brain infections, and other – often very serious – medical causes. In order to treat delirium, the specific etiology must first be identified. For some causes of delirium (such as hallucinogen-induced delirium), the primary treatment is time and supportive therapy. For other causes such as alcohol withdrawal delirium (also known as delirium tremens), the treatment would involve a benzodiazepine or other medication taper. Because of the severe and potentially life-threatening nature of delirium, pregnancy is usually not a contraindication for treatment.
Chronic substance use can also result in a global decline of cognitive functioning, but – unlike with delirium – this decline is usually permanent and not accompanied by a normal level of consciousness. Psychiatrists describe this permanent decline as dementia, and it is usually caused by chronic use of extremely neurotoxic substances such as alcohol or inhalants. Unfortunately, treatment for dementia is largely supportive.
Sleep during pregnancy – especially the third trimester – is often elusive, due to fetal movement, gastroesophageal reflux and other physical changes. Over 90 percent of pregnant women report using over-the-counter antihistamines (e.g., diphenhydramine, doxylamine, hydroxyzine) to help with insomnia . Although a systematic review of antihistamines and birth defects described an association between fetal antihistamine exposure and congenital malformations, the studies reviewed had serious methodological limitations . Another review identified only one study on this topic and it showed no association between fetal antihistamine exposure and congenital malformations .
Prescription sleep aids are also used in pregnancy, although less commonly than the over-the-counter medications. Because benzodiazepines are highly addictive and are often used for euphoric effect in combination with opioids, they are usually contraindicated in women with OUD. In addition, benzodiazepine use has been associated with multiple adverse neonatal outcomes including low APGAR scores, poor feeding, and – in some studies – cleft palate defects [44, 45]. Thus, the use of benzodiazepines for insomnia in this population is minimal. Benzodiazepine-like sleep agents (eszopiclone, ramelteon, and zolpidem) have not been associated with major organ malformations , but longer-term (greater than 90 days) zolpidem use has been associated with low birth weight, preterm birth and cesarean delivery . CBT for insomnia is considered to be the first-line treatment and would be especially appropriate during pregnancy [47, 48].