What medication can be added for weight loss in a patient with schizophrenia and Attention Deficit Hyperactivity Disorder (ADHD) taking Abilify (aripiprazole) 5mg, Adderall (amphetamine and dextroamphetamine) 10mg Extended Release (XR), guanfacine 1mg, and Lamotrigine (lamotrigine) 25mg?

Management of Antipsychotic-Induced Weight Gain in Schizophrenia with ADHD

Add metformin 500 mg once daily, gradually titrating to 1000 mg twice daily, as this is the first-line pharmacological intervention recommended by the American Psychiatric Association to attenuate antipsychotic-associated weight gain. 1

Rationale for Metformin as First-Line Agent

Metformin is specifically recommended to be offered concomitantly with antipsychotics that have poor cardiometabolic profiles to attenuate potential weight gain 1. While aripiprazole (Abilify) generally demonstrates a lower risk for weight gain compared to other antipsychotics 2, individual patients can still experience significant weight gain, making metformin an appropriate intervention.

Key implementation details:

• Start with 500 mg once daily and gradually increase to 1000 mg twice daily as tolerated 1
• Use modified-release preparations when available to minimize gastrointestinal side effects 1
• Metformin achieves approximately 3% weight loss, with 25-50% of participants achieving at least 5% weight loss 1
• Doses greater than 1500 mg are associated with the greatest weight loss 1

Required Monitoring Before and During Metformin Therapy

Before initiating metformin:

• Assess renal function, as metformin should be avoided in patients with renal failure 1
• Obtain baseline BMI, waist circumference, blood pressure, HbA1c, glucose, and lipids 1

Ongoing monitoring:

• Annual liver function tests, HbA1c, renal function, and vitamin B12 levels 1
• Weekly BMI, waist circumference, and blood pressure checks for the first 6 weeks 1
• Repeat all baseline measurements after 3 months and annually thereafter 1

Alternative Considerations if Metformin Fails or Is Contraindicated

Switching antipsychotics: If metformin is ineffective after 3-6 months, consider switching from aripiprazole to lurasidone or ziprasidone, which are the most weight-neutral antipsychotics in the class 2, 1. However, this requires careful psychiatric evaluation to ensure symptom control is maintained.

GLP-1 receptor agonists: These may be considered for weight management, though current global shortages exist and insurance coverage is often restricted to FDA-approved diabetes indications 1. Medicare currently excludes coverage for obesity diagnosis alone, and these medications are costly 1.

Why Not Other Weight Loss Medications in This Case

Bupropion is contraindicated in this patient due to the schizophrenia diagnosis. While bupropion is the only antidepressant consistently shown to promote weight loss 2, 3, 4, it is activating and can exacerbate anxiety or be inappropriate for patients with bipolar disorder or psychotic disorders 2.

Phentermine/topiramate (Qsymia): While FDA-approved for chronic weight management 2, phentermine is a sympathomimetic that could potentially interact with Adderall (also a sympathomimetic) and may exacerbate anxiety or psychotic symptoms 2. Topiramate alone is associated with weight loss 2, but adding another medication when metformin is available as first-line is not warranted initially.

Orlistat: This could be considered as an alternative if metformin fails, particularly if the patient has constipation 2. It blocks absorption of approximately 30% of ingested fat 2, but gastrointestinal side effects (fecal urgency, oily stools) often limit tolerability 2.

Liraglutide (Saxenda): While effective for weight management 2, cost and insurance coverage issues make this a second- or third-line option 1.

Critical Medication Review

Current regimen assessment:

• Aripiprazole 5 mg: Lower risk for weight gain compared to olanzapine, clozapine, quetiapine, or risperidone 2
• Adderall 10 mg XR: Stimulants typically cause weight loss, not gain 5
• Guanfacine 1 mg: Weight-neutral 5
• Lamotrigine 25 mg: Considered weight-neutral 2

The weight gain is most likely attributable to aripiprazole, despite its relatively favorable profile, as individual responses vary 6, 7.

Implementation Algorithm

1. Initiate metformin 500 mg once daily with the evening meal to minimize GI side effects 1
2. After 1 week, increase to 500 mg twice daily if tolerated
3. After 2-4 weeks, increase to 1000 mg in the morning and 500 mg in the evening
4. After 4-6 weeks, increase to target dose of 1000 mg twice daily 1
5. Reassess at 12 weeks: If less than 3% weight loss achieved, consider increasing to 1500-2000 mg daily (if tolerated) or adding alternative interventions 1
6. Implement lifestyle modifications concurrently: Dietary counseling and physical activity promotion 1

Common Pitfalls to Avoid

• Do not abruptly start high-dose metformin, as this increases GI side effects and reduces adherence 1
• Do not forget renal function assessment, as metformin accumulation in renal impairment can cause lactic acidosis 1
• Do not discontinue metformin prematurely if mild GI symptoms occur; these typically resolve with continued use and modified-release formulations 1
• Do not switch antipsychotics without psychiatric consultation, as maintaining symptom control in schizophrenia is paramount for morbidity and mortality outcomes 2