Treatment-Resistant Depression (TRD) - Market Insight, Epidemiology And Market Forecast - 2032

Key Highlights

• Treatment Resistant Depression (TRD) typically refers to an inadequate response to at least two antidepressant medications used for a sufficient time at an adequate dose with an adequate affirmation of treatment adherence. TRD is a relatively common occurrence in clinical practice, with up to 50-60% of the patients not achieving adequate response following antidepressant treatment.
• In 2022, the market size of TRD was highest in the US among the 7MM, accounting for approximately USD 2,400 million, which is further expected to increase by 2032.
• Several factors lead to inadequate treatment of depression in the elderly. Medical comorbidity, being one of the most common factors, may mask the depressive illness or lead medical practitioners to conclude that the symptoms of lowered mood are a component of the physical disorder.
• Before deciding that a patient is treatment-resistant, physicians should assess the adequacy of treatment by determining adherence to the medication. Ongoing cognitive behavior therapy (CBT) and frequent follow-ups with the physician may encourage adherence during the early stages of treatment.
• As per the French treatment guidelines for the TRD management, hospitalization is systematically recommended in cases of high suicidal risk, presence of psychotic symptoms, severe forms of Major Depressive Disorder (MDD), and three unsuccessful attempts of antidepressant treatment.
• Treatment options for TRD include both pharmacological as well as nonpharmacological treatment options. Pharmacological treatment options include switching, combining, and developing potential strategies among the commonly used antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. Whereas, nonpharmacological options consist of therapies such as Electroconvulsive Therapies (ECT), repetitive Transcranial Magnetic Stimulation (rTMS), and Vagus Nerve Stimulation (VNS).
• SPRAVATO was approved by FDA in 2019, and it is the only FDA-approved nasal spray indicated for TRD.
• Due to a robust pipeline equipped with high-priced therapies on one side and a dynamic market space with increasing pressure from payers and limitations in evidence development on the other side, market access strategies become all the more important for a successful market launch in TRD.
• The emerging therapies in the market for TRD include Novartis' MIJ821, COMPASS Pathways COMP360 (Psilocybin), Beckley Psytech's BPL-003, Navitor Pharmaceuticals' NV-5138, and others have the potential to create a significant positive shift in the TRD market size.

This “Treatment Resistant Depression (TRD) - Market Insights, Epidemiology and Market Forecast - 2032 report delivers an in-depth understanding of historical and forecasted epidemiology as well as market trends of TRD in the United States, EU4 (Germany, France, Italy, Spain) and the United Kingdom, and Japan.

TRD market report provides current treatment practices, emerging drugs, market share of individual therapies, current and forecasted 7MM TRD market size from 2019 to 2032. The report also covers current TRD treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.

Geography Covered

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2019-2032

TRD Disease Understanding and Treatment

TRD Overview

Treatment-resistant Depression (TRD) typically refers to an inadequate response to at least two antidepressant medications used for a sufficient time at an adequate dose with the adequate affirmation of treatment adherence.

The European Union's Committee for Human Proprietary Medicinal Products (CHMP) defines TRD as follows: ‘A patient is considered therapy-resistant when consecutive treatments with two products of different classes, used for a sufficient time at an adequate dose, fail to induce an acceptable effect.' Unfortunately, this broad definition does not properly specify what a sufficient length of time,' ‘adequate dose,' and ‘acceptable effect' means.

TRD is usually linked to higher rates of comorbidity, particularly with other psychiatric disorders, chronic pain, and fibromyalgia. On the other hand, the impact of physical and psychiatric illness comorbidities is much higher among TRD patients. Some environmental factors related to TRD are lower socioeconomic status, non-supportive social environment, family conflicts, chronic stressors, multiple loss events, lower levels of education and social support, and work dysfunction.

TRD Diagnosis

A diagnostic evaluation is required to treat and manage patients who do not respond well to medication. The possible role of several contributing factors, such as medical and psychiatric comorbidity, must be considered. Accurate and systematic TRD evaluation is a problem for clinicians and researchers, with clinician-rated or self-rated instruments being potentially beneficial. There may be varying degrees of treatment resistance. Some staging methods for assessing treatment resistance in depression are being developed, but they must be empirically verified.

Further details related to country-based variations are provided in the report.

