Major Depressive Disorder

Major Depressive Disorder (MDD) is a mood disorder characterized by persistent, often daily, low mood and/or decreased interest (anhedonia). There also associated neurovegetative symptoms, such as change in sleep, appetite, cognition, and energy. Suicidal ideation may also occur.

Prevalence

The one month prevalence is 1.3%, one year is 4.0%, and lifetime is 10.8%.[1] Women have a two times higher risk of developing MDD versus men. The reasons for the difference are hypothesized to involve hormonal differences, the effects of childbirth, differing psychosocial stressors for women and for men, and behavioural models of learned helplessness. The average age of onset is about 40 years old.

Risk Factors

MDD occurs most often in persons without close interpersonal relationships or in those who are divorced or separated. There is no correlation has been found between socioeconomic status. It is more common in rural areas than in urban areas.

Criterion A

At least 5 out of 9 symptoms present in the same 2-week period and represent a change from previous functioning

  • At least 1 of the 5 symptoms is either (1) depressed mood or (2) loss of interest or pleasure (anhedonia).
  1. Mood is depressed most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)
  2. Sleep changes: insomnia or hypersomnia nearly every day.
  3. Interest or pleasure markedly diminished in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation.)
  4. Guilt and/or worthlessness (excessive or inappropriate - which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).
  5. Energy decreased or fatigue nearly every day.
  6. Concentration diminished, or indecisiveness, nearly every day (either by subjective account or as observed by others).
  7. Appetite changes: significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gain.)
  8. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
  9. Suicide, 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.

Mnemonic

The mnemonic M SIGECAPS can be used to remember the criteria for major depressive disorder.[2]

  • M Mood
  • S Sleep
  • I Interest
  • G Guilt/Worthlessness
  • E Energy
  • C Concentration
  • A Appetite
  • P Psychomotor Slowing
  • S Suicide
Criterion B

The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Criterion C

The episode is not attributable to the physiological effects of a substance or to another medical condition.

For Your Clinical Consideration

Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individual’s history and the cultural norms for the expression of distress in the contest of loss.
Criterion D

The occurrence of the major depressive episode is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders.

Criterion E

There has never been a manic episode or a hypomanic episode. (i.e. - a bipolar diagnosis trumps a depression diagnosis)

Specifiers

Specifiers

  • With anxious distress
  • With mixed features
  • With melancholic features
  • With atypical features
  • With mood-congruent psychotic features
  • With mood-incongruent psychotic features
  • With catatonia
  • With peripartum onset
  • With seasonal pattern (recurrent episode only)

Severity Specifier

  • Mild
  • Moderate
  • Severe
  • With psychotic features
  • In partial remission
  • In full remission
  • Unspecified
“It’s so difficult to describe depression to someone who’s never been there, because it’s not sadness. I know sadness. Sadness is to cry and to feel. But it’s that cold absence of felling — that really hollowed-out feeling.”
— J.K. Rowling[3]

Various subtypes of depression have been identified. Clinically, it is important to ask the right questions to target the correct treatments to these subtypes.

Seasonal Affective

Seasonal affective disorder (SAD) is a subtype of depression with a usual annual onset between September-November with spontaneous remission in April-May. There is generally an increased prevalence in countries the father it is from the equator (interestingly, Iceland has low rates of SAD[4]). The development of SAD is thought to be due to dark/grey conditions in the winter season, and lack of light availability. Fluctuations in circadian rhythms and melatonin release also plays a role.[5] SAD can be considered as an evolutionary phenomenon and many individuals have non-clinical symptoms of SAD. Clinically symptomatic SAD can occur in up to 2.6% of the Canadian population, with premenopausal women most affected. Individuals with certain serotonin transporter genotypes may be more predisposed to SAD.[6]

