Are you helping or hindering?
Avoiding the use of weight-gaining meds and mitigating their effects.
I will always look back with regret on the young female whose rapid weight gain I contributed to in my first year of practice. She was 20 years old and came in with complaints of overwhelming anxiety that had been worsening over the past 2 years since starting college. Believing it to be more weight neutral than Celexa, I started her on Lexapro. When I saw her back 1 month later to follow up on her anxiety symptoms, she reported her mood was well controlled but that she had gained 5lbs in the 4 weeks she had been on the medication. She was 5’ 1” and hadn’t had any significant change in weight in the last 4-5 years. I reassured her that Lexapro tended to be weight neutral, and she just needed to track her intake and exercise and recommended My Fitness Pal (all the rage at the time). One month later and had gained an additional 5lbs, despite monitoring her intake and exercise. She wanted to stop the medication. Her mood was well controlled, so I didn’t want to disrupt something that was working. At the time, I truly believed that she must have been eating more or exercising less than she was reporting. Thankfully she insisted that I switch the medication. We changed to Zoloft which did just as well for her mood. It took her almost 6 months to get back to her initial weight. Here are some suggestions to consider when starting a potentially obesogenic medication:
1. Choose an alternate medication. Certainly not every patient is going to gain weight simply because it's a potential side effect; however, in patients who are already struggling with their weight these medications are worth avoiding if possible. If there is a weight neutral option, take the time to think it through and even discuss with the patient whether the pros of the obesogenic medication outweighs the risks of weight gain. Stopping the medication after weight gain does NOT just make their weight go back to what it was, so take this potential side effect seriously. Also realize that weight gain for many medications can continue for several years while they are on it, not just the first few weeks or months.
2. Always advise the patient of the potential for weight gain and encourage them to monitor their weight at least weekly at home.
3. Plan for close follow up. If it’s a med that can cause rapid weight gain like gabapentin, have a 2 week follow up. Otherwise, I typically follow up in 1 month and I am quick to blame any weight gain on the medication.
4. Medications like beta blockers can cause a slow continuous gain, so again keeping this in mind as you schedule follow up appointments. Particularly if a patient’s weight has been stable over the last 6 months, if they start gaining even small amounts of weight after starting the potentially obesogenic medication, it is likely the medication.
Below are the most common obesogenic medications along with weight neutral (usually) alternatives.
Diabetes Medications
Obesogenic | Weight Neutral | Weight Negative |
Insulin (short >>long) | DPP-4 Inhibitors | GIP/GLP-1 RA |
Thiazolidinediones | Metformin | GLP-1 RA |
Sulfonylureas | Alpha-glucosidase Inhibitor | Pramlintide |
Meglitinides | | |
Risk factors for increased weight gain: age <65, smoker, Caucasian, baseline A1c >7.2%
Hormonal Contraceptives
Obesogenic | Weight Neutral |
Progestin-only (avg. ~2kg over 6-12 mo) | Mixed Oral Contraceptives |
Injectable progestin-only (avg. 6.2kg over 5 years) | Contraceptive Patches |
Antidepressants
Medication Class | Impact on Weight | Notes |
TCAs | +++ | Amitriptyline is the worst Nortriptyline has least impact |
SSRIs | +/++ | Paroxetine worst, then citalopram. Sertraline effective for Night Eating Syndrome. Novel SSRIs generally no impact |
SNRIs | Typically neutral | Duloxetine most likely to have weight gain |
Mirtazapine | +++ | |
Bupropion | Neutral/- | Good choice for Emotional Eating |
Trazodone | + | Suvorexant, Eszopiclone good alternatives for sleep |
Those with >3% weight gain in the first month at high risk for long-term weight gain.
Antipsychotics
Risk of Weight Gain | Medications |
Low (avg. over 1 year ~1kg) | Lumateperone - may have weight loss Lurasidone Aripiprazole Ziprasidone Brexpiprazole |
Moderate (avg. over 1 year of 1-5kg) | Amisulpride Asenapine Pallperidone. Quetipine Risperdone Lithium |
High (avg. over 1 year >5kg) | Clozapine ++ Olanzapine ++ Chlorpromazine Iloperadone |
Antipsychotic weight gain can be mitigated by metformin
Anticonvulsants
Medication | Weight Effects | Notes |
Valproic Acid Divalproex | + | Greater impact in those with elevated BMI at baseline. Weight gain seen in both adults and children. |
Carbamazepine Pregabalin | + | Pregabalin much less likely than gabapentin |
Gabapentin | ++ | Worse with higher dosing |
Lamotrigine Levetiracetam Phenytoin | Neutral | |
Topiramate Zonisamide | - | Topiramate effective for Binge Eating Disorder |
Antihistamines
Medications | Weight Effect |
1st generation - diphenhydramine, doxylamine, hydroxyzine, meclizine, promethazine | +/++ |
2nd generation - cetirizine, levocetirizine, loratadine, desloratadine, fexofenadine | +/neutral |
Loratadine has lowest risk of weight gain. Consider nasal steroid and allergen avoidance when possible.
Beta-Blockers
Obesogenic | Weight Neutral |
Metoprolol | Bisoprolol |
Atenolol | Sotalol |
Propranolol | Nebivolol |
| Labetalol |
Calcium Channel Blockers
Obesogenic | Weight Neutral |
Amlodipine | Diltiazem |
Felodipine | Verapamil |
Other medications that can be obesogenic: Tamoxifen, Cyclophosphamide, Methotrexate, 5-fluorouracil, aromatase inhibitors, Corticosteroids
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