Part 1 of 2
A two-part report on the global depressed population; the role of technology in causing depression; and a VC’s investment framework for solutions.
Part 1 looks past the current hype (read: media coverage) around depression to primary census data to understand if there are structural changes in the global depressed population over the last 20–60 years (country/data dependent).
Part 2 proposes OMERS Ventures’ investment framework and looks at interesting startups across the life-cycle of care for depressed patients.
Special thanks to the leadership team at OMERS Ventures who supported me with time, intros, and resources to pull together this research over the past few months.
We chose to look specifically at depression (not mental health more broadly) because of the scale and severity of the disease.
Per the World Health Organization, depression is the most common illness in the world and the leading cause of disability, affecting 300 million people every year. Today in Canada, 500,000 people are unable to work due to mental health problems.
Depression is inextricably tied to suicide, which will be the leading global cause of death for people under 18, behind only HIV and AIDS, by 2020. This mirrors the Canadian reality: suicide is the second leading cause of death for young adults, accounting for almost one quarter of all deaths. Globally, two people kill themselves every minute.
We wanted to understand if the current hype (read: media coverage) over depression is justified by a recent surge in diagnoses or if baseline rates of clinical depression have remained unchanged.
To answer this question, we performed a systematic review of academic journals covering depression in the United States, Canada, the UK, and other developed economies. Additionally, we conducted a meta-analysis of primary surveys (mostly census data) to map out the rates of depression over the past 60 years in Canada and the US. Key questions we asked include:
· What is the definition of depression? To what degree does sadness play a role in depression?
· How do we measure depression? Are we more depressed today than in past decades?
· Are we over-diagnosing depression? Are we over-prescribing antidepressants?
Our review of primary data from the World Health Organization, Statistics Canada, and the U.S. Centers for Disease Control and Prevention reveals an observable, but not a watershed or exponential, increase in the number of depressed individuals globally over the past two decades. In fact, the only structural change is the number of people taking antidepressants, which has increased nearly 10x faster than the rates of depression diagnoses in OECD countries. There is a litany of reasons why antidepressants are on the rise globally, including cultural, societal, and commercial influences.
Next, we looked at over a decade worth of evidence linking our increasing use of technology to reports of increased anxiety and depression, especially among younger users. While troubling, the data available today is unable to draw a direct connection between the increased use of technology and an increasing incidence of clinical depression. However, there is strong evidence to believe that this connection will be established within the next decade of research.
Finally, we review the funding ecosystem for solutions that leverage technology to help patients suffering from depression. Specifically, we built a value-based framework to categorize solutions along the lifecycle of patient care: pre-diagnosis, diagnosis, treatment, and post-treatment.
In this piece, we assess technology as both a contributor to and a potential mitigant for modern depression. The duality of this perspective borrows from Professor Kentaro Toyama, a W. K. Kellogg Associate Professor at the University of Michigan School of Information, and his “law of amplification” which states technology is merely a lever which enhances human intent, whether it be malice or benevolence.
History offers clear examples of the dichotomy of technology amplification: high-capacity automatic rifles protect and harm, social media enables both philanthropy and the alt-right.
1.0 Defining Depression and its Costs
Depression has been written about for over 4,000 years, with the Mesopotamians describing the negativity experienced by those possessed by demons. The Greek physician Hippocrates wrote about ‘melancholia’ in 420 B.C. as a clinical syndrome caused by a chemical imbalance of human body fluids, specifically an excess of black bile in the spleen. Hippocrates prescribed treatments included bloodletting, baths, exercise, and diet. Our understanding of the cause of depression has evolved from spiritual and emotional to biophysical and neurochemical and consequentially treatment has moved beyond torture and exile to psychological and pharmacological remedies.
Today, researchers generally agree that there are many causes of depression, including structural differences in brain composition and neurotransmitter levels, inherited traits from genetics, and stressful or traumatic life events. It is believed that several of these forces interact to bring on depression. Biochemically, depression can be brought on by imbalances in brain chemistry, specifically the neurotransmitters serotonin and noradrenaline, or brain composition, specifically an overactive or inflamed amygdala, prefrontal cortex, hippocampus, or related limbic system components.
