Last updated December 18, 2021

Treatment of Depression Across Three Age Cohorts

Recommendations for the Child Population

For initial treatment of child patients with depressive disorders1 there was insufficient evidence to make a recommendation regarding any of the following psychotherapies/interventions:2
• Behavioral therapy
• Cognitive therapy
• Cognitive-behavioral therapy (CBT)
• Family therapy
• Play therapy
• Problem-solving therapy
• Psychodynamic therapy
• Supportive therapy
There was insufficient evidence to make a recommendation regarding pharmacotherapy for child patients with depressive disorders. (Insufficient evidence)
1 Types included: minor depression, major depression, persistent depressive disorder (formerly called “dysthymia”), intermittent depression, or having depression symptoms at or above a prespecified level based on a validated measure of depression severity. The Zhou et al. (2015) review excluded patients with psychotic depression.
2 Throughout the table, interventions are listed alphabetically.
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Recommendations for the Adolescent Population

For initial treatment of adolescent patients with depressive disorders3 the panel recommends that clinicians offer one of the following psychotherapies/interventions4:
• Cognitive-behavioral therapy (CBT)
• Interpersonal psychotherapy for adolescents (IPT-A)
(Recommendation)
3 Types included: minor depression, major depression, persistent depressive disorder (formerly called “dysthymia”), intermittent depression, or having depression symptoms at or above a prespecified level based on a validated measure of depression severity. The Zhou et al. (2015) review excluded patients with psychotic depression.
4 Throughout the table, interventions are listed alphabetically.
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The panel recommends fluoxetine as a firstline medication compared to other medications for adolescent patients with major depressive disorder, specifically when considering medication options. (Recommendation)
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There was insufficient evidence to recommend either treatment (psychotherapy or fluoxetine) over the other for major depressive disorder. (Insufficient evidence)
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If neither recommended psychotherapy is available or neither is acceptable to the patient and their parent/guardian, the panel suggests considering an alternative model. However, at this time, while the following interventions have been evaluated in adolescents, there is insufficient evidence to recommend for or against clinicians offering any one of the following psychotherapies/interventions over the others:
• Behavioral therapy
• Cognitive therapy
• Family therapy
• Problem-solving therapy
• Psychodynamic therapy
• Supportive therapy
(Insufficient evidence)
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Information is lacking regarding other medication options for adolescents. Thus, if fluoxetine is not a treatment option or is not acceptable, the panel recommends shared decision-making regarding medication options with a child psychiatrist in addition to the clinician, patient, and their parents/guardians or family members actively involved in their care. (Conditional recommendation)
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In general, the panel recommends against using the following medications for adolescent patients with major depressive disorder. However, when other options are not available, effective, and or acceptable to the patient, the panel recommends shared decisionmaking between the patient and clinician.
• clomipramine
• imipramine
• mirtazapine
• paroxetine
• venlafaxine

If these medications are being considered, the panel recommends:
• paroxetine over clomipramine when both are being considered.
• paroxetine over imipramine when both are being considered.
• There was no information available for other comparisons between the listed medications.
(Recommendation)
(against)
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Recommendations for the General Adult Population

