Treatment-resistant depression

Treatment-resistant depression refers to a depressive condition in which symptoms persist despite repeated attempts with conventional treatment. The term is typically used when there has been insufficient response to at least two different antidepressants given at adequate dose and duration, often in combination with psychotherapy.

In treatment-resistant depression, more pronounced and persistent alterations in the brain’s regulatory mechanisms are often observed compared with milder forms of depression. Research points to a more stable reduction in activity in prefrontal regulatory regions—particularly the left prefrontal cortex—combined with sustained overactivity in emotional and stress-related networks. This entrenched imbalance makes it more difficult for the brain to respond to conventional treatment alone.

In practice, this means that negative thought patterns, low energy, loss of initiative, and cognitive difficulties can become chronic, and patients often experience repeated treatment changes without sufficient or lasting improvement. For many people with treatment-resistant depression, the burden is substantial and functioning is significantly reduced over long periods.

rTMS is increasingly used specifically for treatment-resistant depression, with the aim of directly influencing the brain’s regulatory circuits rather than working solely through chemical neurotransmitters, as is the case with medication.

In treatment-resistant depression, stimulation typically targets the left prefrontal cortex, which is often persistently underactive. Repeated stimulation over several weeks can increase activity in this area and gradually strengthen the brain’s capacity for top-down regulation of emotional and stress-related networks. The goal is not an immediate “normalisation,” but a slow re-establishment of more flexible and adaptive brain function.

Treatment is provided on an outpatient basis at the clinic. You remain awake throughout the session and can go straight home afterwards. The stimulation itself lasts no more than 20 minutes, and we set aside at least 45 minutes for each appointment to allow time for preparation and a short conversation. A full course of treatment most often consists of 30–36 sessions distributed over approximately six weeks.

In patients with treatment-resistant depression, the effects of rTMS are often more gradual than in less complex depressive courses. Many experience the first changes after 10–20 sessions, typically in the form of increased energy, a lighter mood, improved concentration, or greater mental clarity. For some, improvement emerges subtly and can be difficult to identify from day to day, but becomes clear over time.

The effect develops through neuroplasticity—the brain’s ability to change its function and connections over time—and patience is therefore an important part of the treatment course. rTMS does not work for everyone, even in treatment-resistant depression. Some achieve marked improvement, others a more moderate effect, and a smaller group experience no significant benefit. For this reason, an individual assessment is always carried out before treatment begins.

Side effects are generally mild and transient. The most common are mild headache or discomfort during stimulation, particularly at the beginning of the course.

In treatment-resistant depression, the following are often used:

• Repeated or combined antidepressant treatments

• Psychotherapy, often in longer-term courses

• Adjunctive pharmacological treatment (e.g. mood stabilisers or antipsychotics)

• ECT for severe, chronic, or life-threatening depression

ECT remains the most effective treatment for severe treatment-resistant depression, but is also considerably more invasive, requires anaesthesia, and carries a higher risk of side effects, including effects on memory.

rTMS positions itself as a less invasive alternative or supplement: without anaesthesia, without systemic side effects, and with documented effectiveness in a proportion of patients with treatment-resistant depression.