Mood And Anxiety Disorders - USMLE Step 2

SECTION 1

Historical Context & Motivation

The recognition that disturbances of mood and anxiety constitute distinct medical entities — rather than moral failings or spiritual afflictions — represents one of the most profound shifts in the history of medicine. Ancient Greek physicians, particularly Hippocrates, attributed melancholia to an excess of black bile, framing depressive states within the humoral model of disease. Over the ensuing centuries, mood and anxiety disturbances oscillated between being classified as medical conditions and being relegated to the domain of supernatural or characterological explanations. The modern era of psychiatric nosology began in earnest with Emil Kraepelin's systematic classification and accelerated dramatically with the development of effective pharmacotherapies in the mid-twentieth century.

~400 BCE • Hippocratic Melancholia

Hippocrates described melancholia as a medical condition caused by black bile imbalance, separating it from divine punishment and establishing a biological framework for mood disturbance.

1899 • Kraepelin's Classification

Emil Kraepelin distinguished manic-depressive insanity from dementia praecox (schizophrenia), creating the foundational dichotomy that still organizes psychiatric diagnosis today.

1952 • Discovery of Iproniazid

The serendipitous observation that the tuberculosis drug iproniazid elevated mood in patients led to the development of monoamine oxidase inhibitors (MAOIs), launching the era of antidepressant pharmacotherapy.

1980 • DSM-III Revolution

The DSM-III introduced operationalized diagnostic criteria for mood and anxiety disorders, replacing psychoanalytic formulations with empirically grounded symptom checklists and duration thresholds.

2013 • DSM-5 Reorganization

The DSM-5 separated depressive disorders, bipolar disorders, and anxiety disorders into distinct chapters, reflecting advances in genetics, neuroimaging, and treatment response patterns that distinguish these conditions.

Today, mood and anxiety disorders collectively represent the leading cause of psychiatric disability worldwide, affecting over 300 million people with depression and nearly 280 million with anxiety disorders according to WHO estimates. For the clinician preparing for USMLE Step 2 CK, the central challenge is threefold: correctly identifying these disorders using DSM-5 criteria, differentiating overlapping presentations, and selecting evidence-based treatments appropriate to the specific diagnosis. This lesson systematically addresses each of these objectives.

SECTION 2

Core Principles & Definitions

Before diving into individual disorders, it is essential to establish the conceptual architecture that organizes the DSM-5 approach to mood and anxiety. The overarching principle is that these conditions are defined by distinct clusters of symptoms persisting for specified durations and causing clinically significant distress or functional impairment. A thorough understanding of the following foundational concepts allows the clinician to navigate the differential diagnosis efficiently and avoid common diagnostic pitfalls on examination.

Mood Episodes vs. Mood Disorders

A mood episode (major depressive, manic, or hypomanic) is a building block, not a diagnosis. The specific pattern and combination of episodes determine the mood disorder diagnosis (e.g., MDD, Bipolar I, Bipolar II).

The Monoamine Hypothesis

Deficient serotonergic, noradrenergic, and/or dopaminergic transmission underlies depressive states. Excessive noradrenergic and dopaminergic activity contributes to mania. This model, though oversimplified, guides first-line pharmacotherapy.

Fear vs. Anxiety Distinction

Fear is an emotional response to a real or perceived imminent threat, while anxiety is apprehension about anticipated future threat. This distinction maps onto panic disorder (fear-based) versus generalized anxiety disorder (anxiety-based).

Biopsychosocial Model

Mood and anxiety disorders arise from interacting genetic vulnerability, neurobiological dysfunction, psychological factors (cognitive distortions, learned helplessness), and social stressors. Treatment approaches that address multiple domains yield the best outcomes.

Rule Out Medical and Substance Causes

Before diagnosing a primary psychiatric disorder, always exclude mood/anxiety symptoms attributable to a general medical condition (hypothyroidism, Cushing's, pheochromocytoma) or substance use (alcohol, stimulants, corticosteroids). This is a high-yield USMLE testing point.

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KEY TAKEAWAY

Think of mood episodes as individual LEGO bricks and mood disorders as the complete structures built from them. A single major depressive episode placed alone gives you MDD; add a manic brick and the entire structure becomes Bipolar I, regardless of how many depressive bricks are also present. Meanwhile, anxiety disorders are like a malfunctioning smoke detector — the alarm system (amygdala) fires with excessive sensitivity even when there is no fire, leading to disabling false alarms that the patient cannot simply rationalize away.

