First-Line Treatment for Major Depressive Disorder and Anxiety Disorders
For adults with major depressive disorder or anxiety disorders and no significant medical history, selective serotonin reuptake inhibitors (SSRIs) are recommended as first-line pharmacologic treatment, with sertraline, escitalopram, fluoxetine, paroxetine, or citalopram being appropriate initial choices. 1, 2
Treatment Selection Framework
The American College of Physicians recommends choosing between cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs), which include SSRIs, after discussing treatment effects, adverse effect profiles, cost, accessibility, and patient preferences with the patient. 1, 3, 2 However, when pharmacologic treatment is selected, SSRIs represent the standard first-line approach. 1, 2
Why SSRIs Are First-Line
Efficacy across multiple conditions: SSRIs are effective for major depressive disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, posttraumatic stress disorder, and generalized anxiety disorder. 4, 5, 6
Safety profile: SSRIs have lower toxicity in overdose compared to first-generation antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors) while maintaining similar efficacy. 1, 2
Tolerability: SSRIs have a favorable side effect profile compared to older antidepressants, leading to better patient compliance. 5
Specific SSRI Dosing
Sertraline (Most Commonly Prescribed)
Major depressive disorder and OCD: Start at 50 mg once daily. 7
Panic disorder, PTSD, and social anxiety disorder: Start at 25 mg once daily for one week, then increase to 50 mg once daily. 7
Dose range: 50-200 mg/day based on response; dose changes should not occur at intervals less than 1 week due to the 24-hour elimination half-life. 7
Timing: Can be administered once daily, either morning or evening. 7
General SSRI Considerations
The American Academy of Family Physicians recommends a "start low, go slow" approach, particularly in older adults, with preferred medications including citalopram, escitalopram, sertraline, mirtazapine, and venlafaxine. 1
Treatment Phases and Duration
Acute Phase (6-12 weeks)
Focus on achieving symptom reduction, typically defined as ≥50% reduction in severity measured by PHQ-9 or HAM-D scales. 1, 2
Continuation Phase (4-9 months)
Maintain treatment to prevent relapse (return of symptoms during the same episode). 1, 2
Maintenance Phase (≥1 year)
Continue treatment to prevent recurrence (new distinct episode), especially important for patients with multiple previous episodes. 2, 8
For an initial episode of major depression, clinical guidelines suggest 4-12 months of treatment duration. 1 Patients with recurrent depression may benefit from prolonged treatment. 1, 8
Adverse Effects to Monitor
Common Side Effects
- Gastrointestinal disturbances (nausea is the most common reason for discontinuation) 1, 5
- Headache, sedation, insomnia, activation 5
- Sexual dysfunction (varies by agent) 1, 5
- Weight gain, excessive perspiration, paresthesia 5
Agent-Specific Differences
- Bupropion: Lower rate of sexual adverse events than fluoxetine and sertraline 1
- Paroxetine: Higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, and sertraline 1
- Sertraline and paroxetine: Transfer to breast milk in lower concentrations than other antidepressants 1
Approximately two-thirds of patients receiving second-generation antidepressants experience at least one adverse effect during treatment. 1
When SSRIs Don't Work
Response Rates
SSRIs have response rates of 50-60% in daily practice, with a number needed to treat of 7-8 for achieving remission. 1, 9
Switching Strategy
If insufficient response occurs after an adequate trial (typically 6-12 weeks at therapeutic dose), switching to another SSRI, venlafaxine, or other antidepressant class is appropriate. 9 Response rates after switching vary between 12-86%, with the number of previous antidepressant trials negatively correlating with treatment outcome. 9
Critical Monitoring Points
- Suicidality: Monitor closely, particularly in younger patients during initial treatment 1
- Response assessment: Use validated tools (PHQ-9, HAM-D) at regular intervals 1, 2
- Discontinuation syndrome risk: Increases with long-term use; taper gradually when stopping 8
- Tachyphylaxis: Long-term SSRI use increases risk of reduced efficacy over time 8
The decision to continue or discontinue an SSRI should be an active one, involving both patient and prescriber, and should be revisited periodically with reassessment of the risk-benefit ratio. 8