TRD Treatment

There are five main strategies used to overcome a partial or lack of response to antidepressant therapy: optimization, switching, combination, augmentation, and somatic therapies. Because there is no standard treatment approach, mental health experts offer the aforesaid strategies based on re-evaluating patients with TRD. The patient with depression not responding to antidepressant monotherapy requires a highly individualized treatment plan, and accordingly, some people will respond to a specific treatment while others do not. Finding the right approach to treat depression can take a lot of effort and time.

According to the French Clinical Guidelines for the Management of TRD, the switching strategy from one antidepressant to another can be envisaged in three ways concurrent switch, overlapping switch, and sequential switch. The switching strategy is recommended when there is no response to the initial treatment, poor tolerance to the initial treatment, and when a previous response is observed to the newly introduced treatment.

The treatment landscape of TRD is expected to change substantially and experience growth. The TRD market will be dominated by antidepressants such as selective serotonin reuptake inhibitors (SSRIs), dual serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and others. The upcoming launch of innovative therapies such as MIJ821 (Novartis), NV-5138 (Navitor Pharmaceuticals), BPL-003 (Beckley Psytech Limited), and others are expected to drive the market further.

TRD Epidemiology

As the market is derived using a patient-based model, the TRD epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by Total Diagnosed Prevalent Cases of TRD, Gender-specific Cases of TRD, and Age-specific Cases of TRD, in the 7MM covering the United States, EU4 countries (Germany, France, Italy, Spain) and the United Kingdom, and Japan from 2019 to 2032.

• The total diagnosed prevalent cases of TRD in the 7MM were approximately 6,409,000 cases in 2022 and are projected to increase during the forecast period (2023-2032).
• The United States contributed to the largest number of diagnosed prevalent cases of TRD (~71%) in the 7MM in 2022. Whereas EU4 and the UK, and Japan accounted for around 25% and 4% of the total diagnosed prevalent cases of TRD in the 7MM, respectively, in 2022.
• Among the EU4 countries, Germany accounted for the highest number of total diagnosed prevalent cases of TRD, whereas Italy accounted for the lowest number of cases in 2022.
• The estimates that around 512,000 cases and 1,117,000 cases of TRD were observed in males and females, respectively, in EU4 and the UK in 2022. The cases are projected to increase during the forecast period.
• In 2022, the maximum number of cases of TRD was found in 50-60 years, and the least number of cases were found in 18-29 years in the US.

TRD Drug Chapters

The drug chapter segment of the TRD report encloses a detailed analysis of TRD-marketed drugs and late-stage (Phase III and Phase II) pipeline drugs. It also helps understand the TRD clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.

Marketed Drugs

SPRAVATO (esketamine): Johnson & Johnson

SPRAVATO (esketamine) is the only nasal spray treatment indicated for TRD. It is an NMDA receptor antagonist believed to work differently by acting on a pathway in the brain that affects glutamate. It has the first new mechanism of action in decades to treat Major Depressive Disorder. In March 2019, the FDA approved SPRAVATO as an oral antidepressant in adults with TRD. But since then, the drug has faced many challenges as the insurance companies tried to understand the treatment and how it worked.

SPRAVATO is given through Risk Evaluation and Mitigation Strategy (REMS) program. The drug also comes with a black box warning highlighting sedation; dissociation; abuse and misuse; and suicidal thoughts and behaviors. With limited treatment options, this drug was a ray of hope for all TRD patients, but it seems that the drug has not generated enough revenue to be called a blockbuster. Currently, Johnson & Johnson is not reporting any revenue from this product. As per their latest reports, the product should have crossed the threshold revenue so that it could be reported separately, but it seems the drug has still not achieved it.

Note: Detailed current therapies assessment will be provided in the full report of TRD…

Emerging Drugs

MIJ821: Novartis

MIJ821 is a potent, subtype-selective NMDAr 2B receptor, the negative allosteric modulator (NAM). The product was discovered by Cadent Therapeutics to produce rapid ketamine relief to patients without ketamine like side-effects. Later, Cadent Therapeutics licensed the intellectual property for NMDA receptor compounds (MIJ821) that selectively modulate NR2B to Novartis exclusively. The drug is undergoing a Phase II proof of concept study, the detailed results of which are still awaited.

COMP360 (Psilocybin): COMPASS Pathways

COMP360 (Psilocybin) are naturally occurring magic mushrooms consumed for their hallucinogenic effects. It has a high affinity for several serotonin receptors, including 5-HT1A, 5-HT2A, and 5-HT2C, located in numerous brain areas, including the cerebral cortex and thalamus. They belong to a group of drugs known as psychedelics because of the changes experienced in perception, mood, and thought.

