Additional considerations in gynecologic care

Depression

Major depression is common in women, with a lifetime prevalence of 20% to 25%. Although boys and girls are equally likely to experience depression, major depression is about twice as common in women as in men, starting in adolescence. Worldwide, depression is one of the leading causes of functional impairment and disability. The diagnosis of major depression refers to persistent sadness or lack of interest or pleasure in usual activities, lasting for at least 2 weeks. It is accompanied by symptoms such as changes in eating habits, trouble sleeping, lack of energy and motivation, poor memory or concentration, and feelings of guilt, worthlessness, hopelessness, and despair. In severe cases, depression may lead to suicidal thoughts and actions. The diagnostic criteria for major depression are listed in Box 9.1 . The Patient Health Questionnaire (PHQ-9) ( Table 9.1 ) is a useful screening tool for major depression, can be filled out quickly by the woman in the waiting room or in the office before a visit, and helps in identifying depression, monitoring effects of treatment, and educating the woman about her own characteristic symptoms of depression. Scores of 5, 10, 15, and 20 are cutoff scores indicating mild, moderate, moderately severe, and severe depression, respectively.

The cause of major depression is unclear. It may occur without a clear stress or precipitant, especially in women with a strong family history of depression who are genetically predisposed. A family history of depression, a prior depressive episode, and older age are all risk factors for depression. Rates of depression are higher in women who are socioeconomically disadvantaged. In addition, stressors such as loss of relationships and loved ones, divorce, role transitions, interpersonal conflicts, interpersonal violence, medical illness, or feelings of being trapped in a stressful situation without a way to escape or cope can precipitate depression. Depressive symptoms in a particular person may be uniquely determined by individual factors, such as family relationships while growing up and past experiences that are highly meaningful and evoke negative feelings and memories triggered by current situations or events.

The increased rate of depression in women starting at menarche has also been thought to result from hormonal factors. There are clear increases in risk for depressive symptoms premenstrually, with some women only experiencing mood symptoms at this time and others noting a worsening of underlying depression in the week or two before menses (for a discussion of premenstrual dysphoric disorder, see Chapter 35 ). The postpartum period is a high-risk time for depression and is the highest risk time in a woman’s life for psychiatric hospitalization. There is also an increase in depressive symptoms at the time of menopause and the menopausal transition.

The differential diagnosis of major depression includes adjustment disorder, persistent depressive disorder (dysthymia), depression related to drugs and alcohol or secondary to a medical condition, and bipolar disorder. Adjustment disorder is a stress-related, short-term emotional or behavioral response to a stressful life circumstance. Depressive symptoms begin within 3 months of the onset of the stressor and resolve within 6 months once the stressful circumstance ends. The symptoms do not meet criteria for major depression. The physician can help a woman with an adjustment disorder by helping her to problem solve and cope with the situation she is in or by referring her for short-term therapy or counseling.

Persistent depressive disorder (previously called dysthymic disorder ) is a chronic, low-grade depression, with symptoms present more than half the time for at least 2 years and no more than 2 months without depressive symptoms during that time. The best treatment is antidepressant medication and psychotherapy, but this condition is often harder to treat than major depression because of its chronicity. Depressive symptoms can also be caused by alcohol or drug use or by medical conditions, such as hypothyroidism, vitamin B ₁₂ deficiency, anemia, or cancer (most classically pancreatic cancer). Women presenting with depression should be screened for medical disorders and asked about use of alcohol and drugs.

Probably the greatest dilemma in deciding to prescribe antidepressants is the concern that if the woman has bipolar disorder, antidepressants can cause a “switch” into a manic episode. Manic episodes are characterized by feelings of euphoria or irritability and increased energy or goal-directed activity, with symptoms such as decreased need for sleep, increased activity or agitation, talkativeness, racing thoughts, grandiose and unrealistic plans, and impulsive and risky behavior. If a woman has been hospitalized for mania or has had such symptoms for a week or more in the past, the diagnosis may be clear. However, people often do not recall their manic symptoms or have little insight into them, or they may have had briefer periods of a few days (hypomania) that still predispose them to mania with antidepressants. Screening questionnaires such as the Mood Disorder Questionnaire (MDQ) or clinician-administered Composite International Diagnostic Interview (CIDI) (STABLE Resource Toolkit; , pp. 14-20) can be helpful in assessing the likelihood of a bipolar disorder. Difficulty determining whether or not a woman has bipolar disorder is an indication for psychiatric consultation because bipolar depression usually requires treatment with a mood stabilizer or atypical antipsychotic medication instead of, or combined with, an antidepressant.

Treatment of major depression can include antidepressant medication, psychotherapy, or both. Because both antidepressant medication and psychotherapy are effective, the initial choice of treatment can be made according to the woman’s preference, although for more severe depression medication is indicated. Commonly prescribed antidepressant medications and dosages are listed in Table 9.2 . A 2009 meta-analysis by Cipriani and colleagues suggested that the best combination of efficacy and tolerability is found with sertraline or escitalopram ( ). Because of their more benign side effect profiles, it is reasonable to start a selective serotonin reuptake inhibitor (SSRI) as the first antidepressant in most cases. SSRI side effects include gastrointestinal symptoms (nausea, diarrhea, vomiting), which are minimized by taking the medication with a meal. Other common side effects include initial dizziness and headaches and sexual dysfunction, most commonly delayed orgasm or anorgasmia. Doses of the SSRI citalopram exceeding 40 mg daily are not recommended because of the risk of QT prolongation. SSRIs may also cause uncomfortable withdrawal symptoms if discontinued suddenly. Withdrawal symptoms can include gastrointestinal symptoms, headache, dizziness, and “electric shock” sensations. Fluoxetine, an SSRI with a long half-life, is not generally associated with withdrawal symptoms and women discontinuing other SSRIs can be switched to fluoxetine to minimize withdrawal. Fluoxetine also has the strongest evidence base for medication treatment of major depression in children and adolescents.

