Key Clinical Questions
What are the signs and symptoms of a major depressive episode (MDE)?
What is the pathophysiology of major depression?
What medications, intoxicants, and diseases cause depressed mood?
What is adjustment disorder?
What is the appropriate diagnostic workup for a patient with depressive symptoms?
What is the treatment for major depressive disorder (MDD)?
What are the complications of antidepressant use?
What are the signs and symptoms of bipolar disorder?
What medical conditions and substances can induce mania?
What is the appropriate diagnostic workup for a patient with mania?
How is bipolar disorder treated?
What are the signs and symptoms of anxiety?
What are the common anxiety disorders?
How does generalized anxiety disorder differ from major depression?
What medical conditions present with symptoms of anxiety?
What studies should be ordered for the acutely anxious patient?
What is the treatment for anxiety?
Depression
Major depressive disorder (MDD) is widespread and devastating, with lifetime prevalence greater than17% in the general population. Total costs exceed $44 billion annually, including hospitalization, medications, and loss of productivity. In medically ill patients, mood disorders are even more common; six-month prevalence increases from 5.8% to 9.4% with at least one chronic medical condition. Despite this, many physicians fail to address depressive symptoms, believing them to be appropriate in illness (“I would be depressed too, if I were that sick”). This misconception leads to poor outcomes, as physical recovery is impeded by affective disorders. This chapter will aid the hospitalist in recognition, diagnosis, and treatment of MDD.
A 66-year-old man with a history of type-2 diabetes, hypertension, and tobacco use was admitted for non-ST elevation MI and cardiac catheterization with stent placement. During morning rounds, his care team noted that the patient ate only about 10% of his breakfast and appeared to have a blunted affect. He had a history of multiple episodes of depressed mood, insomnia, and anhedonia over the years. The patient reported feeling “worthless” and sometimes wishing that he’d “just gone ahead and died.” Though initially reluctant because of worries about dependence, Mr. G agreed to try an antidepressant, sertraline. At his 6-week post-hospitalization appointment he is free of mood symptoms, engaged in cardiac rehabilitation and feels hopeful about the future. |
The primary etiology of major depression remains obscure. Dysregulation of CNS monoamine neurotransmitters (including norepinephrine, serotonin, and dopamine) occurs in MDD. Newer theories focus on broader neuroregulatory circuits involving cholingeric activation, GABA hypoactivity, and chronically elevated hypothalamic-pituitary-adrenal activity. Immune system abnormalities and increased inflammation likely play a role.
Major depressive disorder is defined by the occurrence of one or more major depressive episodes (see Table 225-1). Though many patients will readily admit to feeling “sad” or “down,” others may initially deny dysphoria, imagining this to reflect a weakness of character. Direct confrontation may not be fruitful, though observational statements made in a neutral tone might aid with patient disclosure (“you’re upset”). In such cases, mood changes can also be determined by the presence of tearfulness or blunted affect. Depressed mood may also manifest as irritability, particularly in adolescence. However, caution must be taken not to label the angry patient “depressed” in the absence of other signs of MDD. There is a distinct quality and severity of mood in MDD that differs from mere sadness, and the patient who is simply despondent should likewise not be diagnosed with this disorder.
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Loss of interest, or anhedonia, is the most common presenting symptom in MDD (particularly in the elderly). This can be difficult to identify in the context of hospitalization, where the patient’s usual pleasurable activities are curtailed. Lack of engagement with family members or other visitors, as well as refusal to participate in physical therapy, may indicate anhedonia. Anorexia, fatigue, insomnia, and poor concentration may be easily attributed to the direct effects of medical illness. However, if a patient also shows depressed mood and lack of interest, these qualities should be counted toward the diagnosis of MDD. Assessment of insomnia should focus on pattern of sleep and activities during nighttime awakening, as sleeplessness in the hospital may be due to poorly controlled pain or frequent visits by nurses. Middle insomnia (waking in the night and not being able to return to sleep) and early awakening are more typical of depression, and patients often ruminate on negative thoughts. Guilt about illness is a common symptom. Patients may express concern about not meeting financial and interpersonal obligations or about being a burden to their loved ones.
