Case 1: Muscle ache and fatigue
A 37-year-old male Army reservist is evaluated for generalized muscle aches and persistent fatigue three months after returning to the United States from a one-year deployment in Iraq. He also reports that his joints are somewhat stiff and painful, particularly in the back, knees, and hips. He has not had fever, chills, weight loss, cough, or headaches. The patient is accompanied by his wife, who says that her husband has been having problems sleeping and concentrating, and that they have been having problems with intimacy.
Although he says that he is having some problems adjusting to being home, he denies feeling depressed; however, he admits he is not as involved in pleasurable activities as he was before his deployment because he has not felt well since his return. He also describes having nightmares about a roadside bomb that killed several friends.
The patient is hesitant to return to his job as a cross-country truck driver, stating that he feels uncomfortable driving, particularly in heavy traffic, and he is not ready to leave his family. His medical history is noncontributory, and the physical examination is unremarkable. Laboratory studies, including complete blood count, tuberculin skin testing, renal function and liver chemistry tests, serum electrolyte and calcium levels, and urinalysis, are normal.
In addition to cognitive behavioral therapy, which of the following is the best treatment option for this patient?
Case 2: Palpitations, dyspnea and tingling
A 32-year-old man is evaluated during a follow-up examination after visiting the emergency department last night with acute chest heaviness, palpitations, dyspnea, and a tingling in the tips of both fingers and in the perioral region. His symptoms began while he was leisurely walking his dog. He also had mild abdominal discomfort and a subsequent bout of diarrhea consisting of loose stools without blood. He reports having had similar symptoms three times over the past two months, including admission once before to the emergency department, the examination results of which were unremarkable and the symptoms of which were attributed to stress.
The patient used to run three to five miles two to three times weekly but has stopped because of concern over his heart, although he has never experienced these symptoms while running. He also has been reluctant to leave home except to go to work because he is afraid that he might have another episode in public. He drinks alcohol socially and has had no alcohol in the past few weeks. He does not use illicit drugs, has not been taking supplements or weight-loss pills, and takes no medications.
His father died of a myocardial infarction at age 73 years. On physical examination, the patient is alert and oriented. The heart rate is 93 beats/minute, and the blood pressure is 132/78 mm Hg. The rest of the examination, including cardiopulmonary evaluation, is normal. Laboratory studies from last evening's emergency department visit, including serum electrolyte, calcium, creatinine and blood urea nitrogen levels, cardiac enzymes, and urinalysis, were normal. The urine drug screen was negative, and the electrocardiogram taken while the patient was symptomatic was unremarkable.
Which of the following is the most appropriate initial management option for this patient?
A. Adenosine stress testing
B. Serum thyroid-stimulating hormone and 24-hour urine catecholamine and metanephrine measurement
Case 3: Fear of social situations
A 29-year-old woman is evaluated during a follow-up visit for recurrent bouts of depression she has experienced for approximately seven years and for which she has taken antidepressant therapy. Her depression has been well controlled with sertraline, and she denies feeling depressed or experiencing anhedonia on this visit.
She has been considering going back to graduate school but finds she is too embarrassed to do so because she has always found it difficult to go out in public and avidly avoids being the center of attention. She also reports having nightmares in which she attends class in her underwear or trips and falls in front of the whole class. The patient does not use alcohol but her father was an alcoholic.
The physical examination is unremarkable. Laboratory studies, including complete blood count, liver chemistry and renal function tests, serum electrolyte and thyroid-stimulating hormone levels, and urinalysis, are normal.
In addition to cognitive behavioral therapy, which of the following is the most appropriate treatment option for this patient?
A. Add clonazepam
B. Increase sertraline
C. Taper sertraline over next two weeks
D. Substitute paroxetine for sertraline
Case 4: Depression and anxiety
A 37-year-old man is evaluated during a routine visit and reports feeling depressed. The medical history is noncontributory. He meets the criteria for major depression and generalized anxiety disorder. The medical history is otherwise noncontributory. The physical examination, including vital signs, is normal. Laboratory studies are unremarkable.
Which of the following is the most appropriate treatment option for this patient?
Case 5: Fatigue and guilt
A 38-year-old woman is evaluated because she thinks she might be depressed. She reports feeling tired all the time and sometimes cries with little provocation. She denies anhedonia, problems with sleeping or appetite, suicidal ideation, psychomotor retardation, or problems with concentration.
She has two children, ages 4 and 2 years, and finds motherhood frustrating and challenging, but also rewarding. She sometimes feels guilty because she works part-time and believes that she has failed to meet her end of the family's financial responsibilities. Her medical history is noncontributory. She takes no medications except for a multivitamin. She drinks one glass of wine on most evenings and does not use illicit drugs.