SECTION 3

Visual Explanation — Diagnostic Decision Tree

This decision tree illustrates the hierarchical approach to differentiating mood and anxiety disorders. Begin at the top by excluding medical and substance-related causes, then evaluate for manic episodes (Bipolar I), hypomanic episodes with major depressive episodes (Bipolar II), and isolated depressive episodes (MDD) before proceeding to the anxiety disorder branch.

The decision tree above encapsulates the core diagnostic algorithm tested on USMLE Step 2 CK. The first and most critical branch point is the exclusion of substance-induced and medical condition-attributable disorders, which is the single most commonly tested diagnostic pitfall. Hypothyroidism mimicking depression, pheochromocytoma presenting as panic attacks, and corticosteroid-induced mania are classic board scenarios. Once medical and substance causes are excluded, the algorithm prioritizes identification of manic episodes because their presence fundamentally reclassifies the diagnosis. A patient with 20 depressive episodes and a single manic episode carries a diagnosis of Bipolar I — not MDD — and treating such a patient with an antidepressant alone risks precipitating a manic switch.

SECTION 4

Neurobiological Mechanisms

While the USMLE Step 2 CK emphasizes clinical recognition and management over basic science, a working understanding of the neurobiological underpinnings of mood and anxiety disorders is essential for making rational pharmacological choices. The dominant framework remains the monoamine hypothesis, which posits that depression results from reduced synaptic availability of serotonin (5-HT), norepinephrine (NE), and/or dopamine (DA), while mania involves catecholamine excess. This model is supported by the mechanism of action of virtually all effective antidepressants — SSRIs, SNRIs, TCAs, and MAOIs all increase monoaminergic transmission — though the 2–4 week delay between pharmacological onset and clinical response suggests that downstream neuroplastic changes, including BDNF-mediated synaptic remodeling, are the true therapeutic mediators.

Neurotransmitter Systems in Mood Disorders

Neurotransmitter	Role in Depression	Role in Mania	Associated Drug Classes
Serotonin (5-HT)	↓ activity → depressed mood, anxiety, insomnia, appetite changes	Variable; serotonergic modulation stabilizes mood cycling	SSRIs, SNRIs, TCAs, MAOIs
Norepinephrine (NE)	↓ activity → fatigue, psychomotor retardation, poor concentration	↑ activity → hyperarousal, pressured speech, agitation	SNRIs, TCAs, MAOIs, NRIs
Dopamine (DA)	↓ activity → anhedonia, psychomotor slowing, impaired reward	↑ activity → euphoria, grandiosity, goal-directed hyperactivity	Bupropion, MAOIs; antipsychotics for mania
GABA	↓ inhibitory tone may contribute to anxiety comorbidity	↓ inhibition facilitates cortical excitability in mania	Benzodiazepines (anxiety); valproate enhances GABA

Key neurotransmitter systems and their clinical relevance in mood and anxiety disorders

HPA Axis Dysregulation

The hypothalamic-pituitary-adrenal (HPA) axis is consistently hyperactive in both major depression and anxiety disorders. Elevated cortisol levels, non-suppression on the dexamethasone suppression test, and hippocampal volume reduction (due to cortisol-mediated neurotoxicity) are well-documented findings. Chronic stress activates the amygdala, which drives CRH release from the hypothalamus, perpetuating a feed-forward loop. In anxiety disorders, the amygdala hyperactivity and prefrontal cortex hypoactivity create a state in which threat detection is enhanced while top-down inhibitory control is diminished — explaining why patients cannot simply "think their way out" of anxiety.

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High-Yield Clinical Correlation

The dexamethasone suppression test (DST) is not used as a diagnostic tool for depression in clinical practice due to poor sensitivity and specificity. However, non-suppression on the DST has prognostic significance: patients who remain non-suppressors after treatment are at higher risk for relapse. This is a common Step 2 distractor — never choose DST as a first-line diagnostic test for MDD.