The definitive guide for medical practitioners is the fourth version of the Diagnostic and Statistical Manual (DSM-IV) of Mental Disorders which defines an episode of major depressive disorder (MDD) as at least two weeks of a depressed mood as well as at least five other symptoms, such as:
• Sleep issues (either difficulty sleeping or sleeping too much);
• Changes in appetite and weight (delta of more than 5 percent body weight in a month);
• Decreased energy or fatigue almost every day;
• Difficulty concentrating, making decisions, and thinking clearly almost every day;
• Recurrent thoughts of death or suicide, a suicide attempt, or a specific plan for suicide.
What should be strikingly evident from the list of symptoms above is that, beyond suicide, these ailments sit on the same spectrum of sadness that all humans have experienced for millennia. This ambiguity makes it difficult to accurately diagnose depression at scale while simultaneously perpetuating the modern stigma of the disease.
Specifically, it is difficult to ascertain who is exaggerating and who is mentally ill — even for those who are themselves suffering.
Laying on the other side of this ambiguity is the crippling global cost of untreated depression. Globally, studies have calculated the direct (i.e. healthcare, medication, psychiatry visits, etc.) and indirect costs (i.e. loss of productivity, income losses, etc.) to amount to USD $2.5 trillion per year. I personally hate the hyperbolism of global cost claims — but digging into these numbers reveal some very real hard dollars.
For business leaders, the most powerful statistic is that people suffering from depression miss, on average, 25 days of regular activity because of their symptoms, this includes work and important events. A startup of 100 people in Canada, where 5.4% of the population is clinically diagnosed with depression, could lose up to 125 working days per year because of depression.
1.1 Diagnosing Depression: Self-Reporting & Clinical Reporting
Due to the intrinsic ambiguity of diagnosing depression as a severe, prolonged form of sadness — there remain significant barriers to accurately measuring the size of the global depressed population.
The self-diagnosis of depression is not based on the absolute severity of symptoms but by that patient’s interpretation of the severity of their symptoms relative to the imagined pain of others.
From this perspective, depression is an experience that is relative to the sadness we imagine others feel, not an absolutely value or measure we can easily quantify.
This is probably the greatest driver of the “everyone is sad, just suck it up” stigma around depression that is slowly eroding. The World Health Organization estimates that fewer than 50% of those affected in the world (and in many countries, fewer than 10%) seek treatment for depression. In the U.S., the Centers for Disease Control and Prevention (CDC) reports that only 35% of patients with severe depressive symptoms had seen a mental health professional in the past year.
The ambiguity inherent in self-reporting depression can be partially reduced once that patient engages a medical professional. While waiting for a patient to find a medical professional introduces survivorship bias (it is more likely a patient is truly ill if they are willing to accept medical help) it allows for a more concrete diagnosis of depression using a standardized patient survey.
Figure 1 illustrates how clinically depressed patients, with either mild, moderate or severe depression, experience key cognitive manifestations of depression far more frequently than non-depressed individuals.
1.2 Are We More Depressed Today than in the Past?
Using the definition of depression set out in the DSM-IV as the incidence of psychological trauma over a period of at least two weeks, we looked for studies which used consistent definitions and questions over a multi-year or multi-decade time horizon.
Figure 2 shows the number of US adults who experienced a serious psychological distress in the past 30 days with data spanning 1997 to 2017. Over the past 21 years, the incidence of serious psychological distress has not structurally changed for adults in the United States.
Looking at psychological distress in young adults in the US, aged 12 to 17, tells a different story.
From 2006 to 2014, observations by the US Department of Health & Human Services of major depressive episodes in the past year increased by 41.3%, an average annual increase of 4.6%. This increase persisted even after researchers adjusted for substance abuse disorders and sociodemographic factors.
Following the troubling trend seen among the youth, the age-adjusted suicide rate in the United States increased 26.1%, or 1.8% per year from 1999 through 2014. The percent increase in suicide rates for females was greatest for those aged 10 to 14, and for older males aged 45 to 64.