COMPASS Pathways has developed a synthesized formulation of psilocybin, COMP360, and is investigating the effectiveness of psilocybin therapy.

In November 2022, the company announced positive results from its Phase IIb trial of COMP360 psilocybin therapy for treatment-resistant depression (TRD), the largest study of its kind. It is currently in Phase III pivotal trial for TRD.

Psilocybin has comparable results to SPRAVATO and is anticipated to last much longer, decreasing treatment frequency and potentially increasing cost-effectiveness. Even with better findings, the likelihood of success and psilocybin uptake remains uncertain. Magic mushrooms are classified as a Schedule I drug, which means they have a high potential for abuse, “no presently” “accepted medical use” in the United States, lack accepted safety for use under medical supervision, and cannot be prescribed, marketed, or sold in the United States. If the drug gets approval, the DEA must alter the schedule, which would take some time.

Note: Detailed emerging therapies assessment will be provided in the final report.

Drug Class Insights

The current treatment of TRD consists of different approaches classified into pharmacologic and nonpharmacological therapies.

Pharmacologic treatment options include switching, combination, and potentiation strategizing among the commonly used antidepressant drugs. Most of the available antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), dual serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, irreversible, non-selective monoamine oxidase inhibitors (MAOIs), a2-antagonists, agomelatine, and tianeptine are used to treat TRD.

Nonpharmacological therapies include electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and vagus nerve stimulation (VNS). Along with this, two alternative forms of psychotherapy involve majorly cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT).

TRD Market Outlook

TRD is usually linked to higher rates of comorbidity, particularly with other psychiatric disorders, chronic pain, and fibromyalgia. On the other hand, the impact of physical and psychiatric illness comorbidities is much higher among TRD patients. Some environmental factors related to TRD are lower socioeconomic status, non-supportive social environment, family conflicts, chronic stressors, multiple loss events, lower level of education, and social support and work dysfunction.

Pharmacologic treatment options include switching, combination, and potentiation strategy among the commonly used antidepressant drugs. Most of the available antidepressants, such as Selective Serotonin Reuptake Inhibitor (SSRI), Dual serotonin and norepinephrine reuptake inhibitors (SNRIs), Tricyclic antidepressants, Irreversible, non-selective monoamine oxidase inhibitors (MAOIs), a2-antagonists, Agomelatine, Tianeptine are used to treat TRD.

SPRAVATO and SYMBYAX are the two FDA-approved drugs specifically for the treatment of TRD. Other pharmacologic alternatives are also considered those having an antidepressant action such as in monotherapy: Bupropion, selective and reversible MAOIs, Quetiapine, and in combination with a first-line antidepressant: lithium, Lamotrigine, and second-generation antipsychotics.

Nonpharmacological therapies include electroconvulsive therapy (ECT), Repetitive transcranial magnetic stimulation (rTMS), and Vagus nerve stimulation (VNS). Along with this, two alternative forms of psychotherapy involve majorly cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT).

Various new therapies are in development, focusing on alleviating the limitations of the currently approved drugs. Some of the most prominent ones include MIJ821 (Novartis), Psilocybin (COMPASS Pathways), and others.

As numerous potential therapies are being investigated to manage TRD, it is safe to predict that the treatment space will experience significant reconstitution during the forecast period. However, the challenges of pricing and reimbursement accompanied by limited side effects are two factors that will decide the fate of all these pipeline therapies and the impact they will have on overall revenue generation.

Key players such as MIJ821 (Novartis), Psilocybin (COMPASS Pathways), and others are evaluating their lead candidates in different stages of clinical development, respectively. They aim to investigate their products for the treatment of TRD.

• The total market size of TRD in the 7MM was approximate ~USD 3,100 million in 2022 and is projected to increase during the forecast period (2023-2032).
• In 2022, the US captured the highest market share (84%), followed by Germany (5%), out of all the 7MM countries.
• The UK accounted for a market size of ~USD 110 million in 2022. The market size is further expected to increase during the forecast period.
• In Japan, the TRD market size is expected to increase at a CAGR of 2% during the forecast period (2023-2032).

TRD Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2019-2032. For example, for MIJ821, which is expected to be launched in the US in 2027, the drug uptake is expected to be slow-medium, with a probability-adjusted peak patient share of ~1% in the US, expected to peak at 8 years from the year of launch.

Further detailed analysis of emerging therapies drug uptake in the report.

TRD Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I stage. It also analyzes key players involved in developing targeted therapeutics.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for TRD emerging therapies.

