Binge Eating Disorder: 3. Pharmacotherapy James E Mitchell, M.D. Feel free to re-title and remove Penn specific stuff

Pharmacotherapy OF BED Target BE? Target Weight? Target Both? Target Comorbidity? Target All Three?

Disclosure: I was a paid consultant to the pharmaceutical firm that makes LDX in 2016

Pharmacotherapy for Binge Eating Disorder Class Drug Tricyclics eg. Imipramine SSRIs eg. Citalopram SNRIs/NRIs eg. Atomoxetine Lipase Inhibitor Orlistat Amphetamine Pro-drug Lisdexamfetamine Anti-Epileptics eg. Topiramate Other Classes eg. Na Oxybate Combinations eg. Topiramate + Phentermine

Class Drug Effect on Binge Eating Effect on Weight Tricyclics Imipramine ++ +/- Desipramine SSRIs Citalopram Escitaloprm Fluvoxamine Sertraline Fluoxetine SNRIs/NRIs Atomoxetine + Venlafaxine Duloxetine

Decreased Fat Absorption: An Inventive Vocabulary Oily spotting Flatus with discharge Fecal urgency Fatty/oily stool Oily evacuation Increased defecation Fecal incontinence Diarrhea

Fat-Soluble Vitamins and Carotenoids Vitamin A Vitamin D Vitamin E Vitamin K (prothrombin time) Beta-carotene

Anti-epileptic Medications and Lisdexamfetamine Medication Effect on Binge Eating Effect on Weight Topiramate ++ Zonisamide Lisdexamfetamine* (*Only FDA approved agent: Indicated for the treatment of Moderate to Severe Binge Eating Disorder (BED) in adults)

Prior Medications for Obesity Past Various Amphetamines Sibutramine Fenfluramine/phentermine (Fen/Phen) CB1 antagonists

Amphetamines Racemic amphetamine Dextroamphetamine Introduced in the treatment of narcolepsy by Prinzmetal and Bloomberg in 1935 Dextroamphetamine Introduced for calming hyperexcitable-hyperactive children, by Bradley, in 1937 Also tried in the treatment of depression, but with little success

Class Effect on Binge Eating Effect on Weight Drug Effect on Binge Eating Effect on Weight Other Classes Na Oxybate Inadequate Data Baclofen Lamotrigine Acamprosate

Drugs/Combinations with Weight Loss Effects in BED Topiramate (+ Phentermine or Bupropion) Zonisamide (+ Phentermine or Bupropion) Bupropion (+ Naltrexone) Lisdexamfetamine

Drugs/Combinations for Weight Loss in BED with DM Topiramate (+ Phentermine or Bupropion) Zonisamide (+ Phentermine or Bupropion) Bupropion (+ Naltrexone) Lisdexamfetamine Metformin Incretin (GLP-1) Mimetics DPP-4 Inhibitors (+/-)

Phentermine + Topiramate Synergy for weight loss Lower doses can be used

Phentermine + Topiramate Anorexigenic agent 52 year history of use Most widely prescribed weight loss drug in U.S. Topiramate Anticonvulsant agent

Phentermine +Topiramate Mechanism of Action Phentermine Sympathomimetic amine Topiramate Block neuronal voltage-dependent Na+ channels Antagonize AMPA/kainite glutamate receptors Enhance GABA-A activity

Phentermine + Topiramate Mechanism of weight loss Phentermine appetite reduction Topiramate increased satiety increased energy expenditure

Phentermine + Topiramate Common adverse events in clinical trials Paresthesia Dry mouth Constipation Upper respiratory tract infection Nasopharyngitis Headache

Phentermine + Topiramate Cognitive side effects Disturbance in attention/memory/word finding Poor insight into problem Minimize if start Topiramate at 25 mg, increase by 25 mg/week, maximum 200 mg Cognitive disturbances resolves after drug discontinuation.

Bupropion + Naltrexone Antidepressant with Weight loss effects NE and DA reuptake inhibition Mechanism of decreased appetite involves POMC effects Naltexone Long acting narcotic antagonist Opioid blockade enhances effects at POMC

Bupropion + Naltrexone Side-effects seizure activity dry mouth, nausea headache, dizziness, ringing in ears vision changes sore throat muscle pain nausea, vomiting stomach pain or cramping. nervousness irritability .

Lisdexamfetamine (LDX) Red Blood Cells

LDX Side-effects Decreased appetite Headache Irritability Insomnia Not to be used with substance abuse history

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