What treatment management is effective in cases of treatment resistance?

The prevalence of depression continues to increase. Fortunately, there are a variety of therapeutic options to effectively help those affected. Nevertheless, the chosen intervention does not work as desired for all patients. It is well known that the chance of a response decreases with each change of therapy. So what to do if the disease proves resistant to treatment?

(red) Depressive illnesses are on the rise – and not just as a result of the coronavirus pandemic. The uncertain political situation, wars and environmental debates also fuel fears that can lead to a depressive episode. According to current health insurance data in Germany, days of absence due to mental health issues have reached a new high of 301 days of incapacity to work per 100 insured persons. A depressive episode can be diagnosed if at least two of the three main criteria of depressed mood, loss of interest or joylessness and lack of drive or increased fatigue and at least two secondary criteria with a symptom duration of at least two weeks can be detected. Secondary criteria include reduced concentration and attention, reduced self-esteem and self-confidence, feelings of guilt and worthlessness, negative and pessimistic outlooks on the future, suicidal thoughts or actions, sleep disturbances and reduced appetite. Depending on the number of symptoms, the depressive episode is then classified as mild, moderate or severe.

The severity-guided multimodal treatment management of unipolar depression then consists of pharmacotherapy, psychotherapy and neuromodulation. It is now possible to choose from a range of different active ingredients. In a meta-analysis, 21 antidepressants were compared with each other in terms of their effect. The greatest effect was observed for amitriptyline and the least for reboxetine. The advantage, however, was that all the active substances examined proved to be significantly superior to placebo. Nevertheless, it should be borne in mind that some antidepressants such as amitriptyline or mirtazapine can lead to weight gain. The higher the doses of the substances and the longer the therapy lasts, the higher the risk of developing diabetes. For other active substances, such as milnacipran, bupropion, St. John’s wort and agomelatine, weight-reducing and _{HbA1c-lowering} effects have been shown in some cases. With the exception of paroxetine, the administration of selective serotonin reuptake inhibitors (SSRIs) appears to be rather unproblematic.

Just poor adherence or resistance to treatment?

If unipolar depression does not respond to monotherapy with an antidepressant, possible causes should be evaluated. This includes answering questions about a possible misdiagnosis, comorbidities and depressiogenic comedication, sufficient serum levels in the therapeutic range and adherence. If there is a cause in one of these areas, the first step should be to optimize it. This includes, for example, the discontinuation of interacting substances, dose adjustment or adherence-promoting measures. There are different guidelines for the definition of treatment resistance. Generally speaking, treatment resistance is when patients do not respond adequately to at least two antidepressants of different classes for a sufficient duration and dose. This can be countered with the help of combination therapy, augmentation or a switch to another antidepressant with a different mode of action. The risk factors for treatment resistance are a high number of unsuccessful treatment attempts, a long latency until the start of treatment, the duration of the current index episode, severe symptoms before the start of treatment, comorbid anxiety symptoms and personality disorder as well as concomitant somatic illnesses.