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Antidepressant Pharmacogenetics

The Journal Of Precision Medicine, April, 2017

The focus of this year’s World Health Organisation (WHO) world health day on April 7th was major depression. The prominence given to depression reflected recent global statistics. Depression has now become the number one cause of disability globally - in both developed and developing nations. The burden of disease from depression has accelerated, out pacing earlier projections that it would become the lead cause of disability globally by 2030. This is cause for alarm at a population health level. Precision medicine offers hope, and antidepressant pharmacogenetics appears at a ‘tipping point’ of wide clinical wide clinical adoption upon adequate replicated peer reviewed evidence on clinical and health economic utility.

For full article, see Antidepressant Pharmacogenetics

Reference: Ajeet B Singh MD, Ph.D, The Journal Of Precision Medicine (April, 2017) Antidepressant Pharmacogenetics

Melbourne startup CNSDose enters one of the world’s largest medical centres to improve the treatment of depression

StartupSmart, March 3rd, 2017

An Australian medtech startup has entered a four-month accelerator in one of the world’s largest medical centres, after completing the Melbourne Accelerator Program and raising $1 million in 2016.

The Texas Medical Centre in the US spans over 4.6 million square metres, with over 9000 beds across several facilities and 10 million patient encounters a year. Nearly $4 billion ($US3 billion) in construction is underway to further develop the precinct.

Just 25 startups and medtech ventures are accepted into its four-month accelerator program TMCx.

CNSDose, founded by chief executive Ajeet Singh and Dr Harris Eyre, is the youngest medtech venture to be selected from Australia to join the accelerator’s current cohort. Ward Medication, founded by Sue Ward in 1997, and Adelaide-based Personify Care, launched in 2014, were also accepted.

For full article, see Melbourne startup CNSDose enters one of the world’s largest medical centres to improve the treatment of depression

Reference: Dinushi Dias, StartupSmart (March 3rd, 2017) Melbourne startup CNSDose enters one of the world’s largest medical centres to improve the treatment of depression

Texas Medical Center Accelerator’s giant digital health cohort includes Australian contingent

MedCity News, February 17th, 2017

Remote monitoring to identify and address high-risk pregnancies (Babyscripts). Making blockchain part of a diabetes management platform (Healthcoin). Wearables that can diagnose and treat neurobehavioral health issues (DOT). These are some of the members of Texas Medical Center Accelerator‘s fourth cohort of healthcare startups, according to a press statement.

The program is part of the TMC Innovation Institute.

In addition to domestic digital health entrepreneurs seeking to make their mark, healthcare accelerators have a lot of appeal for non-U.S. companies seeking to penetrate one of the largest healthcare markets. This cohort includes a handful of health IT and medical device startups from Australia as part of a Biobridge initiative between TMCx and the Health Informatics Society of Australia that functions as an exchange program.

CNSDose from Melbourne developed a way to use genomics to speed up the identification of suitable antidepressants. Another Melbourne company, Ward Medication Management, has a clinical-decision support tool to provide evidence-based prescribing recommendations. Personify Care, which hails from Adelaide, produced a mobile platform to support remote monitoring as patients recover from hospital stays.

For full article, see Texas Medical Center Accelerator’s giant digital health cohort includes Australian contingent

Reference: Stephanie Baum, MedCity News (February 17th, 2017) Texas Medical Center Accelerator’s giant digital health cohort includes Australian contingent

Asia has a unique opportunity to lead the global fight on depression

Bio Spectrum Asia, BioSpectrum Bureau, October 14th, 2016

Associate Prof Ajeet B Singh, Founder & CEO, CNSDose.com, spoke to BioSpectrum about Asia mental health scenario and the stigma associated with it.

Singapore: The term mental illness strikes fear, embarrassment, and confusion. Yet mental illness is an untold opportunity in the 21st century. An opportunity to not only ease often silent suffering, but an opportunity to improve population productivity, and scale innovative health technologies. Chief among mental illness burdens is major depression.

Some 350 million people globally suffer from major depression. The World Health Organisation projects it will be the lead cause of global disability in developed nations by 2030. In the US alone it is estimated to cost US$210 billion dollars a year in health costs and lost productivity. In India mental illness will cost $6.2 trillion between 2013 and 2030, and cost China $27.8 trillion according to a 2015 study by the National Bureau of Economic Research (The Economist Newspaper Ltd). Such metrics have catalysed many governments to prioritise mental health care, but Asia is at risk of lagging behind.

