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Sometimes physicians encounter symptoms that remain unexplained despite extensive testing. When no clear medical explanation is found and symptoms persist, patients often develop anxiety and/or depression as a consequence of living with an unresolved health problem.
In such situations, treatment frequently focuses on the emotional consequences while the underlying medical mystery remains unsolved.
Yet occasionally, the right question can reveal a surprisingly simple explanation—and an equally simple solution.
Case study: A chronic cough
Linda was 54 years old when she came to see me with a persistent dry cough that had lasted 14 months.
The cough was relatively mild during the day but became relentless at night. She described a constant tickling sensation in her throat. Coughing would briefly relieve the sensation, but within seconds, the tickle would return, triggering another coughing spell.
She tried drinking cold water, warm water, and various home remedies, but nothing provided lasting relief. The chronic cough disrupted her sleep night after night, leaving her exhausted during the day.
As the months passed, Linda became increasingly anxious and depressed.
Apart from her cough and being treated for high blood pressure, she was healthy, exercised regularly, and ate a balanced diet.
Linda had never smoked and had no history of asthma. Her physical examination was normal. Blood tests and chest X-rays were unremarkable.
Over the previous year, she had consulted several specialists.
An ear, nose, and throat (ENT) specialist performed a laryngoscopy to investigate the throat irritation but found no abnormalities. There was no inflammation and no evidence of postnasal drip.
One internist suspected gastroesophageal reflux disease (GERD), reasoning that stomach acid might be irritating her throat at night. Linda was prescribed a proton pump inhibitor for three months, but her symptoms remained unchanged.
Another physician worried about the possibility of early lung cancer and ordered a chest CT scan. The scan was normal.
Fourteen months after the cough began, Linda was still suffering.
Because no explanation had been found and her anxiety and depression were worsening, she was about to be referred to a psychiatrist when she came to see me.
The question that solved the mystery
The most important question turned out to be surprisingly simple:
“What medications are you taking?”
When I reviewed Linda’s medications, I discovered that she was taking an ACE inhibitor to treat her high blood pressure.
Suddenly, everything made sense.
The likely culprit was the medication itself.
What research shows
Linda’s experience is far from unique.
ACE inhibitors (angiotensin-converting enzyme inhibitors), a widely prescribed class of blood pressure medications, are known to cause a chronic dry cough in approximately 5 to 25 percent of patients. The side effect appears to be more common in women and nonsmokers. The cough may begin shortly after treatment starts, but it can also appear months or even years later. [1] [2] [3]
The simplest way to confirm the diagnosis is to discontinue the ACE inhibitor and substitute another class of blood pressure medication. In most patients, the cough improves within days to a few weeks. If the culprit medication is restarted, the cough frequently returns. [4]
Interestingly, this side effect is not usually dose-dependent. Even low doses can trigger coughing in genetically susceptible individuals. [5]
Research suggests that ACE inhibitors lower the threshold of the cough reflex in sensitive patients. As a result, ordinary environmental stimuli that would not normally provoke coughing can suddenly trigger persistent symptoms. [6]
What happened to Linda
I discontinued Linda’s ACE inhibitor and replaced it with a calcium channel blocker, a different class of blood pressure medication.
Within one week, her cough disappeared.
For the first time in more than a year, she was able to sleep through the night. As her sleep improved and her physical symptoms resolved, her anxiety and depression gradually disappeared as well—without the need for psychiatric medication.
Her blood pressure remained well controlled.
The psychological lesson
Linda’s story illustrates an important principle in both medicine and psychology.
When symptoms remain unexplained, it can be tempting to focus solely on treating their emotional consequences. Yet anxiety and depression are often understandable reactions to persistent physical symptoms. Whenever possible, it is important to identify and address the underlying cause rather than treating only the consequences.
Before concluding that a symptom is unexplained or untreatable, clinicians should carefully review all prescription medications, over-the-counter products, and supplements. Sometimes the answer is hiding in plain sight.
Throughout my career, I have encountered numerous patients with chronic dry cough who were treated with allergy medications, acid-reflux therapies, and other interventions while the true cause—an ACE inhibitor—went unnoticed. In some cases, the medication was hidden within a combination blood pressure pill, making it even easier to overlook.
Medicine is both a science and an art. Laboratory tests and imaging studies are invaluable tools, but careful listening and thoughtful questioning remain equally important.
Sometimes the key to solving a medical mystery is not ordering another test—it is asking one more question.
Copyright 2026 @Chris Gilbert, M.D., Ph.D.
