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

2 Pharmacotherapy OF BEDTarget BE? Target Weight? Target Both? Target Comorbidity? Target All Three?

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

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5 Pharmacotherapy for Binge Eating DisorderClass 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

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

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

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

11 Anti-epileptic Medicationsand 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)

12 Prior Medications for ObesityPast Various Amphetamines Sibutramine Fenfluramine/phentermine (Fen/Phen) CB1 antagonists

13 Amphetamines Racemic amphetamine DextroamphetamineIntroduced 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

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

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

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

22 Phentermine + TopiramateSynergy for weight loss Lower doses can be used

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

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

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

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

27 Phentermine + TopiramateCognitive 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.

28 Bupropion + NaltrexoneAntidepressant 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

29 Bupropion + NaltrexoneSide-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 .

30 Lisdexamfetamine (LDX)Red Blood Cells

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33 LDX Side-effects Decreased appetite Headache Irritability InsomniaNot to be used with substance abuse history

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35 Questions/Comments?