Depression’s in Session


The term “depression” is used in multiple ways (e.g., mood state, syndrome, or mental disorder), creating confusion. 

  • Mood state: feelings of sadness, despair, anxiety, emptiness, discouragement, or hopelessness; having no feelings; or appearing tearful. Depressed (dysphoric) mood may be a normal and, at times, adaptive response to loss, disappointment, or perceived failure. In addition, depressed mood may be a symptom of a psychopathological syndrome or another medical disorder.
  • Syndrome: a constellation of symptoms and signs that may include depressed mood. Depressive syndromes that are typically encountered include major depression, minor depression, or dysthymia (persistent depressive disorder).
  • Mental disorder: a distinct clinical condition. As an example, the syndrome of major depression can occur in several disorders, such as unipolar major depression (also called “major depressive disorder”), bipolar disorder, schizophrenia, substance/medication-induced depressive disorder, and depressive disorder due to another (general) medical condition.
Source: Maurer et al. Depression: Screening and Diagnosis. Am Fam Physician. 2018 Oct 15;98(8):508-515.

Recognizing the above, it’s imperative to differentiate major depressive disorder (MDD) from other disorders such as bipolar, grief reaction or bereavement, adjustment disorders, anxiety disorders, and cognitive disorders, among others. 

Disease Burden

Quick facts: 

  • 20x and 27x higher risk of suicide in males and females with MDD, respectively
  • LGBTQ youth are 3x more likely to think about suicide and 3-6x times more likely to attempt suicide than heterosexual-identified youth

Quality of life: 

  • The Global Burden of Disease Study found that depression was the leading health condition worldwide in terms of disability adjusted life years (DALYs)
  • Jia et al estimated quality-adjusted life expectancy for U.S. adults and found that depression led to a 28.9-year quality adjusted life year (QALY) loss at age 18, greatly exceeding the QALY loss for smoking (12.9 years)

Recurrence & Relapse: 

  • Recurrence of MDD treated in specialized mental health settings is very high (60% after 5 years, 67% after 10 years, and 85% after 15 years)
  • Recurrence of MDD is less prominent but still high in the primary care setting (35% after 15 years)
  • The number of previous episodes and subclinical residual symptoms are the most important predictors of relapse

Mortality & Morbidity: 

  • Increased risk of cardiovascular events in patients with CAD (odds ratio, 4.68; 95% confidence interval, 1.94-11.27; P<.001) and a lack of evidence of improvement with treatment of depression (Lespérance, 2000; Shimbo, 2005)
Lespérance et al. Depression and 1-year prognosis in unstable angina. Arch Intern Med. 2000 May 8;160(9):1354-60.
  • A study of 896 patients hospitalized for myocardial infarction found a direct relationship between the severity of the depressive symptoms at hospitalization and the risk of cardiac death over the following 5 years (Lespérance, 2002)

  • Risk of death by all causes increased in depressed patients (Osby, 2001)
  • A study of 5276 elderly men in Perth, Australia investigated the 883 deaths from all causes – adjusted mortality HR with clinical depression was nearly twice that of the total cohort and increased with the severity of depression. The use of antidepressants did not reduce the mortality risk (Almeida, 2010)


USPSTF recommendations by age for depression screening:

Source: Maurer et al. Depression: Screening and Diagnosis. Am Fam Physician. 2018 Oct 15;98(8):508-515.

There is a lack of evidence to recommend one screening instrument over another. The two-item and nine-item Patient Health Questionnaires (PHQs) are the most widely used.

  • The PHQ-2 has a similar sensitivity to the PHQ-9 (83-87% vs 77-81%, respectively), but worse specificity (78-92% vs 91-94%, respectively). Thus, the PHQ-2 is accepted as an initial screening tool in all age groups. If depression is identified, the PHQ-9 (or PHQ-A for adolescents) or a clinical interview should be completed. 
Source: Maurer et al. Depression: Screening and Diagnosis. Am Fam Physician. 2018 Oct 15;98(8):508-515.

There are also multiple other screening modalities: 

  • Beck Depression Index (BDI-I, BDI-II)
  • Hamilton Rating Scale for Depression (HAM-D-6, HAMD-17 aka HDRS)
  • Major Depression Inventory (MDI)
  • Center for Epidemiologic Studies Depression Scale (CES-D)
  • Zung Self-Rating Depression Scale (SDS)
  • Geriatric Depression Scale (GDS)
  • Cornell scale for Depression in Dementia (CSDD)


Major depressive disorder is disabling. Effective management is key, and often occurs in the primary care setting: 

  • An estimated 60% of mental health care delivery occurs in the primary care setting
  • 79% of antidepressant prescriptions are written by providers who are not mental health care providers
  • One study showed that among persons who have attempted suicide, 38% visited a health care provider within the previous week, and 64% visited a health care provider within 4 weeks before the attempt – most visited a primary care practice

Initial treatment of MDD depends on severity: 

