Several prescription medications are proven to increase body weight, and a handful of over-the-counter supplements can help under the right circumstances. The options range from appetite stimulants like megestrol acetate and cyproheptadine, to anabolic hormones like oxandrolone and testosterone, to antidepressants prescribed off-label partly because weight gain is a reliable side effect. Which pill makes sense depends heavily on why you need to gain weight in the first place, because the kind of weight each medication adds and the risks it carries differ considerably.
Prescription Appetite Stimulants
If your main barrier to gaining weight is that you simply cannot eat enough, appetite stimulants are the most direct pharmaceutical approach. Three have the strongest evidence behind them.
Megestrol Acetate
Megestrol acetate (brand name Megace) is a synthetic progestational hormone originally developed for hormone-sensitive cancers. It was approved by the FDA in 1993 specifically for treating anorexia, cachexia, and unexplained weight loss in people with AIDS, and it remains one of the most-studied weight-gain medications available. A Cochrane systematic review found that megestrol improved both appetite and body weight compared to placebo across cancer, AIDS, and other conditions causing wasting.1PubMed Central. Megestrol acetate for treatment of anorexia‐cachexia syndrome In one controlled cancer trial, about 16% of patients on megestrol gained 15 pounds or more, compared to just 2% on placebo.2Journal of the National Cancer Institute. Controlled Trial of Megestrol Acetate for the Treatment of Cancer Anorexia and Cachexia
The weight gain from megestrol includes both fat and lean tissue, and appetite improvements tend to show up within the first month of treatment.3PubMed. Megestrol acetate therapy for anorexia and weight loss in children with malignant solid tumours The downsides are real, though. Because it is a progestational hormone, megestrol raises the risk of blood clots. One study of nursing home residents on the drug found that roughly a third developed deep vein thrombosis, including some who were ambulatory and had no other clotting risk factors.4PubMed. Deep vein thrombosis as a complication of megestrol acetate therapy among nursing home residents Other potential side effects include adrenal suppression and fluid retention. This is not a casual weight-gain pill; it is reserved for people dealing with serious illness-related wasting.
Dronabinol
Dronabinol (Marinol) is a synthetic form of THC, the main psychoactive compound in cannabis. It works on cannabinoid receptors in the brain’s appetite and nausea control centers, and it is FDA-approved for treating anorexia associated with weight loss in adults with HIV/AIDS.5PubMed Central. Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer In a placebo-controlled trial, patients taking dronabinol reported a 38% improvement in appetite versus 8% for placebo, and about 22% of the dronabinol group gained at least two kilograms, compared to about 11% on placebo.6Journal of Pain and Symptom Management. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS
A meta-analysis of cannabinoids in palliative care confirmed that dronabinol outperformed placebo for both weight gain and appetite in people with HIV.7PubMed Central. Systematic review and meta-analysis of cannabinoids in palliative medicine The most common side effects are euphoria, dizziness, and difficulty concentrating. Dronabinol tends to stabilize weight rather than produce dramatic gains, which makes it better suited for preventing further loss than for putting on a lot of new mass.
Cyproheptadine
Cyproheptadine (Periactin) is an older antihistamine that also blocks serotonin receptors, and its appetite-stimulating effect has been used clinically for decades. A systematic review looking across multiple populations found that cyproheptadine led to significant weight gain in the majority of studies examined, and it was generally well tolerated.8PubMed. Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review A randomized, double-blind trial in adults with poor appetite found statistically significant improvements in both appetite scores and body weight compared to placebo.9PubMed. Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study
In children with cancer-related cachexia, cyproheptadine produced an average weight gain of about 2.6 kilograms, with drowsiness being the most commonly reported side effect.10PubMed Central. The effect of cyproheptadine hydrochloride (periactin) and megestrol acetate (megace) on weight in children with cancer/treatment-related cachexia Cyproheptadine is one of the more accessible prescription appetite stimulants because it is inexpensive, available as a generic, and has a milder side-effect profile than megestrol. The main complaint is sedation, which usually eases after the first week or two.
Anabolic and Hormonal Medications
When the goal is lean mass rather than just overall body weight, anabolic agents work differently from appetite stimulants. Instead of making you hungrier, they shift your body’s metabolism toward building and retaining muscle tissue.
