What is the best alternative medication for a 48-year-old female patient with a history of traumatic brain injury, who has been experiencing irritability, mood swings, and restless nights, and has previously tried fluoxetine (Prozac), paroxetine (Paxil), trazodone, and zoloft (sertraline) which was effective but caused itchiness?

Recommended Medication Switch for This Patient

Switch to bupropion (Wellbutrin) as the optimal alternative antidepressant for this patient, given her history of traumatic brain injury, current symptom profile of irritability and mood swings (rather than classic depression), sleep disturbance, and the allergic reaction to sertraline. 1

Rationale for Bupropion

Primary Considerations

• Traumatic Brain Injury Context: Bupropion has demonstrated efficacy in TBI populations and is specifically noted as "activating" with "possible rapid improvement of energy level," which directly addresses her irritability and mood symptoms 1

• Symptom Profile Match: Her presentation of irritability, mood swings, and restless nights—while denying depression and anxiety—suggests a more activating antidepressant would be appropriate rather than another sedating SSRI 1

• Avoids SSRI Class: Since sertraline (an SSRI) caused an allergic reaction (itching), switching to a different mechanism of action is prudent. Bupropion is a noradrenergic reuptake inhibitor with a completely different pharmacological profile 1

• Sleep Considerations: While she has sleep disturbance, the second dose should be given before 3 p.m. to minimize insomnia risk 1

Dosing Strategy

• Start: 37.5 mg every morning
• Titration: Increase by 37.5 mg every 3 days as tolerated
• Target: 150 mg twice daily (maximum dose) 1
• Critical timing: Second dose must be before 3 p.m. to prevent insomnia 1

Alternative Second-Line Options

If Bupropion Is Contraindicated or Ineffective

Mirtazapine (Remeron) would be the next choice:

• Has the fastest onset of action compared to other second-generation antidepressants (statistically significant advantage over SSRIs within 2-4 weeks) 1
• "Potent and well tolerated; promotes sleep, appetite, and weight gain" 1
• Particularly useful given her sleep disturbance 1
• Dosing: Start 7.5 mg at bedtime, maximum 30 mg at bedtime 1

Venlafaxine (extended-release) as third option:

• Showed superior efficacy in treatment-resistant depression in the STAR*D trial when SSRIs failed 1
• Better response rates for anxiety symptoms compared to fluoxetine 1
• However, this is still serotonergic and may carry cross-reactivity risk with her sertraline allergy

Critical Safety Considerations

Contraindications for Bupropion

• Absolute contraindication: History of seizures or seizure disorder 1
• Avoid in: Agitated patients (though her presentation is irritability/mood swings, not agitation) 1
• Must verify no seizure history given her TBI in the past 1

Medication Discontinuation Warning

• Never abruptly stop antidepressants: She previously stopped trazodone without tapering, which was inappropriate 1
• Discontinuation should occur over 10-14 days to limit withdrawal symptoms 1
• The concern about "serotonin syndrome" from stopping medication is actually incorrect—the risk is withdrawal syndrome, not serotonin syndrome 1

Monitoring the Sertraline Allergy

• The itching reaction to sertraline at 25 mg daily, despite using Benadryl and ruling out other causes, represents a true drug reaction requiring discontinuation 1
• Cross-reactivity within the SSRI class is possible but not guaranteed 1

What NOT to Use

Avoid other SSRIs (fluoxetine, paroxetine, citalopram, escitalopram):

• Risk of cross-reactivity with sertraline allergy 1
• She already failed fluoxetine (discontinued during pregnancy) and paroxetine (caused intrusive thoughts) 1
• No significant efficacy differences among SSRIs to justify trying another 1

Avoid tricyclic antidepressants (nortriptyline, desipramine):

• Higher risk of cardiotoxic, hypotensive, and anticholinergic effects 1
• Should be considered third-line treatment only 2

Trazodone already failed and was not well tolerated 1

Evidence Quality Note

The American College of Physicians guidelines 1 provide the highest quality evidence, demonstrating that second-generation antidepressants show no significant efficacy differences overall, making tolerability and side effect profiles the primary selection criteria 1. For TBI-specific depression, sertraline showed a trend toward efficacy but was not statistically significant 3, and bupropion's activating properties make it particularly suitable for this patient's symptom cluster 1.