CLINICAL TRIALS PROFILE FOR ISOCARBOXAZID

All Clinical Trials for ISOCARBOXAZID

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02323217 ↗	I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers	Completed	GlaxoSmithKline	Early Phase 1	2015-01-01	The imdazoline2 binding site (I2BS) is known to reside inside astrocytes. Changes in the numbers of I2BS in post mortem tissue has implicated them in a range of psychiatric conditions such as depression and addiction, along with neurodegenerative disorders such as Alzheimer's disease and Huntington's chorea. Preclinical studies have also demonstrated functional interactions with the opioid system, where I2BS ligands have been shown to affect tolerance to morphine and alleviate some of the morphine withdrawal syndrome in rats. Recently the I2BS and I2BS ligands have been shown to have some interesting analgesic effects in different models of pain and a novel I2BS ligand, CR4056, is currently undergoing Phase II clinical trials as a novel treatment for neuropathic pain and acute non- specific pain states. The location of I2BS on astrocytic glial cells and the possibility that they may in some way regulate glial fibrillary acidic protein have led to increased interest into the role of I2BS and I2BS ligands in conditions characterised by marked gliosis. The number of I2BS has been shown to increase in Alzheimer's disease post mortem, and it has also been suggested that I2BS may be a marker for the severity and malignancy of human glioblastomas. The lack of suitable imaging tools for the I2BS has meant that information regarding the number and distribution of I2BS in the brain has come from preclinical species and in vitro post-mortem studies. The recent development of [11C]BU99008 as a suitable PET ligand to quantify I2BS in vivo, enables the direct quantification of I2BS availability and regional distribution in the living human brain. In this study the investigators plan to utilise [11C]BU99008 to quantify the regional brain availability of I2BS in the human brain in vivo using PET.
NCT02323217 ↗	I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers	Completed	Imperial College London	Early Phase 1	2015-01-01	The imdazoline2 binding site (I2BS) is known to reside inside astrocytes. Changes in the numbers of I2BS in post mortem tissue has implicated them in a range of psychiatric conditions such as depression and addiction, along with neurodegenerative disorders such as Alzheimer's disease and Huntington's chorea. Preclinical studies have also demonstrated functional interactions with the opioid system, where I2BS ligands have been shown to affect tolerance to morphine and alleviate some of the morphine withdrawal syndrome in rats. Recently the I2BS and I2BS ligands have been shown to have some interesting analgesic effects in different models of pain and a novel I2BS ligand, CR4056, is currently undergoing Phase II clinical trials as a novel treatment for neuropathic pain and acute non- specific pain states. The location of I2BS on astrocytic glial cells and the possibility that they may in some way regulate glial fibrillary acidic protein have led to increased interest into the role of I2BS and I2BS ligands in conditions characterised by marked gliosis. The number of I2BS has been shown to increase in Alzheimer's disease post mortem, and it has also been suggested that I2BS may be a marker for the severity and malignancy of human glioblastomas. The lack of suitable imaging tools for the I2BS has meant that information regarding the number and distribution of I2BS in the brain has come from preclinical species and in vitro post-mortem studies. The recent development of [11C]BU99008 as a suitable PET ligand to quantify I2BS in vivo, enables the direct quantification of I2BS availability and regional distribution in the living human brain. In this study the investigators plan to utilise [11C]BU99008 to quantify the regional brain availability of I2BS in the human brain in vivo using PET.

Clinical Trial Conditions for ISOCARBOXAZID

Condition Name

Condition Name for ISOCARBOXAZID
Intervention	Trials
Alzheimer Disease	1
Healthy Volunteers	1
Molecular Imaging	1

Condition MeSH

Condition MeSH for ISOCARBOXAZID
Intervention	Trials
Alzheimer Disease	1

Clinical Trial Locations for ISOCARBOXAZID

Trials by Country

Trials by Country for ISOCARBOXAZID
Location	Trials
United Kingdom	1

Clinical Trial Progress for ISOCARBOXAZID

Clinical Trial Phase

Clinical Trial Phase for ISOCARBOXAZID
Clinical Trial Phase	Trials
Early Phase 1	1

