It was a shock for fans: the unexpected death of “Friends” actor Matthew Perry. According to the autopsy report, he died from the effects of the anesthetic ketamine. Added to this were, among other things, drowning, heart disease and the effects of a drug used to treat opioid addictions. The death was an accident. According to media reports, Perry was on ketamine infusion therapy for depression and anxiety disorders. He probably received a ketamine infusion a week and a half before his death, but according to the medical examiner’s office, this cannot be responsible for his death because ketamine does not stay in the body for that long.

Depression is also a widespread mental illness in Germany. In the course of a year, 5.3 million adult Germans suffer from depression, according to the German Depression Aid. For some sufferers, standard therapy with antidepressants and psychotherapy is not successful. They suffer from what is known as treatment-resistant depression – meaning two or more types of antidepressants have not helped them. It is estimated that up to 30 percent of people with major depression have treatment-resistant depression. The former anesthetic ketamine can help people with such depression. How ketamine works and how it is used – an overview.

Ketamine was developed in 1966 as an anesthetic for animal and veterinary medicine. It was used in operations on American soldiers during the Vietnam War. Ketamine is used in emergency medicine because of its pain-relieving effects. It also expands the bronchi and can stabilize the circulation. Because ketamine also has a certain hallucinatory effect, it is also abused as a drug.

When ketamine was first approved as an anesthetic in the USA in the 1970s, patients also reported the mood-enhancing effects of the anesthesia. Intensive research has been carried out on the antidepressant effects of ketamine since the early 2000s. In 2014, a study with a small number of participants of 20 people showed that taking ketamine through the nose had a rapid antidepressant effect. Since 2019, ketamine in the form of a nasal spray (esketamine) has been approved in the USA and Europe for the treatment of severe, treatment-resistant depression.

For a long time, antidepressants were used exclusively to treat depression because the cause of depression was believed to be a lack of messenger substances, especially serotonin. Some antidepressants target this point and increase the concentration of serotonin between the brain cells. This mode of action can help many people. Until depressed people feel a noticeable effect of the medication, they have to take the antidepressants consistently for two or more weeks. Some patients are unable to take this medication because of possible side effects such as weight gain, headaches, dizziness or sexual dysfunction.

Ketamine affects the brain in various ways, but the effects have not yet been researched in detail. We know that the neurotransmitter glutamate plays an important role in mood. One hypothesis about the effects of ketamine is that it blocks the uptake of the neurotransmitter glutamate into the cell. This sets in motion a number of processes in the brain and reduces negative feelings such as hopelessness and listlessness.

Depression can cause the number and strength of connections (synapses) to decrease in those affected’ brains. This means that the communication highways in the brain are no longer so well connected or some routes have even disappeared completely. Rachel Katz, assistant professor of psychology at Yale University, explains in a university video on YouTube that ketamine causes more connections to form in the brain. This is one reason why ketamine also helps depressed people for whom several antidepressants have had no effect.

Ketamine offers people with severe depression a new treatment option when common antidepressants have failed to help them. One advantage over antidepressants is that ketamine works quickly – sometimes within just a few hours. Those affected do not have to take the medication for weeks to feel an effect. According to a 2021 study, ketamine’s side effects are relatively minor. But treatment with ketamine does not stand alone. The Charité informs that after successful treatment with ketamine, psychotherapy and/or the administration of antidepressants are necessary to avoid a relapse into depression.

In the USA and Germany, ketamine is used to treat severe depression. Ketamine requires a prescription in Germany and is often used in the form of a nasal spray (escatamine) – its use is strictly regulated. In Europe, ketamine may only be used by doctors and treatment may only take place under medical observation. The most common side effects, according to a 2021 study, are headaches, nausea, dizziness, headaches, and a feeling that the body is disconnected from the thoughts. It can also lead to balance problems, an altered sense of taste or psychosis. An increase in blood pressure is also common. In rare cases, panic attacks, mania and out-of-body experiences may also occur.

Ketamine is also abused as a drug. It can be psychologically addictive and long-term consumption can damage the central nervous system.

Anyone who, in addition to treatment-resistant depression, also suffers from poorly controlled high blood pressure, has an overactive thyroid or is in the first trimester of pregnancy should not be treated with ketamine. Patients who have other psychological problems such as personality disorders or addictions should also not undergo ketamine therapy, according to a fact sheet from the Charité.

No, doctors in Europe are not allowed to prescribe the drug for self-medication. In the USA, the US Food and Drug Administration (FDA) warned against self-medication with ketamine in October. A problem has arisen in the USA: Numerous ketamine clinics have been set up that operate in a legal gray area and use ketamine “off label”. So they misuse it. Ketamine is also available online in the form of tablets and nasal spray for self-medication – but this is banned in the USA.

Sources: FDA approval, EMA approval, Columbia University, study 2014, University Medicine Mainz, Max Planck Institute, Yale University on YouTube, FDA warning, study 2021, research in 2000, Ärzteblatt, study on treatment-resistant depression, information sheet Charité, German Depression Aid , Techniker Krankenkasse, Schlossparkklinik Drimstein, with material from the DPA, Ärzteblatt 2