Assessment of suicidality must be direct and avoid euphemisms such as “hurting yourself.” Questions should elicit increasing levels of intent. First ask about passive ideation (“do you ever feel so bad that you wish you were not alive?”). When an affirmative is given, questioning should then focus on active suicidal thoughts and designs. If the patient has access to firearms or potentially toxic medications, a plan should be made for securing them prior to discharge.
Though not explicitly delineated in the DSM criteria, somatic complaints may be a manifestation of depression. Individuals with psychiatric pathology may experience physical discomfort out of proportion to the severity of medical disease. Patients may also have functional pain, consciously or unconsciously converting depressed mood into more culturally sanctioned symptoms.
Medications and intoxicants can both cause depressive symptoms (see Table 225-2). Defining the temporal relationship between onset of mood disturbance and start of a new drug can help determine this correlation. Table 225-3 lists commonly prescribed offending medications.
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Chronic alcohol use leads to depressed mood. Forty percent of patients with an alcohol-related disorder meet criteria for MDD at some point in their lives. Diagnosis of major depression in the context of active alcohol use is difficult at best, and treatment with antidepressants in this situation can be deleterious and even dangerous. Abuse of other sedative-hypnotics (benzodiazepines and barbiturates), as well as opiates, can similarly produce a mood disturbance. Stimulants (cocaine and amphetamines) potentiate monoamine neurotransmitters, leading to depletion and subsequent depressed mood. Effects of stimulants on the brain linger for months to years following cessation.
Addicts usually downplay their drug and alcohol use. Inquiries into the frequency of ingestion and the amount consumed should always be grossly overestimated, thus normalizing the patient’s admission. Surrogate clues must be obtained, including collateral from friends and family. Objective measures, such as a urine drug screen and serum ethanol level, may also provide further insight.
To meet criteria for depression due to a GMC, it is not necessary to have symptoms for any duration of time or to exhibit a certain number of characteristics. Patients must simply display anhedonia or depressed mood that interferes with function and is directly caused by medical illness. When direct causality is not definite, patients should be diagnosed with MDD. However, this is purely a semantic differentiation and should not affect treatment decisions.
Heart disease and major depression are frequently comorbid. In hospitalized patients who have suffered a myocardial infarction (MI), 65% show depressive symptoms and 30% meet criteria for MDD. Depression in the post-MI period imparts a four- to six-fold increased risk of cardiac mortality at 6 and 18 months (independent of epidemiologic factors, medications, or severity of disease). Despite this, only 10% of post-MI patients are diagnosed with MDD in the hospital. This may be due to its anomalous presentation, with hostility and withdrawal more common. Unfortunately, depressed mood may be assessed as appropriate in patients suffering an MI, with many physicians stating, “I would be depressed too if I just had a heart attack.” This conclusion is not only incorrect (as not all patients have post-MI MDD), but negligent, leading to unnecessary suffering and poor patient outcomes.
Mood symptoms are common in cancer, particularly in pancreatic carcinoma and other enteric malignancies. Rates increase in those with a prior psychiatric history. Depression may precede diagnosis, potentially caused by a paraneoplastic process or proinflammatory cytokines. Alternatively, mood changes may occur after cancer is discovered. Major depression can be difficult to differentiate from the existential crisis that arises from the diagnosis. In those without depression, hopelessness generally fades within the first three months. Determination of MDD can also be complicated by its significant symptom overlap with treatment side effects and the disease process itself. Fatigue is frequently described. Lethargy due to radiation and chemotherapy is cyclical, with recovery occurring as time from treatment increases. Fatigue in major depression is akin to amotivation, with difficulty starting tasks and prominent psychomotor retardation. Appropriate diagnosis is further waylaid by the hesitancy of patients to admit to mood changes. Those with cancer often take pride in coping with their illness and do not want to disappoint their doctors by showing signs of depression.
At least a third of stroke survivors experience depressive symptoms. The association is strongest in those with left hemispheric lesions, though physicians should screen for affective changes irrespective of vascular distribution. Degree of disability does not directly correlate to prevalence of mood disturbance, although post-stroke depression imparts greater functional impairment, with less recovery in activities of daily living. Major depression also confers increased overall mortality in this population.
Autoimmune disease is closely linked to affective disorders. Close to half of individuals with systemic lupus erythematosus (SLE) meet criteria for MDD. Rates increase with greater disease severity and activity. Depressive symptoms are likely due to immune dysregulation, with proinflammatory cytokines modulating neural changes. Medications (particularly steroids) may also contribute to mood disturbance. Regardless of etiology, recognition and treatment is essential, as psychological distress in SLE leads to increased physical disability.
