- Clinical science
Major depressive disorder (MDD) is an episodic mood disorder primarily characterized by depressed mood and anhedonia lasting for at least 2 weeks. Women have a higher risk of developing MDD than men. The peak age of onset is the 3rd decade. The etiology is multifactorial, including both biological and psychological factors. Reduced levels of neurotransmitters (serotonin, noradrenaline, dopamine) are believed to be the pathophysiological basis in most cases. Other symptoms of MDD include sleep disturbance, loss of appetite, and thoughts of suicide. There are various subtypes of MDD characterized by additional symptoms or occurrence in specific conditions, such as atypical depression (additionally characterized by, e.g., weight gain and increased appetite), psychotic depression (with additional psychotic features such as hallucinations and delusions), and peripartum depression (which occurs during or shortly after pregnancy). In elderly patients, MDD can also manifest with memory loss and other symptoms seen in dementia, referred to as pseudodementia. Treatment is multifaceted and often requires pharmacotherapy, psychotherapy, and lifestyle changes. First-line treatment mainly consists of SSRIs (e.g., citalopram) and SNRIs (e.g., venlafaxine).
- Sex: ♀ > ♂
- Lifetime prevalence: 10–20% 
- Age of onset: 3rd decade of life
Epidemiological data refers to the US, unless otherwise specified.
- Monoamine hypothesis: Most antidepressants work by inhibiting the reuptake of monoamines (e.g., serotonin, noradrenaline, dopamine), indicating that a lack of monoamines plays a major role in the pathophysiology of depression (and other mood disorders).
- Genetic factors
- First-degree relatives of patients with depression are at increased risk of developing depression.
- The concordance rate in identical twins is ∼ 50%.
- Increased production of stress hormones (e.g., dysfunction of the hypothalamic-pituitary-adrenal axis)
- Psychological factors: traumatic and stressful experiences, behavioral factors (e.g., learned helplessness)
- Comorbidities: neurodegenerative diseases (e.g., Alzheimer disease), chronic inflammatory diseases (e.g., systemic lupus erythematosus or inflammatory bowel disease), and other psychiatric disorders (e.g., panic disorder)
|Diagnostic criteria for major depressive disorder (according to DSM-5)|
Five or more of the nine symptoms listed below, for at least 2 weeks, with at least one of the symptoms being depressed mood or anhedonia
There is clinically significant distress or impaired functioning in important areas of life (e.g., work, school).
Symptoms are not due to the effects of psychoactive substances or organic disease.
Symptoms are not due to another psychiatric disorder.
The presence of symptoms from criteria A to C constitutes a major depressive episode. For a diagnosis of major depressive disorder, the following two criteria must also be present: the symptoms are not due to another psychiatric disorder AND there is no history of a manic or hypomanic episode.
To remember the symptoms, think of “SIGECAPS” (which resembles SIG: E. CAPS, short for “prescribe energy capsules”): Sleep (insomnia or hypersomnia), Interest loss (anhedonia), Guilt (low self-esteem), Energy (low energy or fatigue), Concentration (poor concentration or difficulty making decisions), Appetite (decreased appetite or overeating), Psychomotor agitation or retardation, and Suicidal ideation.
Major depressive disorder with seasonal pattern (seasonal affective disorder, winter depression)
- Occurs yearly in fall and winter
- Patients present with typical symptoms of MDD alongside atypical ones, such as weight gain and requiring more sleep.
- Light therapy has been shown to improve symptoms.
- Mood reactivity: brightening of mood in response to positive events, which is usually not the case in classical MDD
- Two or more of the following features are present:
- Major depression accompanied by psychotic symptoms
- Overactivity of the hypothalamic-pituitary-adrenal axis (increased dopamine activity) is believed to play a major role.
- Treatment should involve atypical antipsychotics; in severe cases, electroconvulsive therapy may be used.
- Depressed mood in addition to ≥ 2 of the following symptoms ;:
- The symptoms are present for most of the day, and for the majority of days, for ≥ 2 years.
- Not asymptomatic for > 2 consecutive months
- Criteria for a major depressive disorder may be present for the duration of the illness.
To remember the symptoms of dysthymia, think of “HE'S 2 SAD”: Hopelessness (insomnia or hypersomnia), Energy loss or fatigue, Self-esteem is low, 2 years minimum of depressed mood, Sleep increased or decreased, Appetite increased or decreased, Decision-making or concentration is impaired.
