Which medication should be discontinued or adjusted to facilitate weight loss in a patient taking Chlorpromazine, Quetiapine, Buspirone, Bupropion, Gabapentin, and Methadone?

Medication Discontinuation for Weight Loss

Quetiapine should be discontinued first, as it is the most significant contributor to weight gain in this regimen and can be replaced with a lower-risk antipsychotic while maintaining efficacy for mood stabilization and psychosis. 1, 2

Rationale for Targeting Quetiapine

Weight Gain Risk Profile

• Quetiapine causes clinically significant weight gain (≥7% from baseline), placing it among the highest-risk antipsychotics for metabolic adverse effects 2
• Second-generation antipsychotics like quetiapine carry a medium-to-high risk of weight gain, substantially higher than other agents in this patient's regimen 1
• The 400mg daily dose represents a substantial metabolic burden that directly impacts quality of life through weight-related comorbidities 2

Redundancy in Current Regimen

• This patient is already receiving chlorpromazine for mood stabilization and psychosis, creating therapeutic redundancy 1
• Maintaining dual antipsychotic therapy without clear treatment-resistant indication increases metabolic risk without proportional benefit 1

Medications to Preserve

Chlorpromazine

• Continue chlorpromazine as the primary antipsychotic since it provides necessary coverage for psychosis and mood stabilization 1
• While first-generation antipsychotics carry their own risks, chlorpromazine has a more established profile in this patient 1

Bupropion

• Bupropion consistently promotes weight loss and should be maintained 3, 4
• This agent provides dual benefit: treating depression while actively facilitating weight reduction 5, 2
• Bupropion demonstrates weight-loss effects of approximately 2.8 kg at 6-12 months 5

Buspirone

• Buspirone is weight-neutral and addresses a distinct indication (anxiety) not covered by other agents 1
• No metabolic concerns warrant discontinuation 1

Gabapentin

• Continue gabapentin for seizure management as this represents a critical safety indication 1
• Switching anticonvulsants for weight concerns would be inappropriate given seizure control priority 1

Methadone

• Methadone must be continued for substance use disorder treatment, as discontinuation risks relapse, overdose, and mortality 5
• The morbidity and mortality risks of untreated opioid use disorder far outweigh weight concerns 5

Discontinuation Protocol for Quetiapine

Tapering Schedule

• Reduce quetiapine by 100mg every 1-2 weeks to minimize withdrawal symptoms and monitor for psychiatric decompensation 1
• Week 1-2: 300mg nightly
• Week 3-4: 200mg nightly
• Week 5-6: 100mg nightly
• Week 7: Discontinue 1

Monitoring During Taper

• Assess for psychotic symptoms, mood destabilization, and sleep disturbance weekly during the taper period 1
• Monitor weight at each visit to document metabolic improvement 6
• If psychiatric symptoms emerge, slow the taper or consider adding aripiprazole (see below) 1

Alternative Antipsychotic if Needed

Aripiprazole as Replacement

• If chlorpromazine alone proves insufficient, add aripiprazole rather than continuing quetiapine, as aripiprazole carries low weight-gain risk 1
• Aripiprazole has demonstrated the ability to reverse antipsychotic-induced weight gain when added to existing regimens 7
• Case reports show weight loss exceeding 37 pounds when aripiprazole replaces higher-risk agents 7

Expected Outcomes

Weight Loss Trajectory

• Switching from high-risk to low-risk antipsychotics typically mitigates or reverses weight gain within 3-6 months 1
• Combined with bupropion's weight-loss effects, expect gradual but sustained weight reduction 5, 4
• Realistic expectation: 3-5 kg weight loss over 6-12 months following quetiapine discontinuation 5, 1

Common Pitfalls to Avoid

• Do not discontinue multiple medications simultaneously, as this prevents identification of which change caused any adverse psychiatric effects 1
• Do not stop methadone for weight concerns, as this prioritizes a modifiable risk factor over life-threatening relapse risk 5
• Do not reduce gabapentin without neurology consultation, given seizure disorder 1