Serotonin and norepinephrine reuptake inhibitors (SNRIs) include venlafaxine and duloxetine. Venlafaxine is associated with a dose-related risk for gradual onset of hypertension, and blood pressure should be monitored carefully on this medication. SNRI side effects include gastrointestinal side effects, headaches, dizziness, anorgasmia, activation, and anxiety. Bupropion appears to exert its therapeutic effect by enhancing effects of dopamine and norepinephrine. It increases energy and can cause insomnia, increased anxiety, headaches, and gastrointestinal side effects. Bupropion also lowers the seizure threshold, especially at doses greater than 450 mg daily, and should not be used in women with a history of a seizure disorder or bulimia. Mirtazapine is an alpha ₂ -adrenergic, 5-HT2, and 5-HT3 receptor antagonist, which also has antihistaminic effects. Its common side effects include sedation and weight gain. Trazodone is a highly sedating serotonergic antidepressant that is used primarily at low doses (25 to 100 mg at bedtime) for insomnia. Tricyclic and monoamine oxidase (MAO) inhibitor antidepressants are infrequently prescribed because of side effects, in addition to dietary restrictions and the risk of hypertensive crisis with MAO inhibitors. It is important to warn women that antidepressant medication can take up to 4 to 6 weeks to work and to schedule a follow-up visit within that time to monitor treatment adherence, side effects, and therapeutic response. The Food and Drug Administration (FDA) has required black box warnings regarding increases in suicidal ideation and behavior with antidepressants in children, adolescents, and young adults . The mechanism for this is unclear but may be in part an increase in energy and motivation before improvement in mood. Women should be warned of this potential phenomenon and instructed to stop the medication and call the provider if this occurs. Overall, antidepressants reduce depression and risk for suicide, but this potentially serious side effect is another indication for close follow-up early in treatment. In particular, patients younger than 25 years should be seen 1 to 2 weeks after beginning antidepressant medication.

Effective psychotherapies for depression include cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). CBT addresses the negative thinking that is characteristic of depression, such as the belief that things are bad now, have always been bad, and will always be bad, or thoughts of worthlessness and guilt. In addition, behavioral activation, or scheduling activities that provide a sense of accomplishment, mastery, or pleasure, is helpful in depression, and exercise has been shown to decrease depressive symptoms. IPT addresses life changes and interpersonal challenges that contribute to depression. These include grief, conflicts in interpersonal relationships including marital or intimate partner conflicts, and transitions in roles within work or the family. These therapies are usually weekly for an hour for 3 to 4 months. In cases of clear-cut couples issues, couples therapy may be indicated, especially after the woman has recovered from depression sufficiently to participate in such therapy. Other nonmedication treatments for depression include morning light for seasonal or winter depression and electroconvulsive treatment (ECT) or repetitive transcranial magnetic stimulation (rTMS) for depression that does not respond to medication and psychotherapy.

Both medication and psychotherapy are significantly more effective than placebo for treatment of major depression, with response rates varying between about 50% and 70%, depending on the patient population. Combined treatment with both psychotherapy and medication is more effective and is indicated for more severe depression.

The goal of treatment for depression is complete remission, or resolution of all depressive symptoms, because even mild residual symptoms increase the risk of relapse. Several measures can increase rates of remission ( ). First, close follow-up, with visits every 1 to 2 weeks at first and then every 2 to 4 weeks, will enhance adherence and response rates. One third of people prescribed an antidepressant discontinue the medication within 30 days. There is considerable stigma associated with taking psychotropic medication or having a psychiatric diagnosis, so addressing the woman’s concerns that depression is a weakness or a character flaw can be helpful. Frequent visits also allow early identification of side effects that decrease adherence. Patient education about the lag in response to antidepressants and the need to take the medication every day for at least 6 to 12 months after symptomatic improvement is important. Tracking symptoms with a scale such as the PHQ-9 is helpful in monitoring progress and identifying residual symptoms. If there is little response in 2 to 4 weeks, a dose increase should be considered. A partial response at 8 weeks should prompt reassessment of the diagnosis; an attempt to ensure that the patient is taking the maximal tolerated dose of the antidepressant; and consideration of switching medications, adding an augmentation agent such as lithium, an atypical antipsychotic, or triiodothyronine (T3), or referral to a psychiatrist. Women who have had three or more episodes of major depression should be continued on maintenance antidepressant treatment.

