- Clinical science
Major depressive disorder (MDD) is an episodic mood disorder primarily characterized by depressed mood and anhedonia that lasts for at least 2 weeks. Females are diagnosed more often than men. The peak age of onset is in the 20s. 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. Additional symptoms of MDD include sleep disturbances, loss of appetite, and suicidal thoughts. Various subtypes include atypical depression (e.g., weight gain, and increased appetite), psychotic depression (e.g., hallucinations and delusions), and peripartum depression (occurring during or shortly after pregnancy). In elderly patients, it may also present with memory loss and resemble dementia, which is 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: ♀ > ♂
- General population: 15–25%
- 1st-degree relatives of patients: 24–30%
- The peak age of onset is in the 20s.
Epidemiological data refers to the US, unless otherwise specified.
The consensus today is that depression is influenced by genetic, neurobiological, socio-psychological, and environmental factors. The most clinically relevant contributing factor appears to be a decrease in monoamine levels.
- Monoamine hypothesis: Most antidepressants work by inhibiting the reuptake of monoamines (e.g., serotonin, noradrenaline, dopamine). This indicates that a lack of these substances plays a major role in the pathophysiology of depression (and other mood disorders).
- Genetic vulnerability
- Increased levels of stress hormones (and dysfunction of the hypothalamus-pituitary axis)
- Psychological factors: traumatic and stressful experiences, personality factors (e.g., learned helplessness)
- Comorbidities: MDD is associated with a wide range of comorbidities, such as neurodegenerative diseases (e.g., Alzheimer disaese), chronic inflammatory diseases (e.g., systemic lupus erythematosus or inflammatory bowel disease) or other psychiatric disorders (e.g., panic disorder).
|Diagnostic criteria for major depressive disorder (DSM-V)|
The criteria A to C constitute a major depressive episode. Major depressive disorder also includes the following two criteria: the symptoms are not better explained by another psychiatric disorder AND no history of a manic or hypomanic episode.
- Pseudodementia: See “Differential diagnosis of subtypes of dementia”
- Pediatric depression: classical symptoms of major depressive disorder (e.g., depressed mood, loss of energy) may be less marked and often resemble attention deficit hyperactivity disorder (difficulties concentrating, memory impairment, restlessness, aggression)
“SIG E CAPS”: 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 Suicidality.
Depression with seasonal pattern (seasonal affective disorder, winter depression)
- Occurs yearly in fall and winter
- Patients suffer from the usual symptoms of MDD along with 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
≥ 2 of the following features
- Increased appetite or weight gain
- Increased sleep
- Leaden paralysis (weighing down of arms and legs)
- Interpersonal rejection sensitivity, which leads to social and occupational impairment
- Major depression accompanied by psychotic symptoms
- Overactivity of the hypothalamic-pituitary-adrenal axis (↑ dopamine activity) is believed to play a major role.
- In the DSM-5, postpartum depression is referred to as major depressive disorder with peripartum onset.
- Definition: depression occurring during pregnancy or within the first four weeks after delivery
- During pregnancy: Most antidepressants cross the placenta and should, therefore, be avoided unless the patient has severe or relapsing depression.
- After delivery: generally the same as for depression unrelated to pregnancy
- For lactating patients: Psychotherapy may be attempted before initiating drug therapy to avoid exposing the baby to antidepressants via breastmilk.
Differential diagnosis: postpartum blues
- Incidence: up to 80% of pregnancies
- Clinical features: mild depressive symptoms that resolve spontaneously within 2 weeks after delivery
- Treatment: reassurance
- Postpartum psychosis (F53.1): Postpartum depression and depression during pregnancy proceeds in some cases to psychosis. The disorder is characterized by delusional symptoms and occasionally by hallucinations. Postpartum psychosis occurs significantly more often than depression or psychosis during pregnancy.