Psychotherapy and Pharmacotherapy

For initial treatment of adult patients with depression,5 the panel recommends the following in the context of sharing decision-making with the patient when considering options:
       1) That clinicians offer either psychotherapy or second-generation antidepressant.6
  • When selecting between treatments, the panel recommends considering the following options:
    • Second-generation antidepressants
    • The panel found that effectiveness studies demonstrated similar effects across psychotherapy. Thus, the panel is not able to recommend specific monotherapies for initial treatment. General models that appear to have comparable effects include:
      • Behavioral therapy
      • Cognitive, cognitive-behavioral (CBT), and mindfulness-based cognitive-therapy (MBCT)
      • Interpersonal psychotherapy (IPT)
      • Psychodynamic therapies
      • Supportive therapy
       2) If considering combined treatment, the panel recommends cognitive-behavioral therapy (CBT) or interpersonal psychotherapy (IPT) plus a second-generation antidepressant.
(Recommendation)
5 The depression recommendations refer to the full range of depression diagnoses identified by the panel for inclusion unless a recommendation specifies otherwise. Note that recommendations do not pertain to psychotic depression.
6 Throughout the recommendations, both the terms “antidepressant medication” and “second-generation antidepressant” are used. Note that “second-generation antidepressants” refers specifically to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) while the term “antidepressant medication” could include second-generation antidepressants as well as other antidepressants.
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For adult patients with depression who are also experiencing relationship distress, if a recommended treatment is not acceptable or available, the panel suggests that clinicians offer problem-focused couples’ therapy.
When selecting between treatments the panel suggests considering the following options:
• Suggest behavioral therapy rather than antidepressant medication alone.
• If considering combined treatment, the panel suggests cognitive therapy plus antidepressant medication to improve likelihood of full recovery in treatment.
(Conditional recommendation)
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For adult patients with depression, there is insufficient evidence to recommend for or against clinicians offering:
• Cognitive-behavioral analysis system of psychotherapy (CBASP)
• Brief problem-solving therapy (10 or fewer sessions) vs. treatment as usual.
(Insufficient evidence)
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Complementary and Alternative Treatments7

7 The panel urges caution when using over-the-counter agents to prevent unintended drug-drug interactions particularly given variable manufacturing practices.
For adults with depression for whom psychotherapy or pharmacotherapy is either ineffective or unacceptable the panel suggests the following options:
  • Exercise Monotherapy8
  • St. John’s Wort Monotherapy9
If neither is acceptable or available, the panel suggests consideration of:
  • Bright light therapy10
  • Yoga11
  • If considering adjunctive treatments, the panel suggests adding acupuncture to antidepressant medication.12
(Conditional recommendation)
8 Patients in these trials had moderate to severe depression, according to the HAM-D Scale (Babyak et al., 2000; Blumenthal et al., 1999, 2007; Hoffman et al., 2008). The panel gave a conditional recommendation because it had only efficacy data and not comparative effectiveness data.
9 The trials included patients with moderate to severe depression.
10 Included patients aged 60 years and older with a diagnosis of MDD.
11 Based on a trial with female patients between 18 to 40 years of age.
12 Trials included patients with a diagnosis of MDD or poststroke depression and were between 33 to 60 years of age.
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There is insufficient evidence to recommend:
  • Tai Chi
  • Acupuncture Monotherapy
  • Combination of second-generation antidepressant and acupuncture
  • Omega-3 Fatty Acids Monotherapy
  • Combination of second-generation antidepressant and Omega-3 Fatty Acids
  • S-Adenosyl Methionine Monotherapy
  • Combination of second-generation antidepressant and exercise
(Insufficient evidence)
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For adult patients with subclinical depression, the panel suggests that clinicians offer psychotherapy13 (psychotherapy in general including both cognitive-behavioral therapy and noncognitive-behavioral therapy psychotherapies [e.g., interpersonal counseling, problem-solving therapy, life-review therapy]). (Conditional recommendation)
13 Recommendation also includes separate examination of non-cognitive behavioral therapy approaches. Psychotherapy in general also found to reduce future episodes of major depressive disorder.
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PARTIAL or NONRESPONDERS to INITIAL ANTIDEPRESSANT TREATMENT