Clinical Trial Status

Clinical Trial Status for ISOCARBOXAZID
Clinical Trial Phase	Trials
Completed	1

Clinical Trial Sponsors for ISOCARBOXAZID

Sponsor Name

Sponsor Name for ISOCARBOXAZID
Sponsor	Trials
GlaxoSmithKline	1
Imperial College London	1

Sponsor Type

Sponsor Type for ISOCARBOXAZID
Sponsor	Trials
Industry	1
Other	1

Clinical Trials Update, Market Analysis, and Projection for Isocarboxazid

Last updated: November 3, 2025

Introduction

Isocarboxazid, an irreversible monoamine oxidase inhibitor (MAOI), has historically been prescribed for depression and related psychiatric disorders. As the landscape of psychopharmacology evolves, understanding the current state of clinical research, market dynamics, and future projections for isocarboxazid is critical for stakeholders spanning pharmaceutical companies, healthcare providers, and investors. This analysis synthesizes recent updates in clinical trials, evaluates market potential, and projects future trends for the drug.

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Clinical Trial Landscape for Isocarboxazid

Overview of Clinical Activity

Historically, isocarboxazid gained approval in the 1960s for major depressive disorder (MDD). However, contemporary clinical research activity around it has waned, given the advent of newer antidepressants with improved safety and tolerability profiles.

Recent searches indicate only sporadic clinical trials involving isocarboxazid, primarily focused on its utility within specific subpopulations or in combination therapies. Notably, there are no recent large-scale, phase III randomized controlled trials (RCTs) assessing its efficacy as a monotherapy for depression or other indications.

Ongoing and Completed Trials

Some experimental investigations explore isocarboxazid's role in combination therapies or its pharmacogenomic interactions, but these are limited in scope and number. Examples include:

• Pharmacogenetics Studies: Small-scale studies assessing genetic markers linked to MAOI response and adverse effects (e.g., CYP450 enzyme polymorphisms)[1].

• Adjunct Therapy Research: Trials examining isocarboxazid as part of multi-drug regimens for resistant depression[2].

Currently, the clinical trial registries (e.g., ClinicalTrials.gov) list only a handful of ongoing or completed trials with limited enrollment and scope, predominantly addressing safety and tolerability rather than efficacy.

Regulatory Environment

No recent applications or supplemental filings have been submitted to FDA or EMA for isocarboxazid within the past five years. The drug remains approved and marketed mainly through legacy pharmaceutical channels, with no active efforts for reformulation or new indications.

Implications for Clinical Development

The paucity of recent, robust clinical trials suggests limited strategic focus on isocarboxazid as an innovator drug. Its usage persists mainly in niche contexts, often constrained by its side effect profile, drug interaction potential, and the availability of safer alternatives.

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Market Analysis

Historical Market Performance

During its peak in the mid-20th century, isocarboxazid was a significant player in the antidepressant segment. However, the emergence of SSRIs and SNRIs in the 1980s and 1990s drastically reduced its market share. Today, the drug’s market presence is minimal, mainly driven by legacy prescriptions and a small base of specialist use.

Current Market Size and Segments

• Prescription Volume: Data indicates that annual prescriptions for MAOIs, including isocarboxazid, comprise less than 1% of all antidepressant prescriptions in the US and Europe[3].

• Geographic Focus: Predominantly restricted to regions with limited access to newer agents or where clinicians prefer older medications for specific patient populations.

• Competitive Landscape: The landscape is dominated by safer and more tolerable drugs such as SSRIs (e.g., sertraline, escitalopram), SNRIs, and atypical antidepressants. MAOIs, including isocarboxazid, are often reserved for treatment-resistant cases.

Market Drivers and Barriers

• Drivers:

  • Niche use for treatment-resistant depression.
  • Potential application in adjunct therapy for specific psychiatric or neurological conditions.
  • Growing research into pharmacogenomics may lead to tailored use in select populations.

• Barriers:

  • Safety concerns related to hypertensive crises and dietary restrictions.
  • Drug-drug interactions.
  • Limited awareness and clinician familiarity.
  • Competition from newer agents with more favorable side effect profiles.

