creation date: 2024-12-29 14:13 tags: Pathologies
Major Depressive Disorder
Background
Definitions
Disorder consisting of a history of at least one major depressive episode without history of mania or hypomania.
A major depressive episode is a period of at least two consecutive weeks with multiple associated symptoms. Criteria is discussed further below.
Etiology and Pathogenesis
Causes of depression are multifactoral with contributions from biological, genetic, environmental, and psychosocial factors.
While theories of the primary causes vary, they agree on downstream disturbances to neurotransmitters. Serotonin, norepinephrine, dopamine, GABA, glutamate, and glycine have all been shown to play a role.
Possible etiologies implicate thyroid and growth hormone abnormalities, early severe stress causing alteration to neuroendocrine responses, and genetic susceptibility.
Per cognitive theory, depression occurs as a result of cognitive distortions in people who are susceptible to depression.
Clinical Presentation
Signs & Symptoms
The classic symptoms are listed using the MSIGECAPS mnemonic:
- Mood: depressed, can manifest as irritable
- Sleep: insomnia or hypersomnia
- Interest: reduced, anhedonia
- Guilt: unrealistic
- Energy: mental and physical fatigue
- Concentration: easily distractible
- Appetite: decreased or increased
- Psychomotor: retardation or agitation
- Suicide: thoughts, plans, behaviours
These symptoms are also described as part of the DSM-5 diagnostic criteria.
History & Physical Exam
Clinical history should ascertain signs and symptoms of depression. A mental status examination should also be performed. Signs and symptoms can be screened using tools listed below.
Inclusion of medical, family, social, and substance use history should be done. Collateral information from family and friends will aid assessment as well.
A complete physical examination should be performed t o rule out underlying causes.
Risk factors
- Alcohol use disorder
- Childhood trauma / ACEs
- Family or personal history of MDD
- Female sex (possible hormonal etiology and underreporting in male sex)
- Lack of social support
- Low SES and/or low educational attainment
- Older age (mean age of onset is 40)
- Poor physical health
- Pregnancy or recent childbirth
- Recent negative life events
Diagnosis
Criteria
Diagnosis is made clinically using criteria set by the DSM-5.
Five or more of the following symptoms have been present in a two-week period that is different from previous functioning. At least one symptom must be depressed mood (1) or loss of interest (2).
- Depressed mood most of the day, nearly every day, as indicated by either subjective report (eg. feels sad, empty, hopeless) or observations made by others (eg. appears tearful). In children and adolescents, can be irritable mood.
- Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (subjective account or observation).
- Significant weight loss when not dieting or weight gain (eg, a change of more than 5% of body weight in a month), or decrease/increase in appetite nearly every day. In children, consider failure to make expected weight gain.
- Insomnia or hypersomnia nearly every day.
- Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
- Fatigue or loss of energy nearly every day.
- Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
- Diminished ability to think or concentrate, or indecisiveness, nearly every day (either subjective account or observed by others)
- Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.
The symptoms must also cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The episodes must also not be attributable to a substance or another medical condition.
In cases of response to a significant life event such as bereavement, clinical judgement must be used to determine if symptoms are a normal response or if MDD is present.
Work-up
In cases of suspected MDD, the Patient Health Questionnaire-9 (PHQ-9) covers the DSM-5 criterion and should be used to evaluate for depression and severity. The PHQ-9 scores from 0-27, with scores ≥10 indicating possible MDD.
The clinician-administered Hamilton Rating Scale for Depression (HAM-D) can be used in hospital settings.
Further workup should be done to rule out organic or medical causes of the depressive symptoms. Routine lab work should include:
- CBC
- Metabolic panel
- TSH, T4
- Vitamin D
- Urinalysis
- Toxicology if suspected
Differential
Other mental health disorders may present with overlapping symptoms:
- Schizophrenia
- Anxiety
- Schizoaffective disorder
- Bipolar disorder
- Eating disorders
Depressive symptoms can also be secondary to:
- Neurological causes (eg. CVA, multiple sclerosis, subdural hematoma, epilepsy, Parkinson disease, Alzheimer disease)
- Endocrinopathies (eg. diabetes, thyroid disorders, adrenal disorders)
- Metabolic disturbances (eg. hypercalcemia, hyponatremia)
- Medications and substances of abuse
- Nutritional deficiencies (eg. vit. D, B12, B6, iron, folate)
- Infectious diseases (eg. HIV, syphilis)
- Malignancy
Red Flags / Complications
MDD can result in significant functional impairment. Patients with MDD are at risk of developing comorbid disorders such as anxiety and substance use disorders.
Depression can exacerbate conditions such as:
- Diabetes
- Hypertension
- COPD
- CAD
Patients with MDD are at risk of suicide and recurrent episodes. Approximately 2/3 of patients with MDD contemplate suicide and 10-15% commit suicide.
Management
Lifestyle / Social
Non-pharmacological management is recommended as initial monotherapy or in conjunction with pharmacological therapy.
Cognitive behavioural therapy (CBT) is recommended but other therapies have shown equivalent benefits.
Exercise is also recommended, especially for patients with mild symptoms.
Pharmacological / Interventional
Selection of antidepressants is largely based on factors such as symptoms, prior antidepressant use, and side effect management. There are no clear differences between the efficacy of different antidepressants.
The different classes and generations of antidepressants are discussed separately.
In most cases, initial therapy starts with a selective serotonin reuptake inhibitor (SSRI):
- Escitalopram (Cipralex) 10mg PO daily; adjusted 5-20mg
- Sertraline (Zoloft) 50mg PO daily; adjusted 25-100mg
Other first line alternatives to SSRIs include mirtazapine or buproprion. In more severe cases, TCAs may be efficacous but may also have more significant side effects.
References
Tools / Guidelines
MDCalc - PHQ-9 Uptodate - Side effects of antidepressants