The annual ECNP Congress is Europe’s most important scientific meeting for disease-oriented brain research and attracts more than 5,000 psychiatrists, neuroscientists, neurologists and psychologists from all over the world every year. The congress covers the entire spectrum of human mood, behavior, cognition and emotions – from basic research to clinical care.
More than 60 years after their introduction, doctors have now found the first reliable evidence that taking benzodiazepines intermittently rather than continuously is associated with fewer side effects and fewer falls, hospitalizations and deaths. Benzodiazepines such as Ativan, Librium and Valium were first used in the early 1960s to treat anxiety and insomnia. Until 1977, these were the most frequently prescribed drugs worldwide. They are still considered reasonably safe and effective (although some patients develop a tolerance and become dependent on the drugs, while the risk of falls and fractures in the elderly is a concern). They are still widely used, but modern antidepressants (such as SSRIs) are prescribed more frequently.
Most studies have only investigated the health effects up to a duration of six to eight weeks, which means that little information is available on the results of long-term use over months and years. This has led to contradictory views. Some doctors believe that the use of benzodiazepines should be limited to a few weeks to avoid the risk of tolerance and dependence, or even that they should not be given at all to people over the age of 65, while other doctors believe that long-term use is acceptable. A large data set from Ontario, Canada, was used to investigate how people over the age of 65 with anxiety or insomnia actually took benzodiazepines [1]. Information was available from 57,000 people who took benzodiazepines regularly most days over a six-month period (chronic users) and from 113,000 people who took the drugs over a similar period but with breaks during which they did not take benzodiazepines (intermittent users). Both groups were then observed for a further year. The results show that switching benzodiazepine use from chronic to intermittent could lead to 20% fewer hip fractures, 7.5% fewer falls requiring hospitalization or emergency room visits, and a 24% reduction in the likelihood of needing long-term care.
Physical changes in the brain due to SSRIs
Selective serotonin reuptake inhibitors (SSRIs) usually take a few weeks to show an effect on mental health, but why does it take so long? A study now provides the first evidence that this is due to physical changes in the brain that lead to greater brain plasticity [2]. This could also explain one of the mechanisms by which antidepressants work. Researchers have conducted a randomized, double-blind, placebo-controlled study on a group of healthy volunteers that shows a gradual difference in the number of brain cell synapses between those taking the antidepressant and a control group, depending on how long the treatment lasts. 17 volunteers received a daily dose of 20 mg of the SSRI escitalopram, while 15 volunteers received a placebo. Between three and five weeks after the start of the study, their brains were scanned with a PET that measured the amount of synaptic vesicle glycoprotein 2A in the brain. These scans showed significant differences between the groups in how synapse density developed over time. In those taking SSRIs, a gradual increase in synapses in the neocortex and hippocampus of the brain was observed over time. No effect was observed in those who took placebo.
Running away from depression?
The first study to compare the effect of antidepressants with running exercise on anxiety, depression and general health shows that they have roughly the same mental health benefits – but a 16-week running course performs better than antidepressants in terms of improving physical health [3]. However, the drop-out rate was significantly higher in the group that initially opted for sport. The researchers examined 141 patients with depression and/or anxiety. They had the choice between a 16-week treatment with SSRI antidepressants or a 16-week running therapy in a group. 45 opted for the antidepressants, 96 took part in the running therapy. The members of the group who opted for antidepressants were slightly more depressed than the members of the group who opted for walking. The antidepressant group took the SSRI escitalopram for 16 weeks. The running group had two to three closely supervised 45-minute group sessions per week. Adherence to the protocol was lower in the walking group (52%) than in the antidepressant group (82%), despite the initial preference for walking. At the end of the study, around 44% in both groups showed an improvement in depression and anxiety, with the running group also showing improvements in weight, waist circumference, blood pressure and heart function, while the antidepressant group showed a tendency towards a slight deterioration in these values.