For adult patients with depression who have either not responded or only partially responded to initial antidepressant medication treatment the panel recommends the following options:
1) Switch from antidepressant medication alone to cognitive therapy alone or,
2) Switch from antidepressant medication alone to another antidepressant medication.
(Recommendation)
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For adult patients with depression who have either not responded or only partially responded to initial antidepressant medication treatment the panel suggests that clinicians offer one of the following psychotherapies/interventions and select between treatments as follows:
1) Add psychotherapy (interpersonal psychotherapy, cognitive-behavioral therapy, or psychodynamic therapy)14 to the antidepressant medication treatment
2) Augment with another antidepressant medication.
(Conditional recommendation)
14 The general group of psychotherapies included in the review (ECRI Institute, 2015) were interpersonal psychotherapy, cognitive-behavioral therapy, and CBASP (cognitive behavioral analysis system of psychotherapy). However, based on additional information, CBASP is not recommended due to the increased burden with limited evidence of additional benefit.
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For adult patients with major depressive disorder who have either not responded or only partially responded to initial adequate second-generation antidepressant treatment attempt there is insufficient evidence to determine differences in treatment effect for the following:
• Switching to another second-generation antidepressant15
• Switching to a nonpharmacologic (i.e., cognitive therapy) monotherapy
• Augmenting with guided cognitive-behavioral therapy self-help
(Insufficient evidence)
15 Switches included various medications such as bupropion, sertraline, venlafaxine, etc. Please see Table E22, pages E35–E37 of Gartlehner et al. (2015) for specific switch details
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RELAPSE PREVENTION

For adult patients with depression who have achieved remission the panel suggests clinicians offer psychotherapy (cognitive-behavioral therapy, mindfulness-based cognitive therapy, or interpersonal psychotherapy) rather than antidepressant medication or treatment as usual to prevent relapse.  (Conditional recommendation)
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There is insufficient evidence to recommend one form of the three psychotherapies listed. (Insufficient evidence)
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Recommendations for the Older Adult Population

Major Depressive Disorder

For initial treatment of older16 adult patients with depression, the panel recommends the following in the context of shared decision-making with the patient:
1) Either group life-review treatment or group cognitive-behavioral therapy (GroupCBT) (either alone or added to usual care) over no treatment
2) Combined pharmacotherapy and interpersonal psychotherapy (IPT) over IPT alone. Of note, while the study upon which this is based used nortriptyline, the panel recommends a second-generation antidepressant due to the reduced risk of side effects.
(Recommendation)
16 While the panel defined older adults as ages 60 and over, there was at least one study included in the older adult reviews that included some individuals as young as 50. However, the majority were ages 60 and over.
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For older adult patients with depression, if a recommended treatment is not acceptable or available, the panel suggests that clinicians offer one of the following psychotherapies/interventions: 
  • Cognitive-behavioral therapy (CBT; individual) (either standalone or in combination with usual care), which was found to be superior to:
    • no treatment
    • a nonspecific talk therapy control
    • usual care
    • desipramine
  • Combination cognitive-behavioral therapy and nonspecific therapeutic techniques (individual) with pharmacotherapy, which was superior to pharmacotherapy alone. Of note, while a specific study upon which this is based used desipramine, the panel recommends a second-generation antidepressant due to the reduced risk of side effects.
  • Interpersonal psychotherapy and pharmacotherapy, which was conditionally superior for preventing recurrence to either:
    • Supportive care
    • IPT and supportive care
    • Of note, while the study on which this is based used nortriptyline, the panel recommends a second-generation antidepressant due to the reduced risk of side effects
  • Problem-solving therapy (group), which was superior to reminiscence therapy (group)
  • Interpersonal psychotherapy (individual), which was superior to supportive care.
(Conditional recommendation)
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For older adult patients with depression, there is insufficient evidence to recommend for or against clinicians offering
  • Problem-solving therapy (inperson) vs. attention control (phone call) for major depressive disorder
  • Problem-solving therapy (video call) vs. attention control (phone call) for major depressive disorder.
(Insufficient evidence)
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Subthreshold/minor depression