SECTION 5

Detailed Classification & Diagnostic Criteria

Depressive Disorders

The DSM-5 classifies several depressive disorders, but Major Depressive Disorder (MDD) and Persistent Depressive Disorder (Dysthymia) are the most frequently tested. MDD requires at least five of nine symptoms present for at least two weeks, with at least one of those five symptoms being either depressed mood or anhedonia — these two are the obligatory anchor symptoms, and their absence precludes the diagnosis regardless of how many other criteria are met. The classic mnemonic is SIG E CAPS, which maps eight letters to the nine DSM-5 criteria as follows: Sleep disturbance (insomnia or hypersomnia), Interest loss / anhedonia, Guilt or worthlessness, Energy loss or fatigue, Concentration difficulty or indecisiveness, Appetite or weight change (increase or decrease), Psychomotor agitation or retardation (observable by others), and Suicidal ideation or recurrent thoughts of death. Note that the mnemonic has eight letters representing nine distinct DSM-5 criteria because depressed mood — the ninth criterion and first anchor symptom — is asked separately in clinical practice rather than folded into the mnemonic. Always confirm that depressed mood or anhedonia is present before counting the remaining SIG E CAPS items. Persistent Depressive Disorder requires depressed mood for most of the day, for more days than not, for at least two years in adults (one year in children/adolescents), along with two or more associated features.

Bipolar & Related Disorders

The critical distinction between Bipolar I and Bipolar II hinges on the severity and duration of the elevated mood episode. Bipolar I requires at least one manic episode lasting ≥7 days (or any duration if hospitalization is required), characterized by elevated, expansive, or irritable mood with increased energy plus at least three of the DIG FAST criteria: Distractibility, Impulsivity/Indiscretion, Grandiosity, Flight of ideas, Activity increase, Sleep decreased, and Talkativeness. Bipolar II requires at least one hypomanic episode (≥4 days, same symptom criteria, but not severe enough to cause marked impairment or require hospitalization) plus at least one major depressive episode. Cyclothymic Disorder involves chronic, fluctuating mood disturbance with hypomanic and subthreshold depressive periods for ≥2 years.

This spectrum diagram illustrates the key difference between Bipolar I, Bipolar II, and MDD. Note that Bipolar I features full manic episodes that cross above the hypomania threshold (orange dashed line), while Bipolar II shows hypomanic episodes that approach but do not cross this threshold. MDD shows depressive episodes only, without any elevation above euthymia.

Anxiety Disorders

Disorder	Core Feature	Duration Criterion	Key Differentiator
GAD	Excessive worry about multiple life domains	≥6 months	Diffuse, uncontrollable worry (not focused on a single trigger)
Panic Disorder	Recurrent unexpected panic attacks + persistent concern	≥1 month worry after attack	Attacks peak within minutes; autonomic surge (palpitations, dyspnea, derealization)
Social Anxiety Disorder	Fear of social/performance situations and scrutiny	≥6 months	Fear specifically of negative evaluation by others
Specific Phobia	Marked fear of a specific object or situation	≥6 months	Circumscribed trigger; exposure provokes immediate fear
Agoraphobia	Fear of ≥2 of: public transport, open spaces, enclosed spaces, crowds, outside home alone	≥6 months	Fear of situations where escape would be difficult; diagnosed independently of panic disorder in DSM-5

DSM-5 Anxiety Disorders — Core Features and Differentiators

SECTION 6

Worked Clinical Example

Clinical vignettes on the USMLE require you to synthesize history, mental status examination findings, and risk factors to arrive at a diagnosis and management plan within a single pass through the stem. The following worked example demonstrates the systematic approach.

Clinical Vignette: 28-Year-Old Woman with Depressed Mood and Weight Loss

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Step 1 — Extract Key Clinical Features

A 28-year-old woman presents with 6 weeks of persistent sadness, loss of interest in activities she previously enjoyed, 10-lb unintentional weight loss, insomnia with early morning awakening, fatigue, difficulty concentrating at work, and passive suicidal ideation ("I sometimes wish I wouldn't wake up"). She denies substance use. TSH and CBC are normal. She has no history of manic or hypomanic episodes.

Identified symptoms: depressed mood (anchor symptom ✓), anhedonia (anchor symptom ✓), weight loss, insomnia, fatigue, poor concentration, suicidal ideation → 7 of 9 DSM-5 criteria met, including both obligatory anchor symptoms
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Step 2 — Apply DSM-5 Diagnostic Criteria

MDD requires ≥5 of 9 symptoms for ≥2 weeks, and — critically — at least one of the five counted symptoms must be either depressed mood or anhedonia. Both anchor symptoms are present here. This patient meets 7 of 9 criteria for 6 weeks. Medical causes (hypothyroidism) have been excluded via normal TSH. No history of manic or hypomanic episodes rules out bipolar spectrum disorders. A unipolar depressive diagnosis is appropriate.

