What is the best antidepressant, such as a selective serotonin reuptake inhibitor (SSRI), to treat grief disorder in adult patients, including those with a history of trauma or post-traumatic stress disorder (PTSD)?

Best Antidepressant for Grief Disorder

For grief disorder (prolonged grief disorder), cognitive-behavioral therapy should be the first-line treatment rather than antidepressants, as CBT has demonstrated superior long-term efficacy in treating this specific condition. 1

Why Psychotherapy Over Medication for Grief Disorder

• CBT specifically designed for prolonged grief disorder produces moderate to large effect sizes and significantly reduces grief symptoms at all post-treatment assessments 1
• The superior long-term effects of grief-focused CBT (measured at 3,6, and 12 months post-treatment) suggest it successfully strengthens patients in facing bereavement-related challenges better than supportive counseling alone 1
• Prolonged grief disorder is a distinct diagnostic entity newly included in ICD-11 and DSM-5 (as persistent complex bereavement disorder), requiring specialized treatment approaches 1

When Antidepressants Are Indicated: Comorbid Depression or PTSD

If pharmacological treatment is necessary due to comorbid major depressive disorder or PTSD (which occurs in 44% of grief cases with trauma history), sertraline is the best antidepressant choice. 2

Why Sertraline Is the Optimal Choice

• Sertraline has FDA approval specifically for PTSD treatment, which is critical given the overlap between grief disorder and trauma-related symptoms 2
• In PTSD trials, 44% of patients had secondary depressive disorder, and sertraline showed significant improvement on both PTSD and depression measures simultaneously 2
• The American Academy of Family Physicians recommends sertraline as a preferred agent for older adults due to its favorable side effect profile and low potential for drug interactions 3, 4

Sertraline Dosing for Grief-Related Conditions

• Start at 25 mg daily for the first week, then increase to 50 mg daily 2
• Dose range of 50-200 mg/day based on clinical response and tolerability 2
• Mean effective doses in PTSD trials were 146-151 mg/day for treatment completers 2
• Treatment should continue for at least 6-12 months after symptom remission 5

Critical Distinction: Grief vs. Depression

Do not confuse normal grief with major depressive disorder—they require different treatment approaches. Prolonged grief disorder is characterized by persistent yearning for the deceased, preoccupation with the death, and difficulty accepting the loss that significantly impairs functioning beyond 6-12 months post-loss 1. This differs from major depression, which involves pervasive anhedonia, worthlessness, and neurovegetative symptoms 3.

Alternative SSRIs If Sertraline Is Not Tolerated

If sertraline causes intolerable side effects:

• Escitalopram or citalopram are reasonable second choices, particularly in older adults, though citalopram should not exceed 40 mg daily due to QT prolongation risk 4, 5
• Avoid paroxetine and fluoxetine in older adults due to higher adverse effect rates and drug interaction potential 3, 4

Common Pitfalls to Avoid

• Never use benzodiazepines for grief disorder or comorbid PTSD—they have high abuse potential and evidence shows worsening outcomes, particularly in patients with substance use history 5
• Do not prescribe cannabis or cannabis-derived products for grief-related PTSD 5
• Avoid nefazodone despite some evidence for nightmare reduction, due to increased hepatotoxicity risk 3
• Do not discontinue treatment prematurely—continue for at least 6-12 months after symptom remission, as relapse rates with sertraline discontinuation range from 26-52% 5

Monitoring and Expected Outcomes

• Evaluate treatment response after 8 weeks of SSRI therapy 5
• In controlled trials, 53-85% of PTSD participants were classified as treatment responders 5
• Begin monitoring within 1-2 weeks of treatment initiation for adverse effects 4
• Most common adverse effects include nausea, diarrhea, sexual dysfunction, and gastrointestinal disturbances, with nausea being the most common reason for discontinuation 3, 4, 5

Integration of Psychotherapy and Medication

• Psychotherapy and pharmacotherapy can be initiated concurrently without waiting for a stabilization phase 5
• Trauma-focused psychotherapy (Prolonged Exposure, Cognitive Processing Therapy, or EMDR) shows 40-87% of patients no longer meeting PTSD criteria after 9-15 sessions 5
• Combined treatment may be superior to medication alone for complex presentations with comorbid mood disorders 5