Oxandrolone
Oxandrolone (Anavar) is a mild anabolic steroid most commonly prescribed for people recovering from severe burns, major surgery, or chronic infections that cause muscle wasting. A systematic review and meta-analysis of burn patients found that oxandrolone treatment produced an additional gain in lean body mass of about 4% after six months and nearly 11% after twelve months.11PubMed. The efficacy and safety of oxandrolone treatment for patients with severe burns: A systematic review and meta-analysis In another burn study, patients receiving oxandrolone along with extra protein gained weight at a significantly faster rate than those receiving protein alone or standard care.12PubMed. Oxandrolone, an anabolic steroid, significantly increases the rate of weight gain in the recovery phase after major burns
Research in children with severe burns also showed improved lean body mass with oxandrolone, especially when combined with an exercise program.13PubMed Central. The effects of oxandrolone and exercise on muscle mass and function in children with severe burns Oxandrolone is considered one of the milder anabolic steroids in terms of androgenic side effects, but it can still affect liver function, cholesterol levels, and hormonal balance. It is a controlled substance and is only appropriate under medical supervision for specific clinical conditions.
Testosterone Replacement Therapy
For men with clinically low testosterone (hypogonadism), replacement therapy reliably adds lean mass. In one study of hypogonadal men, fat-free mass increased by an average of 5 kilograms over the treatment period, and muscle cross-sectional area in both the arms and legs grew significantly.14The Journal of Clinical Endocrinology & Metabolism. Testosterone Replacement Increases Fat-Free Mass and Muscle Size in Hypogonadal Men Another study found that fat-free mass increased by an average of 15% and muscle mass by 20%, with the gains driven by a measurable increase in the rate at which muscle proteins were being built.15The Journal of Clinical Endocrinology & Metabolism. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men–a clinical research center study
The key qualifier here is “replacement.” These studies involved men whose testosterone levels were genuinely below normal. Testosterone therapy in men with already-normal levels carries a different risk-benefit calculus, including potential cardiovascular effects, fertility suppression, and prostate concerns. The gains described above are what happens when a deficient system is brought back to its intended operating range, not what happens when someone with normal hormones takes extra.
Off-Label Medications Known to Cause Weight Gain
Some medications prescribed primarily for depression or psychotic disorders reliably cause weight gain as a side effect. Doctors sometimes use this to their advantage when a patient needs both mood treatment and weight restoration, but these drugs are not typically prescribed for weight gain alone.
Mirtazapine
Mirtazapine (Remeron) is an antidepressant with a well-known tendency to increase appetite. It appears to work partly by shifting the body’s fuel preference toward carbohydrates and increasing hunger, particularly cravings for sweets. A study in healthy men found that mirtazapine raised hunger levels, boosted appetite for sweet foods, and increased insulin release after meals.16PubMed Central. Effect of mirtazapine on metabolism and energy substrate partitioning in healthy men In clinical practice, mirtazapine is sometimes chosen for older adults or cancer patients who are underweight and also dealing with depression, insomnia, or nausea, since it can address all of these at once. Drowsiness and increased appetite are its most common side effects, which in the context of someone who needs to eat more and sleep better can actually be welcome.
Olanzapine
Olanzapine (Zyprexa) is an atypical antipsychotic primarily used for schizophrenia and bipolar disorder, and it is one of the most weight-promoting medications in all of psychiatry. Research in first-episode schizophrenia patients found that increased appetite accounted for about two-thirds of olanzapine-induced weight gain.17PubMed Central. Increased Appetite Plays a Key Role in Olanzapine-Induced Weight Gain in First-Episode Schizophrenia Patients The mechanism involves blocking serotonin 2C receptors in the brain, which normally help regulate satiety. When those receptors are blocked, the brake on eating is loosened.18PubMed Central. The atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2C
Some oncologists have begun prescribing low-dose olanzapine to cancer patients specifically to counteract chemotherapy-related nausea and weight loss. But olanzapine also raises the risk of metabolic problems including blood sugar and lipid abnormalities, so its use purely for weight gain demands careful monitoring.19PLoS ONE. Alterations to Melanocortinergic, GABAergic and Cannabinoid Neurotransmission Associated with Olanzapine-Induced Weight Gain
Tricyclic Antidepressants
Older tricyclic antidepressants, especially amitriptyline, are associated with dose- and time-dependent weight gain. Short-term use of amitriptyline has been linked to gains of roughly 1.5 kilograms, and the weight tends to keep climbing over months of continued use.20PubMed Central. Impact of Antidepressants on Weight Gain: Underlying Mechanisms and Mitigation Strategies Animal research suggests this partly happens through increased food intake driven by changes in pharyngeal pumping and metabolic signaling.21Scientific Reports. Amitriptyline increases food intake via prdx-2 without altering other physiological parameters in C. elegans under a modified bacterial diet Tricyclics carry a heavier side-effect burden than newer antidepressants, including dry mouth, constipation, and cardiac effects, so they are not a first-line choice for weight gain. But in someone already taking amitriptyline for chronic pain or depression, the weight gain it produces is a recognized and sometimes useful secondary effect.