Diagnosis: Major Depressive Disorder, single episode, moderate severity
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Step 3 — Assess Suicide Risk

The patient endorses passive suicidal ideation without a specific plan, intent, or access to means. Risk factors include female sex, current depressive episode, and insomnia. Protective factors include no prior attempts, no substance use, and no psychotic features. This represents moderate risk requiring close outpatient follow-up with a safety plan.

Moderate suicide risk → outpatient management with safety planning appropriate; hospitalization not indicated at this time
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Step 4 — Select First-Line Treatment

For moderate MDD without prior manic or hypomanic episodes, first-line treatment combines pharmacotherapy with psychotherapy. An SSRI (e.g., sertraline 50 mg daily or escitalopram 10 mg daily) is the preferred initial agent due to superior tolerability, safety in overdose, and broad evidence base. SNRIs (venlafaxine, duloxetine) are acceptable alternatives, particularly if comorbid pain is present. TCAs and MAOIs are reserved for treatment-resistant cases due to their adverse effect profiles and lethality in overdose. Cognitive-behavioral therapy (CBT) or interpersonal therapy (IPT) should be initiated concurrently; combination pharmacotherapy plus CBT outperforms either modality alone for moderate-to-severe MDD. The patient must be counseled that therapeutic effects typically require 4–6 weeks and that the medication should not be abruptly discontinued due to discontinuation syndrome risk.

Management: Start SSRI (e.g., sertraline 50 mg daily) + referral for CBT; reassess in 4–6 weeks
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Step 5 — Anticipate Follow-Up Decisions

If the patient shows partial response at 4–6 weeks, optimize the dose (e.g., increase sertraline to 100–200 mg daily). If no response after an adequate trial (8–12 weeks at therapeutic dose), options include switching to a different SSRI, switching to an SNRI, or augmentation with an atypical antipsychotic (aripiprazole, quetiapine), lithium, or thyroid hormone (T₃). For severe, treatment-resistant, or psychotic depression, electroconvulsive therapy (ECT) remains the gold standard. After achieving remission, continue the antidepressant for at least 6–12 months for a first episode to prevent relapse; patients with recurrent episodes require maintenance therapy for ≥2 years or indefinitely. If this patient had a history of even one prior manic or hypomanic episode, antidepressant monotherapy would be contraindicated — a mood stabilizer would be required first to prevent antidepressant-induced manic switch.

Continue antidepressant ≥6–12 months after remission for first episode; ≥2 years for recurrent episodes; ECT for severe or treatment-resistant cases

SECTION 7

Treatment Comparison & Pharmacological Considerations

Selecting the appropriate pharmacotherapy requires balancing efficacy, side effect profile, safety in overdose, and the specific disorder being treated. The following table compares the major drug classes used in mood and anxiety disorders, emphasizing the clinical decision points most frequently tested on USMLE Step 2 CK.

Drug Class	Key Agents	Primary Indications	Major Side Effects / Risks
SSRIs	Sertraline, escitalopram, fluoxetine, paroxetine	MDD, GAD, panic disorder, social anxiety, OCD, PTSD	Sexual dysfunction, GI upset, serotonin syndrome (with MAOIs), QTc prolongation (citalopram), hyponatremia (SIADH)
SNRIs	Venlafaxine, duloxetine, desvenlafaxine	MDD (especially with pain), GAD, fibromyalgia, neuropathic pain	Hypertension (dose-dependent with venlafaxine), discontinuation syndrome, nausea
TCAs	Amitriptyline, nortriptyline, clomipramine, imipramine	Treatment-resistant MDD, OCD (clomipramine), neuropathic pain, enuresis (imipramine)	Lethal in overdose (Na⁺ channel blockade → wide QRS, seizures), anticholinergic effects, orthostatic hypotension, weight gain
MAOIs	Phenelzine, tranylcypromine, selegiline (transdermal)	Treatment-resistant MDD, atypical depression	Hypertensive crisis with tyramine-containing foods, serotonin syndrome with serotonergic drugs, requires dietary restrictions
Mood Stabilizers	Lithium, valproate, carbamazepine, lamotrigine	Bipolar I/II (acute mania, maintenance); lithium has anti-suicidal properties	Lithium: narrow therapeutic index, nephrotoxicity, hypothyroidism, Ebstein anomaly; Valproate: hepatotoxicity, neural tube defects, pancreatitis; Lamotrigine: SJS
Benzodiazepines	Alprazolam, lorazepam, clonazepam, diazepam	Acute anxiety, panic attacks (short-term bridge); NOT first-line maintenance	Dependence, tolerance, respiratory depression (especially with opioids), falls in elderly, rebound anxiety on discontinuation

