Gangguan Depresi

01Pathophysiology

Depression arises from a combination of neurobiological and psychosocial factors working together to produce a sustained disturbance in mood, cognition, and neurovegetative function.

At the neurochemical level, the monoamine hypothesis remains the foundational model. It proposes that depression results from functional deficiency of serotonin (5-HT), norepinephrine (NE), and to a lesser extent dopamine in key brain circuits. Serotonin deficiency correlates with the depressed mood, anxiety, and obsessive rumination. Norepinephrine deficiency links to fatigue, psychomotor retardation, and impaired concentration. Dopamine deficiency underlies anhedonia (the loss of interest and pleasure), which is one of the cardinal symptoms in PPDGJ-III.

The hypothalamic-pituitary-adrenal (HPA) axis is chronically hyperactivated in many depressed patients, leading to elevated cortisol levels. This sustained hypercortisolism damages hippocampal neurons over time, impairing memory, concentration, and attention (gejala lainnya point (a) in PPDGJ-III). It also disrupts the sleep-wake cycle, explaining the sleep disturbance (point (f)).

Neuroplasticity impairment also plays a role. Reduced brain-derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex leads to neuronal atrophy. This contributes to the cognitive symptoms: decreased self-esteem and self-confidence (point (b)), feelings of guilt and worthlessness (point (c)), and the pessimistic outlook toward the future (point (d)).

The connection from pathophysiology to presentation is direct. The three main symptoms in PPDGJ-III map cleanly onto neurotransmitter deficits: depressed affect (serotonin), anhedonia (dopamine), and decreased energy with easy fatigability (norepinephrine). The seven additional symptoms then branch from these core deficits. Understanding this mapping is what helps you predict the vignette before you read it.

Appetite reduction (point (g)) is driven by serotonergic and hypothalamic dysfunction affecting feeding centers. Suicidal ideation or self-harm behavior (point (e)) arises when hopelessness (a cognitive distortion from prefrontal dysfunction) combines with impulsivity from impaired serotonergic regulation.

In recurrent depressive disorder, there is evidence of kindling: each successive episode lowers the threshold for future episodes, such that later episodes may occur with progressively less psychosocial provocation. This is why the PPDGJ-III notes that while stressful life events often precipitate episodes, stress is not essential for diagnosis.

02Classification and Clinical Manifestation

Depressive Episode (Single Episode)

The PPDGJ-III diagnostic framework for a single depressive episode rests on a symptom-counting system drawn from two pools: 3 main symptoms and 7 additional symptoms. The minimum duration for all severity levels is 2 weeks, although a shorter period is acceptable if the onset is unusually rapid and the symptoms are severe.

Three Main Symptoms:

1. Depressed affect (mood)

2. Loss of interest and pleasure (anhedonia)

3. Decreased energy leading to easy fatigability and reduced activity

Seven Additional Symptoms:

1. Decreased concentration and attention

2. Decreased self-esteem and self-confidence

3. Ideas of guilt and unworthiness

4. Pessimistic view of the future

5. Ideas or acts of self-harm or suicide

6. Disturbed sleep

7. Decreased appetite

For mild episodes, the distinguishing feature is that there are no severe symptoms among the additional ones, and the patient can still largely function, albeit with some difficulty. This is the most commonly missed severity on exam because students over-diagnose moderate episodes.

For moderate episodes, the hallmark tested phrase is "kesulitan nyata" (considerable/real difficulty) in continuing daily activities. The patient is struggling noticeably with work, social life, and household responsibilities.

For severe episodes without psychotic features, a critical detail is that all three main symptoms must be present. If the vignette describes only two main symptoms, you cannot call it severe regardless of how many additional symptoms are listed. Also note that if prominent agitation or psychomotor retardation is present, the patient may be unable to report their symptoms in detail, and a comprehensive clinical assessment by the examiner is still considered valid for diagnosis.

