What could be causing excessive hunger in an adult patient with a history of psychiatric illness taking 400mg of lamotrigine, 1200mg of lithium ER, and 40mg of Latuda (lurasidone)?

Excessive Hunger in a Patient on Lamotrigine, Lithium, and Latuda

Primary Culprit: Latuda (Lurasidone)

Latuda (lurasidone) at 40mg is the most likely cause of your patient's excessive hunger, as atypical antipsychotics like lurasidone promote weight gain through antagonism of serotonin and histamine receptors, which directly stimulates appetite and carbohydrate craving. 1, 2

Mechanism of Antipsychotic-Induced Hunger

• Atypical antipsychotics block serotonin receptors and histamine-mediated neurotransmission, which are the primary mechanisms driving increased appetite and carbohydrate hunger 1, 2
• Compounds that antagonize or downregulate serotonin receptors are significantly more likely to stimulate carbohydrate hunger and promote weight gain 1
• Weight gain from antipsychotics is a substantial disadvantage that poses health risks and frequently causes patients to discontinue therapy prematurely 1, 2

Contributory Factor: Lithium

• Lithium is among the psychotropic medications most likely to produce weight gain and appetite stimulation 1
• Even at low doses (your patient is on 1200mg ER), lithium contributes to weight gain, though one study found no significant difference in weight gain between lithium and lamotrigine over 6 months 3
• The weight-promoting effects of lithium occur independently of dose, affecting patients on both low and standard dosing regimens 3

Non-Contributory: Lamotrigine

• Lamotrigine at 400mg does not appear to cause weight gain or appetite stimulation 4
• In maintenance studies, lamotrigine was generally well tolerated without bodyweight gain as a side effect 4
• Lamotrigine is weight-neutral and does not contribute to the patient's hunger complaints 4

Management Algorithm

Step 1: Confirm the Diagnosis

• Rule out metabolic causes: Check fasting glucose, HbA1c, and thyroid function (TSH), as lithium can induce hypothyroidism rapidly (average 32 days), which may contribute to appetite changes 3
• Assess for diabetes mellitus, as antipsychotics can disturb glucose metabolism 2

Step 2: Optimize Current Regimen

• Reduce polypharmacy if possible, as combining multiple weight-promoting medications (lithium + lurasidone) compounds the appetite stimulation effect 2
• Consider whether the Latuda dose can be reduced while maintaining psychiatric stability, as lower doses may produce less appetite stimulation 2

Step 3: Consider Medication Substitution

• If psychiatric stability allows, consider switching from Latuda to an antipsychotic with lower weight gain liability 2
• The choice of antipsychotic significantly affects weight gain risk, and appropriate selection can reduce these disadvantages 2

Step 4: Non-Pharmacological Interventions

• Implement regular weight monitoring to track the progression of weight gain 2
• Enroll the patient in a structured dieting program, which can reduce the disadvantages associated with antipsychotic-induced weight gain 2
• Dietary counseling should focus on managing carbohydrate cravings, which are specifically stimulated by serotonin receptor antagonism 1

Critical Caveat

• Do not abruptly discontinue any of these medications, as this poses significant risks for psychiatric decompensation 4, 5
• Any medication adjustments must be made gradually and with close psychiatric monitoring 4
• The combination of lithium and lamotrigine is commonly used in bipolar disorder management, and both were recommended frequently (26% and 35% respectively) in collaborative care settings 3