Major depression case file

Major Depression Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 25

A 38-year-old woman presents to the office with complaints of weight loss, fatigue, and insomnia of 3-month duration. She feels tired most of the time and frequently does not want to get out of bed. Despite feeling so tired, she has been staying up late at night because she cannot fall to sleep. She does not feel that she is doing well in her occupation as a secretary and states that she has trouble remembering things. She does not go outdoors as much as she used to and cannot recall the last time she went out with friends or enjoyed a social gathering. She denies any recent medication, illicit drug, or alcohol use. She feels intense guilt regarding past relationships because she feels that it was her fault they failed. She states she has never thought of suicide, but has begun to feel increasingly worthless.

Her vital signs and general physical examination are normal, although she becomes tearful while discussing her symptoms. Her mental status examination is significant for depressed mood, psychomotor retardation, and difficulty attending to questions. Laboratory studies reveal a normal metabolic panel, normal complete blood count (CBC), and normal thyroid functions.

⯈ What is the most likely diagnosis?

⯈ What is your next step?

⯈ What are important considerations and potential complications of management?

ANSWER TO CASE

Major Depression

Summary: This is a 38-year-old woman with depression. She meets at least five of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) diagnostic criteria during a 2-week period that represents a change from her previous level of functioning. At least one of the symptoms must be either depressed mood or loss of interest or pleasure.

• Most likely diagnosis: Major depression.
• Next step: Evaluate the patient for suicidal risk; begin pharmacologic and psychotherapeutic management.
• Important considerations and potential complications: Rule out other medical diagnoses such as hypothyroidism, anemia, and infectious processes that could mimic some symptoms of depression; review any recent medication changes for agents that may contribute to these symptoms ( eg, β-blockers, steroids, sedatives, chemotherapy agents), verify that no substance abuse or use is taking place; screen for bipolar disorder and inquire about a family history of mood disorders; investigate and address suicidal ideation.

ANALYSIS

Objectives

1. Recognize the common presenting signs and symptoms of depression.
2. Understand the multifactorial pathogenesis of depression.
3. Learn about the treatment of depression and the sequelae of this condition.
4. Be familiar with the appropriate follow-up of this condition.
5. Recognize the importance of assessing for risk of suicide.

Considerations

The case presented represents a common presentation of depression. The patient often does not come in with a complaint of depression. However, the symptoms of fatigue, insomnia, and mood swings are frequently seen. It then becomes incumbent on the physician to address the topic of depression with the patient. The symptoms of depression, such as memory disturbance or inability to concentrate, might limit your patient's ability to provide a good history. If the patient gives permission, it could be helpful to speak to a close contact of the patient, such as the spouse, to gather information that will confirm the diagnosis.

Once the diagnosis of depression is suspected, it is critical to determine the most appropriate level of care for the patient. The clinician must specifically and directly address the patient's risk of harming herself or others. If she is actively suicidal, such as describing the desire to hurt herself and having a plan to do so, then hospitalization may be necessary. Similarly, if the patient is unable to care for herself

then hospitalization should be considered. If the patient does not have suicidal ideations, is not assessed as a risk to her or others, and has support at home, then outpatient therapy with close follow-up is usually appropriate.

Approach To:

Depression

DEFINITIONS

MAJOR DEPRESSION: One or more episodes of mood disorder each lasting at least 2 weeks. The most prominent symptoms of major depressive disorder are depressed mood and loss of interest or pleasure. Insomnia and weight loss often accompany major depression, but depressed patients may also have weight gain or hypersomnia.

DYSTHYMIC DISORDER: Chronically depressed mood occurring most of the day, more than half the time, for at least 2 years, but does not meet the criteria for major depression, in terms of either severity or duration of individual episodes.