  • Mild depression: psychotherapy and symptom monitoring
  • Moderate depression: psychotherapy, pharmacotherapy, or both
  • Severe depression: psychiatry consultation 

Management: Psychotherapy


  • Psychodynamic therapy (psychoanalysis) – Focuses on unconscious drives/motives as well as developmental influences on thoughts and behavior
  • Cognitive-behavior therapy (CBT) – aims to modify dysfunctional thought patterns (cognitive distortions). Emphasizes homework and out-of-session activities
    • Behavioral activation therapy
    • Exposure therapy
    • Dialectical behavior therapy (DBT)
  • Humanistic approach – unconditional positive regard from therapist
    • Client-centered 
    • Gestalt
    • Existential therapy
  • Systemic approach – addresses how a person functions and relates to the world and systems around them
    • Interpersonal therapy 
    • Social skills training


  • Cuijpers, 2008: Meta-analysis of 53 comparative trials of 7 major types of psychotherapy (2757 patients with mild-to-moderate depression) showed that across all forms of psychotherapy, the response rate was 48% (vs. 19% in control groups) and no ”large” difference (d>0.2) in efficacy among all therapy types
  • Cuijpers, 2014: Another meta-analysis of 92 studies with 6937 patients with MDD showed significantly higher remission rates (62% overall) among patients who received psychotherapy (CBT [66%], psychodynamic therapy [54%], supportive counseling [49%], behavioral activation [74%]) than among those in control conditions (who also showed improvement with remission rate of 43%)
  • Weisz, 2006: Meta-analysis of psychotherapy for depression in children and adolescents showed positive effect (d=0.34), smaller than that reported in prior metanalyses (Reinecke, 1998 d=0.97; Lewisohn, 1999 d=1.27; Michael, 2002 d=0.72)
  • Scogin, 1994: Meta-analysis of psychotherapy (mixed types) in older adults with MDD showed positive effect with effect size 0.76

Management: Pharmacotherapy

Antidepressants alone have been used more often than combination treatment or psychotherapy alone because antidepressants are generally widely available and may be more convenient than psychotherapy. SSRIs are the most widely prescribed class of antidepressants. 

Antidepressants have many nuances: 

  • General: 
    • Anticipate response in 8-12 weeks at therapeutic dose
    • Considerations: relapse vs resistance, nonadherence, alternate diagnoses, other psychiatric comorbidities
  • SSRIs:
    • Fluoxetine – long-acting metabolites, 1-week washout before switching to another agent
    • Sertraline – risk of sexual side effects higher than other SSRIs; best studied in patients with CAD and depression
    • Paroxetine – risk of discontinuation syndrome
    • Citalopram – black box warning >40mg due to QTc prolongation
    • Escitalopram – felt to have fewer side effects
  • SNRIs: 
    • Venlafaxine – risk of discontinuation syndrome, risk of death from overdose greater than other first line agents
    • Duloxetine – may increase energy, can be used for pain conditions
  • Other agents:
    • Bupropion – 0.4% increased risk of seizures, can be used to aid in smoking cessation
    • Mirtazapine – can be used at bedtime for insomnia or low appetite
  • Newer agents:
    • Vilazodone – new SSRI (2011) with less sexual dysfunction than other SSRIs/SNRIs; should be taken with food
    • Vortioxetine – new SSRI (2013) and serotonin modulator receptor – can be effective in patients with cognitive dysfunction
    • Levomilnacipran – new SNRI (2013); fewer side effects than other SSRI/SNRIs

Strategies for failed response: 

  • Increase dose
  • Switch to another agent of the same class
  • Switch to an an agent of another class
  • Augmentation with a non-antidepressant agent (e.g., aripiprazole, olanzapine, quetiapine, risperidone)
  • Add a second antidepressant (e.g., mirtazapine)

STAR*D (Sequenced Treatment Alternatives to Relieve Depression): 

  • The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) trial is the largest clinical trial ever conducted in the field of psychiatry – a multi-site open-label study assessing the efficacy, safety, and tolerability of different treatment strategies for antidepressant non-responders. 
Papakostas GI. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry. 2009;70 Suppl 6:16-25.


  • Advantage of maintaining a partial response to initial therapy; however may add additional risk of side effects
  • Most evidence-based strategy uses second generation antipsychotic agents
  • Meta-analysis of 10 trials involving olanzapine, quetiapine, and risperidone showed efficacy compared to adjunctive placebo with pooled remission rates of 47% versus 22% and NNT = 4
    • However, these agents were also found to be significantly less well tolerated than adjunctive placebo, with more than a 3-fold higher discontinuation rate due to adverse events (P < .0001)
Papakostas GI. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry. 2009;70 Suppl 6:16-25.
Papakostas GI. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry. 2009;70 Suppl 6:16-25.
  • As a result, aripiprazole was approved by the FDA in 2008 as adjunctive therapy to antidepressants for patients with antidepressant-resistant MDD.

Take-Home Points!

Blog post based on Med-Peds Forum talk by Chelsea Boyd, PGY3

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