What alternative treatments are available for a patient with depression and anxiety who has experienced tongue swelling with multiple medications, including Prozac (fluoxetine), Xanax (alprazolam), and Celexa (citalopram), and has not improved with Auvelity, Effexor (venlafaxine), and is currently only taking Buspirone (Buspirone) 7.5 mg twice daily (BID)?

Alternative Treatments for Depression and Anxiety with History of Medication-Induced Tongue Swelling

For a patient with depression and anxiety who has experienced tongue swelling with multiple medications and inadequate response to others, cognitive behavioral therapy (CBT) is strongly recommended as the first-line treatment, with consideration of bupropion as a potential pharmacological option if needed. 1

Understanding the Clinical Situation

This patient presents with a challenging case:

• History of tongue swelling with multiple medications (Prozac/fluoxetine, Xanax/alprazolam, Celexa/citalopram)
• No improvement with Auvelity (bupropion/dextromethorphan)
• Side effects with Effexor (venlafaxine)
• Currently only taking buspirone 7.5 mg BID with persistent depression and anxiety

The tongue swelling reactions suggest potential hypersensitivity reactions that limit medication options.

Treatment Recommendations

First-Line Approach:

1. Non-pharmacological Treatment
   • Cognitive Behavioral Therapy (CBT): Strong evidence supports CBT as equally effective to second-generation antidepressants with fewer adverse effects and lower relapse rates 1
   • Optimal structure: 12-20 sessions focusing on behavioral activation and cognitive restructuring 2

Pharmacological Options (if CBT alone is insufficient):

1. Consider Bupropion

   • Bupropion has a different mechanism of action (norepinephrine and dopamine reuptake inhibitor) compared to SSRIs/SNRIs
   • Associated with lower rates of sexual side effects than fluoxetine and sertraline 1
   • No reported association with tongue swelling in available evidence
   • Start at low dose (e.g., 75mg once daily) and titrate slowly

2. Optimize Current Buspirone Therapy

   • Current dose (7.5mg BID) may be subtherapeutic
   • Consider increasing to target dose of 20-30mg daily in divided doses 2, 3
   • Maximum dose can be up to 60mg daily 2
   • Monitor for drug interactions if combined with other medications 3

3. Low-Dose Mirtazapine

   • Different mechanism of action (NaSSA)
   • Start at 7.5mg at bedtime and titrate based on response
   • Beneficial for patients with anxiety and insomnia
   • No specific association with tongue swelling in available evidence

Important Considerations

Tongue Swelling Evaluation

• Consider referral to allergist/immunologist to evaluate for potential cross-reactivity patterns 4, 5
• Document all medication reactions carefully
• Consider if tongue swelling represents true angioedema or another condition 4

Medication Precautions

• Avoid SSRIs and SNRIs due to previous reactions with multiple agents in this class
• Avoid benzodiazepines for long-term use due to tolerance, addiction potential, and cognitive impairment 2
• Monitor carefully when initiating any new medication, starting at lowest possible doses

Combination Therapy Risks

• Be cautious with combinations that might increase serotonergic activity
• Buspirone combined with SSRIs has been associated with serotonin syndrome in rare cases 6
• Bupropion combined with SSRIs has been associated with serotonin syndrome 7

Monitoring and Follow-up

• Follow up within 1-2 weeks of any medication changes 2
• Use standardized scales to monitor depression and anxiety symptoms
• Assess for side effects and emergence of suicidal ideation, especially during medication transitions 2
• Continue effective treatment for at least 9-12 months after symptom remission 2

Alternative Approaches if Above Strategies Fail

• Consider St. John's Wort - Low-quality evidence shows it may be as effective as second-generation antidepressants with better tolerability, but quality control of preparations in the US is variable 1
• Exercise therapy as an adjunctive treatment
• Referral to psychiatrist for consideration of more specialized treatments or medication combinations

The combination of CBT with careful medication selection and monitoring offers the best chance for managing this patient's depression and anxiety while minimizing the risk of tongue swelling reactions.