Amiloride, a drug that's used to treat hypertension, successfully relieves signs of anxiety and panic in a pre-clinical study. The findings are underpinned and strengthened by epigenetic changes caused by anxiety and panic disorder.

As many as 40 million individuals in the United States live with anxiety disorders.

Around 6 million of them have panic disorder, which is a condition characterized by the sudden onset of panic attacks.

Treatment for anxiety disorders may include psychotherapy and medication such as antidepressants.

However, there are few safe, effective options that provide instant relief for panic attacks.

Panic disorders have a range of risk factors—ranging from hereditary ones to traumatic childhood experiences.

Adverse events in one's childhood, such as a death in the family or separation from one's parents, can have not only a profound psychological effect, but also molecular and genetic ones.

Using existing knowledge on the genetic impact of childhood adversity and the risk of developing anxiety disorders into adulthood, researchers from the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada, investigated whether an existing drug can instantly alleviate the symptoms of panic attacks by acting on the molecular changes that are brought about by childhood adversity.

Dr. Marco Battaglia, associate chief of child and youth psychiatry in the Campbell Family Mental Health Research Institute at CAMH, is the lead author of the new study, which has now been published in the Journal of Psychopharmacology.

Childhood trauma, epigenetics, and anxiety

As Dr. Battaglia and his colleagues explain in their paper, experiments in mice have revealed that repeatedly separating pups from their mothers causes epigenetic modifications.

Epigenetics refers to modifications in the DNA that do not change the DNA's sequence but can affect whether some genes are switched on or off.

Specifically, in this new study, the scientists build on previous research in mice that has suggested that childhood trauma causes changes in the acid-sensing-ion-channel-1 gene, heightened pain sensitivity, and hypersensitivity to carbon dioxide in the air.

As the researchers explain, these physiological changes (such as carbon dioxide hypersensitivity) may lead to physical symptoms, such as difficulty breathing and hyperventilation, which are markers of panic attacks.

Based on this knowledge, the team hypothesized that a drug that can inhibit acid-sensing ion channels can also reduce pain sensitivity and hypersensitivity to carbon dioxide.

So, Dr. Battaglia and his team assessed the effects of the acid-sensing ion channel inhibitor "amiloride," a drug commonly used to treat hypertension.

Inhaled amiloride may treat panic disorder

To circumvent the issue of the brain-blood barrier, the scientists administered the drug to mice via inhalation. This enabled the drug to reach the rodents' brains immediately.

In its inhaled form, one dose of amiloride improved the respiratory signs of anxiety and pain sensitivity in the rodents.

"Inhaled amiloride may prove to have benefits for panic disorder, which is typically characterized by spells of shortness of breath and fear, when people feel anxiety levels rising."

–Dr. Marco Battaglia

"In as much as these results pertain to human anxiety and/or pain hypersensitivity," conclude the researchers, "our findings provide a rationale for studying inhaled amiloride in some anxiety disorders and/or pain syndromes."

Such hopeful pre-clinical results have prompted them to replicate the findings in a clinical setting. Next, Dr. Battaglia and team are planning to see whether the drug relieves anxiety symptoms in humans.