Chronic cough, a condition that lingers for more than two months, affects about one in ten people worldwide. For many, standard treatments that target asthma, acid reflux, or sinus problems bring some relief. Yet, for a large group of patients, the coughing continues no matter what they try. This stubborn version of the illness, known as refractory chronic cough, can be exhausting, disruptive, and frustrating for both patients and doctors.

Now, researchers led by the late Professor Zhongmin Qiu and Professor Kefang Lai from Tongji University and Guangzhou Medical University in China have found that an existing medication, flupentixol-melitracen—originally developed to treat anxiety and depression—may help relieve this type of cough. Their study, published in eClinicalMedicine, suggests that this short-term treatment could meaningfully reduce symptoms in people who have not improved with commonly used nerve-calming drugs such as gabapentin or baclofen, medicines that act on the nervous system to reduce sensitivity in the body’s cough reflex.

Professor Qiu and Professor Lai’s team carried out a carefully controlled clinical study at Tongji Hospital in Shanghai between 2021 and 2023. Adult volunteers who had been coughing for months or years were randomly divided into two groups. One group took the flupentixol-melitracen tablets, while the other group received a lookalike placebo—a harmless pill used to test whether the real medicine makes a genuine difference. The treatment lasted for two weeks, followed by another week of safety observation to check for side effects. By the end of the study, those taking the real medication experienced much greater improvement than those on the placebo.

Overall, about 65% of people who took the drug saw their cough symptom score fall by at least half, compared with 32% of those on placebo, about twice as many. “Our findings suggest that short-term use of flupentixol-melitracen may be an effective and well-tolerated treatment for persistent chronic cough,” explained Professor Lai. “However, the results should be interpreted with caution due to some limitations, such as the lack of direct cough frequency measurements and the single-location study design.”

Flupentixol-melitracen, sold under the brand name Deanxit, contains two active ingredients. Flupentixol is a medicine that acts on dopamine, a brain chemical involved in mood and motivation, while melitracen is a tricyclic antidepressant that stabilizes mood by increasing the activity of serotonin and norepinephrine—two chemicals that regulate mood, stress, and nerve activity. The drug is commonly prescribed for mild to moderate anxiety and depression in China and several other countries. The idea of using it for cough came from the team’s earlier observational study, in which about six in ten patients whose coughs had not responded to other treatments improved on it.

In the new study, people who took flupentixol-melitracen reported clear reductions in how often and how severely they coughed. Many also reported better cough-related quality of life, although this difference from placebo was not large enough to be statistically certain. In smaller subgroup comparisons, the positive effects were especially noticeable in women and in people between about forty and fifty years old, particularly those who had been coughing for years or who coughed mostly during the daytime.

The treatment appeared to be safe for short-term use. About half of the participants taking the drug reported mild side effects, compared with about a third of those on placebo. Drowsiness was the only side effect that was clearly more common with the drug, and all side effects disappeared once the treatment stopped. “Further studies are needed to evaluate the risk–benefit profile of flupentixol-melitracen and to determine its optimal treatment duration and dosage,” said Professor Lai.

The researchers also suggest why this drug might help. Flupentixol and melitracen influence the balance of brain chemicals known as neurotransmitters—substances that allow nerve cells to communicate. These same chemicals, including dopamine, serotonin, and norepinephrine, also play a role in the reflex that triggers coughing. By adjusting how these neurotransmitters work in the nervous system, the medication may reduce the oversensitivity of the nerves that trigger a cough. Because only five participants had depression or anxiety, and mood scores stayed stable, the researchers think the cough relief is unlikely to come from the drug’s effect on mood.

Interestingly, while daytime coughing improved significantly, nighttime coughing did not change much. The researchers think this is because persistent chronic cough tends to bother people mostly during the day, and many patients cough little or not at all at night. They also saw symptoms keep improving during the week after treatment ended.

Despite the encouraging results, the study had some limits. It was conducted at a single hospital, and the changes in coughing were based on patients’ reports rather than recordings from electronic cough monitors—devices that can automatically count and measure coughs. The researchers plan to carry out future studies that include more people from different regions, use digital tools for objective cough tracking, and observe how well the treatment works over longer periods of time.

For now, this research offers an unexpected and hopeful direction: a well-known mood medication that might bring relief to people who have lived for years with uncontrollable coughing after all other treatments have failed. As the team concluded, “Flupentixol-melitracen is associated with improvements in cough symptoms and cough-related quality of life for short-term use, independent of mental health status. Future studies are required to further evaluate the risk–benefit profile for its longer-term use.”

Journal Reference

Chen Qiang, Zhang Mengru, Zhang Li, Aierken Alimire, Dong Ran, Xu Xianghuai, Yu Li, Lai Kefang, Qiu Zhongmin. Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trial. eClinicalMedicine, 2025. DOI: https://doi.org/10.1016/j.eclinm.2025.103367