In summary, the primary data from the U.S. does suggest an increase in the number of depressed and suicidal, particularly for young adults, but not an exponential or structural change in this population.
In Canada, to attempt to gain a broader, historical view of the prevalence of depression, we performed a meta-analysis (combining data from different research studies) by merging five separate surveys that provide the 12-month prevalence of a major depressive episode (MDE) from 1952 to 2012.
These studies span 60 years of Canadian mental health history and record a strikingly consistent message across those six decades: the rate of depression in Canada has remained remarkably consistent since 1952. 
In fact, of 22 data observations across five studies, only four fall outside the range of 4.5% to 6.0%. Put another way, the average standard deviation for years with multiple records was only 0.2% across all years. These results were consistent with third party studies which also found that the prevalence of clinically diagnosed depression and distress has remained generally stable among Canadians over the past 15 years at around 5%.
Globally, particularly in developing nations, the sparsity of survey data makes multi-decade clinical studies nearly impossible. The World Health Organization’s Department of Mental Health notes that the rate of people suffering globally from depression currently is one in twenty, mirroring the Canadian rate of 5%.
1.3 Are we Overly Prescribing Antidepressants?
Antidepressants are medications that help relieve the symptoms of depression, anxiety, and related mental health conditions. The most common antidepressants are selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs). SSRIs block the “reuptake” or absorption of serotonin, which is known as the ‘happy chemical’, thereby stabilizing the patient’s mood. SNRIs block the reuptake of serotonin and norepinephrine — a related neurotransmitter associated with happiness.
One of the most interesting and complex debates in health today is whether patients are over-prescribed antidepressants. On the one hand, organizations like the World Health Organization claim that the treatment rate for depression is well below 10% in many countries. Contrarily, the OECD Health indicator report shows that the number of people taking antidepressants in OECD countries increased by 145.2% between 2000 and 2015, representing a 9.7% average annual increase. The Czech Republic, Slovakia, and Estonia saw total increases of over 200% during this fifteen-year period.
The OECD report notes that the increase in the use of anti-depressants can be explained by a number of factors, including the improved recognition of depression, better access to mental health care, changes in patient or provider attitudes due to fading stigma, as well as anti-depressants being used to treat ailments other than depression, including anxiety, obsessive compulsive disorder, and related disorders. Other researchers have argued that mental health professionals have used a definition of depression that conflates genuine depression with intense, but normal, sadness which has led to the over-prescription of antidepressants. The reality is that we cannot discern the exact reason why 9% of Canadians consume anti-depressants while only 5% are clinically diagnosed with depression. Nor was it our goal to draw conclusions about these discrepancies.
Regardless of the cause, we can conclude from this primary data that the drastic increase in antidepressant prescriptions over the last 15 years is not tied to a similar or proportionate increase in the incidence of depression, namely severe psychological distress, over the same period.
This conclusion has been replicated in other primary data analyses studies in the UK, USA, Canada, and Australia over the past two decades.
For OMERS Ventures, the truth of whether or not patients were previously under-prescribed or are currently over-prescribed is unquestionably out of reach for our organization. However, our organization is uniquely positioned to act on the following conclusions of our research:
1. More people (especially the young) around the world are suffering from depression;
2. A lot more people are seeking clinical (i.e. pharmacological) solutions for mental health and related ailments;
3. There is a visceral disagreement as to whether existing pharmacological solutions (i.e. drugs) are the right solution.
Ah — opportunity.
We could look at the general distain towards antidepressants, which is largely driven by the view that the increase in their consumption is a product of the pharmaceutical-industrial complex, as an opportunity for non-drug solutions to be accepted by a somewhat skeptical, younger, consumer-patient base.
As a technology investment fund, our next step is to dive into emerging research that shows a link between technology use and depression, before determining whether technology can be used as a tool to alleviate the symptoms of those suffering.
