What are the alternative treatment options for an overweight patient taking Invega Sustenna (paliperidone) and Seroquel (quetiapine)?

Managing Weight in Patients on Invega Sustenna and Seroquel

For an overweight patient taking both paliperidone (Invega Sustenna) and quetiapine (Seroquel), prioritize adding semaglutide 2.4 mg weekly with lifestyle modifications as the first-line intervention, as both antipsychotics cause significant weight gain and semaglutide offers the greatest magnitude of weight loss (14.9% at 68 weeks) among available anti-obesity medications. 1

Understanding the Problem

Both medications contribute substantially to weight gain:

• Quetiapine (Seroquel) causes weight gain in 23% of adults (≥7% body weight increase) and is associated with increased cholesterol, triglycerides, and blood sugar 2
• Paliperidone (Invega Sustenna) causes time-dependent weight increases averaging 7% (6 kg) at 12 months, with overweight/obesity prevalence increasing from 33% to 60% 3
• The combination creates additive metabolic risk including hyperglycemia, dyslipidemia, and cardiovascular complications 2

Primary Strategy: Add Anti-Obesity Medication

First-Line: Semaglutide 2.4 mg

Semaglutide 2.4 mg should be prioritized over other anti-obesity medications given its superior efficacy and metabolic benefits. 1

• Start at 0.25 mg subcutaneously weekly, titrate by 0.25-0.5 mg every 4 weeks to target dose of 2.4 mg weekly 1
• Achieves mean weight loss of 14.9% at 68 weeks versus 2.4% with placebo 1
• Provides glucoregulatory benefits particularly important given antipsychotic-induced hyperglycemia risk 1, 2
• Gradual dose titration mitigates nausea and vomiting from delayed gastric emptying 1
• Monitor for pancreatitis and gallbladder disease 1

Second-Line: Liraglutide 3.0 mg

If semaglutide is unavailable or not tolerated:

• Start at 0.6 mg subcutaneously daily, increase by 0.6 mg weekly to 3.0 mg daily 1, 4
• Achieves 8.0% total body weight loss at 12 months 4
• Similar glucoregulatory benefits and side effect profile to semaglutide 1
• Discontinue if <4% weight loss after 16 weeks 4

Third-Line: Phentermine-Topiramate ER

Consider when GLP-1 agonists are contraindicated or ineffective:

• Start 3.75/23 mg daily for 14 days, then 7.5/46 mg daily, maximum 15/92 mg daily 1, 4
• Achieves 9.8% weight loss at 52 weeks with 15/92 mg dose 1
• Critical caveat: Topiramate is teratogenic—requires effective contraception in women of childbearing potential 1, 4
• Monitor blood pressure and heart rate periodically 1
• Discontinue if <5% weight loss after 12 weeks at maximum dose 1, 4
• May be particularly useful if patient has comorbid migraines 1

Fourth-Line: Naltrexone-Bupropion ER

• Consider for patients attempting smoking cessation or with comorbid depression 1
• Avoid in patients with seizure disorders or at seizure risk 1
• Cannot be used with concurrent opioid medications 1
• Monitor blood pressure and heart rate, especially first 12 weeks 1

Secondary Strategy: Optimize Antipsychotic Regimen

Consider Switching from Quetiapine

Switching from quetiapine to aripiprazole may reduce metabolic burden, though weight neutrality in young people is questionable. 3, 5

• One study showed mean 2.25 kg weight loss when switching from olanzapine to quetiapine over 10 weeks, suggesting quetiapine may be less metabolically problematic than olanzapine but still causes weight gain 5
• Aripiprazole LAI shows lower triglycerides and prolactin levels compared to paliperidone, though both cause similar weight gain (7% at 12 months) 3
• Critical consideration: Any antipsychotic switch risks psychiatric destabilization—only attempt if patient is clinically stable and with close monitoring 5

Minimize Paliperidone Dose

• Each 1 mg increase in risperidone/paliperidone dose increases weight by 0.16-0.29% monthly 6
• Use minimum effective dose to reduce metabolic impact 6
• Each additional milligram increases total cholesterol by 0.05 mmol/L and LDL by 0.04 mmol/L annually 6

Essential Monitoring Requirements

Metabolic Parameters

• Weight: Check monthly initially, then every 3 months 2
• Blood glucose: Fasting glucose before starting anti-obesity medication, then every 3 months given antipsychotic-induced hyperglycemia risk 2
• Lipid panel: Baseline and every 3-6 months 2
• Blood pressure: Each visit, especially with phentermine-containing products 1

Psychiatric Stability

• Monitor for symptom exacerbation if considering antipsychotic switch 5
• Assess for anxiety or insomnia that may worsen with phentermine 1

Lifestyle Modifications (Mandatory Adjunct)

All anti-obesity medications require concurrent lifestyle interventions:

• Dietary counseling: 500-750 kcal/day deficit from baseline 1
• Physical activity: 150-300 minutes/week moderate-intensity aerobic exercise plus resistance training 2-3 times weekly 1
• Behavioral counseling: Structured weight management program 1

Discontinuation Criteria

Stop anti-obesity medication if: 1, 4

• <5% weight loss after 3 months (general guideline) 1
• <4% weight loss after 16 weeks for liraglutide 4
• <5% weight loss after 12 weeks at maximum dose for phentermine-topiramate 1, 4
• Any safety or tolerability issues at any time 1

Critical Pitfalls to Avoid

• Do not use orlistat—AGA suggests against its use due to minimal benefit and significant GI adverse effects 1
• Never prescribe anti-obesity medications during pregnancy—all are category X 1
• Do not abruptly discontinue quetiapine—taper to avoid insomnia, nausea, and vomiting 2
• Do not overlook contraception counseling when prescribing topiramate-containing products 1, 4
• Avoid phentermine in patients with cardiovascular disease or uncontrolled hypertension 1