Suicide is a feared and tragic outcome of depression and other mental health conditions. In the United States there were 47,173 suicide deaths in 2017; 6.1 per 100,000 women and 22.4 per 100,000 men died by suicide, and suicide was the 10th leading cause of death. Rates of suicide are highest among people aged 45 to 64 years compared with other age groups and in whites, and Native Americans compared with other ethnic groups. There are about 30 suicide attempts per every suicide death. Risk factors for suicide include depression or other mental health disorders; substance use disorders; a prior suicide attempt; a family history of psychiatric or substance use disorders; family violence, including physical or sexual abuse; access to means such as firearms in the house; and exposure to suicidal behavior by people such as family members, peers, or celebrities. All depressed women should be asked about suicidal thoughts. This should include asking about whether the woman feels hopeless or has had thoughts that life is not worth living or thoughts of ending her life, followed by more specific questions about whether she has made suicide plans and how far she has gone to carry these out. The Columbia Suicide Severity Rating Scale ( ; scale available at http://cssrs.columbia.edu/wp-content/uploads/C-SSRS-Screener-with-Triage-Points-for-Primary-Care-2018-1.docx ) provides a useful structured approach to asking about suicidal thoughts, with a screening form and triage recommendations tailored for primary care settings. Active suicidal thoughts and plans are a psychiatric emergency. The woman should not be left alone. The physician or staff should call 9-1-1 to have her taken to the nearest emergency room. Even in less acute cases, it is important to develop a safety plan with the patient, identifying family members, supportive people, and resources (e.g., crisis lines) she can call on, making a plan to remove firearms and other means of suicide from the home (means restriction), having someone else supervise the woman’s medication, and seeking psychiatric or other mental health consultation as soon as possible.

Eating disorders

Anorexia nervosa, bulimia nervosa, and binge eating disorder are the major eating disorders and have a lifetime prevalence of 0.6%, 1%, and 3%, respectively (for a review of eating disorders, see ). Eating disorders primarily affect younger people and have their peak onset between the ages of 10 and 19. These disorders are more common in women than in men. Many young women with eating disorders are secretive about their disorder, do not view it as a problem, and do not seek treatment for it. Gynecologists may see such girls or women for related problems, such as amenorrhea, menstrual dysfunction, low bone density, sexual dysfunction, infertility, anxiety, depression, hyperemesis gravidarum, or other pregnancy complications. Because the woman may not volunteer information about disordered eating, it is important to have a high index of suspicion for eating disorders. A simple five-question self-rating scale, the SCOFF questionnaire ( Box 9.2 ), is highly sensitive and specific in detecting eating disorders in primary care settings and thus is a useful screening tool. The Diagnostic and Statistical Manual, Fifth Edition (DSM-5), diagnostic criteria for anorexia nervosa, bulimia nervosa, and binge eating disorder are listed in Box 9.3 . Of note, the DSM-5 diagnosis of anorexia nervosa is also specified by current severity, with a body mass index (BMI) of 17 kg/m ² being mild, 16 to 16.99 kg/m ² moderate, 15 to 15.99 kg/m ² severe, and less than 15 kg/m ² extreme.

Anorexia nervosa is characterized by a disturbed body image and fears of becoming fat or gaining weight, even though the person’s body weight is less than expected. Weight loss is achieved by restricting food intake, overexercising, self-induced vomiting, or use of laxatives, emetics, and diuretics. Anorexia is most common in white teenage girls in industrialized Western societies. Societal pressures and standards of attractiveness for women, which emphasize thinness, have long been considered to increase the risk for anorexia nervosa, and a preoccupation with dieting is common in girls at menarche. Increasing evidence indicates, however, that there is clearly a significant genetic contribution to anorexia nervosa and other eating disorders, with heritability estimates of 50% to 80%. Other risk factors include a history of childhood sexual abuse and psychological traits of low self-esteem, perfectionism, and obsessive thinking.

Medical signs and symptoms associated with anorexia nervosa include bradycardia, hypotension, hypothermia, leukopenia, hair loss, skin changes, and constipation. Vomiting or laxative use may cause hypokalemia. Endocrine changes include low estrogen and testosterone levels, amenorrhea, decreased libido, hypercortisolemia, and low bone density. Prolonged QT interval is a serious sequela of anorexia nervosa and has been associated with sudden death. The mortality rate of anorexia nervosa from all causes is 5% to 6% per decade of illness.

Psychiatric symptoms associated with anorexia nervosa include depression, anxiety, social difficulties, sleep disturbance, agitation, poor emotion regulation, rigidity, obsessional thinking, and compulsive behaviors. Interestingly, these symptoms occur in individuals without anorexia nervosa during starvation and resolve with weight gain and so are most likely caused, or at least exacerbated, by the illness.

Anorexia nervosa is difficult to treat (for a review, see ). Women do not usually seek help themselves but instead are brought to treatment by concerned family members. They fear gaining weight, do not see their illness as a problem, are often nonadherent with treatment, feel isolated and do not engage with treatment providers, and may have multiple relapses. About one third recover completely, but this may take a number of years. Early recognition and treatment improve outcome. Family members often become frustrated with the woman’s multiple relapses, lack of insight, and apparent lack of cooperation with treatment and may need support themselves in dealing with her illness.

