Psychiatry · Mood Disorders
The facts most likely to be tested
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SSRIs are first-line (fluoxetine, sertraline, escitalopram); allow 4 weeks before judging response.
Diagnosis requires >=2 weeks of depressed mood or anhedonia plus a total of five SIG-E-CAPS symptoms, a change from baseline.
Never combine an SSRI with an MAOI because of serotonin syndrome.
Always rule out hypothyroidism, the most common medical mimic, and screen for substance use.
~60% of patients have suicidal ideation, so safety must always be assessed.
Tailor agents: bupropion for smokers or to avoid weight/sexual side effects, mirtazapine for insomnia/poor appetite, duloxetine for neuropathic pain.
ECT is the single most effective treatment, reserved for severe, psychotic, refractory, or acutely suicidal patients and safe in pregnancy.
Vignette unlocked
A 34-year-old woman presents with six weeks of depressed mood and loss of interest in activities she previously enjoyed after losing her job. She reports insomnia, decreased appetite with weight loss, low energy, poor concentration, and feelings of worthlessness. She denies any prior episodes of elevated mood, decreased need for sleep, or grandiosity. TSH is normal and a urine drug screen is negative.
Which of the following is the most appropriate first-line pharmacotherapy?
A selective serotonin reuptake inhibitor (SSRI) such as sertraline.
Two or more weeks of depressed mood plus at least five SIG-E-CAPS symptoms, with hypothyroidism and substance use excluded and no history of mania, confirm major depressive disorder. SSRIs are first-line because of their efficacy and favorable safety profile, and four weeks should be allowed before assessing response.
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Etiology / Epidemiology
Common mood disorder linked to decreased norepinephrine, serotonin, and dopamine; the most common medical mimic is hypothyroidism.
Clinical Manifestations
>=2 weeks of depressed mood or anhedonia plus neurovegetative symptoms (sleep, appetite, energy, concentration, guilt, suicidal ideation).
Diagnosis
Clinical (SIG-E-CAPS); rule out hypothyroidism and substance use.
Treatment
SSRIs are first-line; never combine SSRIs with MAOIs (serotonin syndrome).
Prognosis
Highly treatable but recurrent; ~60% have suicidal ideation, always assess safety.
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Epidemiology & Etiology
Major depressive disorder (MDD) is a common, recurrent mood disorder associated with decreased norepinephrine, serotonin, and dopamine, plus decreased REM latency and increased total REM sleep. It is roughly twice as common in women and frequently familial. Numerous medical conditions can cause or mimic depression, the most common is hypothyroidism, and the most common neurologic associations are Parkinson disease and neurocognitive disorders. Stressful life events frequently precipitate episodes.
Pertinent Anatomy
Depression involves dysfunction of monoaminergic projections from brainstem nuclei (raphe nuclei for serotonin, locus coeruleus for norepinephrine) to the limbic system and prefrontal cortex. Functional and structural changes include hippocampal volume loss and altered amygdala-prefrontal connectivity, with chronic HPA-axis (cortisol) overactivity. The therapeutic effect of monoamine-enhancing drugs supports the central role of serotonin, norepinephrine, and dopamine deficiency.
Pathophysiology
The leading model attributes depression to functional deficiency of the monoamines serotonin, norepinephrine, and dopamine within limbic and cortical circuits, accompanied by dysregulated sleep architecture (decreased REM latency, increased REM). Chronic stress activates the HPA axis, elevating cortisol and impairing hippocampal neuroplasticity. Antidepressants increase synaptic monoamine availability and, over weeks, promote neurotrophic adaptation, accounting for the characteristic delay before clinical response.
Clinical Manifestations
Diagnosis requires at least 2 weeks of depressed mood or anhedonia plus a total of five symptoms (mnemonic SIG-E-CAPS: Sleep change, loss of Interest, Guilt/worthlessness, decreased Energy, decreased Concentration, Appetite/weight change, Psychomotor changes, Suicidal ideation), representing a change from prior functioning. A typical vignette is a patient with depressed mood, anhedonia, insomnia, decreased appetite and weight, low energy, and poor concentration after a job loss. Roughly 60% of patients experience suicidal ideation at some point, so safety must always be assessed.
Diagnosis
MDD is a clinical diagnosis based on DSM-5 criteria (>=2 weeks of >=5 symptoms including depressed mood or anhedonia). Always rule out medical causes, most commonly hypothyroidism, and screen for substance use before diagnosing. Distinguish from normal bereavement, which is usually self-limited and does not warrant pharmacotherapy; features favoring MDD over grief include morbid preoccupation with worthlessness, marked psychomotor retardation, psychosis, prolonged functional impairment, and active suicidality. Persistent depressive disorder requires depressed mood for >=2 years.
Treatment
SSRIs are first-line (fluoxetine, sertraline, paroxetine, citalopram, escitalopram) because of efficacy and a favorable side-effect/overdose profile; allow 4 weeks before judging response. Second-line agents are SNRIs (venlafaxine, duloxetine). Tailor choice to comorbidity: duloxetine for coexisting neuropathic pain, bupropion for smokers or to minimize weight gain/sexual side effects, mirtazapine for insomnia/poor appetite. Never combine an SSRI with an MAOI because of serotonin syndrome. ECT is the single most effective treatment and is reserved for severe, psychotic, refractory, or acutely suicidal patients and is safe in pregnancy.
Prognosis
MDD is highly treatable but tends to recur; the risk of relapse rises with each subsequent episode, so maintenance therapy is often warranted after recurrent or severe episodes. The major acute danger is suicide, present in the majority of patients at some point, mandating ongoing risk assessment. Untreated or psychotic depression carries higher morbidity, whereas combined pharmacotherapy and psychotherapy yields the best long-term outcomes.
Differential Diagnosis
Bipolar Disorder: a prior manic or hypomanic episode reclassifies the depression as bipolar, critical because antidepressant monotherapy can trigger mania.
Hypothyroidism: fatigue, weight gain, cold intolerance, and depressed mood with elevated TSH; the most common medical mimic and must be excluded.
Normal Bereavement: grief after a loss that is self-limited (typically <6-12 months) without pervasive worthlessness or active suicidality; treatment is supportive, not pharmacologic.
Persistent Depressive Disorder (Dysthymia): chronic depressed mood for >=2 years that is less severe and does not warrant hospitalization.
Adjustment Disorder with Depressed Mood: depressive symptoms within 3 months of an identifiable stressor that do not meet full MDD criteria.