Researchers from the University of South Carolina and the Imperial College London have found out why selective serotonin reuptake inhibitors (SSRIs) do not work on all patients with depression.

Resistance to SSRIs

Since the U.S Food and Drug Administration approved SSRIs, psychiatrists have used them widely to treat depression. They use SSRIs to ensure serotonin circulates longer in the body, thus improving a patient’s mood.

However, the drug does not work on everyone, as many people exhibit treatment-resistant depression. Some patients even develop side effects to the drugs. Resistance to SSRIs has led some psychiatrists to explore other less safe options such as MDMA and Ketamine. However, this team of researchers states that doctors don’t have to stop using the drug as a treatment option. Instead, they should change how they apply it.

The team found that histamine works in both inflammation and depression through its effect on serotonin. For this reason, the researchers believe that the key is to administer SSRIs with drugs that lower histamine production.

According to Melinda Hersey, a study co-author, and post-doctoral fellow, histamine plays a part in regulating serotonin, whose levels are changed in depression and mediating immune response.

Scientists have found a link between depression and inflammation. Diseases such as inflammatory bowel syndrome, an autoimmune disease, can lead to changes in mood and increased irritability.

How researchers conducted the study

Scientists conducted experiments to examine the link between inflammation and depression using mice hippocampal models. First, they implanted microelectrodes in the mice’s brains to evaluate serotonin levels. Scientists then injected the mice with toxins to induce brain inflammation. After inflammation occurred, serotonin levels decreased significantly.

However, the toxins could not cross the blood-brain barrier on their own, suggesting other factors are involved. They realized that inflammation caused an increase of histamine in the brain, causing a decrease in serotonin levels.

Researchers concluded that SSRIs blocked histamine clearance in patients with inflammation. If histamine levels were high, serotonin levels remained low; hence the treatment was not effective.

When they gave the subjects drugs that inhibited histamine with antidepressants, they noted an increase in serotonin levels.