For a list of other medical diseases associated with depressed mood, see Table 225-4.
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Adjustment disorder is a pathologic response to a specific stressor (see Table 225-5 for DSM IV criteria). Stressors may be multiple, such as financial strain in the context of physical disease. Patients with tumultuous childhoods (loss of a parent, unstable living situation) are particularly at risk for this disorder. It is important to note that this diagnosis cannot be made if the criteria for major depression are met, or if mood symptoms are directly attributable to the effects of a substance or disease process.
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Hypoactive delirium may be mistaken for MDD. Both disorders involve problems with memory, but patients with major depression will have insight and complain of the deficit. Disorientation in delirium may result in complete reversal of day-night sleep-wake cycle. Sleep changes also occur with MDD, but patients have consistent insomnia or hypersomnia. Delirium has an abrupt onset and a fluctuating course. Major depression may also have a relatively discrete onset. However, it rarely has a waxing and waning course (except for melancholic depression, in which mood improves as the day progresses). Unlike MDD, delirium manifests with poor attention and altered level of consciousness.
Laboratory evaluation of a patient with depressive symptoms can help to rule out an organic cause. A basic workup should include a complete blood count with differential, a comprehensive metabolic panel (including liver enzymes), thyroid stimulating hormone, an RPR, an HIV test, B12 and folate levels, electrocardiogram, serum ethanol level, and a urine drug screen. Physical exam should direct the judicious use of further testing, including CT or MRI of the brain, electroencephalogram, lumbar puncture, blood and urine cultures, chest X-ray, ANA panel and rheumatoid factor, and directed cancer screening. The patient’s medication list should be carefully reviewed for possible pharmacologic causes of depression.
There is no test that confirms the diagnosis of MDD. Likewise, there is no laboratory value that can be tracked to determine treatment response. Thus, target symptoms should be identified early and be well documented. This can assist subsequent care providers in determining the patient’s baseline and progress. Because of the apparent subjective nature of this data, it may be helpful to administer a standardized rating scale at regular intervals. Clinician-rated scales, such as the Quick Inventory of Depressive Symptomatology (QIDS) Clinician Report, as well as patient-rated scales, such as the QIDS Self Report and Patient Health Questionnaire (PHQ)-9, are widely available.
While medication is an important treatment modality for depression, psychosocial interventions should be adjunctively employed whenever possible. This includes referrals to psychotherapy as well as to support groups. Some patients may also benefit from meeting with the hospital chaplain. When end-of-life issues arise, palliative care teams are extremely helpful.
Patient education is essential. Physicians should discuss diagnosis, target symptoms, and treatment options. Serious side-effects should be addressed, but not overemphasized. If a patient is reluctant to start treatment, the rationale should be elicited. Many are hesitant to take antidepressants because of social stigma or misconceptions concerning drug dependence and personality changes.
Most classes of antidepressants have been shown to have roughly equal efficacy. Thus, initial selection of pharmacotherapy should focus on previous treatment success, family history of medication response, safety, tolerability, cost, and patient preference. Once a medication has been started, the goal is to titrate to an adequate dose and treat for an adequate period of time. The therapeutic dose differs based on physiology, and for the elderly may be lower than recommended doses. An adequate medication trial is usually defined as 8 to 12 weeks at the therapeutic dose. However, if there is no response after 4 to 5 weeks, a change in medication may be necessary. Duration of treatment for the first major depressive episode should be at least 12 months. In patients with recurrent episodes or depression due to a noncurable illness, lifelong treatment may be necessary. If a patient has been stable on a medication for years but decompensates when faced with a physical or emotional crisis, sudden discontinuation of the previously effective medication should be avoided. Instead, short-term interventions, such as dose increase or augmentation, should be employed.
Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), and Other Antidepressants
Because of their tolerability, efficacy, and ease of dosing, the SSRIs are first-line treatment for major depression. The SNRIs (venlafaxine and duloxetine) may be a good choice for individuals with chronic pain because of the inhibitory effect of norepinephrine and serotonin on descending sensory neurons.
