Diagnosed with treatment-resistant depression? Here's what that means

A diagnosis of treatment-resistant depression (TRD) sounds like the end of the road. Fortunately, it's not.

"Depression, even if it proves to be stubborn, is a very treatable condition," says psychiatrist and psychotherapist Dr Mazda Adli, head of the affective disorders research division at Charité university hospital in Berlin.

So if your doctor says your depression is "treatment-resistant," it doesn't mean nothing more can be done for you. The term is used when adequate dosages of at least two different antidepressants, administered for four to six weeks, don't improve your symptoms.

"It's very important to make clear that 'treatment-resistant' doesn't mean you aren't treatable, but that your depression is simply refractory to treatment," Adli says.

This isn't unusual, he says, noting that about one-third of patients with major depressive disorders don't respond to initial treatment with two antidepressants.

"Patients, their relatives, and also the doctors then need plenty of staying power and patience with treatment," says Adli. There are many ways to help people with depression, he adds, even when medications - and perhaps a first go at psychotherapy - have little effect at the outset.

Should standard treatment methods fail to improve a patient's depression, doctors move on to a clearly specified step-by-stap plan - and even look beyond it - until improvement is achieved.

Possible options are set down in guidelines for the medicinal and psychotherapeutic treatment of depression. They include electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS).

ECT involves a brief electrical stimulation of the brain, under general anaesthesia, that induces a cerebral seizure lasting about a minute. This causes electrical and chemical changes in the brain.

In rTMS, a magnetic coil placed against the patient's scalp delivers magnetic pulses that stimulate brain areas that regulate mood.

While both are proven methods of brain stimulation, less evidence has been gathered to date on the effectiveness of rTMS in improving TRD symptoms.

Dr Andrea Jungaberle, a Berlin-based clinical specialist in anaesthesia and emergency medicine, is also a psychedelic therapist who does research on the therapeutic application of altered states of consciousness - including for depression. She says it's important that doctors and TRD patients together seek further treatment options.

Jungaberle says many doctors, herself included, see substances previously known more as narcotics as giving new hope in treating depression. One of them is esketamine.

Esketamine is a more potent version of ketamine, an established anaesthetic that's also used as a recreational drug - "special K" is one of its street names - and can have hallucinogenic effects. In recent years, esketamine nasal spray has been approved in some places for short-term, emergency treatment of severe depression as well as TRD.

Dr Gerhard Gründer, a professor of psychiatry and director of the Department of Molecular Neuroimaging at the Central Institute of Mental Health (ZI) in Mannheim, Germany, heads a study on the antidepressant effects of psilocybin, a hallucinogenic substance obtained from certain types of ("magic") mushrooms.

At ZI and Charité, 144 TRD patients are being given psilocybin under the supervision of psychotherapists, who prepare them for the experience and then review it with them afterwards.

As Gründer emphasizes, the method is not comparable to a self-experiment with drugs: "Truffles containing psilocybin are legal in the Netherlands, where you can purchase them in shops," he says. "But taking a substance like this is by no means a treatment, which must be well prepared and subsequently evaluated."

Adli, too, underscores the importance of only taking hallucinogenic substances under medical supervision. "After taking them, some people have dissociative experiences," he says. "The feeling, for example, that they're floating through the room, that colours or sound intensities change.

"Some people don't find this at all unpleasant. Others do. And some don't notice anything at all."

As Gründer explains, clinical trials of alternative treatments such as this are aimed at determining their safeness and effectiveness for possible approval by regulatory authorities.

"The euphoria needs to be dampened a bit. In the media - in some articles anyway - psychedelics are touted as a panacea," he says, pointing out that a large number of effective antidepressants are already available, however.

"At the end of the day, psychedelics are simply a very practical - and probably promising - addition to our treatment arsenal."

When it comes to research on the use of psychedelic drugs for medical purposes, Germany, according to Jungaberle, is an international laggard.

"[Research] has been going on considerably longer in Switzerland, and there are studies in Great Britain, the Netherlands and Czech Republic," she says. "Germany has now jumped on the bandwagon, thank God, but we're about five to 10 years behind."

Adli, for his part, would embrace innovative treatments for depression. "We need to develop new antidepressants, and further develop existing ones," he says. "Depression is a very common illness. A particular antidepressant won't help everyone, and more treatment options mean greater treatability."

Psychotherapy is an integral part of treatment for stubborn cases of depression, he notes, adding that physical activity, a balanced circadian rhythm and learning self-care behaviour enhance treatment effectiveness.