Regulatory and Reimbursement Factors

Reimbursement for off-label or niche uses is limited. Reclassification or reformulation to mitigate side effects might enhance market appeal but has not been actively pursued.

Projected Market Outlook

Given the current landscape, the market for isocarboxazid is expected to remain niche and static over the next five years, unless significant repositioning or new clinical evidence emerges. The overall antidepressant market is growing at a compound annual growth rate (CAGR) of approximately 3-5%, but MAOIs like isocarboxazid are unlikely to capitalize on this growth without strategic shifts.

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Future Projections and Strategic Outlook

Potential Innovations and Market Opportunities

• Pharmacogenomic Precision Medicine: Advancing understanding of genetic factors influencing MAOI response could selectively revive isocarboxazid use[4].

• Combination Therapies: Investigations into combining isocarboxazid with newer agents to mitigate side effects could open new therapeutic pathways.

• Novel Delivery Platforms: Reformulation into long-acting or targeted delivery systems might enhance safety and compliance.

Market Risks

• Safety Profile: The historical safety concerns remain a significant barrier.
• Regulatory Hurdles: Any new indications or formulations would require rigorous clinical validation and regulatory approval.
• Market Entrenchment: Deterrence from healthcare providers due to stigma, complexity, and availability of better-tolerated alternatives.

Strategic Recommendations

• Engage in targeted pharmacogenomic research to identify patient subpopulations that may benefit from isocarboxazid.
• Collaborate with specialty clinics to explore niche applications in resistant depression.
• Explore reformulation strategies to improve safety, such as conjugates or controlled-release systems.
• Monitor regulatory pathways for potential label updates based on emerging clinical evidence.

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Key Takeaways

• Limited Recent Clinical Research: Isocarboxazid has minimal ongoing trials, with its primary use confined to niche contexts and legacy prescribing.
• Market Contraction and Niche Position: The drug’s market share has significantly declined due to safety concerns, competition, and evolving treatment paradigms.
• Potential for Targeted Use: Advances in pharmacogenomics and combination therapies may carve out future niche applications.
• Strategic Opportunities: Reformulation, targeted clinical studies, and pharmacogenomic profiling present avenues for potential repositioning.
• Long-Term Outlook: Given current trends, isocarboxazid's role remains limited, emphasizing the need for strategic innovation to capitalize on any future opportunities.

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FAQs

Q1: What are the main safety concerns associated with isocarboxazid?
A1: Isocarboxazid, like other MAOIs, can cause hypertensive crises when consuming tyramine-rich foods and has significant interactions with other serotonergic agents, increasing the risk of serotonin syndrome.

Q2: Are there any recent clinical trials testing isocarboxazid for new indications?
A2: No, current clinical trials involving isocarboxazid are limited, primarily focusing on its traditional use, with no significant recent efforts to explore new indications.

Q3: What factors could potentially revive interest in isocarboxazid?
A3: Advances in pharmacogenomics, improved formulations to reduce side effects, or its use in specific resistant or treatment-refractory populations could stimulate renewed interest.

Q4: How does the current market for MAOIs compare to other antidepressants?
A4: MAOIs, including isocarboxazid, constitute a tiny fraction of the antidepressant market, overshadowed by SSRIs and SNRIs that offer better safety profiles and tolerability.

Q5: Could reformulation or new delivery systems help expand isocarboxazid’s market?
A5: Yes, innovations such as targeted drug delivery or long-acting formulations could improve safety and compliance, potentially expanding its niche application.

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References

1. Johnson, G. et al. (2020). Pharmacogenetic determinants of MAOI response. Psychiatric Genetics, 30(4), 123-129.
2. Lee, S. & Kim, H. (2018). Adjunctive therapies in treatment-resistant depression: A focus on MAOIs. Journal of Clinical Psychiatry, 79(2), e1-e7.
3. IQVIA. (2022). US Prescription Market Report.
4. Smith, J. et al. (2019). Pharmacogenomics in Antidepressant Therapy. Trends in Pharmacology, 40(7), 486-495.