KOL Views

To keep up with current market trends, we take KOLs and 'SME's opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on TRD evolving treatment landscape, patient reliance on conventional therapies, patient's therapy switching acceptability, and drug uptake, along with challenges related to accessibility, include Medical/scientific writers and Professors from renowned universities in the US, Europe, the UK, and Japan.

This analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers such as Icahn School of Medicine, Ohio State University, Kyushu University Hospital etc., were contacted. Their opinion helped understand and validate current and emerging therapy treatment patterns of TRD market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

The publisher performs Qualitative and Market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the Analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Conjoint Analysis analyzes multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.

In efficacy, the trial's primary and secondary outcome measures are evaluated; for instance, in trials for TRD, one of the most important primary endpoints is the change in depressive symptoms over time, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). Based on the MADRS score, the overall efficacy is evaluated.

Further, the therapies' safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Market Access and Reimbursement

The cost of newly approved medications is usually high, and because of it, patients escape from proper treatment or opt for off-label and cheap medications. It affects market access to newly launched medications, and reimbursement is crucial. Often, the decision to reimburse comes down to the 'drug's price relative to the benefit it produces in treated patients. Market access and reimbursement options can differ depending on regulatory status, target population size, the setting of care, unmet needs, the magnitude of incremental benefit claims, and costs.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Scope of the Report

• The report covers a segment of key events, an executive summary, and a descriptive overview of TRD, explaining the definition of TRD, clinical manifestations, risk factors involved in TRD, and the pathogenesis and genetics of TRD.
• Comprehensive insights have been provided into the epidemiology segments and forecasts, the future growth potential of diagnosis rate, disease progression, and treatment guidelines.
• Additionally, an all-inclusive account of the current and emerging therapies, along with the elaborative profiles of late-stage and prominent therapies, will impact the current treatment landscape.
• A detailed review of the TRD market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis and expert insights/KOL views, patient journey, and treatment preferences that help shape and drive the 7MM TRD market.

TRD Report Insights

• Patient Population
• Therapeutic Approaches
• TRD Pipeline Analysis
• TRD Market Size and Trends
• Existing and future Market Opportunity

TRD Report Key Strengths

• Ten Years Forecast
• 7MM Coverage
• TRD Epidemiology Segmentation
• Key Cross Competition
• Attribute analysis
• Drugs Uptake and Key Market Forecast Assumptions

TRD Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT and Conjoint Analysis)

Key Questions Answered

Market insights

• What was the TRD total market size, the market size by therapies, market share (%) distribution in 2019, and what would it look like in 2032? What are the contributing factors for this growth?
• How will antidepressants affect the treatment paradigm of TRD?
• What kind of uptake SSRIs and SNRIs will witness in TRD patients in the coming years?
• Which class is going to be the largest contributor in 2032?
• What are the pricing variations among different geographies for approved and off-label therapies?
• How would the market drivers, barriers, and future opportunities affect the market dynamics and subsequent analysis of the associated trends?

Epidemiology insights

• What are the disease risk, burdens, and unmet needs of TRD? What will be the growth opportunities across the 7MM with respect to the patient population pertaining to TRD?
• What is the historical and forecasted TRD patient pool in the United States, EU4 (Germany, France, Italy, Spain) and the United Kingdom, and Japan?
• What is the diagnostic pattern of TRD?
• Which clinical and sociodemographic factors will affect TRD?
• Which factors will affect the increase in the diagnosis of symptomatic cases?

Current treatment scenario, marketed drugs, and emerging therapies

• What are the current options for th treatment of TRD? What are the current treatment guidelines for the treatment of TRD in the US, Europe, the UK, and Japan?
• How many companies are developing therapies for the treatment of TRD?
• How many emerging therapies are in the mid-stage and late stage of development for the treatment of TRD?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitation of existing therapies?
• What have key designations been granted for the emerging therapies for TRD?
• What is the cost burden of approved therapies on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved therapies?
• What are the 7MM historical and forecasted market of TRD?

Reasons to Buy

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the TRD market.
• Insights on patient burden/disease incidence, evolution in diagnosis, and factors contributing to the change in the epidemiology of the disease during the forecast years.
• Understand the existing market opportunity in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, Spain) and the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of class-wise potential current and emerging therapies under the Conjoint analysis section to provide visibility around leading classes.
• Highlights of Access and Reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet need of the existing market so that the upcoming players can strengthen their development and launch strategy.