Atomoxetine in Melanocortin Obesity Syndrome

Prior treatment

• Use of atomoxetine, viloxazine (another selective norepinephrine-reuptake inhibitor), methylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, phentermine, or any other stimulant medication in the past 30 days. If on other ADHD medications, such as guanfacine and clonidine, must be on a stable dose for \>3 months.
• Initiation of new weight loss program, including diet or medications. If on weight loss medications, must be on a stable dose for \>3 months.
• Current use of monoamine oxidase inhibitors

Other illness

• History of hypersensitivity to atomoxetine.
• History of pheochromocytoma.
• Uncontrolled Stage 2 hypertension (≥95th percentile + 12 mmHg or \>140/90, whichever is lower) at screening. If on antihypertensive medication, must be on stable dose for \>3 months.
• History of a cardiac arrhythmia (not including bradycardia)
• History of Major Depressive Disorder in the past 2 years, lifetime history of suicide attempt, history of any suicidal behavior in the past month, history of other severe psychiatric disorders (e.g. schizophrenia, bipolar disorder)

Lab values

• Hepatic insufficiency including cirrhosis and acute hepatitis (AST or ALT \>3x upper limit of normal)

Other

• Weight loss \>5% in the past 3 months.
• Inability to swallow capsules.
• Narrow angle glaucoma.
• Uncontrolled asthma requiring albuterol more than once weekly over the past 3 months
• Pregnancy or intention to become pregnant during the next year
• PHQ-9 score is ≥15 or suicidal ideation of type 4 or 5 (C-SSR) in the past month
• Unable to comply with study procedures in the opinion of the investigator

• Age 6 years and above
• Documented MC4R variant classified as pathogenic, likely pathogenic, or variant of uncertain significance per ACMG criteria. If testing was done in a research lab, it will be confirmed by a CLIA-approved lab prior to randomization.
• Obesity defined as BMI ≥30 kg/m2 in adults or ≥95th percentile for age and sex in children