Treatment resistance in psychiatry: state of the art and new directions

Summary & key facts

This paper looks at how common and serious treatment resistance is across mental health problems. The authors reviewed how treatment resistance is defined, measured, and studied. They found big gaps: many disorders do not have agreed rules, research and funding are small compared with how common the problem is, and we do not yet understand the brain reasons behind resistance. They give a checklist and a step-by-step way to assess patients, list drug and non-drug treatments being developed, and call for shared definitions and more research to build targeted treatments.

Key facts:

• Treatment resistance means standard treatments stop working or never worked well enough. It affects roughly 20 to 60 out of every 100 people with a psychiatric disorder.
• People with treatment resistance use more medical services and can have costs up to ten times higher than other patients.
• Researchers found 23 official guideline documents that define treatment resistance for some conditions like schizophrenia, major depression, bipolar disorder, and OCD.
• Many conditions do not have agreed definitions. Panic disorder, post-traumatic stress disorder, and substance dependence often lack clear criteria for when they are called treatment resistant.
• The research focus on treatment resistance has increased in recent years, but studies about it are still less than 1% of all psychiatric research, which is much smaller than the problem's size.
• The authors identified nine drugs and several non-drug approaches being developed specifically to treat resistant forms of schizophrenia, major depression, bipolar disorder, and OCD.
• They point out several main problems: different studies use different definitions, we have a poor understanding of the underlying brain biology, there is not enough investment, and there are too few proven treatments.
• To help future work, the paper offers a reporting checklist so studies can be compared, and an assessment algorithm to help clinicians decide if someone really has treatment resistance or if other issues (like not taking medication) explain the failure.

Abstract

Treatment resistance affects 20-60% of patients with psychiatric disorders; and is associated with increased healthcare burden and costs up to ten-fold higher relative to patients in general. Whilst there has been a recent increase in the proportion of psychiatric research focussing on treatment resistance (R2 = 0.71, p < 0.0001), in absolute terms this is less than 1% of the total output and grossly out of proportion to its prevalence and impact. Here, we provide an overview of treatment resistance, considering its conceptualisation, assessment, epidemiology, impact, and common neurobiological models. We also review new treatments in development and future directions. We identify 23 consensus guidelines on its definition, covering schizophrenia, major depressive disorder, bipolar affective disorder, and obsessive compulsive disorder (OCD). This shows three core components to its definition, but also identifies heterogeneity and lack of criteria for a number of disorders, including panic disorder, post-traumatic stress disorder, and substance dependence. We provide a reporting check-list to aid comparisons across studies. We consider the concept of pseudo-resistance, linked to poor adherence or other factors, and provide an algorithm for the clinical assessment of treatment resistance. We identify nine drugs and a number of non-pharmacological approaches being developed for treatment resistance across schizophrenia, major depressive disorder, bipolar affective disorder, and OCD. Key outstanding issues for treatment resistance include heterogeneity and absence of consensus criteria, poor understanding of neurobiology, under-investment, and lack of treatments. We make recommendations to address these issues, including harmonisation of definitions, and research into the mechanisms and novel interventions to enable targeted and personalised therapeutic approaches.

Topics

Bipolar Disorder and Treatment Schizophrenia research and treatment Treatment of Major Depression

Categories

Health Sciences Medicine Psychiatry and Mental health

Tags

Anxiety Biology Bipolar disorder Clinical psychology Cognition Ecology Major depressive disorder Medicine Panic disorder Psychiatry Psychology Resistance (ecology) Schizophrenia (object-oriented programming)

Conditions & symptoms

Anxiety Depression Obsessive-Compulsive Disorder Panic disorder and phobias PTSD Substance abuse disorder Lack of energy or motivation Poor sleep Sadness or low mood