On physical examination, she appears well groomed, alert, and oriented. The rest of the physical examination is unremarkable. Laboratory studies, including complete blood count; measurement of serum electrolytes, creatinine, blood urea nitrogen, and thyroid-stimulating hormone level; and urinalysis, are normal.
Which of the following is the most appropriate management option for this patient?
B. Follow-up monitoring
Case 6: Chronic insomnia
A 47-year-old man is evaluated for difficulty falling asleep and resulting daytime fatigue occurring three to four times a week for the past several months. He denies snoring or sleepwalking, shortness of breath, and chest pain. He recently went through a divorce, which has caused some personal and financial stress. He smokes one-half pack of cigarettes a day.
On physical examination, pulse rate is 72 beats/minute, and blood pressure is 138/85 mm Hg. The BMI is 26. The rest of the examination is normal. Laboratory studies include hematocrit of 42%, leukocyte count of 4200/μL, fasting plasma glucose of 100 mg/dL, and a thyroid-stimulating hormone of 2.5 μU/mL. Chest radiography and electrocardiography are normal.
Which of the following is the most appropriate next diagnostic step?
C. Cardiac stress testing
D. Depression screening
Answers and commentary
Correct answer: D. Sertraline
This patient has post-traumatic stress disorder (PTSD). In conjunction with cognitive behavioral therapy (CBT) and some element of gradual re-exposure to the traumatic event, both sertraline and paroxetine are appropriate for use in patients with PTSD, are Food and Drug Administration-approved for this indication, and are particularly useful for patients with comorbid mood or anxiety disorders. The atypical antipsychotic and anticonvulsant drugs have not been studied in patients with PTSD and would therefore not be appropriate for use in this patient.
There is strong support for the efficacy of CBT across a range of trauma groups, including victims of assault, terrorism, motor vehicle accidents, combat, and childhood abuse and refugees. Exposure therapy has proven to be a reliably effective and safe intervention; however, relatively few randomized-controlled trials of CBT for PTSD have been conducted, and those that have are typically based on small samples.
- Sertraline and paroxetine have Food and Drug Administration approval for treating post-traumatic stress disorder but should generally be used with psychotherapy and are useful in patients with comorbid mood or anxiety disorders.
Correct answer: C. Paroxetine
This patient has panic disorder, for which serotonin reuptake inhibitors (SSRIs), such as paroxetine, are considered firstline therapy. It is recommended that the initial dose of therapy in this patient be low and titrated to moderate doses over the first month of treatment. Partial responders, those with at least a 50% improvement at 4 weeks, should receive augmentation therapy with a benzodiazepine or cognitive behavioral therapy (CBT). Nonresponders should undergo a trial of a different SSRI or a serotonin norepinephrine reuptake inhibitor. Additional augmentation with CBT, if not already initiated, or atypical neuroleptics (risperidone, 1 to 2 mg; olanzapine, 5 to 10 mg; or quetiapine, 25 to 50 mg) should be considered in patients with persistent symptoms after six months of therapy.
The abrupt onset of symptoms, lack of evidence of ischemia or arrhythmias during his two recent evaluations, and the lack of symptoms with strenuous exercise make a cardiac cause of his symptoms unlikely; therefore, adenosine stress testing with a thallium scan is not appropriate in this patient. Although hyperthyroidism might be responsible for some of his symptoms, symptoms of hyperthyroidism are unlikely to be so intermittent and temporally discrete as those occurring in this patient. In addition, no thyromegaly was noted on physical examination, which is present in most cases of Grave's hyperthyroidism. Pheochromocytoma can cause similar symptoms, but this patient's normal blood pressure makes this diagnosis less likely. In addition, pheochromocytoma is a rare disorder, whereas panic attacks occur commonly; therefore 24-hour urine collection for catecholamine and metanephrine measurement is not indicated. Studies to rule out pheochromocytoma should be sought, however, if the patient fails to respond to treatment. Antipsychotic medications are not indicated for panic disorder. Clinical trials have shown CBT to have equal efficacy with pharmacologic treatment, and the combination of CBT with pharmacologic treatment is synergistic, but CBT is not a first-line therapy for this disorder.
- First-line therapy for panic disorder consists of serotonin reuptake inhibitors, such as paroxetine.
Correct answer: A. Add clonazepam
This patient has social anxiety disorder and probably has had this disorder for many years. Because she has good insight, most experts would recommend psychotherapy for this patient at this point, with continuation of the current antidepressant regimen, to produce synergism between the two modalities.