Treatment resistant depression
Around 7% of the adult population in the EU suffered from depression in 2019 and around 20-30% of these patients do not respond to treatment. If sufferers do not respond after two consecutive treatments, they are classified as treatment-resistant depression. Almost all MDD patients undergoing inpatient treatment suffer from treatment-resistant depression. A large clinical study has now shown that the drug esketamine – one of the two main forms of ketamine – performs better than one of the standard treatments for depression [4,5].
The antipsychotic quetiapine is often used for treatment-resistant depression (usually in combination with an antidepressant). However, esketamine NS is the only specifically approved therapy for treatment-resistant depression in Europe. This is a nasal spray that was approved in 2019. The ESCAPE-TRD study was an open-label, single-blind, randomized, controlled trial. The patients were between 18 and 74 years old. All had treatment-resistant depression, and in some cases the depression persisted even after six different treatment attempts. All had taken antidepressants such as SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin and noradrenaline reuptake inhibitors). 336 patients then received esketamine nasal spray plus an SSRI or SNRI, while a further 340 patients received quetiapine plus an SSRI or SNRI. Patients were treated for eight weeks, followed by 24 weeks of maintenance treatment. After eight weeks, 28% of patients taking esketamine plus antidepressants had achieved remission, compared with 18% in the group taking quetiapine. After 32 weeks, 22% of the esketamine patients were still in remission, compared to 14% of the quetiapine group.
Recognizing bipolar mood swings
Bipolar disorder is a mental illness that causes fluctuations in a person’s mood, energy, activity levels and concentration. These fluctuations can make it difficult to carry out everyday tasks and interact with other people. At present, these mood swings are usually diagnosed subjectively, through discussions with doctors or questionnaires. This is time-consuming and requires the immediate presence of a doctor. Now, a group of psychiatrists have used a research-grade wearable device to continuously record multiple physiological biomarkers during the different phases and episodes of bipolar disorder [6]. The physiological biomarkers recorded include electrodermal activity, which indicates the degree of stress caused by the reactivity of the nervous system based on changes in the electrical conductivity of the skin. This is a possible direct indicator of whether someone is in a manic, depressive or normal mood state.
Each participant was given a standard Empatica E4 wristband to wear for around 48 hours. The researchers found that patients with bipolar disorder in their depressive phase exhibited significantly lower electrical skin activity on average than the rest of the bipolar group or the healthy control group. The transition from a manic to a depressive state (or vice versa) was also detectable by a change in electrical skin activity.
Congress: 36th European College of Neuropsychopharmacology (ECNP) Congress
Literature:
- Davies SJC, et al.: Comparative safety of chronic vs intermittent benzodiazepine prescribing in older adults: a population-based cohort study. Journal of Psychopharmacology 2022; 36(4): 460–469.
36. ECNP-Kongress, Barcelona/online. 07.–11.10.2023. - Johansen A, et al.: Escitalopram increases synaptic density in the human brain over weeks. Poster P.0378. 36. ECNP-Kongress, Barcelona/online.
07.–11.10.2023. - Verhoeven JE, et al.: Antidepressants or running therapy: Comparing effects on mental and physical health in patients with depression and anxiety disorders. Journal of Affective Disorders 2023; 329: 19–29. 36. ECNP-Kongress, Barcelona/online. 07.–11.10.2023.
- Vieta E, et al.: Duration and impact of adverse events with esketamine nasal spray and quetiapine extended release in the ESCAPE-TRD phase IIIb trial. Poster P.0149. 36. ECNP-Kongress, Barcelona/online. 07.–11.10.2023.
- Reif A, et al.: Remission/response with esketamine nasal spray versus quetiapine extended release in treatment resistant depression using the Clinical Global Impression-Severity scale. Poster P.0146. 36. ECNP-Kongress, Barcelona/online. 07.–11.10.2023.
- Hidalgo-Mazzei D, et al.: Wearable bracelet tracks bipolar mood swings: changing electrical signals in skin linked to manic or depressed moods. 36. ECNP-Kongress, Barcelona/online. 07.–11.10.2023.
InFo NEUROLOGIE & PSYCHIATRIE 2023; 21(6): 24–25