Comparison of major pharmacological classes for mood and anxiety disorders

Treatment Algorithms: Bipolar Disorders

Treatment selection for bipolar disorders is one of the most heavily tested Step 2 CK topics. The algorithm differs substantially depending on whether the patient is in an acute manic episode, an acute depressive episode, or in the maintenance phase. For acute mania, first-line agents include lithium, valproate, and atypical antipsychotics (e.g., quetiapine, olanzapine, risperidone, aripiprazole). Lithium and valproate are roughly equivalent in efficacy for acute mania; valproate is preferred when rapid loading is needed or when the patient has mixed features (simultaneous manic and depressive symptoms), while lithium is preferred when suicidal ideation is a prominent concern given its unique anti-suicidal properties. Atypical antipsychotics offer more rapid sedation and are favored when agitation or psychotic features are present. Benzodiazepines (lorazepam, clonazepam) may be added short-term as adjuncts for agitation but do not constitute definitive antimanic therapy.

The most critical and commonly tested rule in bipolar pharmacotherapy is the antidepressant-induced manic switch: administering an antidepressant (SSRI, SNRI, bupropion, or TCA) as monotherapy to a patient with bipolar disorder can precipitate a manic episode or induce rapid cycling (≥4 mood episodes per year). On the exam, if a patient with known or suspected bipolar disorder is depressed, the correct answer is never an antidepressant alone — a mood stabilizer or atypical antipsychotic must be established first. For bipolar depression, first-line options include quetiapine monotherapy, lurasidone (with lithium or valproate), or the olanzapine-fluoxetine combination (OFC). Lamotrigine (as add-on to a mood stabilizer) is effective for preventing bipolar depressive episodes but has minimal efficacy for acute mania. For maintenance therapy, lithium remains the gold standard with Level A evidence for preventing both manic and depressive recurrences and for reducing suicide risk. Valproate and lamotrigine are effective maintenance alternatives, with lamotrigine showing particular strength for preventing the depressive pole.

Treatment Algorithms: Anxiety Disorders

For all major anxiety disorders — GAD, panic disorder, social anxiety disorder, and PTSD — SSRIs are the first-line pharmacotherapy. SNRIs (particularly venlafaxine and duloxetine) are equally first-line for GAD and are frequently tested as correct answers in Step 2 vignettes. The choice between an SSRI and SNRI is often guided by comorbidities: SNRIs are favored when comorbid pain syndromes are present, while SSRIs are generally preferred in straightforward anxiety presentations due to their established tolerability. Buspirone is a non-benzodiazepine anxiolytic with evidence specifically for GAD; it is non-sedating and has no dependence potential, making it an important alternative — particularly in patients with substance use histories — though its onset of action requires 2–4 weeks.

Cognitive-behavioral therapy (CBT) is the first-line psychotherapy for all anxiety disorders and has the strongest evidence base for sustained remission and relapse prevention. Exposure-based CBT, in particular, is the treatment of choice for specific phobia and is highly effective for panic disorder with agoraphobia. For specific phobia (e.g., needle phobia, flying phobia), CBT with systematic desensitization is so effective that pharmacotherapy is rarely necessary. Benzodiazepines play a limited and time-restricted role: they are appropriate as short-term bridges (days to weeks) while awaiting SSRI onset, or for acute situational anxiety (e.g., a single flight for a patient with flying phobia), but should never be prescribed as long-term maintenance therapy for anxiety disorders due to dependence, tolerance, and the risk of rebound anxiety upon discontinuation. Beta-blockers (propranolol) are useful for the autonomic symptoms of performance anxiety (a variant of social anxiety disorder) on an as-needed basis but are not first-line for the full anxiety disorder diagnosis.

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KEY TAKEAWAY

The cardinal rule of bipolar pharmacotherapy is: never give an antidepressant without a mood stabilizer. An SSRI or SNRI given alone to a bipolar patient can precipitate a manic switch or rapid cycling. Think of a mood stabilizer as the guardrails on a winding mountain road — the antidepressant provides forward momentum (elevates depressed mood), but without guardrails (mood stabilization), the patient risks careening into mania. Lithium remains the only agent with demonstrated anti-suicidal properties, making it uniquely valuable in bipolar patients with suicidal ideation. For anxiety disorders, remember that SSRIs and CBT are the foundation of treatment — benzodiazepines are a short-term bridge, not a destination.