CLINICAL APPROACH

Background

Depression has a lifetime prevalence of 7% to 12% in men and 20% to 25% in women, with a greater incidence in the elderly and patients with coexisting chronic medical conditions. To meet the DSM-V criteria for major depressive disorder, the patient must experience at least five of the nine following symptoms nearly every day during the same 2-week time period. This must represent a change from previous functioning and include one of the first two symptoms: either depressed mood or anhedonia:

1. Depressed mood
2. Anhedonia: Diminished interest or pleasure
3. Change in appetite or weight: Decreased appetite, or increased appetite associated with specific food cravings; significant weight loss or weight gain
4. Change in sleep patterns: Insomnia or hypersomnia
5. Change in activity: Psychomotor agitation or retardation
6. Fatigue or loss of energy
7. Feelings of worthlessness or excessive or inappropriate guilt
8. Change in cognition: Diminished ability to think or concentrate; indecisiveness
9. Recurrent thoughts of death, suicidal ideation, suicide attempt, or specific plan 

Also,

• Symptoms cause clinically significant distress or impairment of functioning.
• Symptoms are not a result of the direct physiologic effects of a substance or a generalized medical condition.
• There has never been a manic or hypomanic episode.
• Symptoms are not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other psychotic disorders.

It is noted in the DSM-V that responses to a significant loss, such as the death of a loved one, financial ruin, losses from a natural disaster, or serious medical illness can lead to symptoms very similar to that of major depression, and this may be considered a normal response, but it is still important to evaluate for a major depressive episode.

Risk factors for developing depression are family or personal history of depression, female sex, younger age, traumatic brain injury, chronic medical illnesses, chronic pain, low income, low self-esteem, poor social support, chronic minor daily stress, and being single, divorced, or widowed.

The differential diagnosis of depression includes many other psychiatric and medical disorders. Psychiatric disorders include dysthymic disorder, seasonal affective disorder, anxiety disorders, and bipolar disorder. Anxiety and depression often coexist. Numerous medical conditions can cause depressive symptoms. Common among these are dementia in older patients, hypothyroidism, and anemia. The role of pharmacologic agents and substance use, abuse, or dependence also should be investigated, as these can cause significant mood changes. This is especially true of alcohol, sedatives, narcotics, and cocaine.

Screening for depression is recommended by the United States Preventive Services Task Force (USPSTF) for adults and children 12 to 18 years old when there are systems to ensure accurate diagnosis, treatment, and follow-up. Patients with depression should be assessed for suicide risk, but there is no recommendation for screening the general population for risk of suicide. Adult screening can be completed using the 2-question or 9-question Patient Health Questionnaires (PHQ-2 or PHQ-9). For older adults, there is a Geriatric Depression Scale that can be used, and for children the Beck Depression Inventory and Children's Depression Inventory can be used.

Pathophysiology

The etiology of depression is thought to be multifactorial, due to a complex interaction of genetic, psychosocial, and neurobiologic factors. Theoretical psychosocial contributors include stressful life events, particularly involving loss of a loved one, early childhood stress, and lack of positive reinforcement. Depression does run in families, but the mode of inheritance is unknown. Multiple neurotransmitter systems are involved, including the serotonergic, noradrenergic, and dopaminergic systems. Evidence of the effects of neurotransmitters on mood disorders is supported by the mechanism of action of antidepressant medications: all currently available antidepressant agents appear to work by increasing the amount of neurotransmitter available to the postsynaptic nerve. This is accomplished by (1) enhancing neurotransmitter release, (2) reducing neurotransmitter breakdown, or (3) inhibiting the reuptake of the neurotransmitter by the presynaptic neuron.

Clinical Findings

On presentation, patients may complain of sadness, irritability, or mood swings. Difficulty concentrating or loss of energy and motivation are common. Thinking is often negative, and frequently accompanied by feelings of worthlessness, hopelessness, or helplessness. Some may complain of poor memory or concentration. Women are more likely to experience seasonal depression and atypical symptoms such as hypersomnia, hyperphagia, carbohydrate craving, weight gain, and evening mood exacerbations. Some patients with depression may present to the physician with various somatic complaints and decreased energy level rather than a complaint of depression. The diagnosis of depression needs to be considered in scenarios where a patient presents with multiple unrelated physical symptoms. Some typical nonspecific symptoms of depression include headache, neck or back pain, joint pain, abdominal pain, constipation, poor sleep, change in weight or appetite, weakness, and fatigue. The elderly may present with confusion or a general decline in function.