For full article, see Asia has a unique opportunity to lead the global fight on depression

Reference: Bio Spectrum Asia, BioSpectrum Bureau (October 14th, 2016) Asia has a unique opportunity to lead the global fight on depression

Melbourne based start-up CNSDose seeks to develop and refine the way antidepressants are prescribed to individuals by using a genomic test

Bio Spectrum Asia, Aishwarya Venkatesh, August 19th, 2016

Singapore: WHO estimates that globally, nearly 350 million people suffer from depression. As explained by the health governing bodies, depression is a common illness worldwide and is different from mood fluctuations and short responses to daily challenges in life. Affecting more women than men, depression is considered as a major cause of disability, and a major contributor to global disease burden. When long-lasting and with moderate or severe intensity, depression may become a serious health condition and can cause the affected person to suffer greatly and function poorly at work, at school and in the family. At its worst, depression can lead to suicide. Over 800 000 people die due to suicide every year. Suicide is the second leading cause of death in 15-29-year-olds. The burden of depression and other mental health conditions is on the rise globally. A World Health Assembly resolution passed in May 2013 has called for a comprehensive, coordinated response to mental disorders at country level.

For full article, see Melbourne based start-up CNSDose seeks to develop and refine the way antidepressants are prescribed to individuals by using a genomic test

Reference: Bio Spectrum Asia, Aishwarya Venkatesh (August 19th, 2016) Melbourne based start-up CNSDose seeks to develop and refine the way antidepressants are prescribed to individuals by using a genomic test

Evidence Brief: Pharmacogenomics-guided Antidepressant Treatment versus Usual Care for Major Depressive Disorder

U.S. Department of Veterans Affairs, July, 2016

Genetic variation has long been explored as a potential contributor to individual differences in antidepressant treatment outcome. Whether using genetic information can help predict how an individual might respond to a particular antidepressant – referred to as 'pharmacogenomics' – is of great interest for further advancing precision medicine efforts. The clinical rationale behind using pharmacogenomic data to inform antidepressant therapy is that a patient's unique genetic profile may help predict whether a patient will tolerate or respond to a drug, or help tailor the dose that will have the best effectiveness and tolerability.

In January 2015, the White House identified VA as a participating agency in the Precision Medicine Initiative, which takes into account individual differences in people's genes, environments, and lifestyles. To inform this initiative, VA's Office of Research and Development (ORD) is developing a clinical study that builds on the Million Veteran Program (MVP) by implementing Precision Medicine in Mental Health (PMH). The PMH committee focused on depression because of its high prevalence, a need for better treatment strategies, and a growing use of genetic testing for decision-making. To inform study development, ORD commissioned the Evidence-based Synthesis Program Coordinating Center (ESP CC) to conduct an evidence brief on the clinical utility of pharmacogenomics-guided treatment for major depressive disorder (MDD).

For full article, see Evidence Brief: Pharmacogenomics-guided Antidepressant Treatment versus Usual Care for Major Depressive Disorder

Reference: U.S. Department of Veterans Affairs (July, 2016) Evidence Brief: Pharmacogenomics-guided Antidepressant Treatment versus Usual Care for Major Depressive Disorder

Angel investors inject $1m into Melbourne biotech venture CNSDose to tackle depression

Tech Wire Asia, July 14th, 2016

IT’S been a big week for startup venture CNSDose – they just closed a seed investment of about US$1 million from two angel investors, as well as welcoming former Australian trade minister Andrew Robb to its advisory board.

The biotech startup, based in Melbourne, seeks to develop and refine the way antidepressants are prescribed to individuals by using a genomic test. CNSDose aims to use the money to finance a U.S. trial launch on October this year.

CNSDose was founded by psychologist and pharmacogeneticist, Dr Ajeet Singh, who started the venture after coming across a patient who received numerous inaccurate doses for his depression. By the time the patient was referred to Dr Ajeet, he had lost his job, his marriage, and attempted suicide, according to a blog post.

For full article, see Angel investors inject $1m into Melbourne biotech venture CNSDose to tackle depression

Reference: Tech Wire Asia (July 14th, 2016) Angel investors inject $1m into Melbourne biotech venture CNSDose to tackle depression

Melbourne startup CNSDose secures $1 million and brings former trade minister Andrew Robb on as an advisor

Startup Smart, Denham Sadler, July 13th, 2016

A Melbourne biotech startup has secured nearly $1 million in seed funding and brought former federal trade minister Andrew Robb on as an advisor as it looks to improve the way antidepressants are prescribed.