SECTION 8

Advanced Concepts & Special Populations

The USMLE Step 2 CK frequently tests your ability to modify standard management algorithms for special clinical scenarios. Several high-yield advanced topics merit particular attention, including treatment-resistant depression, peripartum mood disorders, and the distinction between appropriate grief and pathological depression.

Concept	Standard Approach	Advanced / Special Consideration
Treatment-Resistant Depression	Adequate trial of 2+ antidepressants from different classes at therapeutic doses for 6–8 weeks each	ECT is the most effective treatment for severe, treatment-resistant depression and MDD with psychotic features. Esketamine (intranasal) and TMS are newer FDA-approved options.
Peripartum Depression	Screen all peripartum patients using Edinburgh Postnatal Depression Scale; SSRIs are first-line	Sertraline preferred during breastfeeding (low milk transfer). Brexanolone (IV allopregnanolone analog) is FDA-approved for postpartum depression. Paroxetine and valproate are contraindicated in pregnancy (teratogenicity).
Normal Grief vs. MDD	Grief: sadness in waves associated with reminders of the deceased; self-esteem preserved	MDD: pervasive sadness unrelated to specific reminders, feelings of worthlessness, persistent suicidal ideation, psychomotor retardation, marked functional impairment lasting >2 weeks. Grief and MDD can co-occur.
MDD with Psychotic Features	Antidepressant monotherapy for standard MDD	Requires antidepressant + antipsychotic combination, or ECT. Psychotic features are typically mood-congruent (e.g., nihilistic delusions, delusions of guilt). Never use antidepressant alone — antipsychotic adjunct is mandatory.
Pediatric/Adolescent Depression	SSRIs first-line for adults	Fluoxetine is FDA-approved for children ≥8 years; escitalopram for ≥12 years. FDA black box warning: SSRIs may increase suicidal ideation in patients <25 — requires close monitoring, especially during first 4 weeks. Irritability may be the predominant mood symptom rather than sadness.

Standard vs. Advanced Approaches in Special Populations

Looking beyond the Step 2 CK, the field of psychiatry is rapidly evolving with the integration of precision medicine approaches, including pharmacogenomic testing to guide antidepressant selection (CYP2D6 and CYP2C19 genotyping), the development of rapid-acting antidepressants targeting the glutamatergic system (ketamine/esketamine), and neuromodulation techniques such as deep brain stimulation for refractory cases. The recognition of inflammation-mediated depression and the role of the gut-brain axis in mood regulation represent frontier areas that may reshape diagnostic and therapeutic paradigms in the coming decade.

SECTION 9

Practice Problems

Question 1: CONCEPTUAL

A 32-year-old woman presents to her primary care physician with a 3-week history of depressed mood, anhedonia, poor concentration, insomnia, fatigue, and feelings of worthlessness. She denies suicidal ideation. She has no significant past medical or psychiatric history and takes no medications. Physical examination and laboratory studies, including thyroid function tests, are within normal limits. Which of the following is the minimum duration of symptoms required to diagnose major depressive disorder?

A. 1 week
B. 2 weeks
C. 4 weeks
D. 6 weeks
E. 3 months

Show answer

The correct answer is B. Major depressive disorder (MDD) requires the presence of at least 5 depressive symptoms (including depressed mood or anhedonia) for a minimum of 2 weeks, causing significant functional impairment. This patient meets criteria with her 3-week history of multiple qualifying symptoms. Answer A (1 week) is incorrect because this duration is too short to meet DSM-5 criteria for MDD, though brief depressive episodes may occur in adjustment disorders. Answer C (4 weeks) is incorrect; while persistent depressive disorder (dysthymia) requires symptoms for at least 2 years, MDD only requires 2 weeks. Answer D (6 weeks) is incorrect and may be confused with the typical duration used to assess medication response. Answer E (3 months) is incorrect and may be confused with the duration criteria for generalized anxiety disorder (GAD), which requires excessive anxiety for at least 6 months.

Question 2: BASIC CALCULATION

A 45-year-old man with a history of major depressive disorder presents for a follow-up visit. He was started on sertraline 50 mg daily 4 weeks ago. He reports mild improvement in mood but continues to have significant insomnia and poor appetite. He denies suicidal ideation. His PHQ-9 score has decreased from 22 to 16. Which of the following is the most appropriate next step in management?