For severe episodes with psychotic features, the exam loves to test the content of the psychotic symptoms. Delusions are typically mood-congruent: guilt, poverty, impending catastrophe, with the patient feeling responsible. Hallucinations are characteristically auditory (accusatory, demeaning voices) or olfactory (smell of rotting flesh or filth). Severe psychomotor retardation can progress to stupor. The examiner may ask whether the psychotic features are mood-congruent or mood-incongruent.

Somatic Syndrome

The somatic syndrome designation (applies only to mild and moderate episodes) is present when the patient has features such as marked loss of interest/pleasure, lack of emotional reactivity, early morning awakening (2+ hours before usual time), depression worse in the morning, psychomotor retardation or agitation, marked appetite loss, weight loss (5%+ in one month), and marked loss of libido.

Recurrent Depressive Disorder

This diagnosis is used when a patient has had two or more depressive episodes, each lasting at least 2 weeks, separated by an interval of at least several months free of any significant mood disturbance.

Critical distinction the exam tests: The categories for a single depressive episode (mild, moderate, severe) are used only for the first episode. Once the patient has a second qualifying episode, the diagnosis must shift to recurrent depressive disorder with the appropriate current-episode qualifier. Students frequently miss this reclassification rule.

Exclusion criteria for recurrent depressive disorder: There must be no history of independent manic episodes meeting criteria for mania. If a manic episode has occurred, the diagnosis shifts to bipolar affective disorder. However, a brief episode of hypomania (meeting criteria for hypomania) occurring immediately after a depressive episode, possibly triggered by antidepressant treatment, does not disqualify the recurrent depressive disorder diagnosis.

Recovery between episodes is usually complete (sempurna), although a small proportion of patients may develop chronic, persistent depression, especially in older age.

03Diagnostic Workup

The diagnosis of a depressive episode is fundamentally clinical. There is no laboratory test or imaging study that confirms depression. The purpose of the workup above is strictly to exclude organic/medical causes that can mimic a depressive presentation.

The best initial diagnostic step is always a structured clinical interview using the PPDGJ-III criteria: identify which of the 3 main symptoms are present, then count the additional symptoms from (a) through (g), assess the duration (minimum 2 weeks), and evaluate the degree of functional impairment. The functional impairment is what distinguishes mild from moderate from severe in practice.

When the vignette gives you a patient with depressed mood, fatigue, insomnia, and weight loss, the exam may tempt you to jump to ordering a TSH or other labs. The correct first step is completing the clinical assessment to establish the psychiatric diagnosis. Labs come next to rule out organic mimics, not to confirm depression.

For the somatic syndrome subtyping in mild and moderate episodes, pay attention to whether the vignette describes early morning awakening, diurnal variation (worse in the morning), marked anhedonia with lack of emotional reactivity, psychomotor changes, or significant appetite/weight loss. These features cluster together and determine the fifth-character coding.

When psychotic features are described (severe with psychotic features), the exam may test your ability to determine mood congruence. Mood-congruent psychotic features have content consistent with depressive themes: guilt, deserved punishment, nihilism, somatic decay. Mood-incongruent features (persecutory delusions, thought insertion, broadcasting) are less typical and should prompt you to reconsider the diagnosis (consider schizoaffective disorder).

04Management and Treatment

Acute management

For mild episodes, the exam commonly tests whether pharmacotherapy is needed. The answer is generally no, at least initially. Psychotherapy (cognitive behavioral therapy or interpersonal therapy) is the first-line approach. An SSRI should be started if the patient does not respond to psychotherapy within 6-8 weeks, if psychotherapy is unavailable, or if the patient prefers medication.

For moderate episodes, the standard approach is to combine an SSRI with structured psychotherapy. The most commonly tested SSRIs are sertraline (starting dose 50 mg/day, titrated up to 200 mg/day) and escitalopram (starting dose 10 mg/day, up to 20 mg/day). An adequate trial means at least 4-6 weeks at a therapeutic dose before concluding the medication has failed. This timeline is frequently tested.

For severe episodes without psychotic features, pharmacotherapy is non-negotiable. An SSRI or SNRI at full therapeutic dose is the first-line agent. If the patient presents with prominent suicidal ideation, plan, or intent, hospitalization is the next best step. Electroconvulsive therapy (ECT) should be considered when: (1) the patient is not responding to adequate medication trials, (2) the patient is in a life-threatening state (refusing food/fluids, active suicidality), or (3) rapid response is needed.

