What medication adjustments are needed for a patient on Wellbutrin (bupropion) 450 mg and Remeron (mirtazapine) 30 mg who presents with suicidal ideation and a plan to overdose on fentanyl?

Immediate Medication Management for Acute Suicidal Crisis

This patient requires immediate discontinuation of bupropion (Wellbutrin) 450 mg due to its association with increased suicidal ideation during acute crises, and consideration of switching to an antidepressant with demonstrated anti-suicidal properties such as an SSRI, while maintaining close inpatient monitoring. 1, 2

Critical Safety Concerns with Current Regimen

Bupropion at Maximum Dose

• Bupropion carries a black box warning for suicidal thoughts and behaviors, particularly during initial treatment periods and dose changes, with specific concern for emergence of suicidal ideation, agitation, and impulsivity 1
• The FDA label explicitly states that symptoms including "agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania" may represent precursors to emerging suicidality 1
• At 450 mg daily (maximum dose), this patient is at the highest seizure risk threshold, which is particularly dangerous given the stated plan to overdose on fentanyl—a combination that could be lethal 1
• Recent evidence from the VAST-D trial (2024) found that switching to or combining with bupropion was associated with higher rates of suicidal ideation during treatment compared to aripiprazole augmentation 3

Mirtazapine (Remeron) Considerations

• Mirtazapine 30 mg can remain in the regimen as it has not been specifically associated with increased suicidal ideation and may help with sleep and appetite 4
• However, the American Academy of Child and Adolescent Psychiatry notes that any medication in suicidal patients must be carefully monitored by a third party 2, 4

Recommended Medication Adjustments

Immediate Actions (Inpatient Setting Required)

1. Discontinue bupropion 450 mg immediately given the acute suicidal crisis with specific plan 1
2. Initiate or switch to an SSRI (e.g., sertraline 50 mg daily, titrating to 100-200 mg), as SSRIs have been shown to reduce suicidal ideation in adults with depression, though careful monitoring during the first 10-14 days is essential 5, 2
3. Continue mirtazapine 30 mg for its sedating properties and lack of association with increased suicidal ideation 4
4. Consider short-term anxiolytic/hypnotic if severe anxiety or insomnia present, though benzodiazepines should be prescribed with caution as they may increase disinhibition 2, 5

Alternative Evidence-Based Options

• Lithium augmentation should be strongly considered once acute crisis stabilizes, as it has the most robust evidence for reducing both suicide attempts and completed suicide in patients with unipolar and bipolar depression 2, 5, 6
• Ketamine infusion (0.5 mg/kg single dose) may provide rapid improvement in suicidal ideation within 24 hours, with benefits lasting up to 1-6 weeks, though this requires specialized administration 2

Monitoring Requirements

Intensive Observation Protocol

• Daily face-to-face assessment by psychiatric team for emergence of worsening suicidal ideation, agitation, akathisia, or behavioral changes 1, 2
• Third-party medication administration and monitoring is mandatory—family or staff must control all medications and report any mood changes, increased agitation, or side effects immediately 2, 4
• Particular vigilance during first 10-14 days of any new antidepressant treatment when risk of suicidal behavior is highest 5
• Screen specifically for akathisia (psychomotor restlessness), as this side effect is associated with higher risk of developing suicidal ideation on SSRIs 2, 4

Environmental Safety Measures

Means Restriction

• Ensure secure inpatient environment without access to lethal means, including removal of all medications from patient control 5
• Address the specific fentanyl overdose plan by involving addiction services if substance use disorder is present 5
• Given the stated plan involves fentanyl, assess for opioid use disorder and consider integrated treatment 5

Common Pitfalls to Avoid

1. Do not continue bupropion at maximum dose in an acutely suicidal patient—the FDA label explicitly warns about this scenario and the VAST-D trial confirms increased SI risk 1, 3
2. Do not rely solely on mirtazapine monotherapy for acute suicidal depression—it lacks specific anti-suicidal evidence compared to SSRIs or lithium 2, 5
3. Do not discharge prematurely—the American Academy of Child and Adolescent Psychiatry emphasizes that establishing therapeutic alliance and attending first treatment sessions improves continuation 2
4. Do not prescribe tricyclic antidepressants as they are potentially lethal in overdose and should not be first-line treatment for suicidal patients 2
5. Avoid excessive benzodiazepine use beyond short-term management, as they may increase disinhibition and suicide attempts in some individuals 2, 4