A. Continue current dose and reassess in 2-4 weeks
B. Increase sertraline to 100 mg daily
C. Switch to a different SSRI
D. Add aripiprazole augmentation
E. Discontinue sertraline and start a tricyclic antidepressant

Show answer

The correct answer is B. After 4 weeks on an adequate trial of an SSRI with only a partial response (PHQ-9 decreased but still in the moderately severe range), the most appropriate next step is to increase the dose of the current medication. A partial response suggests the medication class is appropriate, but the dose needs optimization. Answer A is incorrect because, although some patients need more time, this patient has had only a partial response after 4 weeks, and dose optimization should be attempted before simply waiting longer. Answer C (switching SSRIs) is premature because the current medication has not been optimized to its maximum dose; switching is more appropriate after failure of an adequate trial at maximum tolerated dose. Answer D (augmentation with aripiprazole) is typically reserved for patients who have failed to respond adequately to at least two optimized antidepressant trials. Answer E is incorrect because switching to a tricyclic antidepressant is generally not a first-line strategy given the greater side effect burden and risk profile of TCAs compared to SSRIs.

Question 3: INTERMEDIATE

A 28-year-old woman is brought to the emergency department by her husband after she was found organizing all the furniture in their house at 3 AM. Her husband reports that over the past 5 days, she has slept only 2-3 hours per night, has been talking rapidly and making impulsive purchases totaling $15,000, and believes she has been selected by the government for a special mission. She has no prior psychiatric history. On examination, she is euphoric, has pressured speech, and is easily distracted. Urine drug screen is negative. Which of the following is the most appropriate pharmacological treatment to initiate?

A. Fluoxetine
B. Lithium
C. Lamotrigine
D. Clonazepam alone
E. Bupropion

Show answer

The correct answer is B. This patient presents with a classic manic episode (elevated mood, decreased need for sleep, pressured speech, impulsivity, grandiose delusions) lasting at least 5 days, consistent with bipolar I disorder. Lithium is a first-line mood stabilizer for the treatment of acute mania and long-term maintenance in bipolar disorder. Answer A (fluoxetine) is incorrect because antidepressants, particularly SSRIs used as monotherapy, can worsen mania or precipitate rapid cycling in bipolar disorder and should be avoided during a manic episode. Answer C (lamotrigine) is incorrect because while it is FDA-approved for maintenance treatment of bipolar disorder, it is primarily effective for preventing depressive episodes and has limited efficacy for acute mania. Answer D (clonazepam alone) is incorrect because while benzodiazepines can be used as adjunctive treatment for agitation in acute mania, they do not treat the underlying manic episode and should not be used as monotherapy. Answer E (bupropion) is incorrect because, like other antidepressants, it carries a risk of inducing or worsening mania and is not indicated for the treatment of manic episodes.

Question 4: APPLIED

A 55-year-old man with a history of bipolar I disorder managed with lithium presents to the clinic for a routine follow-up. He reports feeling well with stable mood for the past 6 months. His current lithium level is 0.8 mEq/L. Laboratory studies show a serum creatinine of 1.8 mg/dL (baseline 1.0 mg/dL 1 year ago), BUN of 28 mg/dL, and TSH of 8.2 mIU/L (normal 0.5-4.5 mIU/L). Urinalysis reveals dilute urine with a specific gravity of 1.003. Which of the following is the most likely explanation for this patient's laboratory findings?

A. Lithium-induced nephrogenic diabetes insipidus and hypothyroidism
B. Lithium toxicity causing acute kidney injury
C. Primary hyperparathyroidism unrelated to lithium
D. Syndrome of inappropriate antidiuretic hormone secretion
E. Central diabetes insipidus from a pituitary adenoma