Clonazepam would be a good complementary treatment choice in this patient to provide immediate relief while she awaits the results of therapy. Benzodiazepines are very effective in patients with social anxiety disorder, with up to 80% improvement, although these patients often have difficulty in tapering or discontinuing these agents; therefore, benzodiazepines should be reserved for patients at low risk for substance abuse and given at minimum therapeutic doses and for immediate relief of symptoms in conjunction with anticipated improvement from antidepressant therapy or psychotherapy.
Because she has responded well to her current medication regimen, increasing her dosage of sertraline or substituting it for another selective serotonin reuptake inhibitor is not likely to be more effective for treating her symptoms of social anxiety disorder. Given the recurrent nature of depression in patients who do not take their medication, weaning sertraline would not be appropriate.
- Clonazepam is an appropriate complementary treatment choice in patients with social anxiety disorder for providing immediate relief while they await the results of psychotherapy.
Correct answer: A. Paroxetine
This patient has major depression and generalized anxiety disorder and should receive paroxetine. All the selective serotonin reuptake inhibitors and the serotonin norepinephrine reuptake inhibitors are effective for depression and generalized anxiety disorder and have Food and Drug Administration (FDA) approval for these indications.
Bupropion is a proven antidepressant and clonazepam is a proven anxiolytic, but neither is FDA-approved for treating depression and anxiety. The atypical antipsychotic agents, such as risperidone, olanzapine, and quetiapine, are sometimes added to antidepressant therapy to augment response in patients with treatment-resistant major depression and dysthymia but are not indicated as monotherapy for major depression and dysthymia or generalized anxiety disorder.
Patients with depression commonly have some symptoms of anxiety also, and approximately one-third meet the criteria for a concomitant anxiety disorder. Depressive symptoms often respond more quickly to treatment than do anxiety symptoms, and it is not uncommon for anxiety to be “unmasked” during the first few weeks of antidepressant treatment.
- All the selective serotonin reuptake inhibitors and the serotonin norepinephrine reuptake inhibitors are effective for depression and generalized anxiety disorder and have Food and Drug Administration approval for these indications.
- Depressive symptoms often respond more quickly to treatment than do anxiety symptoms, and it is not uncommon for anxiety to be “unmasked” during the first few weeks of antidepressant treatment.
Correct answer: B. Follow-up monitoring
This patient has minor depression for which the best management approach is regular follow-up evaluation to monitor for the progression from minor to major depression. Minor depression, also known as subthreshold depression, occurs in up to 15% of patients in primary care. Minor depression consists of the presence of either depressed mood or anhedonia (or both) with other symptoms that total more than two but less than the five total symptoms required to establish a diagnosis of major depression. Although follow-up data are sparse, the limited evidence suggests that minor depression is transient in most patients, with approximately only 10% to 15% progressing to major depression.
Although minor depression decreases functional status, several treatment trials of pharmacotherapy and psychotherapy have reported that treatment outcomes for these modalities are no better than those associated with placebo.
- Minor depression consists of the presence of either depressed mood or anhedonia (or both) with other symptoms that total more than two but less than the five total symptoms required to establish a diagnosis of major depression.
- Although minor depression decreases functional status, several treatment trials of pharmacotherapy and psychotherapy have reported that treatment outcomes for these modalities are no better than those associated with placebo.
Correct answer: D. Depression screening
Depression can be a treatable cause of insomnia, and this patient has some risks for depression, including a recent divorce and other life stressors. Screening for depression is indicated prior to treatment of primary insomnia. The diagnosis of chronic insomnia can be established clinically. It is generally defined as a complaint of insufficient or inadequate sleep when one has the opportunity to sleep.
The American Psychiatric Association Diagnostic and Statistical Manual 4th Edition (DSM-IV) defines primary insomnia as difficulty initiating or maintaining sleep or nonrestorative sleep for at least one month. The sleep disturbance must cause clinically significant distress or impairment of functioning and not be caused by another diagnosable sleep or mental disorder.
Polysomnography is needed only in patients with insomnia who have symptoms of a sleep-related breathing disorder, narcolepsy, sleepwalking, or are employed as pilots or truck drivers. None of these criteria apply to this case.
This patient has risk factors for pulmonary disorders (smoking and being overweight) and cardiac disease (smoking, being overweight, male sex, and age); however, he does not have symptoms or findings indicative of chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, or coronary artery disease (CAD). Therefore, further evaluation for COPD with spirometry or stress testing for CAD is not indicated. Sleep hygiene recommendations, including avoidance of strenuous exercise or alcohol within a few hours of bedtime, developing a relaxing evening routine, and avoidance of afternoon caffeine, are an appropriate first step in intervention once a diagnosis of primary insomnia is established.
- Good sleep hygiene includes avoiding strenuous exercise or alcohol close to bedtime, developing a relaxing evening routine, and avoiding afternoon caffeine.
- Depression is a treatable underlying cause for insomnia.