The panel suggests considering one of the following options for subthreshold or minor depression:
  • Cognitive-behavioral therapy (internet) for subthreshold depression
  • Cognitive-behavioral therapy (individual) and usual care for minor depressive disorder
  • Cognitive-behavioral therapy (group) and usual care for treating minor depressive disorder
  • Combination cognitive-behavioral therapy and treatment as usual rather than combination of talking control17 (individual) and usual care for older adults with minor or major depressive disorder
  • Life review course (group) rather than an educational video for older adults with subclinical depression
  • Problem-solving therapy (individual)
  • paroxetine
    • Of note, while the study on which this is based used paroxetine, some argue that paroxetine is contraindicated in older adults due to its anticholinergic side effects and many geriatric psychiatrists would prefer another SSRI (i.e., escitalopram or sertraline). The panel encourages shared decision-making with patients of benefits versus harms of treatment.
(Conditional recommendation)
17 Participants in this condition received attention and warm interactions from therapists during discussion of neutral topics.
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The panel had insufficient evidence to recommend the following treatments:
  • Behavioral bibliotherapy (self-guided) vs. treatment as usual for subthreshold depression
  • Life review therapy (individual) vs. treatment as usual for subclinical depression.
(Insufficient evidence)
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MDD or minor depression + cognitive impairment/dementia

The panel suggests considering one of the following options for MDD or minor depression in the context of cognitive impairment or dementia:
  • Problem-solving therapy (individual) for older adult patients with major depressive disorder and executive dysfunction18
  • Problem-solving behavioral therapy (individual) or pleasant events behavioral therapy (individual) for minor or major depressive disorder in older adults with dementia.
()
18 Disruption to cognitive processes generally housed in the frontal lobes of the brain.
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The panel had insufficient evidence to recommend the combination of behavioral activation therapy (individual) and treatment as usual over treatment as usual for depressive symptoms in older adults with mild to moderate cognitive impairment. (Insufficient evidence)
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Persistent depressive disorder

The panel suggests considering one of the following options for MDD or minor depression in the context of cognitive impairment or dementia:
  • Problem-solving therapy (individual) or paroxetine for persistent depressive disorder
Of note, while the study on which this is based used paroxetine, some argue that paroxetine is contraindicated in older adults due to its anticholinergic side effects, and many geriatric psychiatrists would prefer another SSRI (i.e., escitalopram or sertraline). (Conditional recommendation)
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MDD with medical or other complications

The panel suggests considering the following options for patients with both depression and the indicated complicating factors:
  • Combination of cognitive-behavioral therapy (individual) and usual care for minor or major depressive disorder with type II diabetes mellitus or chronic obstructive pulmonary disease
  • Multicomponent intervention (individual) for treating symptoms of depression in temporarily homebound African American adults
  • Coping improvement (group) rather than psychotherapy19 on request (individual) for older adults with mild to severe depressive symptoms and HIV.
(Conditional recommendation)
19 Participants in this condition were able to access typical psychosocial services from the community (e.g., 12-step programs, support groups for AIDS, individual therapy). They also were given three brief phone calls to assess for any clinical concerns that may have arisen.
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PREVENTION OF RECURRENCE-MDD

For older adult patients with a history of depression, the panel recommends clinicians offer any of the following options:
  • Either:
    • Combination interpersonal psychotherapy and pharmacotherapy or
    • Combination supportive care and pharmacotherapy.
Of note, while the study on which this is based used nortriptyline, the panel recommends a second-generation antidepressant due to the reduced risk of side effects. (Recommendation)
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The panel suggests considering the following option if the prior options are not acceptable or available:
  • Interpersonal psychotherapy (individual) alone.
(Conditional recommendation)
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For older adult patients with a history of depression there is insufficient evidence to recommend between clinicians offering cognitive-behavioral therapy (group) plus pharmacotherapy and pharmacotherapy alone for preventing recurrence. Thus, the panel makes no recommendations of one treatment over the other. (Insufficient evidence)
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Recommendation Grading

Overview

Title

Treatment of Depression Across Three Age Cohorts

Authoring Organizations

Publication Month/Year

February 16, 2019

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adolescent, Adult, Child

Health Care Settings

Ambulatory

Intended Users

Psychologist

Scope

Management, Treatment

Diseases/Conditions (MeSH)

D003863 - Depression

Keywords

depression, antidepressants, Antidepressants, major depressive disorder