2.0 The Role of Technology in the Modern Depressed Population
There is rampant public speculation that the increasing use of technology is causing mass isolation and depression — especially among young adults. Recent articles from Forbes, CNN, The Independent, Science Daily, and others reference studies of what is broadly referred to as “technology addiction”, the obsessive use of both hardware (i.e. mobile, tablets, gaming consoles) and software (i.e. messaging, social networks, mobile games, new media [YouTube, Snapchat, etc.]).
The difficulty with establishing a connection between technology addiction and a structural change in depression rates is that spot studies show self-reported feelings of “isolation” or “depressed mood” — and however troubling these data might be — they are often dismissed for not meeting the DSM-IV standard for clinical depression.
In this section, we lay out the basic construct of the argument which suggests a connection between technology addiction and depression and discuss where we expect this debate to evolve with future research.
The argument supporting technology addiction is generally based on the assertion that “things are changing faster than ever”. This platitude is driven by the global adoption of technology over the past decade; perhaps best illustrated by the rate at which we adopted modern social networks over the past few years, shown below. 
We can see the implications of this trend in the number of hours spent with digital media which has increased by 122% over the past decade.
This massive change in the way humans spend 1/3 of their waking hours (dare I say ‘woke’ hours) has not gone unnoticed. Researchers have invested a significant amount of time and energy to try to solidify a link between this new behavior and negative effects on the modern human psyche, especially amongst young adults.
Specifically, researchers have shown that adolescents, aged 13 to 18, who spend more time on social media and smartphones are more likely to report mental health issues than adolescents who spend more time on non-screen activities, even when controlling for cyclical factors like the state of the broader economy. Additional research targeted at Facebook shows that a 1-standard-deviation increase in activity on the social network results in a 8% decrease in self-reported mental health. Another 2016 peer-reviewed study showed that Facebook users had significantly lower life satisfaction than non-users.
Importantly, these researchers admit that there is no way to determine the nature of the relationship — perhaps adolescents who are depressed seek refuge in online communities and new media. In fact, the last study from 2016 noted that the deleterious effects of Facebook were most pronounced in users who were passively using the product — defined as just surfing through and consuming content — while users who were actively contributing, connecting, and engaging with others on Facebook had an increase in life satisfaction compared to non-users. This directly supports our perspective of technology as an amplifier of both positive and negative human experiences.
In general, these modern studies of technology addiction and depression suffer from a lack of direct causality between a specific activity and the medical consequence.
This persistent ambiguity is shockingly similar to the challenges faced by scientists who sought to establish a link between cigarette smoking and respiratory disease.
Centuries ago, smoking tobacco was used a remedy for infected wounds, headaches and colds. Starting their work in the 1950s, it took researchers decades to accumulate a critical mass of data to reach scientific consensus around the harms of smoking. In this vein, we expect to see further lobbying and academic research activities by large technology companies with a vested interest in the continued use of their products, seeking to influence the scientific consensus — likely taking the form of spot surveys or anecdotes (i.e. look how much our tech helped this person). We will continue to look to large, multi-decade, cross-sectional studies for the true impact of technology on incidence of clinical depression.
Beyond the ambiguity of direct attribution, the other difficulty with establishing causality is that technology can absolutely be used to improve our mental health. Online communities create opportunities for engagement beyond physical or geographic boundaries; virtual cyber-psychologists have zero marginal cost and can be universally accessible.
Studies like the one conducted by mobile time management app Moment help illustrate the incredible dichotomy that can exist between happy users who like checking-in on an app and unhappy users who are addicted to the technology. 
Moving forward, we expect to see mounting evidence of a causal link between technology use and depression, especially among young adults in developed countries.
Check out Part 2 for an overview of the landscape of technology companies addressing the patient life-cycle of depression.
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 DPAX 1 = “Depression and Anxiety Questionnaire 1“; DPAX 2 = “Depression and Anxiety Questionnaire 2“; DIS = “Diagnostic Interview Schedule“; NPHS = “National Population Health Survey”; CCHS;MH = “Canadian Community Health Survey — Mental Health”
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 Moment is a time management mobile application that tracks how much time you spend using specific apps on your phone and provides analytics, insights, notifications, and locks to help you reduce smartphone dependence.
 How heavy use of social media is linked to mental illness, The Economist, 2018.