Other treatment options include nefazodone, trazodone, mirtazapine, and buproprion. Because it lowers the seizure threshold in a dose-dependent manner, buproprion should not be prescribed for patients with epilepsy, heavy alcohol use, or structural brain anomaly. Unlike the SSRIs, buproprion does not cause sexual dysfunction or weight gain. It can also aid in smoking cessation.
See Table 225-6 for more information on the individual characteristic of these antidepressants.
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The TCAs inhibit reuptake of norepinephrine and serotonin. These medications have significant anticholinergic, antihistaminergic, and antiadrenergic actions. The tertiary amines include amitriptylene, imipramine, trimipramine, doxepin, and chlomipramine. Desipramine, nortriptylene, and protriptylene are secondary amines. The secondary amines are less sedating and have less anticholinergic activity than the tertiary amines. At therapeutic doses, these medications have good efficacy. However, their use is often limited by side effects and drug interactions. Addition of medications that inhibit cytochrome p450 2D6 may cause serum TCA levels to rise to dangerous levels. Initiation of the tricyclics should occur in consultation with psychiatry. Medically ill patients who are maintained on TCAs should have cardiac monitoring, with daily repletion of potassium and magnesium.
Monoamine oxidase (MAO) degrades biogenic amines in the CNS and GI tract. Phenelzine, tranylcypromine, isocarboxazid, and selegeline inhibit this enzyme. Despite their efficacy (particularly in atypical and anxious depression), these medications are considered third-line because of their adverse side effect profile as well as medication and food interactions. Monoamine oxidase inhibitors (MAOIs) can cause severe orthostasis, as well as sexual side effects, insomnia, headache, dizziness, dry mouth, and constipation. Ingestion of tyramine (present in aged cheeses, smoked or cured meats, wine, and beer) while taking an MAOI can lead to hypertensive emergency. Malignant hypertension is more likely to occur when MAOIs are taken with sympathomimetics and certain anesthetics (especially meperidine). Combination of MAOIs with other serotonergic agents can cause serotonin syndrome (see discussion below). Use of MAOIs should occur in consultation with psychiatry.
ECT consists of the delivery of electricity to a patient’s scalp in order to produce seizure activity. The patient is placed under general anesthesia and a neuromuscular blocking agent is given to inhibit muscle contraction. ECT is generally indicated for treatment-resistant depression and for states when immediate results are necessary for the patient’s safety, such as suicidality, catatonia, or psychosis. Side effects include headache, dysphoria, muscle aches, and memory loss. Retrograde amnesia may be permanent. There are no absolute contraindications to ECT, and most of the risk ensues from anesthesia. Unstable cardiac or cerebrovascular disease increases risk. However, ECT is an efficacious and well-tolerated procedure for medically ill patients with severe depression who do not respond to pharmacotherapy or who cannot tolerate medication side effects.
Necessary medications may cause depressive symptoms. When this is suspected, treatment substitutions or dose reduction (particularly with steroids) should be considered. If this is not possible, then the provider must take into account duration of treatment with the offending agent, level of dysfunction caused by mood symptoms, and patient willingness to add another medication. Certain medications (such as interferon) are notorious for inducing mood symptoms, and prophylactic treatment with an antidepressant is recommended. There are improved outcomes with administration of paroxetine prior to initiation of interferon-α for hepatitis C infection.
When depression is caused by an intoxicant, the best course of action is clearly to discontinue its ingestion. Unfortunately, this is not often so simple. Patients with addiction may be unwilling (or unable) to quit using drugs and alcohol. Treatment with antidepressants in the context of continued intoxication will provide no relief of depressive symptoms and will not prevent the patient from using. When sobriety has been confirmed, yet depressive symptoms persist, there is no clear consensus as to time until treatment initiation. One reasonable approach would be to wait about four weeks after cessation to begin treatment for depression, particularly when the mood symptoms are causing impairment of function or extreme distress.
If a medical condition is permanent and causes major depression, then pharmacotherapy should not be delayed. In cases in which medical illness is thought to be short-lived, the physician must consider the effects of the mood symptoms on the course of illness and the patient’s quality of life. If mood symptoms cause suffering or worsen medical disease, treatment is indicated. The high prevalence of major depression in certain conditions may event merit prophylactic antidepressant use. In acute stroke survivors, there is evidence for prophylactic use of escitalopram.
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Preventing and Managing Adverse Patient Events: Patient Safety and the Hospitalist
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