The best treatment for anorexia nervosa involves referral to a multidisciplinary team, with medical, nutritional, psychological, and psychiatric expertise in this area. The focus is on gradual refeeding to achieve weight gain and on outpatient treatment, with hospitalization only for acute, dangerous medical or psychiatric complications. In adolescents, family therapy focused on eating disorder behavior and weight gain or, in nonintact families, adolescent-centered individual psychotherapy is most effective ( ). In adults, several different types of specialized psychotherapy show promise, including cognitive behavioral, psychodynamic, and supportive therapies adapted specifically for treatment of anorexia. In one randomized controlled trial (RCT), focal psychodynamic therapy seemed to help recovery most at 12 months, whereas enhanced CBT was more effective with speed of weight gain and improvement in eating disorder thinking ( ). Few studies address relapse prevention, although a structured aftercare program after inpatient treatment reduces risk of relapse. There is no clear evidence supporting treatment of anorexia with psychotropic medications. Antidepressants do not promote weight gain or reduce eating disorder symptoms during acute treatment, and their efficacy for relapse prevention is unclear. The atypical antipsychotic olanzapine has been tried with the goal of addressing weight gain and distorted thinking about weight and body shape. A 16-week randomized placebo-controlled trial of 152 outpatients with anorexia nervosa (75 treated with olanzapine and 77 with placebo) showed greater weight gain with olanzapine but no significant differences in psychological symptoms such as obsessional thinking ( ). In this study, olanzapine was prescribed at 2.5 mg daily for 2 weeks, 5 mg daily for 2 weeks, then 10 mg daily, as tolerated.

Bulimia nervosa is characterized by binge eating, combined with inappropriate compensatory mechanisms to avoid weight gain, such as self-induced vomiting, misuse of laxatives or diuretics, or fasting or excessive exercise. Binge eating and compensatory behaviors occur an average of once a week for 3 months (see Box 9.3 for full diagnostic criteria). Bulimia, like anorexia, is most common in young women, has a significant genetic component, may follow teasing or criticism about the woman’s weight or shape, and is thought to involve disturbances in hunger-satiety pathways, the drive system and rewarding characteristics of food, or self-regulation. Comorbidity with mood and anxiety disorders, addictions, and suicidal thoughts and behaviors is common. All-cause mortality rates, including suicide rates, are elevated, with a mortality rate of 3.9% over 8 to 25 years of follow-up.

Women with bulimia nervosa and purging may develop hypokalemia, hyponatremia, hypochloremia, a metabolic alkalosis as a result of vomiting, or a metabolic acidosis with laxative abuse. Recurrent self-induced vomiting can result in loss of dental enamel, parotid gland enlargement, or calluses and scars on the dorsal aspect of the hand. Rare but serious complications include esophageal tears, gastric rupture, rectal prolapse, and cardiac arrhythmias.

There is strong evidence for the efficacy of CBT for bulimia nervosa, although complete remission of binging and purging occurs in only 30% to 40%. Other therapies for which there is some evidence of efficacy are IPT, dialectical behavior therapy (DBT) focusing on emotion regulation, and family therapy in adolescents. Antidepressants are superior to placebo in treatment of bulimia, with the agent of choice being fluoxetine 60 mg daily. Of note, the antidepressant bupropion is contraindicated in women with a history of bulimia because of an elevated risk of seizures, presumably because of electrolyte abnormalities. The outcome of bulimia is full recovery in 45%, significant improvement in 27%, and a chronic, protracted course in about 23%.

In binge eating disorder, the woman binge eats (as in bulimia nervosa) an average of once a week for at least 3 months, but she does not engage in compensatory behaviors such as purging, fasting, or excessive exercise. As a result, she may also develop obesity but does not develop the medical complications associated with purging or low weight. Treatment for binge eating disorder includes nutritional consultation, diet, physical activity, education, and specific psychotherapies. There is strong evidence for the efficacy of CBT in binge eating disorder and other psychotherapies, such as DBT and IPT, are also effective. Medication treatments include antidepressants such as SSRIs. Weight loss agents, topiramate, and stimulants may also be effective.

Obesity

Although obesity is not uniquely a gynecologic condition, obesity and overweight affect a substantial proportion of patients for whom gynecologists provide care. The prevalence of obesity continues to increase in the United States. The World Health Organization (WHO) definitions for BMI are shown in Table 9.3 . Table 9.4 outlines classification by BMI. In 2016, 39.8% of U.S. adults were obese and 71.6% were overweight or obese. The prevalence of obesity is higher in adults aged 40 to 59, minority women, and low-income women and varies by geographic region. Non-Hispanic Black and Hispanic women have slightly higher prevalence of obesity than non-Hispanic white women, whereas non-Hispanic Asian women have the lowest prevalence. The WHO describes obesity as a global epidemic, contributing substantially to chronic disease and disability.

Waist circumference is another parameter by which to measure obesity and when combined with BMI can be a predictor of obesity-related morbidity. Increased central adiposity is associated with increased risk of morbidity and mortality. The waist circumference can be measured at the level of the anterior superior iliac spine, at the end of expiration. For women with a BMI of 25 to 34.9 kg/m ² (overweight or class I obesity), a waist circumference of more than 35 inches (88 cm) is associated with heart disease and diabetes mellitus. Risks are increased even more for those with BMI of 35 kg/m ² or greater (class II or III obesity).

There is a strong relationship between mortality and increased BMI greater than 25 kg/m ² (and less than 20 kg/m ² ) ( Fig. 9.1 ). Even in healthy people who have never smoked, at age 50 years there is still an elevated risk of death for persons whose BMIs are between 25 and 30 kg/m ² ( ). The risk of death increases 20% to 40% in the overweight group and by two to three times among obese persons. Severe obesity is a health hazard that carries a 12-fold increase in mortality.

