What are the considerations for using GLP-1 (Glucagon-like peptide-1) medications in patients with mental health conditions, particularly eating disorders?

GLP-1 Medications in Psychiatric Practice: Essential Considerations

GLP-1 receptor agonists are safe and effective for weight management in patients with mental illness, showing beneficial effects on mental health without worsening psychiatric symptoms, but are absolutely contraindicated in patients with active anorexia nervosa or bulimia nervosa. 1

Absolute Contraindications in Eating Disorders

Naltrexone/bupropion combination is contraindicated in anorexia nervosa and bulimia nervosa 1, but the evidence regarding GLP-1 agonists specifically in active eating disorders requires careful consideration:

• Active anorexia nervosa and bulimia nervosa represent contraindications based on the mechanism of action (appetite suppression, delayed gastric emptying, nausea/vomiting) which could exacerbate restrictive eating patterns and purging behaviors 1, 2
• The 2023 APA Eating Disorders guideline emphasizes comprehensive assessment of weight control behaviors and compensatory mechanisms before any pharmacological intervention 1
• GLP-1 RAs may paradoxically benefit binge eating disorder (BED), as they reduce binge eating episodes and improve control over eating behaviors 3, 2, 4

Safety Profile in Mental Illness

GLP-1 receptor agonists demonstrate a favorable psychiatric safety profile across multiple mental health conditions:

Mental Health Outcomes

• No worsening of mental state, suicidality, or new-onset mental illness in systematic reviews of patients with pre-existing psychiatric disorders 5
• Beneficial effects on depression and anxiety symptoms reported in both patients with and without baseline mental illness 5, 3
• Improved quality of life and perceived control over eating behaviors, particularly relevant for patients with binge eating patterns 3
• No increased psychiatric admissions associated with GLP-1 RA use 5

Monitoring Requirements

Monitor for suicidal ideation and behavior as listed in FDA safety warnings for both liraglutide and semaglutide, though clinical evidence does not support increased risk 1

Specific Clinical Scenarios

Antipsychotic-Induced Weight Gain

Liraglutide and exenatide are recommended as augmentative agents for antipsychotic-induced metabolic dysfunction:

• Clozapine and olanzapine cause the most severe metabolic consequences (weight gain, hyperglycemia, dyslipidemia) 6
• Liraglutide and exenatide have moderate-quality evidence for reducing antipsychotic-induced weight gain and improving glycemic control 6
• Add to metformin therapy rather than using as monotherapy for antipsychotic-induced metabolic disorders 6
• Effects diminish after discontinuation: modest benefits persist at 1-year follow-up, requiring long-term metabolic monitoring 6

Binge Eating Disorder

GLP-1 receptor agonists show promise for BED treatment:

• Reduce binge eating frequency and improve eating control in qualitative studies 3, 4
• Mechanism aligns with reducing loss-of-control eating through appetite regulation and delayed gastric emptying 4
• Randomized controlled trials are needed to establish efficacy specifically for BED 2, 4

Depression and Anxiety

GLP-1 RAs can be used safely in patients with depression and anxiety:

• Liraglutide is noted as appropriate for patients requiring concomitant psychiatric medications 1
• No evidence of worsening depressive or anxiety symptoms 5
• Contrast with naltrexone/bupropion, which requires caution in severe depression and has safety data lacking in patients with depression 1

Practical Prescribing Algorithm

Step 1: Screen for Contraindications

• Absolute: Active anorexia nervosa, active bulimia nervosa, personal/family history of medullary thyroid carcinoma or MEN2, history of pancreatitis 1
• Relative: Unexplained weight loss in older adults with cognitive impairment 1

Step 2: Choose Agent Based on Clinical Profile

Semaglutide 2.4 mg weekly (first-line for most patients):

• Greatest weight loss efficacy: 14.9% vs 3.1% placebo 1
• Titrate every 4 weeks: 0.25 mg → 0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg 1
• Monitor hydration status due to nausea/vomiting risk 1

Liraglutide 3.0 mg daily (alternative):

• Weight loss: 8.0% vs placebo 1
• Titrate weekly by 0.6 mg increments 1
• FDA-approved for adolescents ≥12 years 1
• Preferred when weekly injections are not feasible 1

Step 3: Titration Strategy to Minimize GI Side Effects

• Slow titration is essential: GI side effects (nausea 31-44%, vomiting 12-25%, diarrhea 23-32%) are dose-dependent 1
• Behavioral modifications: Reduce portion sizes, increase fiber intake to mitigate symptoms 1
• If patient tolerates current dose and loses ≥1 lb/week, consider maintaining dose rather than escalating 1

Step 4: Monitoring Protocol

Baseline:

• Weight, BMI, waist circumference 1
• Fasting glucose, HbA1c (if diabetic or prediabetic) 1
• Mental health screening using validated tools 1
• Pregnancy test for women of reproductive age (GLP-1 RAs contraindicated in pregnancy) 1

Ongoing:

• Hydration status if nausea/vomiting present 1
• Signs/symptoms of pancreatitis or gallbladder disease 1
• Hypoglycemia risk if patient takes insulin or sulfonylureas—dose reduction of these agents required 1
• Mental health status: suicidal ideation, mood changes, eating behaviors 1
• Contraception effectiveness: GLP-1 RAs delay gastric emptying and may reduce oral contraceptive absorption—add barrier method for 4 weeks after initiation and each dose increase 1

Step 5: Efficacy Assessment

Discontinue if inadequate response:

• Liraglutide: <4% weight loss at 16 weeks 1
• Semaglutide: Apply similar threshold of <5% weight loss at 12-16 weeks (extrapolated from other agents) 1

Common Pitfalls to Avoid

Do not prescribe GLP-1 RAs for weight loss in patients with active restrictive eating disorders (anorexia nervosa, atypical anorexia) or active purging behaviors (bulimia nervosa)—the appetite suppression and GI side effects will worsen these conditions 1, 2

Do not assume psychiatric medications preclude GLP-1 RA use—these agents are safe with most psychotropics and may counteract metabolic side effects 5, 6

Do not forget to reduce insulin/sulfonylurea doses when initiating GLP-1 RAs to prevent hypoglycemia 1

Do not overlook the need for enhanced contraception counseling—delayed gastric emptying reduces oral contraceptive reliability 1

Do not discontinue abruptly if patient achieves weight loss—metabolic benefits diminish after discontinuation, requiring long-term treatment 6

Special Populations

Older Adults

• Use caution with GLP-1 RAs in older adults with unexplained weight loss, anorexia, or inconsistent eating patterns due to GI side effects 1
• Volume depletion risk may be higher in older adults 1

Patients on Chronic Opioids

• GLP-1 RAs are safe; naltrexone/bupropion is contraindicated with chronic opioid use 1

Emerging Evidence

GLP-1 receptor agonists may have direct psychotropic effects beyond metabolic benefits, with potential efficacy for treating mental illness itself—this requires further investigation in dedicated psychiatric trials 5, 2

Longer-term RCTs are needed to establish durability of mental health benefits and optimal treatment duration in psychiatric populations 5, 6