In the future, a new class of anti-inflammatory drugs could be used to treat depression, say University of Cambridge researchers.
Drugs such as aspirin and ibuprofen treat inflammation, the body’s immune response to infections or pathogens. During an inflammatory response, immune cells flood the bloodstream with proteins known as cytokines.
Drugs to counteract these cytokines are the newest generation of anti-inflammatories. Some are so new, clinical trials are still testing their efficacy and safety for human use.
These trials form the basis of the Cambridge research that was published Tuesday in the journal Molecular Psychiatry.
Based on previous findings about depression, the team looked at the side effects experienced by patients given anti-cytokine drugs in 20 separate studies. All the participants had chronic autoimmune inflammatory diseases, which occur when healthy cells are mistaken for infected cells, causing the immune system to attack the body and leading to inflammation.
Anti-cytokine drugs “dampen down inflammation by blocking the actions of specific inflammatory cytokines … with ‘surgical precision’ and are now routinely used for treating patients who respond inadequately to standard treatments for inflammatory conditions such as rheumatoid arthritis, psoriasis and Crohn’s disease both in the US and Europe,” explained Dr. Golam Khandaker, a clinical lecturer in Cambridge’s department of psychiatry and lead author of the new study.
Using data from the 20 studies, Khandaker and his colleagues found that anti-cytokine drugs improved symptoms of depression, regardless of whether they lessened the symptoms of physical illness.
Two implications
“The findings suggest that inflammation may contribute to the pathogenesis of depression,” Khandaker said. The findings also suggest that “anti-inflammatory drugs may be helpful in treating patients with depression who are chronically inflamed.”
The immune system acts like a thermostat, turned down low most of the time but cranked up when we have an infection, according to Khandaker. In some people, the thermostat is always set slightly higher, behaving as if they have a persistent low-level infection.
In previous research, Khandaker found that children with high everyday levels of inflammatory markers — a higher thermostat — are at greater risk of developing depression and psychosis in adulthood.
Also, research conducted in the Netherlands suggests that anti-inflammatory drugs used in conjunction with antipsychotic drugs may be more effective than antipsychotics alone.
For the current report, Khandaker and his colleagues looked at studies of drugs blocking specific cytokines.
Khandaker said that five of the 20 studies focused on one specific cytokine. All five showed the same result, that blocking the action of this cytokine to reduce inflammation lessened symptoms of depression.
Two clinical trials examined by Khandaker focused on another drug blocking the action of a different cytokine, and both studies showed it improved symptoms of depression.
Looking to the future
Meta-analyses such Khandaker’s “can be valuable,” said Dr. Charles Raison, a psychiatrist and professor at the University of Wisconsin-Madison.
“Evidence at this point suggests that cytokine antagonists — which are much more specific in their anti-inflammatory effects than drugs like aspirin — show modest antidepressant effects in individuals with depression and increased inflammation,” said Raison, who did not participate in in Khandaker’s research.
Though it’s still too early to prescribe these drugs to depressed patients, Khandaker believes that anti-inflammatory drugs may offer hope to people who find current antidepressants ineffective.
“We need more studies,” he said, particularly research involving patients with depression who are inflamed but healthy to investigate the effect of these drugs on depression. Their potential side effects also must be investigated, Khandaker said, adding that “we and other research groups from both sides of the Atlantic are currently planning and conducting such randomized control trials.”