Most patients with depression have no significant physical abnormalities on examination. A mental status examination is very important, including mood, affect, appearance, behavior, speech, thought process, and content, etc. Those who have more severe symptoms may reveal decline in grooming or hygiene along with weight changes. Speech may be normal, slow, monotonic, or lacking in content. Pressured speech is suggestive of mania, whereas disorganized speech suggests the need to evaluate for psychosis. The thought content of patients with depression includes feelings of inadequacy, helplessness, or hopelessness. Sometimes patients complain of being overwhelmed. Psychomotor retardation can manifest as slowing of movements or reactions, especially in the elderly. The physical examination should include evaluation for possible underlying causes of depressed mood, and a cognitive examination may be helpful in older adults.

Morbidity and Mortality

Depression causes significant morbidity and mortality in numerous ways. The World Health Organization states that depression is the fourth leading cause of disability in the world, and it causes more disability and social impairment than diabetes, arthritis, hypertension, or coronary artery disease. Depression is frequently reported in persons with underlying medical conditions, such as stroke, Parkinson disease, traumatic brain injury, diabetes, coronary atherosclerotic disease, pancreatic cancer, and other terminal illnesses. Patients with depression are more likely to develop atherosclerotic coronary artery and cerebrovascular disease, diabetes, and osteoporosis. It is a common occurrence following myocardial infarctions and cerebrovascular accidents. Persons with depression and preexisting cardiac disease have three times greater risk of dying after a heart attack than do patients without depression, and patients with coexisting depression and diabetes have more microvascular and macrovascular complications. Studies also show that persons with depression have a greater chance of developing or dying from cardiovascular disease,

Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed.

Washington, DC: American Psychiatric Association Press; 2013; Sernyak MJ, Jr., Rohrbaugh RM. Emergency psychiatry.

In: Ebert MH, Loosen PT, Nurcombe 8, Leckman JF, eds. Current Diagnosis & Treatment: Psychiatry. 2nd ed. New York,

NY: McGraw-Hill; 2008; U.S. Preventive Services Task Force. Screening for suicide risk in adolescents, adults, and older

adults in primary care: recommendation statement. Am Fam Physician. 2015 Feb 1;91(3):190F-1901.

even after controlling for risk factors such as smoking, gender, weight, activity, blood pressure, and cholesterol. Depression also contributes to the disruption of interpersonal relationships, the development of substance abuse, and absenteeism from work and school.

All depressed patients should be screened for suicidal and homicidal/violent ideations. A history of suicide attempts or violence is a significant risk factor for future attempts. Major depression plays a role in more than half of all suicide attempts. Women, especially those younger than age 30, attempt suicide more frequently than men, but men are more likely to complete suicide. Firearms are the most commonly used method in completed suicides. Table 25-1 lists the risk factors for suicide attempts and completed suicides.