CNSDose is working to develop a genomic test to tailor the prescription of antidepressants for patients and avoid the need for trial and error when prescribing.

The concept has been developed by registered psychiatrist and CNSDose founder Ajeet Singh across nearly a decade.

A DOSE OF SEED FUNDING

The startup recently closed a seed round of nearly $1 million from two anonymous individuals, with the funding used for a trial launch in the US in October.

For full article, see Melbourne startup CNSDose secures $1 million and brings former trade minister Andrew Robb on as an advisor

Reference: Denham Sadler (July 13th, 2016) Melbourne startup CNSDose secures $1 million and brings former trade minister Andrew Robb on as an advisor

Ex Trade Minister Andrew Robb to advise genetic testing startup CNSDose

AFR Weekend, Michael Bailey, July 11th, 2016

Former trade minister Andrew Robb will advise a Geelong start-up that's invented a genetic guide to antidepressant drug dosage, in the mental health advocate's first corporate role since retiring from politics at the recent federal election.

CNSDose, founded at University of Melbourne's MAP accelerator last year by alumni Ajeet Singh, has just raised $1 million and in January inked a distribution deal with a US-wide chain of DNA testing labs, AlphaGenomix.

Now Mr Robb, inspired by his own experience battling depression, is helping the start-up make connections with pathology lab chains in China, Hong Kong and the US, based on his own networks.

For full article, see Ex Trade Minister Andrew Robb to advise genetic testing startup CNSDose

Reference: Michael Bailey (July 11th, 2016) Ex Trade Minister Andrew Robb to advise genetic testing startup CNSDose

Melbourne biotech venture CNSDose secures $1m from two angel investors

Deal Street Asia, Shiwen Yap, July 13th, 2016

Melbourne biotech startup venture CNSDose has closed a seed investment of nearly $1 million from two angel investors. CNSDose seeks to refine how antidepressants are prescribed to individual patients through the use of a genomic test.

In addition to securing funding, the former Australian federal trade minister Andrew Robb is joining the venture’s advisory board. The former head of the psychiatry department at the University of Melbourne, John Tiller, and US medical technology investor Mark Heinemeyer, are already serving as advisors to CNSDose.

Conceptualised and developed by CNSDose founder Dr Ajeet Singh, a psychiatrist and pharmacogeneticist for nearly a decade, the proceeds from the investment will finance a US trial launch in October 2016. This will be followed by its raising of a Series A round to finance global expansion in 2017.

For full article, see Melbourne biotech venture CNSDose secures $1m from two angel investors

Reference: Shiwen Yap (July 13th, 2016) Melbourne biotech venture CNSDose secures $1m from two angel investors

CNSDose Assembling Psychiatric PGx Business Strategy Around Local Distribution Partners

GenomeWeb, Molika Ashford, May 12th, 2016

NEW YORK (GenomeWeb) – Psychiatric pharmacogenomics startup CNSDose announced this week that it is developing a genomic test to predict psychiatric drug dose requirements specifically for Asian populations, in addition to the panel it is already developing primarily for Caucasian populations.

Ajeet Singh, the company's founder and CEO, told GenomeWeb this week that the Australian firm has also recently inked a new distribution partner, Atlanta-based Alpha Genomix, through which it plans to launch the latter test for patients in the US this fall.

For full article, see CNSDose Assembling Psychiatric PGx Business Strategy Around Local Distribution Partners

Reference: Molika Ashford (May 12th, 2016) New PGx Firm CNSDose to Launch Depression Drug Dosing Test. GenomeWeb

Commercial pharmacogenetic-based decision-support tools in psychiatry

The Lancet Psychiatry, Chad A Bousman, Malcolm Hopwood, Apr 25th, 2016

Despite a compendium of pharmacotherapies available for treating psychiatric illnesses, suboptimal response to these therapies is typical and thought to be in part a result of genetic variation. This notion has sparked a personalised psychiatry movement, which has in turn led to the development of several commercial pharmacogenetic-based decision support tools marketed to psychiatrists as an alternative to typical, trial-and-error, prescribing. However, there is considerable uncertainty about the validity and usefulness of these tools and whether there is suffi cient evidence to support their adoption. In this Personal View, we provide an introduction to these tools and assess their potential usefulness in psychiatry practice. We conclude with clinical considerations and development strategies for improving future pharmacogenetic-based decision support tools for clinical use.

