PUBLISHER: DelveInsight | PRODUCT CODE: 1259773
PUBLISHER: DelveInsight | PRODUCT CODE: 1259773
Key Highlights
'DelveInsight's"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.
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.
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 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 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.
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.
Delveinsight's 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
We perform 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-Asberg 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.
Key Questions
Market Insights
Epidemiology Insights
Current Treatment Scenario, Marketed Drugs, and Emerging Therapies