TREATMENT

Initial pharmacotherapy should be based on physician familiarity with medication, anticipated safety and tolerability, anticipation of adverse effects, and history of prior treatments. Pharmacotherapy with psychotherapy is more effective than either pharmacotherapy or psychotherapy alone. Physicians should encourage their patients to pursue both therapies to improve chances of success. A helpful tool is the PHQ-9, which can be used to assess symptom severity and track improvement over time. An adequate trial of an antidepressant requires a minimum of 4 to 6 weeks on an appropriate dose. Up to half of patients may not respond to the first antidepressant they try, and will need to be switched to another agent. Treatment failures typically result from medication noncompliance, inadequate duration of therapy, or inadequate dosing. No class of medication has been proven to be more effective than other classes. Once in remission, patients treated for a first episode of major depression should be treated for at least 4 to 9 months. At least 60% of patients will experience a relapse at some point, and recurrent depression needs to be treated for longer periods of time. The need for lifelong therapy is higher with increasing number of episodes of depression. All antidepressants carry a Food and Drug Administration (FDA) "black box" warning that they increase the risk of suicidal thoughts and behaviors in children, adolescents, and young adults, especially in the first months of treatment. Women may have more side effects from antidepressants because absorption of these medications may be higher due to decreased gastric acid secretion, slower gastrointestinal transit, and higher body fat-to-muscle ratio (which increases volume of distribution) in women.

CLASSES OF MEDICATIONS

Table 25-2 lists the medications used in the treatment of depression.

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) increase the amount of the neurotransmitter serotonin (5-hydroxytryptamine) available to the postsynaptic neuron by blocking the presynaptic neuron's ability to reabsorb serotonin. Because it can take 3 to 6 weeks of therapy before significant improvement in mood occurs, dosage adjustments of these medications should occur no more often than monthly. These agents have a low risk of toxicity if taken as an overdose (either accidentally or intentionally), making them very safe to use. Common side effects include sexual dysfunction, weight gain, nausea/gastrointestinal disturbance, insomnia or somnolence, and agitation. Because of their efficacy and safety, SSRIs are frequently used as first-line agents for the treatment of depression. SSRIs are first-line treatment

for depression in children, and fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and escitalopram (Lexapro) have been approved for use in children.

However, when used in combination with other serotonergic agent the clinician should be aware of the possibility of developing serotonin syndrome. There may also be a slight increase risk of bruising, nosebleeds, and other bleeding episodes. Patients who are on nonsteroidal anti-inflammatory drugs (NSAIDs) or antiplatelet medications may be at increased risk for significant bleeding.

Serotonin-Norepinephrine Reuptake Inhibitors

Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect both the serotonergic and noradrenergic systems. They act primarily on the serotonergic system at lower dosages and have a more balanced effect on the serotonergic and noradrenergic systems at higher dosages. Their side effects are similar to SSRIs. They can be used as first-line treatment for depression and because of their effects on two neurotransmitter systems, may be used as second-line agents in SSRI failure.

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) are older agents that affect, to varying degrees, the reuptake of norepinephrine and serotonin. They are effective for the treatment of depression and because they have been in use for many years, they are inexpensive. However, they have numerous side effects from antimuscarinic effects (dry mouth, blurry vision, constipation, urinary retention, and sinus tachycardia), histamine blockade (sedation, drowsiness, weight gain), and α-1 receptor blockade (orthostatic hypotension and sedation). Because of the side effects and risks, TCAs have largely been replaced by SSRIs as the first-line treatment of depression.

Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors (MAOIs) cause increased amounts of serotonin and norepinephrine to be released during nerve stimulation. Patients taking MAOIs must be on a tyramine-restricted diet to reduce the risk of severe, and sometimes fatal, hypertensive crisis. MAOIs also interact with numerous other medications, including SSRIs and meperidine (Demerol). These interactions can also be fatal. Because of the risks, MAOIs should only be used by experienced practitioners and only when the benefits outweigh the risks.

A typical Agents

The different atypical agents may act similarly to SSRIs, TCAs, and MAOIs, in varying degrees. Their primary benefit is a lower incidence of sexual disturbance as a side effect. Bupropion is associated with increased risk of seizure at higher doses and is contraindicated in patients with a history of seizure disorders. Trazodone carries the risk, although rare, of causing priapism. It is also highly sedating and is frequently used as a sleep aid. Mirtazapine can be a good choice for patients with insomnia or anorexia, as it can improve sleep latency and duration and stimulate appetite. It is also less likely to cause sexual dysfunction or gastrointestinal (GI) side effects, has little α-1 blocking effects (like orthostatic hypotension), and can also help reduce anxiety.

