Drugs That Cause Weight Gain

More than one-third of American adults are obese,[1] a condition that is associated with an increased risk of death along with a number of chronic diseases, including hypertension, high blood fat levels, type 2 diabetes, coronary heart disease, stroke, gallbladder disease, sleep apnea, respiratory problems and certain types of cancer.[2]

Harmful lifestyle habits, such as a lack of physical activity and unhealthy eating patterns, increase the risk of obesity. In addition, weight gain is an adverse event associated with many widely used medications and may lead to significant overweight and obesity, especially in susceptible individuals.[3]

These medications can induce weight gain through a variety of mechanisms.[4] Some increase body fat by stimulating appetite, slowing down the body metabolism or affecting how the body absorbs and stores glucose, leading to fat deposition in certain body areas. Other medications cause water retention, which adds weight but not necessarily fat. Medications also can cause shortness of breath and fatigue, making exercise difficult.

You can protect yourself and your loved ones from this risky adverse event by learning about some of the common drugs that are known to result in weight gain.

Antidepressants

Tricyclic antidepressants, such as amitriptyline (available in generic only) and doxepin (SILENOR), frequently cause weight gain, especially during the first months of treatment.[5] Certain monoamine oxidase inhibitors used for depression, such as phenelzine (NARDIL), also may cause weight gain.[6]

Weight gain has been reported with some, but not all, selective serotonin reuptake inhibitors. For example, paroxetine (PAXIL, PEXEVA) is associated with significant weight gain[7] in up to a quarter of patients,[8] whereas fluoxetine (PROZAC, SELFEMRA)[9] and sertraline (ZOLOFT)[10] have been linked to weight loss in adults and decreased rates of weight gain in children.

Antiepileptics and mood stabilizers

Certain antiepileptics (anti-seizure medications) cause significant weight gain, but others are weight-neutral or even induce weight loss. For example, carbamazepine (CARBATROL, EPITOL, EQUETRO, TEGRETOL, TERIL), divalproex (DEPAKOTE), gabapentin (NEURONTIN), pregabalin (LYRICA) and valproic acid (DEPAKENE) are commonly associated with weight gain.[11] However, lamotrigine (LAMICTAL) and phenytoin (DILANTIN, PHENYTEK) do not appear to affect weight. In contrast, felbamate (FELBATOL), topiramate (QUDEXY XR, TOPAMAX, TROKENDI XR) and zonisamide (ZONEGRAN) can cause weight loss.

Weight gain is a widespread adverse event among patients taking lithium (LITHOBID),[12] a mood stabilizer used as a maintenance medication for bipolar disorder. Studies show that threequarters of lithium users gain nine pounds on average during the first two years of therapy. Other evidence shows that lithium treatment can cause weight gain of up to 26 pounds.[13]

Antipsychotics

Antipsychotic therapy is strongly associated with weight gain and obesity: Up to half of patients receiving longterm drug therapy for schizophrenia experience significant weight gain.[14] Conventional (typical) antipsychotics, such as chlorpromazine (available in generic only) and haloperidol (HALDOL), cause mild-to-moderate weight gain.[15]

Weight gain is a more common feature of atypical (second-generation) antipsychotics, which account for the majority of the antipsychotics currently used, but there is a marked variability in the weight-gain profiles of these drugs.[16] For example, clozapine (CLOZARIL, FAZACLO) and olanzapine (SYMBAX, ZYPREXA) have the greatest weight-gain risk. Quetiapine (SEROQUEL) and risperidone (RISPERDAL) are associated with mild-to-moderate weight gain, whereas iloperidone (FANAPT) and aripiprazole (ABILIFY, ARISTADA) have minimal effects on weight.

Diabetes drugs

It is well established that insulin therapy frequently causes weight gain,[17] especially during intensive treatment.[18] Similarly, glucose-lowering sulfonylureas, such as glipizide (GLUCOTROL) and tolbutamide (available in generic only), carry a risk of weight gain.[19] Conversely, metformin (FORTAMET, GLUCOPHAGE, GLUMETZA) does not induce significant weight gain with either short-term or long-term use.[20],[21]

Female sex hormones and related drugs

Long-term treatment with injected progestins commonly used for contraception, such as medroxyprogesterone (DEPO-PROVERA, DEPO-SUBQ PROVERA), is associated with weight gain.[22] Similarly, weight gain has been reported in women treated with etonogestrel implants (NEXPLANON).[23]

However, combined progestin and estrogen oral contraceptives, such as drospirenone and ethinyl estradiol (YASMIN) and norgestimate and ethinyl estradiol (ORTHO TRI-CYCLEN), can cause either weight gain or weight loss.[24] High-dose estrogen has been linked to weight gain.

Steroids

Chronic use of glucocorticoids, often used to treat chronic inflammatory diseases (such as rheumatoid arthritis and inflammatory bowel disease), causes weight gain.[25] Examples of oral corticosteroids include hydrocortisone (CORTEF), methylprednisolone (DEPO-MEDROL, MEDROL) and prednisone (RAYOS).

The extent of weight gain in patients taking these drugs depends on the average dose and the duration of treatment. Short-term therapy limited to 1 to 2 weeks, such as the type used to treat a sudden allergic reaction, rarely leads to weight gain, even when taken in high doses. In contrast, longterm, low-dose therapy frequently causes weight gain and obesity. Therefore, the prevailing principle to minimize weight gain caused by steroids is to use them in the lowest effective dose for the shortest time possible.

Other drugs

Several studies have showed that patients treated with antihistamines commonly used for allergies, such as cyproheptadine (available in generic only) and diphenhydramine (available in generic only), are associated with weight gain.[26],[27]

Some blood pressure medications can cause weight gain, including the beta-blockers, especially propranolol (HEMANGEOL, INDERAL, INNOPRAN XL),[28] and certain calcium channel blockers, such as nisoldipine (SULAR).

