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Many psychiatric and medical illnesses—as well as normal reactions to stressors—have symptoms that overlap with those of depressive disorders, including outwardly sad or dysphoric appearance, irritability, apathy or amotivation, fatigue, difficulty making decisions, social withdrawal, and sleep disturbances. This cluster of symptoms forms a readily observable behavioral phenotype that clinicians may label as depression before considering a broader differential diagnosis.
To better understand what other conditions belong in the differential diagnosis, we reviewed a sample of 100 consecutive medical/surgical inpatients referred to our consultation-liaison psychiatry practice for evaluation of “depression.” Ultimately, only 29 of these patients received a depression diagnosis. Many of the other diagnoses given in our sample required attention during inpatient medical or surgical care because they were potentially life-threatening if left unaddressed—such as delirium—or they interfered with managing the primary medical or surgical condition for which the patient was hospitalized.
Hurried or uncertain primary care clinicians frequently use “depression” as a catch-all term when requesting psychiatric consultation for patients who seem depressed. A wide range of conditions can mimic depression, and the art of psychosomatic psychiatry includes considering protean possibilities when assessing a patient. We identified 7 diagnoses that mimic major depression and developed our “8 D” differential to help clinicians properly diagnose “depressed” patients who have something other than a depressive disorder. Although our sample consisted of hospitalized patients, these mimics of depression may be found among patients referred from other clinical settings for evaluation of possible depression.
The perils of misdiagnosis
Depression is common among patients hospitalized with medical or surgical conditions. DSM-IV-TR diagnostic criteria for a major depressive episode (MDE) include the presence of low mood and/or anhedonia, plus ≥4 other depressive symptoms for ≥2 weeks.1 Growing evidence suggests that the relationship between depression and morbidity and mortality in medical illness is bidirectional, and nonpsychiatrists are becoming increasingly aware of major depression’s serious impact on their patients’ physical health.2-5
Although improving nonpsychiatrists’ recognition of depression in medically ill patients is laudable, it comes with a high false-positive rate. In a study of primary care outpatients, Berardi et al found that 45% of patients labeled “depressed” did not meet ICD-10 criteria for major depression, but >25% of those patients were prescribed an antidepressant.6 In a large retrospective study, Boland et al found that approximately 40% of patients referred to an inpatient psychiatric consultation service for depression did not meet criteria for a depressive illness, and primary medical services often confused organic syndromes such as delirium and dementia with depression.7 Similarly, Clarke et al found that 26% of medical and surgical inpatients referred to psychiatry with “depression” had another diagnosis—commonly delirium—that better accounted for their symptoms.8
What is the harm in overdiagnosing depression? Missing a serious or life-threatening diagnosis is a primary concern. For example, unrecognized delirium, which frequently was misdiagnosed as depression in the Berardi,6 Boland,7 and Clarke8 studies, is associated with myriad difficulties, including higher morbidity and mortality.9 Substance use disorders, which also commonly masquerade as depression, frequently are comorbid with medical illness. Delays in appropriate treatment of withdrawal syndromes—particularly of alcohol and sedative/hypnotic medications—are risk factors for increased mortality in these illnesses.10
Inappropriate, potentially harmful interventions are another concern. Many patients diagnosed with depression are prescribed antidepressants, but this is not always a benign intervention. Smith et al found that >10% of adult medical inpatients referred to a psychiatry consultation service who were started on an antidepressant had an adverse drug reaction severe enough to warrant discontinuing the medication.11 Antidepressant side effects relevant to medically ill patients include hyponatremia, serotonin syndrome, and exacerbation of delirium.12
Polypharmacy in medically ill patients increases the risk for serious drug-drug interactions. For example, serotonergic antidepressants can increase the risk for serotonin syndrome when combined with the analgesic tramadol, which has serotonergic activity,13 or the antibiotic linezolid, which is a reversible monoamine oxidase inhibitor.14 Many antidepressants—including paroxetine, fluoxetine, bupropion, sertraline, and duloxetine—are moderate to strong inhibitors of cytochrome P450 2D6 and therefore affect metabolism of many medications, including several beta blockers and antiarrhythmics, as well as the anti-estrogen tamoxifen. In the case of tamoxifen, which is a prodrug converted to active form by 2D6, concomitant use of a 2D6 inhibitor can substantially reduce the medication’s in vivo efficacy and lead to higher morbidity and mortality in breast cancer patients.15 As with any treatment, a decision to prescribe antidepressants needs to carefully be weighed in light of individual risks and benefits. This analysis starts by ensuring that an antidepressant is indicated.