Show answer

The correct answer is A. Lithium is well known to cause nephrogenic diabetes insipidus (NDI) by impairing the kidney's ability to concentrate urine through interference with aquaporin-2 channels, resulting in polyuria and dilute urine. Lithium also commonly causes hypothyroidism by inhibiting thyroid hormone synthesis and release, which explains the elevated TSH. The rising creatinine suggests chronic lithium-induced nephrotoxicity (tubulointerstitial nephritis). Answer B is incorrect because the lithium level is within the therapeutic range (0.6-1.2 mEq/L), and lithium toxicity typically presents with neurotoxicity (tremor, ataxia, confusion) rather than isolated renal changes. Answer C is incorrect because although lithium can cause hyperparathyroidism, this does not explain the dilute urine and hypothyroidism; furthermore, the constellation of findings is best explained by direct lithium effects. Answer D (SIADH) is incorrect because SIADH would produce concentrated urine and hyponatremia, which is the opposite of what is seen here. Answer E is incorrect because central diabetes insipidus would respond to exogenous desmopressin, whereas lithium-induced NDI is a renal tubular problem and would not; additionally, a pituitary adenoma would not explain the hypothyroidism pattern seen with elevated TSH.

Question 5: CRITICAL THINKING

A 34-year-old woman presents to the emergency department with palpitations, diaphoresis, chest tightness, shortness of breath, and an intense fear that she is dying. The episode began suddenly 10 minutes ago while she was at work. She reports having had 4 similar episodes over the past month, each lasting 10-20 minutes and occurring without a clear trigger. Between episodes, she avoids crowded places and has stopped taking the subway due to fear of having another attack. ECG, troponin, D-dimer, and thyroid function tests are all normal. She has no significant medical history. She asks about treatment options. In addition to cognitive behavioral therapy, which of the following is the most appropriate first-line pharmacotherapy for this patient's condition?

A. Alprazolam scheduled three times daily
B. Sertraline daily
C. Buspirone daily
D. Propranolol as needed
E. Hydroxyzine as needed

Show answer

The correct answer is B. This patient presents with panic disorder with agoraphobia, characterized by recurrent unexpected panic attacks with persistent concern about future attacks and maladaptive behavioral changes (avoidance of crowded places and the subway). SSRIs such as sertraline are the first-line pharmacotherapy for panic disorder due to their efficacy, safety profile, and lack of dependence potential. Answer A (alprazolam scheduled TID) is incorrect because while benzodiazepines can provide rapid relief of panic symptoms, they are not recommended as first-line monotherapy due to the risk of dependence, tolerance, and withdrawal; they may be used short-term as a bridge while waiting for SSRI efficacy. Answer C (buspirone) is incorrect because it is primarily indicated for generalized anxiety disorder and has not demonstrated significant efficacy in panic disorder. Answer D (propranolol as needed) is incorrect because beta-blockers are more commonly used for performance anxiety (a subtype of social anxiety disorder) and do not adequately treat the full spectrum of panic disorder symptoms, particularly the cognitive and affective components. Answer E (hydroxyzine as needed) is incorrect because while it has anxiolytic properties, it is not considered first-line for panic disorder and primarily provides sedation without addressing the underlying pathophysiology or preventing future attacks.

SUMMARY

Summary

Mood and anxiety disorders represent the most common psychiatric conditions encountered in clinical practice and on the USMLE Step 2 CK. The diagnostic approach begins by excluding medical and substance-related causes (hypothyroidism, pheochromocytoma, corticosteroids, stimulants). Major Depressive Disorder requires ≥5 of 9 SIG E CAPS symptoms for ≥2 weeks, with at least one of the five being depressed mood or anhedonia (the obligatory anchor symptoms), and with SSRIs as first-line treatment. Bipolar I is defined by at least one manic episode (≥7 days, DIG FAST criteria), while Bipolar II features hypomania (≥4 days) plus major depressive episodes. For acute mania, first-line agents are lithium, valproate, or atypical antipsychotics; antidepressants must never be given without a mood stabilizer due to the risk of antidepressant-induced manic switch or rapid cycling. Mood stabilizers (lithium, valproate, lamotrigine) are the foundation of bipolar treatment; lithium is the only agent with proven anti-suicidal properties and is the gold standard for maintenance therapy.

Among anxiety disorders, GAD (diffuse worry ≥6 months), Panic Disorder (recurrent unexpected attacks with autonomic surge), Social Anxiety Disorder (fear of social scrutiny), and Specific Phobias (circumscribed triggers) are the most tested entities. SSRIs and SNRIs are first-line pharmacotherapy for all anxiety disorders; benzodiazepines are short-term bridges only due to dependence risk. CBT is the psychotherapy of choice across mood and anxiety disorders and has the strongest evidence for sustained relapse prevention. Always perform a suicide risk assessment, monitor for treatment response at 4–6 weeks, and remember that ECT remains the gold standard for severe, treatment-resistant, and psychotic depression.