Was it a mistake not to start a selective serotonin reuptake inhibitor (SSRI) immediately for a patient with post-traumatic stress disorder (PTSD) and comorbid bipolar mood disorder?

No, It Was Not a Mistake—SSRIs Should Be Avoided in Bipolar Disorder with PTSD

You made the correct clinical decision by not starting an SSRI immediately in a patient with comorbid PTSD and bipolar disorder, as SSRIs can destabilize mood and precipitate manic episodes in bipolar patients. 1, 2

Why SSRIs Are Contraindicated in This Population

Risk of Mood Destabilization

• SSRIs can trigger manic or mixed episodes in patients with bipolar disorder, even when prescribed for comorbid conditions like PTSD 1, 2
• The FDA drug label for sertraline explicitly warns that "treating such an episode with an antidepressant alone may increase the likelihood of precipitation of mixed/manic episode in patients at risk for bipolar disorder" 2
• Any manic episode precipitated by an SSRI is classified as substance-induced, though it may represent unmasking or disinhibition of the underlying bipolar disorder 1

Additional Safety Concerns

• If the patient is also taking stimulants (like Adderall), combining with an SSRI creates extreme risk for serotonin syndrome, which can be life-threatening 1, 2
• Serotonin syndrome presents with mental status changes, neuromuscular hyperactivity, autonomic instability, and in severe cases can progress to seizures, arrhythmias, and death 1, 2

The Correct Treatment Algorithm for This Patient

Step 1: Optimize Mood Stabilization First

• The current mood stabilizer (aripiprazole) should be optimized before considering any antidepressant intervention 1
• If depressive or PTSD symptoms persist, add or switch to a different mood stabilizer rather than adding an SSRI 1
• The patient must achieve adequate mood stabilization before any consideration of antidepressant therapy 1

Step 2: Consider Trauma-Focused Psychotherapy

• Prolonged exposure (PE) therapy is feasible and preliminarily efficacious for patients with comorbid bipolar disorder and PTSD 3
• In a 2024 study, 75% of bipolar patients with PTSD completed all ten PE sessions, with significant reductions in PTSD symptoms, suicidality, depression, and anxiety—while mania scores remained stable throughout treatment 3
• Cognitive-behavioral therapy for PTSD shows that 42-65% of patients no longer meet PTSD criteria after treatment, with lower relapse rates compared to medication discontinuation 4

Step 3: Only If Absolutely Necessary—SSRI as Last Resort

• SSRIs should only be used as adjuncts when the patient is already taking at least one mood stabilizer and only if symptoms remain severe and refractory 1
• The only FDA-approved antidepressant combination for bipolar depression is olanzapine plus fluoxetine—not aripiprazole plus an SSRI 1
• SSRIs should be used with extreme caution and never as monotherapy in bipolar disorder 1, 2

Clinical Context: The Burden of Comorbidity

Prevalence and Impact

• The prevalence of lifetime comorbid PTSD in bipolar disorder is approximately 16-20%, roughly double the general population rate 5, 6
• Patients with both conditions experience accelerated illness progression, earlier age of onset, more manic episodes, higher rates of substance use, more suicide attempts, and worse quality of life 5
• PTSD is specifically associated with increased depressive symptoms in bipolar disorder but not necessarily with manic symptoms 7

Why Psychotherapy Should Be Prioritized

• Trauma-focused psychotherapy addresses the root cause without risking mood destabilization 3
• Working on trauma experiences in therapy may directly impact depressive symptoms in those with bipolar disorder and comorbid PTSD 7
• Unlike medication, psychotherapy shows sustained benefits at 6-month follow-up without rebound symptoms 3

Common Pitfalls to Avoid

• Never start an SSRI as first-line treatment for PTSD symptoms in a patient with known bipolar disorder 1, 2
• Do not assume that treating PTSD with standard protocols (which often include SSRIs) is safe in bipolar patients—the bipolar diagnosis changes the entire treatment algorithm 1
• Be vigilant about serotonin syndrome if multiple serotonergic agents are prescribed, particularly with stimulant co-administration 1, 2
• Screen all patients with depressive symptoms for bipolar disorder before initiating antidepressants, including detailed psychiatric and family history 2

Your clinical judgment to withhold the SSRI was sound and evidence-based. The appropriate next step is optimizing mood stabilization and initiating trauma-focused psychotherapy. 1, 3