What is the recommended treatment regimen for a patient with depression?

Treatment Regimen for Depression

For adults with moderate to severe major depressive disorder, initiate treatment with either cognitive behavioral therapy (CBT) or a second-generation antidepressant (SSRI or SNRI), with selection based on patient preference, accessibility, cost, and side effect profile. 1

Initial Treatment Selection

First-Line Options

• Second-generation antidepressants (SSRIs and SNRIs) are equally effective as CBT for achieving response and remission in moderate to severe depression, and the choice should be made through shared decision-making after discussing treatment effects, adverse effects, cost, and accessibility 1, 2
• All second-generation antidepressants demonstrate equivalent efficacy for treatment-naive patients with general depressive symptoms, with a number needed to treat of 7-8 for achieving remission 2
• Do not prescribe antidepressants for mild depression or subsyndromal depressive symptoms without a current moderate-to-severe episode, as antidepressants are most effective in patients with severe depression 2

Specific SSRI Selection and Dosing

For adults:

• Start with fluoxetine 20 mg daily, sertraline 50 mg daily, or escitalopram 10 mg daily as first-line agents 1, 2
• Sertraline 50 mg/day is the optimal dose when considering both efficacy and tolerability for most patients 3
• Dose increases may be considered after several weeks if insufficient clinical improvement is observed, with maximum doses of fluoxetine 80 mg/day, sertraline 200 mg/day, or escitalopram 20 mg/day 1, 4
• The full therapeutic effect may be delayed until 4 weeks of treatment or longer 4

For adolescents (12-17 years):

• Fluoxetine is the only FDA-approved antidepressant for children and adolescents with depression; escitalopram is approved only for adolescents aged 12 years and older 1
• Start fluoxetine at 10 mg/day for one week, then increase to 20 mg/day 1, 4
• In lower weight children, the starting and target dose may remain at 10 mg/day 4

For older adults (≥60 years):

• Preferred agents are citalopram, sertraline, venlafaxine, and bupropion 2
• Avoid paroxetine and fluoxetine in older adults due to higher anticholinergic effects and less favorable profiles 2
• Start citalopram at 10 mg daily or sertraline at 25 mg daily 1

Symptom-Targeted Selection

• For cognitive symptoms (difficulty concentrating, indecisiveness, mental fog), bupropion is the most effective first-choice due to its dopaminergic and noradrenergic effects and lower rate of cognitive side effects 2
• SNRIs (venlafaxine or duloxetine) are second-choice for cognitive symptoms, as their noradrenergic component may improve attention and concentration better than SSRIs 2

Monitoring Requirements

Initial Monitoring

• Assess patients in person within 1 week of initiating antidepressant treatment 1
• For adolescents, monitor closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months or at times of dose changes 1
• Telephone contact may be as effective as in-person visits for monitoring adverse events 1

Ongoing Assessment (at 4 and 8 weeks)

At every assessment, inquire about:

• Ongoing depressive symptoms using standardized validated instruments 1
• Risk of suicide 1
• Adverse effects from treatment (including use of specific adverse-effect scales) 1
• Adherence to treatment 1
• New or ongoing environmental stressors 1

Treatment Adjustment

• If symptoms are stable or worsening after 8 weeks despite good adherence, adjust the regimen by adding a psychological intervention, changing the medication, or switching from group to individual therapy 1
• If adequate response is not achieved within 6-8 weeks, treatment modification is indicated 5

Common Adverse Effects and Management

• Approximately 63% of patients on second-generation antidepressants experience at least one adverse effect 2
• Most common adverse effects include nausea and vomiting, diarrhea, dizziness, dry mouth, fatigue, headache, and sexual dysfunction 2
• Bupropion has lower rates of sexual adverse events than fluoxetine and sertraline 2
• Paroxetine has higher rates of sexual dysfunction than other SSRIs 2
• All SSRIs should be slowly tapered when discontinued due to risk of withdrawal effects 1

Treatment Duration

First Episode

• Continue treatment for at least 4-9 months after achieving remission for a first depressive episode 1, 2, 5
• The full effect may be delayed until 4-5 weeks of treatment or longer 4

Recurrent Depression

• For patients with 2 or more episodes, extend treatment to at least one year to prevent recurrence 2, 5
• Consider longer-term maintenance therapy, as depression is frequently a chronic, recurrent condition 6

Critical Contraindications and Pitfalls

• All SSRIs are contraindicated with monoamine oxidase inhibitors (MAOIs) 1
• At least 14 days should elapse between discontinuation of an MAOI and initiation of an SSRI 4
• At least 5 weeks should be allowed after stopping fluoxetine before starting an MAOI 4
• Do not use tricyclic antidepressants as first-line agents due to higher adverse effect burden, overdose risk, and lack of superiority over second-generation antidepressants 2
• Do not start SSRIs at higher than recommended starting doses, as deliberate self-harm and suicide risk is more likely with higher initial doses 1
• Monitor for hyponatremia, falls risk in elderly patients, drug interactions, and gastrointestinal symptoms 2