What are the recommended types of antidepressants for adults with depression, considering their individual needs and medical history?

Types of Antidepressants for Adults with Depression

Second-generation antidepressants—specifically SSRIs (selective serotonin reuptake inhibitors), SNRIs (serotonin-norepinephrine reuptake inhibitors), bupropion, and mirtazapine—are first-line therapy for adult depression, with selection based on adverse effect profiles, cost, and patient preferences rather than efficacy differences. 1, 2

Major Classes of Antidepressants

Second-Generation Antidepressants (First-Line)

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline 1
• Number needed to treat of 7-8 for achieving remission in primary care populations 1, 2
• Greater benefit demonstrated in severe versus mild-to-moderate depression 1, 2
• Sertraline and escitalopram show superior efficacy compared to other new-generation antidepressants in meta-analyses 3

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Include venlafaxine and duloxetine 1
• Remission rate marginally superior to SSRIs (49% vs 42%) in major depressive disorder 1
• Provide additional benefits for patients with comorbid pain disorders 1

Atypical Antidepressants

• Bupropion: Lower rates of sexual adverse effects compared to fluoxetine or sertraline 2
• Mirtazapine: Promotes sleep, appetite, and weight gain; particularly useful for depression with insomnia or anorexia 1, 4

Older Antidepressants (Second-Line)

Tricyclic Antidepressants (TCAs)

• Include amitriptyline, desipramine, and nortriptyline 1
• Number needed to treat of 7-16 for remission 1
• May be more efficacious for severe (melancholic/endogenous) depression 5
• Potentially lethal in overdose, limiting their use as first-line agents 5

Monoamine Oxidase Inhibitors (MAOIs)

• Require dietary restrictions and have significant drug interactions 6
• Reserved for treatment-resistant cases 7

Selection Algorithm by Clinical Scenario

Standard Adult Depression

• Start with an SSRI (sertraline or escitalopram preferred) or SNRI 1, 2, 3
• Base choice on cost, patient preference, and anticipated adverse effects rather than efficacy 1, 2

Depression with Comorbid Pain

• Select an SNRI (duloxetine or venlafaxine) for dual benefit 1

Depression with Sexual Dysfunction Concerns

• Choose bupropion to minimize sexual adverse effects 2

Depression with Insomnia or Poor Appetite

• Consider mirtazapine for its sedating and appetite-stimulating properties 1, 4

Older Adults (≥65 years)

• Preferred agents: citalopram, escitalopram, sertraline, mirtazapine, or venlafaxine 1, 2
• Avoid: paroxetine (anticholinergic effects) and fluoxetine (agitation risk) 1
• Start at 50% of standard adult dose and titrate slowly using "start low, go slow" approach 1, 2

Breastfeeding Women

• Sertraline and paroxetine transfer to breast milk in lower concentrations than other antidepressants 1, 2
• Fluoxetine and venlafaxine produce highest infant plasma concentrations and should be avoided 1

Dosing Ranges and Practical Considerations

Common Starting and Therapeutic Doses:

• Citalopram: 20-40 mg/day 1
• Escitalopram: 10-20 mg/day 1
• Sertraline: 50-200 mg/day 1
• Fluoxetine: 20-80 mg/day 1
• Venlafaxine: 37.5-225 mg/day 1
• Duloxetine: 40-120 mg/day 1
• Bupropion SR: 100-400 mg/day 1
• Mirtazapine: 15-45 mg/day 1

Treatment Duration and Modification

• Continue treatment for 4-12 months for an initial episode of major depression 1, 2, 4
• Patients with recurrent depression may benefit from prolonged treatment 1
• Modify treatment if inadequate response after 6-8 weeks of therapy 2
• Response rate to initial drug therapy may be as low as 50%, necessitating treatment adjustments 2

Critical Safety Warnings

Suicidality Risk

• SSRIs increase risk for suicide attempts compared to placebo, particularly in adults 18-24 years of age 1, 2
• Monitor closely during initial treatment and dose adjustments 8
• Risk is neutral for adults 25-64 years and protective for those ≥65 years 1

Common Adverse Effects

• About two-thirds of patients experience at least one adverse effect with second-generation antidepressants 1
• Nausea and vomiting are most common reasons for discontinuation 1
• Sexual dysfunction occurs in approximately 40% of patients 1

Drug Interactions

• Fluoxetine inhibits CYP2D6, requiring dose adjustments for drugs with narrow therapeutic indices 8
• Avoid combining with MAOIs due to serotonin syndrome risk 8
• Caution with NSAIDs, aspirin, or warfarin due to increased bleeding risk 8

Common Pitfalls to Avoid

• Do not use low-dose sedating antidepressants as adequate treatment for major depression with comorbid insomnia 2
• Do not assume all second-generation antidepressants have equivalent efficacy—while differences are modest, sertraline and escitalopram show slight superiority 3
• Do not overlook the need for dose reduction in renal or hepatic disease for specific agents (bupropion, duloxetine, venlafaxine require adjustment) 1
• Recognize that antidepressants show greater benefit over placebo in severe depression versus mild-to-moderate cases 1, 2