Obesity often coexists with medical conditions such as hypertension, diabetes mellitus, dyslipidemias, arthritis, and obstructive sleep apnea (OSA). Obesity has been linked to increased operative morbidity and mortality, as well as obstetric and gynecologic conditions, including miscarriage, infertility, endometrial hyperplasia, and some types of cancer. High BMI has also been associated with increased vasomotor symptoms in menopause. One meta-analysis of increased BMI and cancer risk found a strong association between a five-point BMI increase and risk of endometrial cancer (relative risk [RR] 1.59, P < .0001), gallbladder cancer (RR 1.59, P = .04), esophageal adenocarcinoma (RR 1.51, P < .0001), and renal cancer (RR 1.34, P < .0001). A weaker positive association was found with postmenopausal breast, pancreatic, thyroid, and colon cancer plus leukemia, multiple myeloma, and non-Hodgkin lymphoma. The mechanisms of cancer’s association with obesity may be linked to hormone systems like insulin, insulin-like growth factor, sex steroids, adipokines, and other substances.

Pharmacologic interventions

Pharmacologic therapy should be used as an adjunct to diet, exercise, and lifestyle modifications, rather than a solo approach. FDA-approved formulations are associated with varying degrees of weight loss. Some medications are approved only for short-term (up to 12 weeks) use, whereas others can be used for a longer duration. Although surgical interventions generally result in greater levels of weight loss than do medications, many approved formulations have been associated with low to moderate weight loss in clinical studies. Medications may be a reasonable approach for those with BMI greater than 30 kg/m ² or those with BMI 26 to 29.9 kg/m ² and comorbidities. The initial choice of pharmacologic agent may depend on these and other factors.

Examples of pharmacologic weight loss therapy include orlistat, lorcaserin, phentermine-topiramate, and metformin, although there are several others as well.

• Orlistat inhibits dietary fat absorption and is considered first-line treatment because of its favorable safety profile. It is approved for up to 4 years of use. Most subjects can expect about 3% loss of initial weight, though side effects of fecal urgency, flatulence, and oily stools may occur.

• Lorcaserin is a serotonin 2c receptor agonist, which reduces appetite. It is an alternative for patients who cannot take orlistat. Over 1 year, about 50% of patients lost at least 3% of their body mass. Side effects include headache, dizziness, fatigue, nausea, and constipation.

• Phentermine-topiramate is an acceptable option for postmenopausal women who do not have hypertension or cardiac disease. Up to 70% of individuals taking this medication will lose weight ( ). Warnings include metabolic acidosis, increased heart rate, anxiety, insomnia, and increased creatinine levels. Both lorcaserin and phentermine-topiramate have warnings about memory, attention, and depression.

• Metformin is a reasonable initial therapy for individuals who require glycemic control in addition to weight loss.

TABLE 9.5

Guide to Selecting Treatment

From National Heart, Lung, and Blood Institute and North American Association for the Study of Obesity. The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, MD: National Institutes of Health; 2000.

Body Mass Index Category
Treatment	25-26.9 kg/m 2	27-29.9 kg/m 2	30-34.9 kg/m 2	35-39.9 kg/m 2	>40 kg/m 2
Diet, physical activity, and behavior therapy	With comorbidities	With comorbidities	+	+	+
Pharmacotherapy		With comorbidities	+	+	+
Surgery			With comorbidities	With comorbidities	With comorbidities

The + represents the use of indicated treatment regardless of comorbidities.

There are other available medications as well; a comprehensive list is beyond the scope of this chapter. Long-term safety and efficacy data are limited for many weight loss medications. A guide to selecting treatment for obesity is given in Fig. 9.5 .

Anxiety disorders, obsessive-compulsive disorder, and posttraumatic stress disorder

Anxiety disorders are the most common psychiatric disorders in the general population. They usually have their onset in childhood, adolescence, or early adulthood and are more common in women than in men. Anxiety is a normal, adaptive response to danger or threat and is associated with physical symptoms (e.g., increased heart rate, sweating, shaking) and cognitive symptoms (e.g., worry, fear). Increases in anxiety are common with life stressors, including medical appointments, diagnoses, and procedures. In addition, anxiety may result from a number of drugs (e.g., caffeine, cannabis, cocaine, methamphetamine, withdrawal of alcohol or opiates), medications (e.g., theophylline, steroids), or medical conditions (e.g., asthma, arrhythmias, temporal lobe epilepsy). Some people experience primary anxiety disorders, which involve excessive anxiety that interferes with daily functioning without apparent explanation or out of proportion to any stressor. Primary anxiety disorders include panic disorder, generalized anxiety disorder (GAD), social anxiety disorder, and specific phobias (for a review of primary anxiety disorders and their treatment, see ). Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD), although categorized separately from anxiety disorders in DSM-5, also involve significant anxiety and fear.

Panic disorder is characterized by sudden, intense attacks of fear. The symptom criteria for a panic attack are shown in Box 9.4 . People with panic disorder have recurrent, unexpected panic attacks, with at least one of the attacks followed by a month or more of persistent concern about having additional attacks or worry about their consequences (e.g., losing control, having a heart attack, going crazy) or a maladaptive change in behavior because of panic attacks (e.g., avoiding certain situations for fear of having an attack). About one third of people in the general population have at least one panic attack during their lives, so that a woman presenting with a single panic attack can be reassured that this is very common. Panic attacks can be precipitated by frightening situations or heightened stress, in which case they are called situational panic attacks. People with only situational panic attacks are not diagnosed with panic disorder. Panic attacks without apparent precipitant are called spontaneous.