What You Can Do

Ask your doctor about the potential for weight gain before you start taking a new medication. If possible, avoid taking any medication that is known to cause significant weight gain, especially if you are overweight or obese and there is an equally effective alternative.

Consult your doctor if you suspect that a medication that you are currently taking is causing you to gain weight. In many cases, your doctor will be able to switch you to another medication that treats your condition but does not cause weight gain.

If your doctor determines that the benefit of the medication outweighs the risk of weight gain, then you should monitor your weight and make lifestyle and dietary changes to offset the risk of obesity. Do not stop taking any of your medications without first talking with your doctor because stopping a medication suddenly can result in potentially serious complications.

References

[1] Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of Obesity Among Adults and Youth: United States, 2011–2014. NCHS data brief, no 219. Hyattsville, MD: National Center for Health Statistics; 2015. https://www.cdc.gov/nchs/data/databriefs/db219.pdf. Accessed October 5, 2017.

[2] National Heart, Lung, and Blood Institute. Managing overweight and obesity in adults: Systematic evidence review from the Obesity Expert Panel. 2013. https://www.nhlbi.nih.gov/sites/www.nhlbi.nih.gov/files/obesity-evidence-review.pdf. Accessed October 5, 2017.

[3] Verhaegen AA, Van Gaal LF. Drug-induced obesity and its metabolic consequences: a review with a focus on mechanisms and possible therapeutic options. J Endocrinol Invest. 2017 Jun 28. doi:10.1007/s40618-017-0719-6.

[4] Kyle T, Kuehl B. Prescription medications & weight gain – What you need to know. June 25, 2013. https://issuu.com/oacywm/docs/prescription_medications. Accessed October 5, 2017.

[5] Drug-induced weight gain. Prescrire Int. 2012;41(123):11-14.

[6] GAVIS Pharmaceuticals, LLC. Label: phenelzine. December 2010. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=40483372-448f-4284-976c-8462ef256661&type=pdf&name=40483372-448f-4284-976c-8462ef256661. Accessed October 5, 2017.

[7] Verhaegen AA, Van Gaal LF. Drug-induced obesity and its metabolic consequences: a review with a focus on mechanisms and possible therapeutic options. J Endocrinol Invest. 2017;Jun 28. doi:10.1007/s40618-017-0719-6.

[8] Hsieh A, Sweeting A, Suryawanshi A, Caterson ID. Drugs that cause weight gain and clinical alternatives to their use. In: Bray GA, Bouchard C, eds. Handbook of Obesity - Volume 2: Clinical Applications. 4th ed. Boca Raton, FL: CRC Press; 2014:219-232.

[9] Eli Lilly. Label: fluoxetine (PROZAC). March 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018936s103,021235s023lbl.pdf. Accessed October 5, 2017.

[10] Pfizer. Label: sertraline (ZOLOFT). June 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019839s088,020990s046lbl.pdf. Accessed October 5, 2017.

[11] Hsieh A, Sweeting A, Suryawanshi A, Caterson ID. Drugs that cause weight gain and clinical alternatives to their use. In: Bray GA, Bouchard C, eds. Handbook of Obesity - Volume 2: Clinical Applications. 4th ed. Boca Raton, FL: CRC Press; 2014:219-232.

[12] Drug-induced weight gain. Prescrire Int. 2012;41(123):11-14.

[13] Torrent C, Amann B, Sánchez-Moreno J, et al. Weight gain in bipolar disorder: pharmacological treatment as a contributing factor. Acta Psychiatr Scand. 2008;118(1):4-18.

[14] Baptista T. Body weight gain induced by antipsychotic drugs: mechanisms and management. Acta Psychiatr Scand. 1999;100(1):3-16.

[15] Hsieh A, Sweeting A, Suryawanshi A, Caterson ID. Drugs that cause weight gain and clinical alternatives to their use. In: Bray GA, Bouchard C, eds. Handbook of Obesity - Volume 2: Clinical Applications. 4th ed. Boca Raton, FL: CRC Press; 2014:219-232.

[16] Ibid.

[17] Ibid.

[18] Carlson MG, Campbell PJ. Intensive insulin therapy and weight gain in IDDM. Diabetes. 1993;42(12):1700-1707.

[19] Drug-induced weight gain. Prescrire Int. 2012;41(123):11-14.

[20] DeFronzo R, Goodman A. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med. 1995;333(9):541-549.

[21] UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854-865.

[22] Drug-induced weight gain. Prescrire Int. 2012;41(123):11-14.

[23] Organon USA. Label: etonogestrel implant (IMPLANON). May 2017. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=50ed7e31-b9b7-4f0a-8e36-91ed5af86b81&type=pdf&name=50ed7e31-b9b7-4f0a-8e36-91ed5af86b81.Accessed October 6, 2017.

[24] Drug-induced weight gain. Prescrire Int. 2012;41(123):11-14.

[25] Hsieh A, Sweeting A, Suryawanshi A, Caterson ID. Drugs that cause weight gain and clinical alternatives to their use. In: Bray GA, Bouchard C, eds. Handbook of Obesity - Volume 2: Clinical Applications. 4th ed. Boca Raton, FL: CRC Press; 2014:219-232.

[26] Ibid.

[27] Hasnain M, Vieweg WV. Weight considerations in psychotropic drug prescribing and switching. Postgr Med. 2013;125(5):117-129.

[28] Cheskin LJ, Bartlett SJ, Zayas R, et al. Prescription medications: A modifiable contributor to obesity. South Med J. 1999;92(9):898-904.