Over-the-Counter Supplements
No OTC supplement works as reliably as the prescription drugs above, but a couple have decent evidence for specific situations.
Creatine Monohydrate
Creatine is the best-studied sports supplement for increasing body weight, though the mechanism is not what most people assume. In the short term, creatine pulls water into muscle cells, which shows up on the scale as weight gain. One study found that creatine users gained about 1.7 kilograms of total body weight over the supplementation period, and nearly all of that gain was accounted for by increased body water rather than new tissue.22PubMed. Creatine monohydrate supplementation on body weight and percent body fat Over the longer term, though, creatine helps you train harder, which leads to genuine increases in lean mass. Research combining creatine with a resistance training program showed significant gains in fat-free mass and strength.23PubMed Central. The effects of pre versus post workout supplementation of creatine monohydrate on body composition and strength Another study found that creatine supplementation during a weight-training program added nearly a kilogram of lean body mass above what training alone produced.24PubMed. Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program
Creatine is cheap, widely available, and has an excellent safety profile in healthy people. If you are trying to gain weight and are willing to do resistance training, it is the most evidence-backed OTC option. Without training, it mostly just adds water weight that disappears when you stop taking it.
Zinc
Zinc supplementation is unlikely to help you gain weight unless you are actually zinc-deficient, but for people who are, the effect can be meaningful. A study of undernourished children found that those with low serum zinc levels experienced greater improvements in appetite and growth when given zinc supplements.25PubMed. Cut-off Serum Zinc Concentration Affecting the Appetite, Growth, and Nutrition Status of Undernourished Children Supplemented With Zinc In a controlled trial of women hospitalized for anorexia nervosa, those receiving zinc increased their body mass index at twice the rate of the placebo group.26International Journal of Eating Disorders. Controlled trial of zinc supplementation in anorexia nervosa
Zinc deficiency is more common than many people realize, especially in older adults, vegetarians, and people with chronic digestive conditions. If poor appetite and low weight are your problem and you have not had your zinc levels checked, it is worth looking into before jumping to prescription appetite stimulants.
The Difference Between Fat Gain and Lean Gain
Not all weight gain is equal, and the type of tissue you add matters for long-term health. Appetite stimulants like megestrol and dronabinol generally increase overall caloric intake, which tends to produce a mix of fat and lean tissue. Anabolic agents like oxandrolone and testosterone, by contrast, preferentially build muscle. Creatine supports lean mass only when paired with resistance training.
This distinction matters because gaining fat and gaining muscle have different metabolic consequences. A cohort study tracking young adults found that increases in fat mass were more strongly tied to worsening cardiovascular risk markers, including unhealthy blood lipid levels, than increases in lean mass.27PLoS Medicine. Body muscle gain and markers of cardiovascular disease susceptibility in young adulthood: A cohort study If you are underweight because of a serious illness that causes muscle wasting, the ideal is to regain lean tissue rather than simply pack on fat. In practice, getting enough calories is the first priority, and the composition of the gain is a secondary concern for people who are severely underweight.
