What are the recommended treatments for managing depression?

Depression Management in Adults

For adults with major depressive disorder, initiate treatment with either second-generation antidepressants (particularly SSRIs like sertraline, escitalopram, or citalopram) or evidence-based psychotherapy (cognitive behavioral therapy, behavioral activation, or interpersonal therapy), with combined treatment preferred for moderate-to-severe or chronic depression. 1, 2

First-Line Treatment Selection

Pharmacotherapy Options

• Second-generation antidepressants are the preferred first-line medications, with SSRIs, SNRIs, bupropion, and mirtazapine all considered appropriate initial choices 1
• SSRIs demonstrate modest superiority over placebo with a number needed to treat of 7-8, while the benefit is more pronounced in patients with severe depression 1
• All 21 antidepressant medications studied show small- to medium-sized effects over placebo (standardized mean difference ranging from 0.23 to 0.48), indicating clinically meaningful benefit across the class 2
• Specific medication selection should prioritize cost, adverse effect profile, and patient preference rather than assuming major efficacy differences between agents 1

Psychotherapy Options

• Six specific psychotherapies have demonstrated medium-to-large effect sizes: cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy (SMD 0.50-0.73 over usual care) 2
• These psychotherapies are equally effective as first-line options and should be offered based on availability and patient preference 1, 2

Combined Treatment Strategy

• For moderate-to-severe or chronic depression, combined psychotherapy plus antidepressant medication is superior to either treatment alone (SMD 0.30 over psychotherapy alone, SMD 0.33 over medication alone) 2
• Combined treatment should be the default approach for patients with severe symptoms, recurrent episodes, or chronic depression 1, 2

Treatment Monitoring and Adjustment

Initial Assessment Timeline

• Assess treatment response at 4 weeks and 8 weeks using standardized validated instruments (such as PHQ-9 or HAM-D) 1
• Monitor for adverse effects, suicidal ideation, and treatment adherence at each assessment 1
• If symptoms are stable or worsening at 8 weeks despite good adherence, adjust the treatment regimen 1

Second-Line Strategies for Inadequate Response

When initial antidepressant treatment fails (which occurs in up to 70% of patients), three strategies have approximately equal likelihood of success 1, 2:

1. Switch to a different antidepressant medication (different class or mechanism)
2. Add a second antidepressant medication (combination therapy)
3. Augment with a non-antidepressant medication (such as atypical antipsychotics or lithium)

• Network meta-analyses show no clear superiority among these switching and augmentation strategies, so selection should be based on prior treatment history, side effect profile, and patient preference 1
• For patients receiving psychotherapy with inadequate response, consider adding pharmacotherapy or switching from group to individual therapy 1

Treatment Duration

Initial Episode

• Continue treatment for 4-12 months after achieving remission for a first episode of major depression 1
• This continuation phase is critical to prevent relapse, as discontinuing antidepressants at the end of the acute phase does not prevent recurrence 1

Recurrent Depression

• After two episodes, the probability of recurrence increases to 70%; after three episodes, it reaches 90% 1
• Patients with recurrent depression (three or more episodes) benefit from prolonged maintenance treatment of at least 12-24 months or longer 1
• Randomized trials demonstrate significantly lower recurrence rates with continued antidepressant treatment versus placebo in patients with recurrent depression 1

Special Populations

Older Adults

• Use a "start low, go slow" approach with initial doses approximately 50% of standard adult starting doses 1, 3
• Preferred medications include citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion 1, 3
• Avoid paroxetine due to high anticholinergic effects and sexual dysfunction; avoid fluoxetine due to long half-life and risk of drug accumulation 1, 3
• Monitor closely for falls risk, hyponatremia, drug interactions, and gastrointestinal symptoms within 1-2 weeks of initiation 3

Pregnancy and Breastfeeding

• High-quality evidence on benefits and harms of antidepressant use in pregnancy is lacking 1
• For breastfeeding mothers, sertraline and paroxetine transfer to breast milk in lower concentrations than other antidepressants 1

Common Adverse Effects and Management

Tolerability Profile

• Approximately two-thirds of patients receiving second-generation antidepressants experience at least one adverse effect 1
• Nausea and vomiting are the most common reasons for treatment discontinuation 1
• SSRIs as a class are better tolerated than tricyclic antidepressants (NNT for dropout prevention = 20) 1, 4

Critical Safety Monitoring

• Monitor for serotonin syndrome when combining antidepressants with other serotonergic agents (triptans, tramadol, linezolid, St. John's wort) 5
• Assess for increased bleeding risk when SSRIs are combined with NSAIDs, aspirin, or warfarin 5
• Avoid combining fluoxetine with pimozide due to QTc prolongation risk 5
• Monitor lithium levels closely when coadministered with fluoxetine, as both increased and decreased lithium levels have been reported 5

Collaborative Care Implementation

Collaborative care programs with systematic follow-up and outcome assessment significantly improve treatment effectiveness (SMD 0.42 over usual care), making this approach essential for optimizing depression management in primary care settings 2