Panic disorder occurs in 1% to 2% of the population and is about twice as common in women than in men. Risk factors include a family history of panic disorder and significant life stress in the year before the development of symptoms. The disorder has a genetic component, with a heritability of about 30%. Complications include depression in about two thirds of people, and one third are depressed at the time of clinical presentation. Especially because panic attacks are unpredictable, they often lead to anticipatory anxiety (anxiety about having the next panic attack) and phobic avoidance, or avoidance of situations in which the person has had or would fear having a panic attack. These situations commonly include crowds, being in lines or in the middle of an audience, driving (especially in tunnels, over bridges, or in freeways), or other situations in which the woman would feel trapped, unable to get out, or publicly embarrassed. With time, the fear and avoidance surrounding panic attacks often become significantly more distressing and disabling than the attacks themselves and may lead to agoraphobia, or avoidance of multiple situations and activities. Panic disorder, like other anxiety disorders, is also associated with an increased rate of alcohol use as a form of self-medication. Finally, panic and other anxiety disorders are associated with an increased risk for suicide attempts. Thus even though a woman presents with anxiety and does not endorse depression, she should be asked about hopeless or suicidal thoughts.

The treatment of panic disorder includes reassurance, education, general measures, medication, and psychotherapy. Fortunately, treatment response rates are high, so it is possible to be optimistic that the woman has a highly treatable condition. She may fear that she is dying, has a life-threatening or serious medical illness, or that she is “going crazy,” and she can be reassured that, although panic attacks are terrifying, none of these fears is true. Presenting a model of panic attacks as being the body’s natural, healthy “alarm system” that is malfunctioning and being triggered for no reason is often helpful. As general measures, the woman should be counseled to avoid exacerbating factors, such as caffeine, alcohol, stimulants, or other illicit drugs, and to examine possible modifiable sources of increased life stress.

Panic disorder responds well to both medication and psychotherapy. In more severe cases or with significant comorbid phobic avoidance, a combination of both treatments is preferable. However, because both are effective, the approach to treatment can be determined by the woman’s preference. The first-line medication treatment for panic disorder is SSRIs. There are two important differences in prescribing these medications for panic disorder versus for depression. First, people with panic disorder are often very sensitive to medication side effects. Because panic attacks involve feeling out of control of physical sensations and one’s own body, side effects can initially increase anxiety and panic. Thus although ultimately doses need to be similar to antidepressant doses, it is wise to start treatment at a low dose (e.g., a daily dose of 12.5 mg sertraline, 5 mg citalopram), increasing the dose rapidly after a few days if the woman has no side effects. Second, whereas antidepressants take 4 to 6 weeks or less to relieve depression, they can take up to 12 weeks to have their full effect on panic and anxiety, with some effect expected by 6 weeks. It is important to educate the woman about this delayed and gradual onset of action. Many women present in distress and ask about something that will act more rapidly. In cases of severe disability resulting from panic attacks (e.g., inability to function, work, or go to school), it is reasonable to prescribe a benzodiazepine along with an SSRI, with the expectation that the SSRI will be the long-term treatment and the benzodiazepine will be tapered after at most 12 weeks. A benzodiazepine such as clonazepam, which has a longer half-life, requires only twice a day dosing and maintains more constant blood levels, is preferable to shorter-acting agents such as alprazolam. For women with a history of substance use disorders or who need to avoid the potential slowed reflexes, psychomotor impairment, and cognitive slowing associated with benzodiazepines, other alternative adjuncts to reduce anxiety and panic quickly could include hydroxyzine or gabapentin. Buspirone has not been proven effective for panic disorder. In those who do not tolerate SSRIs, most other antidepressants (e.g., venlafaxine, mirtazapine) are also effective for the long-term treatment of panic disorder, with the exception of bupropion, which can increase anxiety symptoms.

Psychotherapy is a highly effective treatment for panic disorder. The best established therapy treatment is CBT, which focuses on addressing the catastrophic thoughts associated with panic attacks (e.g., “I’m dying,” “I’m going to crash my car and kill myself and other people”), learning coping and anxiety reduction strategies (e.g., relaxation, paced breathing to combat hyperventilation), and a gradual approach to feared situations to decrease disability. CBT for panic disorder is a weekly therapy for about 12 to 16 weeks, has significant improvement rates equal to or better than the 70% response rate with medication, yields long-term benefits after therapy is over, and increases the patient’s sense of mastery and control, which is valuable in a disorder that makes people feel out of control. CBT can also help patients tolerate medication side effects and benzodiazepine withdrawal symptoms.

Overall, of the varied symptoms of panic disorder, panic attacks are the easiest to treat and quickest to resolve with both medication and therapy. Phobic avoidance and anticipatory anxiety usually linger for a longer time because of the unpredictability of panic attacks. People with panic disorder in most cases have a relapsing and remitting condition that requires long-term medication treatment (at least a year and often longer) and may recur in periods of increased stress.

In contrast with the sudden attacks of fear in panic disorder, GAD is characterized by excessive anxiety and worry about a number of life situations (e.g., work, school, family members) occurring more days than not for at least 6 months. The patient experiences her worries as excessive and difficult to control and as causing significant distress or trouble functioning. In addition, she has three or more of the following symptoms associated with her anxiety and worry: restlessness, insomnia, muscle tension, fatigue, trouble concentrating, or irritability. GAD usually begins early in life, is about twice as common in women than in men, has a genetic component, and has a lifetime prevalence of 5%. This is often a chronic disorder, with other lifetime psychiatric diagnoses (depression, other anxiety disorders, substance use disorders) superimposed in up to 90% of people. The restlessness and trouble concentrating associated with GAD and anxiety in general may lead to a misdiagnosis of attention deficit disorder.

