Several classes of medications can cause pulmonary hypertension, a dangerous rise in blood pressure within the arteries of the lungs. The best-documented culprits are appetite suppressants (fenfluramine and dexfenfluramine), certain chemotherapy drugs, methamphetamines, and dasatinib, a leukemia treatment. Beyond these, interferon therapies, some antidepressants, and even herbal supplements like St. John’s wort carry varying degrees of risk.
Researchers classify these drugs into tiers based on the strength of evidence. “Definite” means large studies have confirmed a causal link. “Likely” or “possible” means case reports or smaller studies suggest a connection, but proof is less airtight. At the 2024 World Symposium on Pulmonary Hypertension, two chemotherapy agents, carfilzomib and mitomycin C, were added to the “definite” list for the first time.
Appetite Suppressants: The First Known Trigger
The link between weight-loss drugs and pulmonary hypertension was discovered in the 1960s when aminorex, a European appetite suppressant, triggered an epidemic of cases. The drug was pulled from the market in 1972. Then in the 1980s and 1990s, fenfluramine and dexfenfluramine (the “fen” in fen-phen) repeated the pattern. People who took these drugs for longer than three months had a 30-fold increase in the risk of pulmonary hypertension compared to the general population. Benfluorex, a related compound used in Europe, was later added to the same category.
These drugs all share a common mechanism: they flood the lungs with serotonin, a chemical messenger that, among many roles, controls how blood vessels tighten and relax. Normally, smooth muscle cells lining the pulmonary arteries keep serotonin in check through a transporter protein on their surface. Fenfluramine-type drugs block that transporter and simultaneously trigger a massive release of serotonin into the bloodstream. The excess serotonin stimulates the smooth muscle cells to multiply, thickening the artery walls and narrowing the passage for blood. Some people appear genetically more vulnerable because they naturally produce higher levels of this transporter protein, making them more sensitive to the disruption.
All of these appetite suppressants have been withdrawn from the market, but their legacy matters. If you took fen-phen or a similar drug years ago and have unexplained shortness of breath, the connection is worth mentioning to a doctor.
Methamphetamines and Stimulants
Methamphetamine use is now one of the most recognized causes of drug-induced pulmonary hypertension. The damage involves several overlapping processes: disrupted serotonin signaling (similar to the appetite suppressants), oxidative stress that injures blood vessel walls, and an imbalance between chemicals that constrict and relax the pulmonary arteries. Over time, this remodels the lung’s blood vessels in ways that permanently raise pressure.
Cocaine and amphetamine-type stimulants are classified as possible or likely risk factors. Phenylpropanolamine, a decongestant and appetite suppressant that was once available over the counter, also falls into the “possible” category.
Dasatinib and Cancer Treatments
Dasatinib, a targeted therapy used for chronic myeloid leukemia, causes pulmonary arterial hypertension in an estimated 0.45% of patients who take it. That may sound small, but for a condition as serious as pulmonary hypertension, it’s a meaningful risk. The most important step in managing it is stopping the drug. Once dasatinib is discontinued, many patients improve, though some need additional treatment to bring their pressures back down. Patients who develop this complication should not restart dasatinib; alternative medications in the same class are available.
Two chemotherapy agents, carfilzomib (used for multiple myeloma) and mitomycin C, were upgraded to “definite” risk factors in 2024 based on accumulating evidence. Alkylating agents, a broader class of chemotherapy drugs, are also on the definite list. If you’re undergoing cancer treatment and notice new or worsening shortness of breath, fatigue, or swelling in your legs, these symptoms deserve prompt attention.
Interferon Therapy
Interferon-alpha and interferon-beta, used to treat hepatitis C, multiple sclerosis, and certain cancers, carry a small but real risk of pulmonary hypertension. In a study of more than 20,000 patients who received interferon therapy, 71 developed pulmonary hypertension. The risk increased with duration of treatment: 0.36% at three years, 0.86% at six years, and 1.77% at nine years. While these numbers are low in absolute terms, they are several times higher than the rate in the general population.
The biological explanation involves endothelin-1, a potent vessel-constricting substance. Type I interferons stimulate pulmonary artery cells to release endothelin-1. In animal studies, mice engineered to lack the interferon receptor were protected from developing pulmonary hypertension under conditions that would normally trigger it. In human patients with scleroderma, those who had detectable interferon levels were more likely to have pulmonary hypertension and higher endothelin-1 levels.
Antidepressants and SSRIs
Selective serotonin reuptake inhibitors (SSRIs), one of the most commonly prescribed classes of antidepressants, appear on some classification lists as a possible or likely risk factor. Because SSRIs work by increasing serotonin activity, the theoretical concern mirrors the mechanism seen with appetite suppressants. The risk, if it exists, appears to be very low given how widely these drugs are used. This is not a reason to stop an antidepressant on your own, but it’s worth being aware of if you take SSRIs and develop unexplained breathing difficulties.
Hormones and Herbal Supplements
Estrogen-containing therapies have been classified as a definite risk factor for drug-induced pulmonary hypertension in some expert lists. The exact mechanism is still being worked out, but estrogen affects the signaling pathways that regulate blood vessel tone in the lungs.
St. John’s wort, an herbal supplement widely used for mild depression, is listed as a possible risk factor. L-tryptophan, an amino acid supplement once popular as a sleep aid, falls into the “likely” category. These may seem surprising given their reputation as “natural” products, but their effects on serotonin pathways overlap with the same mechanisms that make prescription drugs dangerous to the pulmonary vasculature.
What Happens After Stopping the Drug
The single most important step when a medication is causing pulmonary hypertension is to stop taking it. For some drugs, particularly dasatinib, stopping often leads to meaningful improvement. The timeline varies. Some patients see pressures drop within weeks to months, while others sustain permanent vascular damage that requires ongoing treatment with medications designed specifically for pulmonary hypertension.
The likelihood of recovery depends on how long you were exposed, how much remodeling has occurred in the lung’s blood vessels, and your individual biology. Drug-induced pulmonary hypertension that is caught early, before extensive structural changes have set in, generally has a better outlook than cases diagnosed late. This is why unexplained shortness of breath, dizziness during exertion, chest pressure, or swelling in the ankles or legs should prompt a conversation about any medications or supplements you’re taking, including over-the-counter and herbal products.