- Clinical diagnosis; (see “Diagnostic criteria for major depressive disorder”)
- Suicide screening and assessment: indicated for all patients
- Polysomnography: indicated in sleep-onset insomnia (the patient is unable to fall asleep) and sleep-maintenance insomnia (the patient fall asleep but wakes up often)
- Thyroid function tests: to rule out hypothyroidism
- Pediatric depression: rule out organic disease
|Persistent depressive disorder||Major depressive disorder|
|Timing|| || |
|Diagnostic features|| |
Bereavement  (normal grief)
- Bereavement is a situation involving the loss or death of someone close to an individual.
- It can precipitate or worsen psychiatric disorders (e.g., major depressive disorder).
- Shares some symptoms with major depressive disorder.
- For differences see table below.
|Bereavement||Major depressive disorder|
|Identifiable loss is present||Identifiable loss may or may not be present|
|Major complaint is feeling of loss||Major complaint is depressed mood|
|Normal self-esteem||Feeling of worthlessness|
|Negative feelings of pain and grief are mixed with positive memories/feelings of loved one|| |
Feelings are predominantly negative
|Guilt over specific aspects of the loss||Generalized feeling of guilt|
|Closeness of others can be comforting||Social isolation is preferred|
|Generally, no suicidal ideation||Often suicidal ideation|
|Daily functioning maintained||Daily functioning often impaired|
- Refers to a pathological grieving process.
- Death of a close other
- Clinical significant yearning for the deceased persist for at least 6-12 months
- Difficulty adjusting to a life without the deceased
- Disturbance impairs daily life (socially, occupational)
- Yearning is inconsistent with cultural norms
- Hallucinations of deceased
- Somatic complaints
Depressive disorder due to another medical condition
Certain medical conditions affect mood and may resemble major depressive disorder:
- Parkinson disease
- CNS neoplasms
- Other neoplasms (e.g., pancreatic cancer)
- Stroke (especially ACA stroke)
- Parathyroid disorders
Substance-induced mood disorder
The differential diagnoses listed here are not exhaustive.
- Most drugs have comparable efficacy but differ in regards to their side effects.
- Take > 4 weeks to take effect
- Always start with the lowest dose and increase in small steps.
- Single episode: continue medication for ≥ 6 months
- Multiple episodes: continue medication for ≥ 2 years
- If the patient is in remission: continue antidepressants for at least 4–9 months.
- Tapering of medication over 6–8 weeks
- First-line: SSRIs
- Other options
- Treatment-resistant depression: Switch to a different drug from the same class or to a different drug from a different class.
- Suicidal patients: Lithium should be combined with an antidepressant as prophylaxis to prevent recurrence.
Palliative patients: Psychostimulants (e.g., methylphenidate) are effective for the urgent treatment of depressive symptoms in terminally ill adults with a short life expectancy or severe symptoms.
- SSRIs can be introduced concurrently in patients with an anticipated life expectancy of several months.
- Cognitive-behavioral therapy
- Interpersonal therapy
- Psychodynamic psychotherapy
- Family and couples therapy
- Lifestyle changes (aerobic exercise, nutrition, sleep hygiene, social support, stress reduction)
- Light therapy
- Transcranial magnetic stimulation (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, but does not last.
- Goal: restoration of physiological sleep architecture
Implementation: 3 cycles/week as follows
- Staying awake from 7 a.m. of day 1 to 7 p.m. of day 2
- Recovery sleep from 7 p.m. of day 2 to 7 a.m. of day 3
- Sleep deprivation should be repeated again as explained above.
- Short sleep phases in between diminish the antidepressive effect and hence should be avoided.
Sleep-phase-advance (follows a sleep deprivation phase)
- Changing the sleep phase to approximately 6 hours
- In combination with sleep deprivation and antidepressants
- Worsening of depressive symptoms
- Sleep deprivation therapy should be carried out with caution in patients suffering from bipolar disorders.
- Proceed with extreme caution in patients with a history of convulsions!
- Electroconvulsive therapy: reserved for severe or refractory depression or psychotic depression