For full article, see Commercial pharmacogenetic-based decision-support tools in psychiatry

Reference: Chad A Bousman, Malcolm Hopwood (Apr 25th, 2016) Commercial pharmacogenetic-based decision-support tools in psychiatry. The Lancet Psychiatry

New PGx Firm CNSDose to Launch Depression Drug Dosing Test

GenomeWeb, Molika Ashford, Feb 04th, 2016

NEW YORK (GenomeWeb) – Psychiatric pharmacogenomics firm CNSDose announced its entry into the commercial market during last week's Personalized Medicine World Conference, with plans to launch its depression medication dosing test this May.

The assay's architect, Ajeet Singh, a privately practicing psychiatrist and pharmacogenetics researcher, began his efforts to develop and bring CNSDose to market by demonstrating in a blinded, randomized trial that his proprietary polygene approach improved outcomes over the trial-and-error prescribing that characterizes standard psychiatric practice.

For full article, see New PGx Firm CNSDose to Launch Depression Drug Dosing Test

Reference: Molika Ashford (Feb 04th, 2016) New PGx Firm CNSDose to Launch Depression Drug Dosing Test. GenomeWeb

A 10-Year Quest.

LinkedIn, January 15th, 2016

I became a psychiatrist in February 2005. The story of one of my first patients has shaped my career.

The patient was a gentleman in his 40’s who had suffered two years of crippling depression. He had no history of childhood maltreatment, nor history of excessive life stress, substance misuse, or physical illness to explain his plight. His local doctor escalated venlafaxine (an antidepressant) to 225mg – the maximum recommend dose. But his depression only partially responded. Earlier trials of other antidepressants failed. Psychological counselling failed. By the time he was referred to me, he had lost his job, his marriage, and had attempted suicide.

Psychiatrists have license to exceed maximum manufacturer recommend doses if - on very careful consideration - such seems clinically appropriate. High dose antidepressants are well described in the literature, assisting a subset of patients – putatively due to their metabolism making it very hard for medication to reach their brain at average doses. I gradually escalated the patient’s venlafaxine to 450mg. He fully remitted – depressive symptoms (including suicidal ideations) completely resolved, and after a few months his confidence had returned. I thought to myself – imagine if his first doctor could have known he needed a high dose to recovery, imagine all the personal and economic losses that could have been saved! I didn’t know it at the time, but that was the start of a 10 year quest.

After my first year in psychiatric practice, it was apparent to me that psychiatric prescribing was entirely trial and error. I wanted to try and change this. I made time to see my local professor. I described the mission I had in mind. He responded “That’s interesting, I just got off the phone to a professor in Melbourne, he’s starting a genetics trial to guide antidepressants, interested?” - I said yes!

When I started research I imagined things happened fast – after all it was medical research and people needed answers ASAP. Boy was I wrong! Ethics approval, funding, team logistics, patient recruitment, data collection, data analysis, publication politics, paper rewrites, a thesis, and so several years passed!

I focussed on trying to unlock the pharmacogenetic keys of the blood-brain-barrier – the genetic ‘combination lock’ to get medications into the brain. A doctoral, post-doctoral, and commercial trial followed. 10 years accounted for!

In healthcare I believe there are three realities: academic reality, clinical reality, and commercial reality. It seems people tend to get siloed into one or the other of these realities. Academics complain about clinicians lacking science backed practice. Clinicians complain about academics being out of touch with clinical reality. Both complain about industry focussing on profits more than people. But our patients (and their loved ones) just want better solutions to their suffering. I believe it is at the intersection of academic, clinical, and commercial reality that there is greatest opportunity to find implementable solutions.

Next week I am launching a company in Silicon Valley. A company born from the real world ‘pain point’ of trial and error antidepressant prescribing. A company based on a decade of peer reviewed research. A company whose intent is to affordably reduce trial and error prescribing. I am a clinician, come researcher, come start-up entrepreneur – all in hopes of better serving patients.

Assoc. Prof. Ajeet B Singh (MBBS MPsych MD FRANZCP) is an Australian Psychiatrist & Pharmacogeneticist, Founder & CEO of cnsdose.com

Precision Medicine: Genetically Guided Healthcare is Coming.

LinkedIn, November 21st, 2015

Imagine a future where your risk of diseases like cancer or dementia could be inexpensively genetically predicted, enabling intensified preventative and screening opportunities should one be at above average risk. Imagine a future where if you do get sick, medication is tailored to your unique genetic profile - reducing trial and error to find the right medication. Just ten years ago this vision of the future was considered science fiction, yet such genetic testing has started to become a technological reality in recent years.

