Last updated:
March 30, 2026
Major Depressive Disorder (Unipolar Depression)
Depression is a very common condition associated with significant dysfunction. It is usually underdiagnosed and often chronic or recurrent. It commonly presents in patients with other general medical conditions. Multiple safe and effective treatment options are available, including electroconvulsive therapy.
The diagnosis of severe depression requires ≥ 5 of SIG E CAPS signs and symptoms for at least 2 weeks, with at least one from the big 2 (low mood and anhedonia). No drug/substance abuse, medical condition, manic or Schizophrenia spectrum disorder, or bereavement (symptoms < 2 months)
Depression is more common in women. The average age of onset 40 years old. 1st episode is common in late teens and early adulthood (18 – 25 years). It affects 1.6 per 100 men and 2.9 per 100 women. It has a high recurrence rate (80% of patients relapse after the first episode) and has the highest lifetime prevalence of any disorder. It affects 5 – 10 % of the general population and is extremely high in the primary care setting (15 – 30 %).
Severity of depression (can be measured objectively using the PHQ-9/10)
| Severity | Description |
|---|---|
| Subthreshold depressive symptoms | Less than 5 symptoms |
| Mild depression | Few, if any, symptoms in excess of the 5 required to make the diagnosis, and symptoms result in only minor functional impairment |
| Moderate depression | Symptoms or functional impairment are between ‘mild’ and ‘severe.’ |
| Severe depression | Most symptoms, and the symptoms markedly interfere with functioning. Can occur with or without psychotic symptoms. |
Etiology
- General risk factors for depression
- Sex: Females at higher risk (2:1)
- Age: Depression starts earlier in women (25-35 years) than in men (45 -55 years)
- Marital status: singles (not by choice) are at a higher risk than married individuals with children
- Race: more in whites than blacks
- Socioeconomic status: rates are higher in low SES than high SES (unlike bipolar disorders)
- Religion: Religion can predispose and precipitate. Christians are at a higher risk than Muslims, Hindus, and Buddhists. Among Christians, Evangelicals > Protestants> Catholics.
- Jobless
| Biological factors | Description |
|---|---|
| Genetics | 2-10X risk if first-degree relative has depression; 50% monozygotic concordance, 20% dizygotic concordance. 40 – 48% heritability. |
| Biochemical | Markedly reduced serotonin (5-HT), norepinephrine (NE), and dopamine (DA) in the brain and spinal cord |
| Neuroendocrine axis dysfunction | Depressed patients may have comorbid hypothyroidism (5-10%), elevated cortisol (50%), decreased growth hormone, and somatostatin |
| Neuro-immunological regulation dysfunction | Increased levels of cortisol (50%) |
| Neuro-anatomical changes | Reduced movement, posture problems, and emotions due to dysfunction of the basal ganglia and limbic system. Reduced blood flow to the cortex (frontal lobe, anterior cingulate, caudate nucleus). Atrophy in the reticular activating system (RAS) and diencephalon. Increased ventricle: brain ratio (BPID and psychotic depression > MDD) |
| Age |
| Psychosocial factors | Description |
|---|---|
| Personality | Cluster C personality (OCPD, Avoidant, Dependent) and Cluster B personality (BPD, Histrionic) are at increased risk |
| Losses | Bereavement, job, failed exams, conflicts in relationships, failed relationships, business/financial, serious acute/chronic physical illness; early loss of parents; early separation of parents |
| Adverse early childhood experiences | Parental loss before adolescence, a deprived and disrupted home environment, divorce, or separation. The brain is very sensitive in childhood due to changes in cortical levels, neurotransmitter sensitivity, and myelination. |
| Learnt helplessness | From operant learning theory. The patient learns to give up completely. This explains depressive symptoms in some cultures or tribes. |
| Cognitive theory | Depressed persons have problems with cognition. This is important in CBT, where cognitive restructuring is performed. Cognitive triad: negative, pessimistic feelings about themselves, the world, and the future. Cognitive distortions: minimization, magnification, and abstracting. Cognitive schemas: errors in logic |
Clinical Presentation
| Presentation | Signs and symptoms |
|---|---|
| Classic symptoms | Insomnia, anorexia, weight loss, easy fatiguability |
| Reversed symptoms | Hypersomnia, overeating, weight gain (more common in men than women) |
