Hope for previously hopeless cases: a one-hour treatment with nitrous oxide can quickly and sustainably relieve the symptoms of treatment-resistant depression, shows a study with severely affected patients. In order to achieve the effect, a comparatively low concentration of the gas is sufficient, which entails a low risk of side effects, according to the results. After further clinical studies, the method could now develop into a promising form of therapy.
Everyone is occasionally “in a bad mood”, but a depression is different: The pathological state of mind lies like a gray veil over life – depressed, lacking drive and uninterested, millions of people drag themselves through life. In the most severe form – the so-called major depression – nothing is left of the quality of life and many sufferers develop suicidal intentions. Unfortunately, in these cases, treatment with antidepressants is often ineffective: The drugs only take effect about two weeks after they have been taken, and in many patients they don’t work at all. New treatment options are therefore in demand.
In an earlier pilot study, researchers led by Peter Nagele from the University of Chicago have already shown the potential of laughing gas (nitrous oxide) to treat depression. This substance has a long tradition as an anesthetic and is also known for its mood-changing effects. So far, the scientists had already shown that inhaling a gas mixture containing 50 percent nitrous oxide can relieve the symptoms of severe depression over the course of 24 hours. As they explain, unlike standard antidepressants, nitrous oxide acts on the NMDA glutamate receptors in the brain and can therefore improve symptoms within hours.
Potential for optimization?
So far, however, there has been a problem with the treatment with nitrous oxide: the rather high dosage resulted in considerable side effects such as nausea, vomiting and headaches in many test subjects. “In the current study, we wanted to find out whether a lower dose of nitrous oxide compared to the previously tested one is just as effective and also how long the antidepressant effect of the treatment lasts,” says Nagele.
The phase 2 clinical trial included 24 volunteers suffering from severe depression who had not yet been able to achieve symptom relief from taking antidepressants. Each participant received three treatments about a month apart: In one session, the patients breathed in a gas for one hour that consisted of half nitrous oxide and half oxygen. In the second treatment, the same patients breathed in a mixture that was only 25 percent nitrous oxide. The third treatment was the placebo control: the subjects only breathed oxygen and no nitrous oxide. “It can be very useful to compare a person to yourself,” says Nagele. In this way, conclusions can be drawn about the effectiveness even with a smaller study scope, explains the scientist.
Sustainable and gentle
The investigation of the effect of the treatments on the symptoms of depression showed that both the 50-50 mixture with oxygen and the 25 percent nitrous oxide treatment led to significant improvements in mood in 17 of the study participants, which lasted for at least two weeks. In detail, it was shown that the majority of the test subjects experienced a significant improvement in at least half of their depressive symptoms as a result of the nitrous oxide treatment. Many even went into remission – they were no longer classified as clinically depressed, the researchers report.
The low dosage also proved to be comparatively gentle: “In our study, feelings of nausea only occurred during the 50 percent treatment. This side effect did not occur with the 25 percent mixture. The lower dose was just as effective as the higher dose in relieving symptoms of depression, ”says co-author Charles Conway of Washington University in St. Louis. Nagele adds: “The patients do not get high or euphoric, but often fall asleep”.
The team now sees the study results as another important step towards developing a new form of therapy for depression. “The fact that we saw rapid improvements in many of these patients in the study suggests that nitrous oxide might help people with really severe, resistant depression,” says Conway. The next step, according to the scientists, is a more extensive clinical study in which the efficacy and safety of nitrous oxide in the treatment of depression will be investigated in many patients. “So far we only have pilot studies,” says Nagele. “Now we need to be accepted by the wider medical community so that this can become a treatment that could become easily available to many affected,” said the scientist.
Source: Washington University, Article: Science Translational Medicine, doi: 10.1126 / scitranslmed.abe1376