Medication for Grief and Depression
For treating depression, start with a second-generation antidepressant (SSRI or SNRI) selected based on the patient's specific symptom profile, adverse effect tolerance, and cost considerations—these medications are equally effective for treatment-naive patients with moderate to severe depression. 1, 2
Initial Medication Selection
SSRIs and SNRIs are first-line agents for pharmacologic treatment of moderate to severe depression, with no clinically meaningful efficacy differences between them. 3, 1, 2 The number needed to treat for achieving remission is 7-8 for SSRIs. 3, 1
Symptom-Targeted Selection
For cognitive symptoms (difficulty concentrating, indecisiveness, mental fog): Choose bupropion first due to its dopaminergic and noradrenergic effects and lower cognitive side effects. 1 SNRIs (venlafaxine or duloxetine) are second-choice for cognitive symptoms. 1
For patients concerned about sexual dysfunction: Choose bupropion, which has significantly lower rates of sexual adverse events compared to fluoxetine or sertraline. 3, 1, 2 Avoid paroxetine, which has the highest rates of sexual dysfunction among SSRIs. 3, 1, 2
For older adults: Prefer citalopram, sertraline, venlafaxine, or bupropion. 3, 1, 2 Specifically avoid paroxetine and fluoxetine in older patients due to higher anticholinergic effects and less favorable profiles. 3, 1
Critical Prescribing Considerations
Only prescribe antidepressants for moderate to severe depression—they are most effective in patients with severe depression, with the drug-placebo difference increasing with initial severity. 1, 2 Do not use antidepressants for initial treatment of mild depressive symptoms or subsyndromal depression without a current moderate-to-severe episode. 1
Monitoring Protocol
Begin monitoring within 1-2 weeks of initiation for therapeutic response, adverse effects, and emergence of suicidal thoughts or behaviors. 3, 2 The risk for suicide attempts is greatest during the first 1-2 months of treatment, and SSRIs are associated with increased risk for suicide attempts compared to placebo. 3, 2
Treatment Duration
- First episode: Continue treatment for at least 4-9 months after symptom resolution. 3, 1, 2
- Recurrent depression: Consider prolonged treatment of at least one year to prevent recurrence. 3, 2
When to Modify Treatment
If adequate response (defined as 50% reduction in measured severity) is not achieved within 6-8 weeks, modify treatment by switching agents, increasing dose, or adding adjunctive therapy. 3, 2
Common Adverse Effects
Approximately 63% of patients experience at least one adverse effect. 3, 1 The most common include nausea and vomiting (most frequent reason for discontinuation), diarrhea, dizziness, dry mouth, fatigue, headache, and sexual dysfunction. 3, 1 SNRIs (duloxetine and venlafaxine) have slightly higher discontinuation rates due to adverse effects, particularly nausea and vomiting, compared to SSRIs as a class. 3
Pitfalls to Avoid
- Do not use tricyclic antidepressants (TCAs) as first-line agents due to higher adverse effect burden (number needed to harm of 4-30 vs. 20-90 for SSRIs) and overdose risk. 3, 1
- Do not assume all SSRIs are identical—paroxetine has notably higher anticholinergic effects and sexual dysfunction rates. 1
- Do not prescribe for grief alone or mild symptoms without a diagnosed moderate-to-severe depressive episode. 1