INPATIENT MANAGEMENT

Inpatient management is indicated when the patient presents a significant risk to self (suicide, inability to care for self ) or others (risk of violence), or the symptoms are sufficiently severe to initiate treatment in controlled settings. Involvement of a psychiatrist is warranted in the care of patients in whom more severe symptoms require more intensive care (suicidal ideations, psychosis, mania, and severe decline in physical health).

ELECTROCONVULSIVE THERAPY

Electroconvulsive therapy (ECT) is typically reserved for treatment-resistant depression. It may also be used for patients who cannot tolerate medications or in cases of severe or psychotic depression. It has been found to be more effective than placebo, simulated ECT, and antidepressants, but long-term efficacy is not known. The primary adverse effect of ECT is short-term memory loss or cognitive impairment which usually resolves in a few days to a few weeks.

OTHER MOOD DISORDERS

Anxiety Disorders

Anxiety disorder is a classification of mood disorders that are common in the population such as panic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder, posttraumatic stress disorder (PTSD), and phobia. Patients with generalized anxiety disorder have excessive and difficult-to-control worry and anxiety that causes physical symptoms, including restlessness, irritability, sleep disturbance, and difficulty concentrating. Panic disorder is characterized by recurrent panic attacks, which are defined as periods of intense fear of abrupt onset. OCD manifests as either obsessions (recurrent, intrusive, and inappropriate thoughts) or compulsions (repetitive behaviors) that are unreasonable, excessive, and cause much distress to the patient. PTSD is a response to a severe traumatic event in which the patient suffers fear, helplessness, or horror. A phobia is an irrational fear that causes a conscious avoidance of a situation, subject, or activity. Patients with anxiety disorders are at high risk for developing comorbid depression.

Bipolar Disorder (Manic Depression)

This mood disorder affects genders equally but often presents in young people. Symptoms of mania include the abrupt onset of elevated or irritable mood, inflated self-esteem, decreased need for sleep, pressured speech, racing thoughts, distractibility, increased goal-directed activity, and engaging in pleasurable activities with potentially painful consequences. Concomitant substance abuse should always be investigated. Episodes of mania must last at least 1 week (or any duration if hospitalization is needed) and occur during a distinct period, not continuously. Continuous behavior of this type suggests personality disorders or schizophrenia. A single episode of mania is sufficient for the diagnosis of bipolar disorder. All patients diagnosed with depression should be questioned about mania, as the treatments are different. Bipolar disorder is typically treated with mood stabilizers, which include valproate, carbamazepine, and lithium. The use of antidepressant agents in bipolar disorder may precipitate acute manic behaviors.

Dysthymic Disorder

This mood disorder presents with continuous low mood as the primary symptom, lasting at least 2 years. Dysthymia is less acute but longer in duration than major depression It often includes at least two of the following: change in appetite or weight, change in sleep patterns, low energy or fatigue, poor concentration or difficulty making decisions, and feelings of hopelessness. If a major depressive episode takes place during an episode of dysthymia, then by definition, the patient suffers from major depression.

CASE CORRELATION

• See also Case 15 (Thyroid Disorders).

COMPREHENSION QUESTIONS

25.1 A 62-year-old man presents for a follow-up visit for severe depression. His symptoms have included crying episodes, insomnia, and decreased appetite. He has suicidal ideations and states that he has a gun in his home that he might use. He has had auditory hallucinations, saying he hears a voice telling him that his wife is the devil. His symptoms have not been relieved by maximum doses of sertraline (Zoloft), venlafaxine (Effexor), or citalopram (Celexa). He is currently taking duloxetine (Cymbalta), which has also failed to improve his symptoms. Which of the following would most likely provide the quickest relief of his symptoms?