Atypical

Atypical depression is characterized by mood reactivity (moods that are strongly reactive to environmental circumstances, and feeling extremely sensitive - this is a must have feature), hypersomnia, carbohydrate craving/increased appetite, leaden paralysis (profound fatigue), and chronic rejection sensitivity. Atypical depression results in more disability than melancholic depression, because individuals often have more interpersonal difficulties. It is also associated with conduct disorder, social phobia, interpersonal dependency, low self-esteem, and parental substance abuse.[7] Atypical depression has a poor response to TCAs and ECT, but excellent response to MAOis, due to suspected elevated MAO activity.[8][9] Atypical depression is also associated with higher rates of early childhood trauma, whereas melancholic depression is not.[10] This again suggests a difference in the etiology and pathophysiology of different depression subtypes.[11]

Are atypical depression, borderline personality disorder, bipolar II disorder, and cyclothymic disorder overlapping conditions?

The common feature in all these diagnoses are emotional dysregulation and mood reactivity. The research hints that these disorders may all exist on a continuum.[12][13][14] Clinically, it can be very challenging to distinguish between these disorders.

Melancholic

Melancholic depression (sometimes known as “endogenous depression”) as a subtype of depression characterized by a profound sense of sadness, lack of mood reactivity (i.e. - absolutely nothing can brighten one's mood), and anhedonia. It is considered to be a biologically-based depression. Individuals often have hypercortisolemia.[15] Theories on the pathophysiology of melancholic depression include disruption of the HPA axis.[16][17] Melancholic depression often progresses into psychotic depression (where delusions are usually nihilistic in nature). Females are less affected in melancholic depression, and there is typically an older age of onset. Melancholic depression is shorter in duration and more episodic. It also features diurnal variation (early-morning worsening of mood, with an afternoon slump or evening worsening). There is concern from older clinicians that the proper diagnosis and treatment of melancholic depression has been overshadowed by the introduction of mass-marketed SSRIs.[18] There is evidence to suggest that melancholic depression responds better to TCAs and ECT.[19][20]

Geriatric

Geriatric depression is one of the major geriatric giants (dementia, delirium, and depression). TCAs and MAOis have been shown to be more efficacious in the treatment of geriatric depression.[21] If there is treatment-refractory depression, it is important to manage this actively. The only treatment for which there was replicated evidence was lithium augmentation.[22] There is no evidence that treatment of depression in individuals with dementia is efficacious.[23]

Various scales can be used to measure depression severity in an individual. Below are the most common ones, with an indication for each.

Psychometric Scales for Depression

Beck Depression Inventory (BDI)
Rater Patient
Description A 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression. Designed for individuals aged 13 and over.
Download BDI Download
Patient Health Questionnaire (PHQ-9)
Rater Patient
Description A 9-question instrument given to patients in a primary care setting to screen for the presence and severity of depression.
Download PHQ-9 Download
Hamilton Rating Scale for Depression (HAM-D/HDRS)
Rater Clinician
Description Rates patient between 17 to 29 dimensions (depending on version) with a score on a 3 or 5 point scale. Max Hamilton maintained that his scale should not be used as a diagnostic instrument.
Download HAM-D Download
Montgomery–Åsberg Depression Rating Scale (MADRS)
Rater Clinican
Description 10-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.
Download MADRS Download
Quick Inventory of Depressive Symptomatology (QIDS-C)
Rater Clinican
Description A 16-item clinician rating of the patient's depressive symptoms
Download QIDS-C Download
Quick Inventory of Depressive Symptomatology (QIDS-SR)
Rater Patient
Description A 16-item patient's self-report of depressive symptoms
Download QIDS-SR Download
Name Rater Description Download
Beck Depression Inventory (BDI) Patient A 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression. Designed for individuals aged 13 and over. BDI Download
Patient Health Questionnaire (PHQ-9) Patient A 9-question instrument given to patients in a primary care setting to screen for the presence and severity of depression. PHQ-9 Download
Hamilton Rating Scale for Depression (HAM-D/HDRS) Clinician Rates patient between 17 to 29 dimensions (depending on version) with a score on a 3 or 5 point scale. Max Hamilton maintained that his scale should not be used as a diagnostic instrument. HAM-D Download
Montgomery–Åsberg Depression Rating Scale (MADRS) Clinican 10-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. MADRS Download
Quick Inventory of Depressive Symptomatology (QIDS-C) Clinican A 16-item clinician rating of the patient's depressive symptoms QIDS-C Download
Quick Inventory of Depressive Symptomatology (QIDS-SR) Patient A 16-item patient's self-report of depressive symptoms QIDS-SR Download