Why the Underlying Cause Shapes the Treatment
Weight loss from cancer or AIDS is not the same as weight loss from poor appetite in an elderly person living with dementia, and neither is the same as someone who is naturally thin and wants to be bigger. Cancer cachexia, for example, is driven by inflammatory signals from the tumor itself. Cytokines like IL-6 and tumor necrosis factor-alpha ramp up muscle breakdown, promote fat loss, and suppress appetite all at once, making the wasting extremely difficult to reverse with food alone.28PubMed Central. What Role Do Inflammatory Cytokines Play in Cancer Cachexia? That inflammatory backdrop is why cancer patients often need pharmaceutical appetite stimulants on top of nutritional support.
For people with dementia who struggle with feeding, a systematic review found that high-calorie oral supplements can help with weight gain, though they did not clearly improve other outcomes like cognitive function or survival.29PubMed Central. Oral feeding options for people with dementia: a systematic review The point is that the best weight-gain strategy depends on the underlying problem. A doctor treating cancer cachexia might reach for megestrol and consider olanzapine. A doctor treating a hypogonadal man who has lost muscle might prescribe testosterone. A geriatrician working with an elderly patient might try cyproheptadine or mirtazapine alongside calorie-dense meals. Matching the medication to the mechanism behind the weight loss gives the best chance of success.
Experimental Approaches on the Horizon
Researchers have been exploring ghrelin receptor agonists as a newer class of weight-gain medication. Ghrelin is the hormone your stomach releases when you are hungry, and drugs that mimic its action could theoretically boost appetite and shift body composition. A meta-analysis of two such agonists in malnourished adults found that they increased calorie intake, improved body composition, and strengthened grip, suggesting genuine functional benefit beyond just adding pounds.30PubMed Central. Two ghrelin receptor agonists for adults with malnutrition: a systematic review and meta-analysis These agents are not yet widely available as standard treatments, but they represent a promising direction for people whose wasting does not respond well to current options.
Safety Risks With Unregulated Weight-Gain Supplements
If you browse online for “weight gain pills,” you will find a sea of OTC supplements making bold claims. Many of these products sit in a regulatory gray zone. The FDA does not approve dietary supplements the way it approves drugs, and analyses of supplements flagged by the agency have repeatedly found hidden pharmaceutical ingredients. A review of the FDA’s tainted supplements database covering 2007 through 2021 identified over a thousand products adulterated with active drug ingredients, with weight-related and muscle-building supplements among the most common offenders.31PubMed. Continued Risk of Dietary Supplements Adulterated With Approved and Unapproved Drugs: Assessment of the US Food and Drug Administration’s Tainted Supplements Database 2007 Through 2021
A separate analysis specifically examining weight-related supplements that had drawn FDA warnings found that the most common hidden ingredient was sibutramine, a drug pulled from the market in 2010 because of cardiovascular risks. It was detected in about 85% of adulterated weight-loss products tested. Phenolphthalein, a laxative withdrawn due to cancer concerns, also showed up frequently.32PubMed Central. Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings While these findings focused on weight-loss products rather than weight-gain products specifically, the broader pattern is clear: supplements that promise dramatic body-composition changes are the category most likely to contain undeclared drugs. Sticking with well-established supplements like creatine and zinc from reputable manufacturers is far safer than gambling on a product that claims to add 10 pounds in two weeks.
Calorie-Dense Nutrition as the Foundation
No pill replaces the need for a caloric surplus. Every medication discussed above works by either increasing appetite so you eat more, altering your hormones so your body builds tissue more efficiently, or both. If you are not eating enough total calories, even the strongest appetite stimulant will underperform. For people without a medical condition causing wasting, the most effective “weight gain pill” is often no pill at all. Calorie-dense foods like nut butters, whole milk, avocados, olive oil, and protein shakes added to existing meals can close the gap between what you are eating and what you need to grow. Oral nutritional supplements, the kind you can buy at a pharmacy without a prescription, have shown benefits for weight gain in populations as varied as older adults with dementia and children recovering from illness.29PubMed Central. Oral feeding options for people with dementia: a systematic review
For otherwise healthy people who want to gain weight, the combination of a consistent caloric surplus, progressive resistance training, adequate protein, and creatine supplementation is the approach with the strongest evidence and the fewest risks. Prescription options become worth considering when appetite is genuinely suppressed by a medical condition, when illness is actively breaking down muscle, or when a hormonal deficiency is preventing normal growth and recovery. A conversation with your doctor about the specific reason you are underweight is the first step toward figuring out which approach, pharmaceutical or not, fits your situation.