For severe episodes with psychotic features, the critical teaching point is that an antidepressant alone is not enough. The combination of antidepressant + antipsychotic is required. ECT is highly effective for this subtype and can be considered as a primary treatment option, particularly when the patient is in depressive stupor.

Maintenance and recurrence prevention

This is one of the most tested topics. After a single episode, antidepressant treatment should continue for at least 6-9 months after full remission before considering a gradual taper. For recurrent depressive disorder (2 or more episodes), maintenance therapy for at least 2 years is recommended. After 3 or more episodes, or if episodes were severe or closely spaced, indefinite maintenance may be appropriate.

The antidepressant dose during maintenance should be the same dose that achieved remission. A common exam trap is the option to reduce the dose during maintenance; this is incorrect and increases relapse risk.

Contraindications and cautions:

SSRIs are relatively contraindicated in patients concurrently taking MAO inhibitors (risk of serotonin syndrome). Fluoxetine has a long half-life and significant CYP450 interactions, which matters in medically complex patients. TCAs (amitriptyline, imipramine) are second-line due to cardiotoxicity and lethality in overdose, a crucial concern in suicidal patients. For pregnant patients, sertraline is generally considered the safest SSRI option. Paroxetine is avoided in pregnancy due to teratogenic risk (cardiac malformations).

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students lose points on depression questions falls into a few predictable patterns.

Trap 1: Miscounting severity. The PPDGJ-III system is purely arithmetic at its core. Students frequently upgrade a mild episode to moderate because the vignette "sounds bad." Go back to the criteria: how many main symptoms? How many additional symptoms? What is the functional impact? If only 2 main and 2 additional symptoms are present, it is mild, even if the patient sounds distressed. Conversely, if all 3 main symptoms plus 4 or more additional symptoms are present with near-total functional disability, it is severe. Count the symptoms methodically.

Trap 2: Forgetting the single-episode vs. recurrent reclassification. This is a hallmark PPDGJ-III rule. If the vignette describes a patient presenting with their second or subsequent depressive episode, the correct diagnosis is recurrent depressive disorder, not "another depressive episode." Students who select the single-episode category lose the point even if they correctly identify the severity.

Trap 3: Missing the 2-week duration requirement. The minimum duration is 2 weeks for all levels of severity. However, the PPDGJ-III allows a shorter duration for severe episodes if the onset is unusually rapid and the symptoms are very intense. The exam may present a 10-day history with all 3 main symptoms, 5 additional symptoms of high intensity, and marked functional impairment, then ask whether the diagnosis can be made. The answer is yes, but only for severe episodes.

Trap 4: Antidepressant monotherapy for psychotic depression. A common wrong-answer choice is prescribing an SSRI alone for a patient with severe depression plus delusions or hallucinations. The correct answer always requires combination therapy (antidepressant + antipsychotic) or ECT.

Trap 5: Misidentifying brief hypomania as bipolar. The PPDGJ-III explicitly states that a brief hypomanic episode occurring immediately after a depressive episode (especially if precipitated by antidepressant treatment) does not change the diagnosis to bipolar disorder. The recurrent depressive disorder diagnosis is retained. Students who see "hypomania" anywhere in the vignette and reflexively switch to bipolar will get this wrong.

Trap 6: Confusing mood-congruent and mood-incongruent psychotic features. When the vignette describes a severely depressed patient hearing voices telling her she is worthless and deserves to die, these are mood-congruent and consistent with severe depression with psychotic features. If the patient instead reports that her thoughts are being broadcast on television and strangers are plotting against her, these are mood-incongruent features, and the diagnosis may be schizoaffective disorder rather than psychotic depression.

The core competency being tested across all depression questions is your ability to (1) identify the correct number of symptoms from two defined pools, (2) match the symptom count and functional impairment to the correct severity level, (3) apply the single vs. recurrent distinction based on episode history, and (4) select the appropriate treatment intensity that corresponds to the severity level.