How should I manage a patient with borderline personality disorder and major depressive disorder, possible attention‑deficit/hyperactivity disorder, who is taking citalopram 40 mg daily and bupropion extended‑release 300 mg daily, with improved concentration but persistent mood swings?

Management of Persistent Mood Swings in BPD/MDD with Possible ADHD

Add dialectical behavior therapy (DBT) immediately and formally assess for ADHD with structured diagnostic tools—if ADHD is confirmed, initiate a stimulant trial (methylphenidate or lisdexamfetamine) while continuing current antidepressants, as untreated ADHD will perpetuate mood instability and functional impairment despite adequate antidepressant therapy. 1

Diagnostic Clarification: Confirm or Exclude ADHD

The patient reports improved focus on the current regimen, which raises a critical question: is this true ADHD symptom improvement, or simply activation from bupropion? Formal ADHD assessment using the Adult ADHD Self-Report Scale (ASRS) part A is essential before proceeding with ADHD-specific pharmacotherapy. 2

• Around 10% of adults with recurrent depression have comorbid ADHD, and treatment of depression alone will likely be inadequate to restore optimal quality of life when ADHD remains unaddressed 2
• Individuals with ADHD who stopped psychostimulant medication experienced significant increases in depressive symptoms despite remaining on antidepressants, demonstrating that mood stabilization requires treating both conditions 2
• The "improved focus" on bupropion may represent partial ADHD response, but bupropion is explicitly a second-line agent for ADHD with smaller effect sizes than stimulants 1

Primary Recommendation: Address the Mood Swings Through BPD-Specific Treatment

The persistent mood swings are most likely driven by untreated BPD core symptoms, not inadequate antidepressant dosing. Medication alone cannot address the affective instability characteristic of BPD. 3, 4

Initiate DBT as First-Line for BPD

• DBT is the evidence-based psychotherapy specifically designed for BPD and should be implemented immediately 5
• A naturalistic study of 158 BPD patients showed significant decreases in impulsiveness, anger, depression, and hopelessness after 4 weeks of intensive DBT, with effect sizes ranging from small to large 5
• Medications should be considered only as adjuncts to BPD-specific psychotherapy, not as primary treatment 3

Optimize Current Pharmacotherapy

The current regimen (citalopram 40 mg + bupropion XL 300 mg) is reasonable for MDD but does not directly target BPD symptoms:

• Citalopram is at maximum FDA-recommended dose (40 mg) due to QTc prolongation risk at higher doses 6
• Bupropion 300 mg is a standard therapeutic dose but can be increased to 450 mg maximum if needed 1
• SSRIs like citalopram can be effective for mood symptoms, anxiety, and impulse dyscontrol in BPD, but evidence is limited 4

If ADHD is Confirmed: Add Stimulant Therapy

Do not rely on bupropion alone to treat both ADHD and mood symptoms—no single antidepressant is proven for this dual purpose. 1

Stimulant Selection and Dosing

• Methylphenidate or lisdexamfetamine are first-line options with 70-80% response rates for ADHD 1
• Start methylphenidate 5-10 mg in the morning, titrating by 5-10 mg weekly to 20 mg twice daily (typical maintenance dose) 1
• Alternatively, start lisdexamfetamine 20-30 mg once daily, titrating by 10-20 mg weekly to 50-70 mg daily 1
• Long-acting formulations provide all-day coverage and reduce rebound symptoms 1

Evidence for Stimulants in BPD-ADHD Comorbidity

• A naturalistic study of 59 BPD-ADHD patients showed that methylphenidate treatment significantly improved response to DBT for trait-state anger, motor impulsiveness, depression severity, and ADHD severity compared to those without stimulant medication 5
• An open trial of bupropion SR in adults with ADHD plus bipolar disorder (90% bipolar II) showed 55% reduction in ADHD symptoms without significant activation of mania, suggesting safety in mood-unstable populations 7
• Stimulants can be safely combined with SSRIs—there are no significant pharmacokinetic interactions between citalopram and stimulants 1

Critical Safety Considerations

• Never use MAO inhibitors concurrently with stimulants or bupropion due to risk of hypertensive crisis; at least 14 days must elapse between MAOI discontinuation and stimulant initiation 1
• Monitor blood pressure and pulse at baseline and each visit during stimulant titration 1
• Screen for substance use history—if present, consider long-acting formulations with lower abuse potential or atomoxetine as first-line 1
• Avoid benzodiazepines in BPD patients due to disinhibiting effects and reduced self-control 1

Alternative: If ADHD is Not Confirmed or Stimulants Are Contraindicated

Consider Mood Stabilizers for Affective Instability

• Specific antiepileptics (valproate, lamotrigine) can be useful for mood instability, impulsiveness, and anger in BPD 4
• Second-generation antipsychotics (quetiapine, aripiprazole) at low doses can target mood symptoms and impulse dyscontrol 4
• However, polypharmacy should be avoided, and the prescription of medications should be considered only as an adjunct to psychotherapy 3

Augmentation Strategies for Depression

• If depressive symptoms persist despite citalopram 40 mg, augmenting with bupropion (already in place) is appropriate 2
• Augmenting citalopram with bupropion showed lower discontinuation rates due to adverse events compared to buspirone augmentation 2
• Switching from one SSRI to another (e.g., citalopram to sertraline) showed no difference in response or remission rates in the STAR*D trial 2

Monitoring and Follow-Up

• Weekly contact during medication titration and monthly follow-up during maintenance phase 1
• Use standardized rating scales to track ADHD symptoms (if confirmed), mood symptoms, and functional impairment 1
• Monitor for suicidal ideation at every visit, particularly given BPD diagnosis and antidepressant use 1
• Track sleep quality, appetite changes, and any emergence of manic/hypomanic symptoms 1

Common Pitfalls to Avoid

• Do not assume bupropion alone will adequately treat both ADHD and depression—it is a second-line agent for ADHD with smaller effect sizes than stimulants 1
• Do not increase citalopram above 40 mg due to dose-dependent QTc prolongation risk 6
• Do not initiate stimulants without first confirming ADHD diagnosis with structured assessment tools 2
• Do not rely solely on medication to treat BPD—psychotherapy (specifically DBT) is the cornerstone of treatment 3, 5
• Do not use tricyclic antidepressants due to greater lethal potential in overdose, particularly relevant in BPD population 1