Diffusion tensor imaging (DTI) imaging has shown that the cingulum bundle microstructure is altered in people at risk for depression. The uncinate fasciculus and medial forebrain bundle microstructures are also altered during acute depression in adults.[24]

  • When clinically indicated, a laboratory assessment should be performed, including liver function tests and a metabolic workup
  • TSH

The following treatment recommendations are based on the Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder.[25]

Medications

See also main article: Introduction to Antidepressants

Depression is a highly placebo-sensitive condition. Placebo response rates can be anywhere up to 30-40%.[26] If there is a poor response to the initial antidepressant, consider switching to another antidepressant when: it is the first antidepressant trial, if there are poorly tolerated side effects to the initial antidepressant, if there is no response (<25% improvement) to the initial antidepressant, there is more time to wait for a response (less severe, less functional impairment), or patient prefers to switch to another antidepressant.

Consider a adding an adjunctive medication when: there have been 2 or more antidepressant trials, the initial antidepressant is well tolerated, there is partial response (>25% improvement) to the initial antidepressant, there are specific residual symptoms or side effects to the initial antidepressant that can be targeted, there is less time to wait for a response (more severe, more functional impairment), or the patient prefers to add on another medication.

Pharmacotherapy for major depressive disorder

1st line Agomelatine, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mianserin, milnacipran, mirtazapine, paroxetine, sertraline, venlafaxine, vortioxetine
2nd line Amitriptyline, clomipramine, other tricyclics, levomilnacipran, moclobemide, quetiapine, selegiline (transdermal), trazodone, vilazodone
3rd line Phenelzine, tranylcypromine, reboxetine

Adjunctive pharmacotherapy for major depressive disorder

Adjunctive therapy (1st line) Aripiprazole, quetiapine, risperidone
Adjunctive therapy (2nd line) Brexpiprazole, bupropion, lithium, mirtazapine, mianserin, modafinil, olanzapine, triiodothyronine
Adjunctive therapy (3rd line) Other antidepressants, other stimulants (methylphenidate, lisdexamfetamine), tricyclic antidepressants, ziprasidone
Not recommended Pindolol
Nutrition

There is evidence to suggest that nutrition can help elevate serotonin levels as well. Studies have shown that tryptophan can have anxiolytic effects.[27][28][29][30]

Psychotherapy

Phototherapy

Phototherapy is indicated for treatment of depression with seasonal affective subtype. It requires exposure to intense light under specified conditions (i.e. - sitting in front of light with eyes open, not staring directly at the light, and used in the mornings). The standard intensity of light needed is usually 5000-10,000 lux, ranging from 30-60 minutes per day. Overuse beyond the recommend amount does not confer any additional benefits. Phototherapy is effective in 2 out of every 3 SAD patients treated. It works rapidly, but also loses efficacy rapidly upon discontinuation (and thus requires daily, consistent use). Individuals who have symptoms of high carbohydrate cravings and/or hypersomnia have the best response to phototherapy.[31] Risks of phototherapy include phototherapy-induced mania/hypomania in those predisposed, interactions with light sensitizing medications (digitoxin, ibuprofen, chlorpropamide), and a relative contraindication is there is existing retinal disease. As light is a stimulant, some users can develop nausea, irritation, and headaches (similar to taking psychotropic stimulants). Bupropion has been shown to be effective in the prevention of SAD by starting treatment prior to the winter season.[32]

ECT

References