| Auxiliary symptoms (Somatic) | Headaches, pains/aches, pressure/fullness in the head, coldness, heavy limbs, fullness/bloating, nausea, constipation, palpitations, sweating, burning sensation, amenorrhoea, and low libido |
| Psychotic symptoms | Are mood congruent. Delusions of sin, poverty, imminent disaster, or nihilistic (delusions are usually paranoid and against the patient). Auditory hallucinations are internal, defamatory, and accusatory. Olfactory hallucinations could be of rotting filth or decomposing flesh |
| Cognitive dysfunction | 68% of patients with major depression have cognitive impairment. Memory impairment (pseudodementia) can be seen. |
MSE findings in depression
| Component | Findings |
|---|---|
| Appearance and behavior | Stooped posture, no spontaneous movements, poor eye contact (reduced, downward, averted), psychomotor agitation (hand wringing, pulling, pacing), socially withdrawn, disorganized behavior (mute, soiled, not bathing, catatonia), stereotypies |
| Mood and affect | Feeling low, flat affect |
| Speech | Decreased rate, tone, and volume; Slow to answer; Single-word answers |
| Thought | Pessimistic (negative view of the world, themselves, and the future); mood-congruent delusions; overvalued ideas, obsessions; ruminations; suicidal ideation; thought block, slow process; overemphasizes the bad and minimizes the good |
| Perception | Mood-congruent hallucinations – few may have mood incongruent hallucinations |
| Sensorium and cognition | May not have the energy to answer questions, poor attention, and concentration. Poor memory (pseudodementia). |
| Insight | Partial insight. Unlikely to find Insight level I and full insight (V). |
- The elderly patient who is depressed
- More likely to have Somatic complaints (to the point of hypochondriasis). Manifests as easy fatiguability.
- More likely to describe the Guilt part of SIG E CAPS as Worthlessness (Worthlessness vs Fullfilment stage – Erik Erikson)
- More likely to exhibit psychomotor agitation or retardation
- More likely to exhibit psychotic delusions with their MDD
- More likely to commit suicide (patient > 55y make up 12% of MDD pts but represent 25% of MDD suicides)
- Risk factors for suicide in elderly patients with MDD
- Living alone
- Alcoholism
- Male sex
- Comorbid physical conditions
Management
- Investigation
- TFTs: rule out hypothyroidism
- Adrenal function tests: rule out ushing disease
- HIV testing: rule out HIV
- Viral serologies: rule out chronic mononucleosis, Influenza
- Blood slide for malaria parasites: rule out malaria
- CBC: rule out chronic anaemia
- Urine tox screen: rule out drug use (alcohol, benzodiazepines, and amphetamines)
- Head CT: rule out tumour, CVA
- Neurological diseases: Parkinson’s, Alzheimer’s, Epilepsy
- Medications: anti-hypertensives (beta blockers, methyldopa, clonidine), sedatives/hypnotics (long-acting benzos and barbiturates), steroids (prednisone, OCPs), antipsychotics (phenothiazines), anti-neoplastics, ARVs
- Metabolites of neurotransmitters in urine, serum, and CSF
- Psychometrics for Depression (PHQ, Hamilton depression scale, Beck’s depression rating scale)
- Differentials
- Hypothyroidism
- Hyperadrenalism
- Indications for admission
- Suicidal
- Not eating
- Insight level I
- No social support
- Severe depression with a severe comorbid medical condition
- Pharmacotherapy
- SSRIs (sertraline, citalopram, paroxetine, escitalopram, fluoxetine, or fluvoxamine): first-line therapy. Readily available, fairly affordable
- TCAs (imipramine, amitriptyline): readily available and affordable. More side effects. Preferred for patients with insomnia (one SE is hypersomnia)
- Buproprion: an alternative for patients on SSRIs who have sexual dysfunction
- Esketamine: reserved for severe, resistant depression
- Atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine): adjuvants, potentiate antidepressant effect, and treat psychotic symptoms
- Thyroid hormones (levothyroxine, liothyronine): adjuvant,
- Lithium, lamotrigine, pindolol
- Benzodiazepine: if agitated, anxious, insomnia for a few days.
- Rehydration: IVF, Multivitamins, amino acids
- Physical therapies
- Electroconvulsive therapy: Very effective. Used as a last resort in severe refractory cases (after SSRIs and Psychotherapy have failed). Can be started in patients with catatonia, severe psychomotor retardation, suicidal, not eating, or who can’t tolerate side effects. Improvement usually occurs with 2 sessions. May need 4 or more sessions in total.