The dawn of a new era – genetically guided healthcare – is arguably one of the greatest technological revolutions of all time. This transformational healthcare space is gathering pace – evidenced by ‘precision medicine’ (genetically guided healthcare) being a centrepiece of President Barack Obama’s most recent state of the union address.

Precision medicine’s likely widespread public healthcare value is best reflected in the US and UK governments’ recent direct investments to genetically sequence 1.1 million people. Dramatic accelerated discovery of further clinical benefits from genetics will likely flow over the next few years. The potential benefits are many.

Benefits which stand to reduce premature deaths. Benefits which stand to reduce human suffering. Benefits which stand to reduce spiralling healthcare costs. For these reasons precision medicine is a big deal, but key aspects of both clinical evidence and commercial regulation remain in evolution.

For several years the excitement about precision medicine exceeded the evidence of clinical value. Evidence itself is a complicated area. Different experts have different views about what constitutes adequate evidence for precision medicine to enter routine use.

Third party payers such as governments and insurers also want to see evidence of precision medicine being a good healthcare spend – more cost effective than care as usual.

Finally, consumers and carers have also been demanding greater autonomy and rights to direct their own care. There’s less acceptance of the traditional paternalistic dynamics in the doctor-patient relationship.

These issues leave the regulators – charged with thwarting ‘genetic-snake-oil’ without impeding genuine innovation - in a complex but crucial position. How they regulate clinical decision support systems based on genetic guidance will powerfully determine how well and how quickly innovation in this space is translated into care, and crucially if consumers can directly drive genetic technology uptake.

The depth of evidence deemed necessary by regulators to demonstrate clinical value is pivotal to the field. An overly low evidentiary threshold runs risks of genetic-snake-oil harming people. An overly high evidentiary threshold runs risks of stifling genuine innovation, high entry costs leaving commercialisation to just a few large companies to dominate the market.

There is no perfect answer to these issues. What regulators decide will largely determine if the ‘big pharma’ model is replicated in this space or not. I think a balance between pubic domain and proprietary innovation will optimally bring the future forward – a future of clinically valuable accessible precision medicine for all.

Associate Professor Ajeet B Singh MD is an Australian Psychiatrist & Pharmacogeneticist.

A Big Problem with Antidepressants.

LinkedIn, August 6th, 2015

I’m a private Psychiatrist. Helping those with major depressive presentations is my core work. Sounds like a burnout job? It would be if not for the fact that most people get better. That’s the good news. The bad news - it usually takes months (sometimes years) of trial and error to find the right treatment.

I’ve noticed three main patterns over the years. For some their depression is underpinned by unresolved internal stress stemming from a difficult/damaging childhood. For others their depression is driven by life stress exceeding their capacity to adjust. Finally, for some their mood circuits seem to under function. For this group antidepressant medication can be vital.

A big problem with antidepressants is trial and error prescribing. This process delays recovery and wastes enormous amounts of time.

Traditionally, clinicians have looked for side effects in the first week of treatment and advised patients to reduce the dose if such arise. Then they have to wait a few weeks to see if the medication helps. Ways to reduce trial and error have been a key research area given this drawn out process.

A most promising research front has been genetics. Specifically, genetically determining the unique metabolic profile of a patient to predict which medication might suit best.

The high cost of genetic testing had been prohibitive, but advances in gene sequencing have exponentially cut costs. This makes the technology widely accessible to both researchers and (if clinical benefit is shown) patients.

Genetic technology is exciting. But excitement about potential clinical benefits and evidence of such are not one and the same thing. Many potential medical innovations have come and gone, not delivering claimed benefits. But some advances have gained traction, becoming standard of care over time.

The drive for precision medicine (genetically guided healthcare) has gathered pace. As early association studies move to more definitive comparator trials, it’s on the cards genetically guided prescribing will enter routine practice – if evidence is sufficient. But what constitutes sufficient evidence?

Randomized controlled trials (RCTs) are the gold standard. An RCT entails randomly allocating patients to either have genetically guided prescribing or prescribing as usual. This is crucial as factors (both known and unknown) that could influence the outcome (confounders) even out between the two groups with randomization and a sufficient number of participants. Thus, the only difference between the compared groups is the genetic guidance. Blinding is also necessary – neither patient nor outcome assessor knows who is receiving genetic guidance, preventing study bias.

Such blinded RCTs are underway, and if positive with a large effect size, they will pave the way for reduced trial and error prescribing. When replicated RCTs emerge, genetically guided antidepressant prescribing will become the new standard of care.

Associate Professor Ajeet B Singh MD is an Australian Psychiatrist & Pharmacogeneticist.

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