Recipient(s) will receive an email with a link to 'Depression' and will have access to the topic for 7 days.
(Optional message may have a maximum of 1000 characters.)
A primary mood disorder characterized by a sustained depressed mood and/or decreased interest in things that used to give pleasure (anhedonia), which represents a change from previous functioning.
Variants: (i) major depressive disorder (MDD), (ii) dysthymic disorder, and (iii) depressive disorder not otherwise specified (NOS). (Last two disorders have slightly different diagnostic criteria but are still treated as below.)
16.2% lifetime risk of having MDD
Patients can relapse; risk decreases with longer remission period but increases in patients with severe episodes, episodes at a younger age, and multiple episodes.
Monoamine-deficiency hypothesis: symptoms related to decreased levels of norepinephrine (dullness and lethargy) and serotonin (irritability, hostility, and suicidal ideation) in multiple regions of the brain; other neurotransmitters involved include dopamine, acetylcholine, γ-aminobutyric acid (GABA), glutamate.
Stress/hypothalamic-pituitary-adrenal axis: Abnormalities in cortisol response lead to depression; elevated cortisol levels can be associated with depression, but cortisol tests are not indicated for diagnosis.
Other areas of research interest: inflammatory processes and abnormal circadian rhythms; impaired synthesis/metabolism of neurotransmitters
Environmental factors and learned behavior may affect neurotransmitters and/or have an independent influence on depression.
Female > male (2:1)
Severity of first episode
Persistent sleep disturbances
Presence of chronic disease(s), recent myocardial infarction (MI), cardiovascular accident (CVA)
Strong family history (depression, bipolar, suicide, substance abuse), spouse with depression
Substance abuse and dependence, domestic abuse/violence
Losses, stressors, unemployment
Single, divorced, or unhappily married
Bipolar disorder, cyclothymic disorder, grief reaction, anxiety disorders, somatoform disorders, schizophrenia/schizoaffective disorders
Criterion A: ≥5 of the following symptoms present nearly every day during the same 2-week period, with at least one of the five being either depressed mood or loss of interest or pleasure:
Criterion B: Symptoms cause significant social, occupational, or functional distress or impairment.
Criterion C: symptoms not attributable to substance effects or other medical conditions
Difficult to diagnose due to medical comorbidity
Can present with memory difficulties as chief complaint; treatment reverses memory difficulty.
Can be the initial presentation of irreversible dementia
Geriatric Depression Scale (GDS 15) improves rate of diagnosis in primary care setting 2,3[A].
Can present as irritable or angry rather than sad or dejected
Failure to make expected weight gains can substitute weight loss symptom above.
A sudden and remarkable drop in grades can indicate difficulty concentrating.
Can present with separation anxiety
Psychiatric: depressed phase of bipolar disorder— inquire if prior mania, family or personal history of bipolar disorder, prior agitation or excitement with antidepressant medication. If positive, monitor carefully for mood elevation or destabilization, adjustment disorder, and bereavement.
Neurologic or degenerative CNS diseases, dementias
Medical comorbidity: adrenal disease, thyroid disorders, diabetes, metabolic abnormalities (hypercalcemia), liver/renal failure, malignancy, chronic fatigue syndrome, fibromyalgia, lupus
Nutritional: pernicious anemia, pellagra
Medications/substances: abuse, side effects, overdose, intoxication, dependence, withdrawal
A clinical diagnosis made by eliciting personal, family, social, and psychosocial factors
The Patient Health Questionnaire-9 (PHQ-9) is a brief screening test valid for diagnosis of MDD in primary care settings 3[A].
Other validated standard rating scales include the following: Beck Depression Inventory, Zung, GDS 15, and so forth. Rating scales are also useful to track response to treatment over time 3[A].
Rule out hypothyroidism, anemia, and metabolic disorders with TSH, CBC, and comprehensive metabolic panel (CMP).
Order urine drug screen if symptoms suggest intoxication.
Refer immediately for active suicidal ideations, psychosis, severe agitation, severe self-neglect, and significant risk of self-harm.
Refer to psychiatry for failed response to medication trials, suspected bipolar disorder, more persistent suicidal thoughts, and self-neglect.
Effectiveness of medications is comparable between/within classes; selection should be based on provider familiarity and patient characteristics/preferences 5[A].
Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are effective, but TCAs are second line due to side effects and lethality in overdose. Tolerability is much poorer than newer antidepressants.
First-line SSRIs* (starting dose; usual dose)
Others (starting dose; usual dose)
TCAs (starting dose; usual dose)
α2-Antagonists (sedating) (starting dose; usual dose)
Significant potential interactions
Black box warning: increased risk of suicidality in children, adolescents, and young adults up to age 25 years who are treated with antidepressants. Although this has not been extended to adults, suicide risk assessments are warranted for all patients.
Serotonin syndrome—a rare but potentially lethal complication from rapid increase in dose or new addition of medication with serotonergic effects
Caution with personal or family history of bipolar disorder: Antidepressants can precipitate mania.
Electroconvulsive therapy (ECT) for refractory cases
Repetitive transcranial magnetic stimulation (rTMS) may be helpful for TRD 6[A].
Hypericum perforatum (St. John's wort): multiple drug interactions; not safe in pregnancy
Data do not support S-adenosyl methionine (SAM-e) or acupuncture.
Inpatient care is indicated for severe depression, patients at risk of suicide/homicide, and for comorbid conditions.
Discharge criteria: depressive symptoms abating, no longer suicidal, appropriate outpatient follow-up in place
Depression is a common medical illness, not a character defect.
Emphasize the need for long-term treatment and follow-up, which includes lifestyle changes.
Exercise, good sleep hygiene, good nutrition, and decreased use of tobacco and alcohol are recommended. The optimal regimen is one the patient prefers and will adhere to.
70% show significant improvement
Of patients with a single depressive episode, 50% will relapse over their lifetime.
Lower quality of life
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
Patient Health Questionnaire (PHQ) Screeners: http://www.phqscreeners.com/overview.aspx?Screener=03_GAD-7
F32.9 Major depressive disorder, single episode, unspecified
F33.9 Major depressive disorder, recurrent, unspecified
F34.1 Dysthymic disorder
F32.8 Other depressive episodes
F33.8 Other recurrent depressive disorders
F32.3 Major depressv disord, single epsd, severe w psych features
F32.2 Major depressv disord, single epsd, sev w/o psych features
311 Depressive disorder, not elsewhere classified
296.20 Major depressive affective disorder, single episode, unspecified
300.4 Dysthymic disorder
296.30 Major depressive affective disorder, recurrent episode, unspecified
300.9 Unspecified nonpsychotic mental disorder
35489007 Depressive disorder (disorder)
36923009 Major depression, single episode (disorder)
78667006 Dysthymia (disorder)
66344007 Recurrent major depression (disorder)
Therapeutic alliance is important to treatment success.
Given the high recurrence rates, long-term treatment is often necessary.