13 January 2021

Since the outbreak of the corona virus, many of us have been staying at home in order to limit our social interactions. We do this to keep ourselves and others safe from the spread of Covid-19. Yet, there’s also concern about what social distancing and anxiety generated by media reports are doing to people's mental health. Two researchers at Radboudumc and the Donders Insitute Department of Psychiatry talk about the current situation and the grants they have received for their research on depression.

“Department of Psychiatry has set up a National Register for Covid-19 in Psychiatry, together with the University of Utrecht and the Dutch Society for Psychiatry. Its aim is twofold,” explains neuroscientist Indira Tendolkar. Her research focuses on stress-related adaptation and maladaptation of the so-called declarative memory system and she is on the steering committee of this national initiative.

Studying the effects of the virus

“On the one hand, we’re gathering information on the impact that Covid-19 has on patients already suffering from severe psychiatric diseases, of which major depression is one of the most common.

“On the other hand, we’re looking into what we call ‘de novo neuropsychiatric effects’ of the virus itself, because we know that it affects the brain. So, it's not only that the socio-economic consequences have an enormous impact, but it's also that we need to learn what the virus itself does to the brain.

“It’s also important for us to look at the role the media plays in the crisis. All the media attention makes dispiriting news difficult to ignore for those who are naturally inclined to focus on the negative. It adds to their tendency to catastrophize. Depression and anxiety are twins, co-occurring. We, as professionals, have the duty to check with our patients how they are dealing with the constant bombardment of information.”

The stigma of ECT

Collaborative research led by the Donders Institute and Amsterdam UMC has recently received a €600,000 ZonMw grant. The grant is for research on electroconvulsive therapy (ECT) – a treatment for people suffering from chronic depression. ECT is also known as ‘shock therapy’ – a term that evokes negative connotations. "And not just among patients and their families, but also among many caregivers," Indira explains. "The grant was awarded to discover why there’s resistance to the treatment so that we can alleviate the fear and better inform people of its effectiveness.

“People still associate ECT with a painful form of treatment that does lasting damage to the brain and is usually given without consent. This idea is outdated. Under general anaesthesia, small electric currents in the brain change brain chemistry and induce plasticity as a way to tackle symptoms. The currents can be delivered with increasing precision. Often, a patient receives this treatment twice a week until remission of symptoms or a plateau is reached. After that, patients are put back on other forms of therapy.”

If-all-else-fails treatment

“In the Netherlands, the treatment is only permitted if strict guidelines are followed. Patients get ECT when medication and at least one validated form of psychotherapy have failed. Our research, however, shows that, especially for the elderly, it might be more effective if it were given sooner. In other words, we think that ECT should be an option earlier in a treatment program. There is an extra benefit here – the fact that it’s no longer being used as an if-all-else-fails treatment will help reduce fear of ECT.

“We want to develop a constantly updated decision tool that can help, for example, both GPs and children of elderly patients to decide what the best options are. My goal, in the long run, is to replace ECT with minimally invasive and targeted treatment options. But if my mother were to develop severe depression tomorrow, not eating and maybe having nihilistic delusions, and we know that this can quickly lead to very severe complications, I would ask for an ECT consultation. You could say I'm biased, but I believe that in severe cases ECT can be effective. It’s now given too late and in only 1.2 percent of patients who could potentially be helped.”

Reducing antidepressants

P2-3 Eric RuheIndira’s colleague and psychiatrist Eric Ruhé also recently received a large ZonMw grant. His TAPER-AD study aims to answer the question how best to taper antidepressants to mitigate ‘discontinuation’ symptoms. “Antidepressants can be valuable for curing people with depression," Eric explains. "However, we estimate that some 30 to perhaps 60 per cent of patients have difficulty getting off the medication after recovery.”

Eric and his fellow researchers at the Donders Institute and Amsterdam UMC will gradually reduce the dose of antidepressants before total discontinuation. “The discontinuation symptoms that some people have are likely related to the speed of how fast their serotonin transporter (SERT) occupancy – which is the primary target of antidepressants – is reduced. Conventional doses of drugs deliver very high levels of SERT occupancy in a curvilinear way. If you reduce the dose linearly, the lower you get, the faster the decrease of SERT occupancy. This is why the last step in conventional reduction ­– from 10 milligrams to 0 mg of paroxetine – has such a large impact. What happens if we taper off the drug based on a linear decrease of SERT occupancy, based on calculations of the dose-occupancy relationship? Importantly, with the double-blind randomised design of TAPER-AD, we’ll control for both placebo and nocebo effects, which is unprecedented.”

He also investigates whether reducing antidepressants more smoothly will help regulate the recurrence of depressive episodes. This is connected to his other research, SMARD, in which he studies both the neurobiological basis of recurrent depression in the brain and smartphone interventions to reduce the risk of recurrence. “We should not underestimate the burden of recurring depression and the fear of patients for a new episode.”

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