- Clinical diagnosis
- Screening: Patient Health Questionnaire-2
- Assessment of suicide risk: indicated for all patients
Laboratory evaluation: indicated to rule out organic disease
- Thyroid function tests; : to rule out hypothyroidism, which can manifest with lethargy, cognitive impairment (slowed mentation, poor concentration), psychomotor retardation, social withdrawal, and depressed mood
- Urine toxicology: to screen for drug use causing depressive symptoms, such as benzodiazepine withdrawal, amphetamine use, and cocaine “crash”
- Neuroimaging: to evaluate for structural brain disease if suspected
In pediatric patients, remember to first rule out organic causes, which are the most common cause of depression in this population.
|Major depressive disorder|| || |
|Persistent depressive disorder (dysthymia)|| |
|Depression with seasonal pattern|| || |
|Minor depressive disorder|| || |
|Mood disorder due to another medical condition|| || |
|Substance-induced depressive disorder|| |
|Disruptive mood dysregulation disorder (DMDD)|| || |
|Adjustment disorder|| || |
- Definition: normal reaction to the loss or death of a loved one
- Intense sorrow, yearning, emotional distress, guilt, anxiety, insomnia, anorexia, weight loss (often occurs in waves)
- Preoccupation with the deceased and circumstances surrounding their death
- No suicidal ideation (may have thoughts of joining the deceased loved one)
- Simple hallucinations of deceased loved ones
- No functional impairment
- Duration can vary significantly among different cultural groups
- Some symptoms are similar to those seen in MDD (e.g., depressed mood, disturbed sleep)
- Definition: a pathological grieving process
- The death of someone close
- Clinical significant yearning for the deceased that persists beyond 12 months (adults) or 6 months (children)
- Difficulty adjusting to life without the deceased
- The disturbance impairs social and/or occupational functioning.
- Yearning that is inconsistent with cultural norms
- Hallucinations of the deceased
- Somatic symptoms
- Definition: depressed mood; and/or anhedonia attributable to a general medical condition
- Conditions associated with depressive disorder include the following:
- Definition: depressed mood; and/or anhedonia attributable to the use of, or withdrawal from, substances or medications
- Substances or medications associated with depressive disorder include the following:
- Definition: : A disorder characterized by persistent irritability and episodes of extreme behavioral dyscontrol; in children under 18 years of age.
- Can manifest with severe temper outbursts (verbal or behavioral) ≥ 3 times/week, sometimes with severe, persistent irritability in between outbursts
- Duration of symptoms: ≥ 12 months
- Prognosis: Individuals with DMDD are at increased risk of developing ; or anxiety disorders in adulthood.
The differential diagnoses listed here are not exhaustive.
- For initial treatment of adult patients, pharmacotherapy and psychotherapy can be used alone or in combination.
For nonresponders to initial pharmacotherapy, consider one of the following:
- Switching the modality to psychotherapy
- Adding psychotherapy
- Switching to another antidepressant
- Adding an augmenting agent
- Therapy should be continued until the patient is in remission.
- Patients with ≥ 3 prior major depressive episodes or chronic MDD (≥ 2 years) should receive maintenance therapy (see below).
- Most drugs have comparable efficacy but different side effects.
- Most antidepressants require > 4 weeks to take effect.
- Always start with the lowest dose and increase in small steps.
- Initial treatment: 6–12 weeks
- If the patient is in remission, continue antidepressants for at least 4–9 months (continuation phase).
- If the patient has had ≥ 3 prior major depressive episodes or severe episodes (e.g., including suicide attempt or psychosis) or has risk factors for recurrence , or chronic MDD, continue antidepressants for at least 1–3 years (maintenance phase).
- Tapering off medications should be done over 6–8 weeks because this can help to:
- First-line: SSRIs
- Atypical antidepressants
- TCA and MAO inhibitors: cause more side effects than SSRIs
- Augmenting agents: lithium, second-generation antipsychotics (e.g., aripiprazole), thyroid hormones 
- Cognitive-behavioral therapy (CBT)
- Interpersonal therapy
- Psychodynamic psychotherapy
- Family and couples therapy
- Lifestyle changes (aerobic exercise, nutrition, sleep hygiene, social support, stress reduction)
- Light therapy
- Repetitive (rTMS)
Sleep deprivation therapy
- Approach: complete or partial (second half of the night) sleep deprivation
- Effect: A short-term antidepressive effect is achieved on the same day.
- Goal: restoration of physiological sleep architecture
- Electroconvulsive therapy: reserved for severe, refractory, and/or psychotic depression
|Postpartum blues||Major depressive disorder with peripartum onset (postpartum depression)||Postpartum psychosis|
|Epidemiology|| || || |
|Timing|| || || |
|Clinical findings|| || |
|Diagnosis|| || || |
|Treatment|| || || |
Depression in palliative patients
- Definition: depressive symptoms or thoughts of suicide in patients with a limited life expectancy
- Classical symptoms of major depressive disorder (e.g., depressed mood, loss of energy)
- Symptoms may be less marked than in adults.
- MDD in pediatric patients often resembles attention deficit hyperactivity disorder (difficulties concentrating, impaired memory, restlessness, aggression).
- Treatment