- Transcranial magnetic stimulation, vagus nerve stimulation, deep brain stimulation: not commonly done, very expensive
- Phototherapy: Depression with seasonal pattern
- Psychotherapies
- CBT: cognitive restructuring (combines cognitive and behavioral therapy)
- Supportive psychotherapy
- Patient psychoeducation
- Caretaker education: illness nature, Treatment modality, course, and prognosis, signs of suicidal tendencies
- Family/marital therapy
- Psychoanalytically oriented psychotherapy
- Other therapies
- Herbal therapy/Chinese
- Spiritual
- Music therapy
- Relaxation/yoga
- Nutritional supplements
- Exercise
Prognosis
- Good prognostic factors
- Mild depression
- No psychotic features
- Short hospital stay
- Stable family
- Strong social function 5 years preceding illness
- Solid friends during adolescence
- No comorbid psychiatric condition
- Late age of onset (40s or 50s in women)
- Poor prognostic factors
- Presence of dysthymia
- Substance abuse
- More than 1 previous episode
- Anxiety symptoms
- Relapse
- Family history
- Psychotic features
- Early age of onset
- Objective scales used to diagnose and monitor improvement in patients with depression
Persistent Depressive Disorder (Dysthymia)
Persistent depressive disorder is a chronic disorder with a period of mild depression (< 5 SIG E CAPS) lasting more than two years. It can be thought of as a lingering and less severe depression.
- Differentials (same as MDD + dementia)
- Hypothyrodism
- Hyperadrenalism
- Dementia: consider if the patient is older
- Treatment
- Rule out hypothyroidism
- Cognitive Behavioral Therapy (CBT)
- SSRIs can be used
Seasonal Affective Disorder (SAD)
Seasonal affective disorder is a period of mild depression that comes on in the fall and winter months in the northern and southern hemispheres. A repetitive history is common (patients repeatedly get these symptoms in the winter).
- Theory
- Decreased UV exposure → Decreased MSH, which is implicated in mood
- Differentials
- MDD
- Cyclothymia
- Persistent Depressive Disorder (Dysthymia)
- Treatment
- SSRIs
- Phototherapy (evidence is limited and is not routinely recommended)
- Do not prescribe sleeping tablets as these can worsen symptoms
Bereavement
It is normal for people to feel sad and grief after the death of their loved ones.
Potential stages a person may go through when in grief:
- Denial (includes numbness, pseudohallucinations – auditory and visual, and focusing on things that remind them of the deceased)
- Anger (commonly directed against family members and medical professionals)
- Bargaining
- Depression
- Acceptance
Not all patients go through all 5 stages.
An abnormal or atypical grief reaction is more likely to occur in women if the death is sudden and unexpected.
- Risk factors for atypical grief reaction
- Problematic relationship before death
- Minimal social support
- Features of atypical grief reaction
- Delayed grief: occurs more than 2 weeks after the event
- Prolonged grief: this period is difficult to define since normal grief reactions can take as long as 12 months
- Changes in the bereavement exclusion in DSM-5
- Cut-off no longer than two months (Patients can have protracted bereavement)
- Patients can have MDD superimposed on bereavement (Use clinical judgement based on history and cultural norms to differentiate)
- Patients who have a past medical history of MDD are at higher risk of relapsing from bereavement
- If bereavement is severe enough (suicidality, etc.) SSRIs can be given
Grief vs depression
| Prepatory Grief | Depression |
|---|---|
| Mood fluctuates | The patient feels sad or low most of the time. Tearfulness |
| The patient can enjoy seeing and interacting with friends and family | Protracted feelings of worthlessness and guilt |
| The patient is able to enjoy seeing and interacting with friends and family | The patient withdraws from friends and family. Less talkative |
| The patient can experience pleasure in various activities. | Anhedonia. The patient experiences a loss of interest in activities. |
| The patient is able to look forward to special occasions. | Thought of early death or suicide. May frequently ask physicians to hasten death. |
| Decreased ability to focus and concentrate | |
| Inability to make decisions | |
Premenstrual Dysphoric Disorder
Premenstrual dysphoric disorder is a depressive or other mood symptoms (consistent with SIG E CAPS criteria) in the majority of menstrual cycles that come on within one week before menses and improve in the days after.