Common medications that cause weight gain

Many factors undermine dieting and weight loss. One common but underappreciated variable that can sabotage even the most sincere efforts to lose weight involves prescription medications.

In the past month, nearly half of all North Americans will have taken a medication for some condition. Although pharmacotherapy is intended to treat disease, drugs carry the risk of various adverse effects, including weight gain. Excess weight gain is linked to numerous health consequences, and when weight gain is caused by a drug, it can lead to nonadherence. In light of the weight-gain implications of prescribed drugs—which exacerbate the obesity crisis—experts recommend that physicians consider the weight effects of medications when prescribing.

Unfortunately, much still needs to be elucidated with respect to this topic. According to the authors of a review published in Diabetes & Metabolic Syndrome: “There are several clinical guidelines that categorize medications as those that promote weight loss, weight gain or have weight neutral effects. However, inconsistencies exist when defining the weight effects of medication. Further, existing weight estimates are sparse, which makes it challenging for clinicians to recommend medications while considering the weight effects.”

As a result, weight-related side effects of prescription medications are often overlooked. 

To that end, here are five drugs that can lead to unwanted weight gain and interfere with dieting and weight maintenance, based on current data.

Beta-blockers

Beta-blockers—especially older ones like atenolol and metoprolol—can lead to weight gain, possibly due to slowing metabolism. During the first few months of treatment, beta-blockers are usually linked to weight gain (about 1.2 kg on average), followed by a plateau.

The amount of weight gain may only be moderate, with atenolol causing weight changes in the range of -0.5–3.4 kg; propranolol, -0.5–2.3 kg; and metoprolol, 1.2–2.0 kg. Alpha-blockers such as prazosin and clonidine, yield little, if any, weight gain. And timolol and acebutolol are weight neutral. Furthermore, when switching from a diuretic to a beta-blocker, some weight gain can be expected.

Older beta-blockers that can lead to weight gain are usually only prescribed when other lines of therapy for hypertension fail. They are also prescribed for specific heart conditions.

Of note, weight gain is an ominous sign in patients with heart failure. Sudden weight gain can indicate edema in the legs, abdomen, or chest—a sign that heart failure is worsening. Specifically, weight gain of 1–1.4 kg in a day or 2.3 kg in a week warrants immediate clinical attention. 

Corticosteroids

Corticosteroids are mainstays of treatment for conditions including rheumatoid arthritis, asthma, lupus, and allergies. These drugs can lead to weight gain due to fluid retention, increased appetite, and decreased ability to exercise. They also cause extra fat deposits around the abdomen.

Brief use of corticosteroids probably doesn’t lead to weight gain, but long-term use—3 months or more—is tied to weight gain in the range of 1.5–4.4 kg for prednisolone, 1.7–5.8 kg for prednisone, and 1.5–8.4 kg for cortisone. 

Disconcertingly, results from one study following patients with Wegener’s granulomatosis (ie, granulomatosis with polyangiitis) suggested that more than 20% of participants with this autoimmune disease who received steroid treatment gained more than 10 kg during the first year of treatment.

Although few alternatives exist for steroid therapy, certain strategies can minimize weight gain, including alternate-day dosing of prednisone, for example, which may attenuate weight gain or even result in weight loss. Moreover, once steroid therapy is discontinued, weight gain should also stop. 

Antipsychotics

Psychotropics are closely linked to weight change, and those with mental illness have two to three times greater risk of becoming obese compared with others. During the course of treatment with psychiatric drugs, about 70% of patients will gain some weight.

Weight gain due to antipsychotic prescription is a major concern for psychiatrists and other clinicians, with olanzapine and clozapine carrying the highest risk. Although switching to another agent is an option to curb weight gain, this change carries the risk of relapse.

Patients taking clozapine and olanzapine gain an average of 4.5–16.2 kg and 3.6–10.2 kg, respectively, with 29% to 89% of those taking clozapine gaining some weight, and 8% to 37% of patients taking olanzapine gaining 7% or greater of their body weight.

Weight gain with antipsychotics is most substantial during the first few weeks of treatment, with the rate gradually stabilizing after several months. It can take between 4 and 9 months for weight gain to plateau while on olanzapine, and between 42 and 46 months with clozapine. In other words, patients on antipsychotics can continue to gain weight for up to 1–4 years while on treatment.

Mechanisms underlying weight gain due to antipsychotics are varied. With olanzapine and clozapine, for instance, different effects on the receptors serotonin 5-HT2A and 5-HT2C, dopamine D2 and D3, histamine H1, and muscarinic M3 receptors have been implicated. Furthermore, these drugs may change levels of neuropeptides linked to appetite control and energy metabolism, such as leptin, adiponectin, and ghrelin.

Unfortunately, there seems to be no easy fix for tackling weight gain in patients taking antipsychotics, per the authors of a review published in Neuropsychiatric Disease and Treatment: “The available data describe several strategies to attenuate antipsychotic-induced weight gain. They are reducing the dose, switching to an antipsychotic with less weight gaining potential, adding pharmaceutical adjuvants, and nonpharmacologic interventions.”

“Combination of interventions may be helpful. Interventions will have to be tailored according to individual needs. Preventing weight gain in patients treated with antipsychotics should be considered a priority,” they concluded.

Mood stabilizers

Mood stabilizers, which are used to treat bipolar disorder, are linked to added weight. For instance, in 25% of those taking lithium, weight gain ranges from 4.5–12 kg over the course of treatment. This weight gain may be due to increased appetite, fluid retention, lithium-related subclinical hypothyroidism, or lithium-induced polydipsia from drinking sugar-sweetened beverages. 

Between 20% and 25% of those taking valproate end up gaining weight, with a range of 3–10 kg over a period of 3–12 months. 

Anti-epileptics

Overlap exists between drugs used as mood stabilizers and those used as anti-epileptic agents. 

In antiepileptic contexts, valproate has been shown to cause weight gain in the range of 5–49 kg, with weight gain more common in women and during the first 3 months of treatment. Valproate can also lead to polycystic ovarian disease in women, which results in weight gain. 

When prescribing treatment with valproic acid for epilepsy, weight should be monitored, and those gaining 2 kg or more during the first month of treatment may need to switch to an alternative anti-epileptic medication.

Although also a cause of weight gain, carbamazepine (when used as an anti-epileptic) causes less weight gain than does valproate. When used as a bipolar agent, the weight gain from carbamazepine is even lower. 

Gabapentin likely leads to the least amount of weight gain among the listed anti-epileptic agents. 

Notably, the mechanisms underlying the relationship between weight gain and anti-epileptics remains to be elucidated, but it may be genetically predisposed, per the experts.

Bottom line

Weight gain caused by medications is a source of consternation for patients and physicians alike. For those taking certain medications, weight loss and weight maintenance can be incredibly difficult. With the implicit understanding that extra weight is hard to lose once gained, the clinician must always consider the potential for drugs to cause weight gain—especially in those with high BMIs who are trying to lose weight to treat or prevent metabolic disease and osteoarthritis.

“Clinicians should select medications associated with more favorable weight profiles when first initiating treatment, or consider changing medications if patients are experiencing the weight gaining side effects, if clinically possible,” wrote the authors of the aforementioned review published in Diabetes & Metabolic Syndrome. “When it is not feasible to change medications, adjunctive therapies or lifestyle intervention may help to combat weight gaining side effects.”