A. Electroconvulsive therapy (ECT)

B. Bupropion (Wellbutrin)

C. Stopping duloxetine and starting on an MAO inhibitor

D. Behavioral modification

25.2 A 40-year-old woman sees you in follow-up of treatment for recurrent depression. Her symptoms are improved a little after 2 months of fluoxetine (Prozac) 10 mg a day and weekly counseling sessions with a psychologist. She is having no medication side effects and both she and her husband state that she is taking her medication regularly. Which of the following would be the most appropriate next step?

A. Continue with your current plan and give it more time.

B. Increase the fluoxetine dose to 20 mg daily and continue counseling.

C. Discontinue fluoxetine and start paroxetine 10 mg daily.

D. Continue fluoxetine and add bupropion as adjunctive therapy.

E. Discontinue medications and arrange for psychiatric consultation for ECT.

25.3 Three weeks after starting a 22-year-old man on an SSRI for a first episode of depression, you receive a call from his mother stating that he hasn't slept in days, is speaking very rapidly, and has maxed-out his credit card buying electronic equipment. Which of the following is the most likely explanation for this situation?

A. He is having a medication side effect.

B. He is secretly taking too much of his SSRI.

C. His SSRI has unmasked underlying bipolar disorder.

D. His SSRI has precipitated a hyperthyroid state.

ANSWERS

25.1 A. This patient has psychotic depression with suicidal ideation and has not responded to maximum doses of several antidepressants. He is more likely to respond to electroconvulsive therapy than to counseling or a change in medication.

25.2 B. The most common causes of treatment failure or poor response to therapy are inadequate medication dosing, inadequate length of treatment, or noncompliance. In this setting, where the patient is compliant and has had adequate time for response, increasing the dose of medication from 10 mg (a low starting dose) to 20 mg would be your first step. Typically, antidepressant medication dosages can be increased after 4 weeks of treatment if the response is inadequate.

25.3 C. In bipolar patients, the use of an SSRI can precipitate a manic state. It is critically important to assess for a history of manic episodes prior to starting antidepressant therapy. In some cases, bipolar disorder may initially present as major depression, so the institution of antidepressant medication may unmask an undiagnosed bipolar condition. Another condition to assess for in this situation is the concomitant use of recreational drugs, such as cocaine or methamphetamine.

CLINICAL PEARLS

⯈ While working up depression, other medical diagnoses such as hypothyroidism, anemia, or infectious processes that could mimic some symptoms of depression must be ruled out.

⯈ Always investigate the use of alcohol and drugs when evaluating for mood disorders.

⯈ Suicidal and homicidal ideation should always be investigated and thoroughly addressed when diagnosing depression.

⯈ The addition of any new medication should be investigated to ensure it is not contributing to the patient's symptoms.

REFERENCES

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013. 

Bhatia SC, Bhatia SK. Childhood and adolescent depression. Am Fam Physician. 2007;75(1):73-80. 

Douglas OM. Screening for depression. Am Fam Physician. 2012Jan 15;85(2):139-144. 

Eisendrath SJ, Cole SA, Christensen JF, Gutnick D, Cole M, F eldman MD. Depression. In: F eldman MD, Christensen JF, Satterfield JM, eds. Behavioral Medicine: A Guide for Clinical Practice. 4th ed. New York, NY : McGraw-Hill; 2014. 

Guck TP, Kavan MG, Elsasser GN, et al. Assessment and treatment of depression following myocardial infarction. Am Fam Physician. 2001;64:641-648, 651-652. 

Lisanby SH. Electroconvulsive therapy for depression. N Engl] Med. 2007;359(19):1939-1945. 

Little A. Treatment-resistant depression. Am Fam Physician. 2009Jul 15;80(2):167-172. 

Shim RS, Primm A. Depression in diverse populations and older adults. In: South-PaulJE, Matheny SC, Lewis EL, eds. Current Diagnosis & Treatment: Family Medicine. 4th ed. New York, NY: McGraw-Hill; 2015. Available at: http://accessmedicine.mhmedical.com. Accessed May 25, 2015.

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