The treatment of GAD often depends on the need to treat comorbid psychiatric conditions, which may have actually led the woman to seek medical help. GAD itself responds to general measures such as avoiding caffeine, alcohol, and illicit drugs; medication; and psychotherapy. Antidepressants are effective for GAD, and the first-line long-term medication treatment is an SSRI. Buspirone 30 to 60 mg daily is effective for GAD and has few side effects. Hydroxyzine and beta-blockers have been shown to be effective, as have benzodiazepines. However, given the chronic, often lifelong course of GAD, benzodiazepines are not recommended. Psychotherapy for GAD focuses on addressing and coping with worry (“What if” thoughts).

Social anxiety disorder (or social phobia) refers to anxiety in and avoidance of social situations, where the patient is or feels as though she is the center of attention and fears humiliation, embarrassment, or being judged negatively by other people (for diagnostic criteria, see Box 9.5 ). Symptoms of social anxiety disorder can include full-blown panic attacks, but these are provoked by social situations and are not spontaneous. In many cases, social anxiety disorder is restricted to specific situations, most often public speaking or other public performances. Some people have a more pervasive form of this disorder, in which fears and avoidance relate not just to public performance but to most social situations and interactions, such as meeting new people, parties, initiating and maintaining conversations, dating, group projects, speaking with authority figures, or asserting oneself.

Social anxiety disorder has lifetime and 12-month prevalences of 13% and 8%, respectively. Age of onset is usually early in life (mean 13 years), and women are more commonly affected than men. In Asian cultures, social anxiety often focuses on fears of giving offense to other people—for example, through making inappropriate eye contact, body odor, flatulence, or blushing. There is evidence for a genetic or familial risk for this condition. Women with social anxiety disorder may have associated poor self-esteem, difficulty asserting themselves, depression, or problematic alcohol use. Social anxiety disorder may be difficult to differentiate from shyness, although by definition social anxiety disorder involves marked distress or impairment in functioning.

Treatment of social anxiety disorder also includes medication and psychotherapy ( ). SSRIs are the first-line medication treatment and, as in other anxiety disorders, may take 8 to 12 weeks to have their full therapeutic effect. The SNRI venlafaxine is also effective. MAO inhibitors, though effective, bring with them dietary restrictions and risk of hypertensive crisis. Beta-blockers are helpful for performance anxiety but not for more generalized social anxiety disorder. Benzodiazepines are effective but should be used with caution because of the chronicity of this disorder, its comorbidity with alcohol use disorder, and risks of tolerance, dependence, withdrawal, sedation, psychomotor slowing, and cognitive effects with benzodiazepines. There is some evidence for efficacy of gabapentin or pregabalin. Women with social anxiety restricted to public speaking may benefit from practicing public speaking in a safe setting. CBT for social anxiety disorder is very effective. CBT includes individual treatment focusing on distorted thoughts about social situations (e.g., thoughts that the patient will make a fool of herself, has embarrassed herself, and that this will have catastrophic consequences) and on problem solving around and role-playing feared situations. Surprisingly, group CBT is also effective for social anxiety disorder. CBT and SSRIs yield response rates of 50% to 65% compared with a placebo response rate of 32%. Other psychotherapies, including mindfulness-based stress reduction, IPT, and psychodynamic therapy, appear promising but require further study.

Specific phobias occur in up to 20% of the general population and include fears of specific animals (e.g., snakes, spiders), phenomena (e.g., lightning), or situations (e.g., heights, flying in airplanes, driving, medical or dental procedures). People usually come to medical attention for specific phobias when these interfere with daily life or with their medical treatment. For example, people may develop specific phobias related to repeated medical events like chemotherapy treatments or to necessary aspects of their daily life, such as driving or traveling by plane. The best treatment for a specific phobia is desensitization, or gradually confronting the feared situation with the aid of an anxiety reducing strategy such as relaxation or imagery. In an acute situation, a benzodiazepine may help the woman to get through the particular event, but this will not reduce her future fear of the same situation.

OCD is characterized by persistent, repetitive thoughts, ideas, or images that the patient finds irrational and intrusive (obsessions), and with repetitive behaviors or rituals (compulsions) designed to decrease the anxiety caused by obsessions. Common obsessions include fears of contamination, dirt, germs, and illness; doubts (e.g., about having locked the door, turned off the oven, run over someone in one’s car); needing to have things in order; and sexual or religious images or preoccupations. Compulsions include repetitive and excessive washing, cleaning, checking, putting things in order, or asking for reassurance. These obsessions and compulsions are distressing, time-consuming, or interfere with functioning. The full diagnostic criteria are shown in Box 9.6 . Although most people with OCD realize that their obsessions and compulsions are irrational, some have poor or absent insight and think that their OCD-related beliefs may be true.

OCD has a lifetime prevalence of 2% to 3% and is more common in monozygotic than dizygotic twins and in first-degree relatives of affected individuals than in the general population. Rates are similar in men and women. However, men have an earlier peak age of onset than women (6 to 15 years old vs. 20 to 29 years old) and a higher comorbidity with Tourette’s syndrome and tic disorders. In people with OCD, the incidence of Tourette’s is 5% to 7% and of tics is 20% to 30%. Other conditions commonly associated with OCD, in both genders, include major depression, anxiety disorders, hypochondriacal concerns, and excessive use of alcohol and sedatives.

