Treatment-Resistant Depression in Real-World Clinical Practice: A Systematic Literature Review of Data from 2012 to 2022

Summary & key facts

Researchers reviewed 20 studies done in regular clinical settings over the last 10 years to see what happens to people with treatment-resistant depression, which means they did not get better after trying at least two adequate treatments. They found that people usually had depression for many years and had moderate to severe symptoms. Studies were small and used many different definitions and methods, so it is hard to compare treatments or know which ones work best in everyday life.

Key facts:

• The review looked at 20 real-world studies published from 2012 to 2022.
• Treatment-resistant depression here means people did not respond to two or more treatments.
• People in the studies had lived with depression for many years, usually between about 1 and 17 years.
• At the start of the studies, depression severity was usually in the moderate to severe range.
• Most studies were small, often including about 15 to 400 people each.
• How long people were followed varied a lot, from a few weeks to almost 9.5 years.
• Remission, which means symptoms mostly go away, was usually uncommon, but remission rates tended to be higher when people were followed for longer.
• Only two studies measured how depression affected people’s overall quality of life and work, so we know little about day-to-day impact.
• Studies used different definitions and measurement methods, which makes it hard to compare results across studies.
• The authors say there is a need for faster and more effective treatments and for future studies to use common ways to measure severity and outcomes.

Abstract

Real-world evidence in treatment-resistant depression (TRD; commonly defined as non-response to ≥ 2 consecutive treatments at adequate dosage and duration) is lacking. A systematic literature review was conducted to understand disease burden and treatment outcomes for patients with TRD, studied in a real-world setting over the last decade. A literature search was conducted in May 2022 in MEDLINE, Embase, The Cochrane Libraries and PsycINFO, comprising studies published from 2012 to 2022. Bibliographies of all relevant identified systematic reviews and relevant conference proceedings from 2020 to 2022 were manually hand-searched. Real-world studies, including cohort, cross-sectional, case–control, chart review and registry studies, published in English and reporting outcomes in adults with TRD, were included. Extracted data included study and baseline disease characteristics, treatment type, treatment response, clinical outcomes and health-related quality of life. Twenty studies were included. Criteria for TRD varied, but patients typically experienced long-lasting depression (range 1.4 to 16.5 years). Across studies, mean disease severity scores demonstrated moderate to severe depression, reflecting a high burden of disease at baseline. Remission rates were typically low but generally increased with longer follow-up durations. However, the heterogeneity of interventions, follow-up durations (range 2 weeks to 9.4 years) and assessment tools precluded their quantitative synthesis. Studies were frequently limited by low sample size (range 14 to 411 patients) and health-related quality of life was infrequently assessed. There is a lack of clinical consensus regarding the definition, assessment and monitoring of TRD in real-world practice. Nevertheless, TRD carries a high burden of illness and there is an unmet need for faster and more effective treatments. To better understand the personal burden of affected patients, future studies would benefit from standardisation of severity assessment and measures of treatment effectiveness, as well as greater consideration of health-related quality of life. Many people continue to experience depression even after trying two or more medications. This is called treatment-resistant depression (TRD). Most of the information we have on TRD comes from clinical trials, which take place under tightly-controlled conditions. It is important to understand the effects of TRD and TRD treatments on people in their day-to-day lives. Researchers studying people’s day-to-day lives call this researching in a “real-world setting”. We searched for studies carried out in real-world settings in the last 10 years. We found 20 relevant studies. As these studies were in real-world settings, there were many differences between them, including differences in how TRD was diagnosed, the treatments used, how long people were monitored and how results were measured. This made it difficult to compare how successful different treatments were. Most studies included a small number of people and monitored them for a relatively short time. We found people with TRD had usually lived with it for many years and their symptoms were moderate or severe. Only two studies asked people how TRD affected their lives. These two studies found health-related quality of life and work productivity was low. Most studies found lots of people still had symptoms of depression after treatment. However, symptoms typically improved more when studies monitored people for a longer time. To improve our knowledge of TRD, future studies should monitor more people for longer and use the same ways of measuring results. They should also ask how TRD affects people’s daily lives.

Topics

Digital Mental Health Interventions Mental Health Treatment and Access Treatment of Major Depression

Categories

Health Sciences Medicine Pharmacology

Tags

Amygdala Depression (economics) Economics Internal medicine Law Macroeconomics Major depressive disorder Medicine MEDLINE Meta-analysis Nursing Physical therapy Political science Psychiatry Psychological intervention PsycINFO Quality of life (healthcare) Systematic review Treatment-resistant depression

Substances

Ketamine

Conditions & symptoms

Depression Difficulty focusing Lack of energy or motivation Poor appetite or overeating Poor sleep Sadness or low mood