The antidepressant properties of party drug ketamine have been confirmed in a large population study involving 41,000 patients. In the process, scientists also found that Botox used in cosmetic surgery appeared to alleviate depression.

Ketamine is used as a human anaesthetic or an animal tranquilliser and was approved in clinical practice by the US Food and Drug Administration (FDA) in 1970. Due to its side effects, such as hallucinations, it also became rapidly used as a recreational drug.

In recent years, there has been renewed interest for the drug among health professionals, as small studies and anecdotal evidence appeared to suggest that in strict clinical settings, it had positive effects on people suffering from severe depressions.

Depression is considered by the World Health Organisation as the fourth highest disease burden in the world – but millions of people do not respond well to current treatments.

No large-scale clinical trials had previously been conducted to look at the effects of ketamine on depression – primarily because of ethical concerns. However, researchers have now conducted a large-scale population analysis to investigate the issue. Their findings are published in the journal Scientific Reports.

Absence of antidepressant symptoms

The team, from Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego, analysed data from more than 41,000 patients, which they found in the FDA Adverse Effect Reporting System (FAERS) database.

They looked at how often people who reported taking ketamine as a way to alleviate pain reported symptoms of depression.

"While most researchers and regulators monitor the FAERS database for increased incidences of symptoms in order to spot potentially harmful drug side effects, we were looking for the opposite – lack of a symptom," said co-lead author Isaac Cohen.

The scientists found that people who reported taking ketamine had also significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain. The incidence of depression symptoms in these patients dropped by 50 percent compared to those who took any other drug or drug combination for pain.

They also identified three other compounds which also surprisingly appeared to have antidepressant effects – Botox, diclofenac (an anti-inflammatory drug) and minocycline, an antibiotic.

The scientists think that both diclofenac and minocycline may alleviate depression by reducing inflammation. The mechanism behind Botox's antidepressant properties is less clear, but may be due to the fact it makes people feel beautiful and thus more inclined to feel good about themselves.

"The approach we used here could be applied to any number of other conditions, and may reveal new and important uses for thousands of already approved drugs, without large investments in additional clinical trials," co-lead author Tigran Makunts concluded.