Treatment of OCD includes both medications and psychotherapy ( ). The first-line treatment is serotonergic antidepressants, specifically SSRIs and clomipramine, which is a highly serotonergic tricyclic antidepressant. People with OCD may require higher doses of these medications than do depressed patients and take about 12 weeks for a full response. Response rates tend to be lower than in anxiety disorders and are generally 40% to 60%. It is uncommon for a patient with OCD to have complete resolution of symptoms, and this is usually a chronic, relapsing and remitting disorder requiring ongoing treatment. The specific psychotherapy treatment most helpful in OCD is exposure and response prevention. This treatment involves gradually increasing exposure to the feared situation, without performing the compulsive ritual (e.g., exposure to dirt without the ability to wash one’s hands). Patients who agree to this treatment must tolerate significant anxiety, which, however, subsides with time after each exposure and diminishes over the course of treatment.

PTSD refers to a characteristic set of responses to a traumatic situation that involves exposure to actual or threatened death, serious injury, or sexual violence, either to oneself or experienced by witnessing the trauma occurring to others , learning that the trauma has happened to a close friend or family member, or working in a setting with repeated or extreme trauma exposure. The characteristic responses include symptoms of reexperiencing the event, avoidance of stimuli associated with the event, negative thoughts and mood associated with the trauma, and increased arousal. The full diagnostic criteria and lists of symptoms are given in Box 9.7 . It is common for people to experience symptoms like this in the first month after a major trauma, in which case the diagnosis is acute stress disorder. After a month, when most people would have recovered, persistent symptoms are then diagnosed as PTSD.

PTSD has an estimated lifetime prevalence of 8% in adults in the United States. Rates of PTSD vary from one third to more than half of people exposed to specific traumas, such as combat, rape, or captivity. Risk factors for development of PTSD in people exposed to a specific trauma include female sex, younger age, severity and duration of the event, lack of social support, history of prior trauma, and history of preexisting psychiatric disorders. There is also evidence that people with greater autonomic arousal (higher heart rate and blood pressure) after the trauma are at increased risk. Although PTSD would appear to be a quintessentially environmentally determined disorder, the risk of development of PTSD after trauma appears to be heritable. PTSD is associated with depression, panic attacks and anxiety, substance abuse and dependence, suicidal thoughts and attempts, and, in severe cases, psychotic symptoms such as hallucinations or paranoia.

Several types of individual and group psychotherapy are effective in the treatment of PTSD. These therapies include coping with current life problems and triggers, exposure to and reexperiencing of the trauma through a trauma narrative with desensitization (e.g., prolonged exposure, eye movement desensitization, and reprocessing therapies), and examining any distorted thoughts about the trauma, such as guilt that the woman brought this on herself or could have done more to prevent or stop it (cognitive processing therapy). It is important to recognize that many people are retraumatized and their symptoms worsened by retelling the story of the trauma, especially if this is not in the context of a structured, ongoing psychotherapeutic treatment.

Medications are often used to address symptoms of PTSD. For example, SSRIs are effective in reducing depression, anxiety, and emotional numbing. Hypnotics may be helpful for insomnia. Prazosin, an alpha-adrenergic antagonist, may be helpful in reducing trauma-related nightmares and more general PTSD symptoms. Benzodiazepines should be used with caution, given the comorbidity with substance use disorders and reports of increased impulsivity in patients with PTSD given these medications. Acute management immediately after the trauma of a rape is discussed further later in the chapter.

Psychotropic medications and oral contraceptives

The gynecologist often sees women who are taking psychotropic medications for one of the disorders described earlier or for other less common psychiatric disorders such as bipolar disorder or schizophrenia and may be called on to advise them about options for birth control. There are several psychotropic medications that alter the metabolism and efficacy of oral contraceptives (OCs) or whose metabolism is in turn altered by OCs ( ).

Induction of the hepatic cytochrome P450 3A4 enzyme can increase OC metabolism and cause contraceptive failure. Psychotropic medications that induce 3A4 and that have been associated with spotting, breakthrough bleeding, or unwanted pregnancy include the mood stabilizers carbamazepine (Tegretol) and oxcarbazepine (Trileptal), topiramate (Topamax; at doses >200 mg daily), and the wakefulness-enhancing agent modafinil (Provigil). St. John’s wort, commonly used over the counter as an antidepressant, also induces 3A4 and can cause contraceptive failure. OC activity may be increased or prolonged by 3A4 inhibitors such as the antidepressants fluoxetine (Prozac) and possibly fluvoxamine (Luvox).

OCs are themselves moderate 1A2 and 2C19 inhibitors and mild 2B6 and 3A4 inhibitors. Thus OCs can increase levels and effects of amitriptyline (Elavil), bupropion (Wellbutrin), chlordiazepoxide (Librium), chlorpromazine (Thorazine), clozapine (Clozaril), diazepam (Valium), imipramine (Tofranil), and possibly olanzapine (Zyprexa). Drugs whose clearance is increased with OCs and therefore have lower blood levels include nicotine and the mood stabilizers lamotrigine (Lamictal) and valproic acid (Depakote). Lamotrigine levels have been found to be 84% higher in the week off ethinyl estradiol. Given the risk of Stevens-Johnson syndrome with fluctuating levels of lamotrigine and the likelihood of worsening mood symptoms with variations in blood levels of mood stabilizers such as lamotrigine and valproic acid, it is best to advise women taking these medications to use a continuous OC or another form of birth control.