Despite numerous efforts to categorize the depressed population, there still remains investigation as to how many people are truly afflicted with depression. A Johns Hopkins study1 reports that 60% of depression diagnoses are actually misdiagnoses. Misdiagnoses cause more people to purchase medication—spending amounts to $11.3 billion annually. Do antidepressants, in fact, really work? A 2008 study2 from Irving Kirsch of Harvard Medical School estimates that 75% of the time, “an antidepressant’s effect could have been obtained merely by taking [a] placebo.” Where are the flaws in our methodology regarding depression? I believe they lie in inadequate diagnosis criteria and treatment plans for depressed patients, propagated by the current status of depression research.
Insufficient standards for depression diagnosis, uncertainty among clinicians, and deficient knowledge of the depressed brain leads to misdiagnosis and mistreatment of patients. Improving our cognizance of depression depends on our ability to quantify emotion through neuroscience research. Advancing the scientific quantification of depression by improving the efficacy of research practices and funding will reform the current inadequacy of depression diagnosis and treatment.
A Global Call for Reform
Improving standards for diagnoses and treatments to help doctors identify and treat genuine cases of depression in patients is threefold. With 9 % of the U.S .and 4% of the world diagnosed with depression,3 domestic and international pervasiveness is the first reason for reform. Giving the public, and the doctors who treat them, more precise information about the mental disorder will increase awareness concerning proper identification and treatment.
Additionally, the implementation of new reformation tactics proves to be pertinent, as depression diagnoses are built upon a subjective medical framework. The backbone of depression diagnosis rests with the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM). According to the DSM,4 one must have five or more symptoms “over a two-week period, most of the day, nearly every day.” These symptoms include “depressed mood,” “significant weight loss [or weight gain] when not dieting,” “insomnia or increased desire to sleep,” and “fatigue or loss of energy,” which can be based on “your own feelings” or the “observations of someone else.”5
The medical formulation for diagnosis is qualitative and open to interpretation. Finally, refining suitable treatments for depression is essential. Over-prescription of antidepressants can lead to the unnecessary propagation of adverse side effects. The Food and Drug Administration mandates that all antidepressants carry a “black box” notice—the strictest label warning for prescription drugs due to an increased risk of suicide.5 We need to reevaluate the usefulness of modern antidepressants by taking patients who can truly benefit from them and the repercussions of over prescribing a global population into account.
What We Currently Know About Depression and Happiness
To move away from subjective diagnoses and treatments, the first step is to find more concrete evidence showing a physical link to emotion in the brain. For example, the hippocampus has garnered attention regarding inter-regional brain signaling. Doctor Siddhartha Mukherjee of Columbia University says in his article2 “Post Prozac Nation” for the New York Times, “in the non-depressed brain, circuits of nerve cells in the hippocampus may send signals . . . to regulate mood,” but “when the hippocampus malfunctions,” emotional pain can be exaggerated and blown out of proportion. Thus showing that specific brain regions may play certain roles in properly functioning emotions. The brain has several other chemical signals incorporated into its proper functioning, such as serotonin, norepinephrine, and dopamine. Neuroscientist Susan Greenfield in her book6 (p41), The Private Life of the Brain, posits that these neurotransmitters act like “fountains,” greatly affecting the brain and causing neurons to generate electrical signals. Mukherjee2 adds that they are “dynamic factors that make nerves grow, perhaps forming new circuits.” Scientists and researchers agree that these neurotransmitters play a role in emotion, but this is the only suggestion that has provided significant implications towards establishing consensus on the research topic.
Additionally, emotions can be linked innately to genetics. For example, a study was conducted on 2,574 teens as part of a research study analyzing the effects of 5-HTTLPR, a gene that makes serotonin transporter molecules.7 This study showed that those with the two long versions of the gene were twice as likely to report that “they were satisfied with life” than participants who had two short versions.7 Genetic research on characterizing depression is driven by the ideology that there are specific genes involved in depressive emotions7. Therefore, genetics can explain discrepancies in treatment responses for different individuals.5 Personalizing treatment plans through an identification of unique genetic and neurobiological factors properly acknowledges depression’s multiple forms.
An individual’s confluence of neurobiology and genetics dictates normal emotional states, as well as the extent of his or her nonstandard reactions to emotional stimuli. Advanced technologies such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and fast scan voltammetry (FSV) allow measurement of brain activities and neurotransmitters associated with emotion8 (p234). The networks of neurotransmitters and brain regions create a working spectrum of emotion. A malfunctioning of any one system mitigates the chances for another connected system to work properly, leading to disorder, which posits a necessity in further investigation of the depressed population. Given the link between depression and emotion, proper neurobiological clarification is needed in elucidating the exact depth of depression and its effects on the population.
Treatments Are a Guess and Check
Furthermore, gaining awareness on treatment measures is equally as important. Current treatments aim to alleviate depressive emotions by increasing the likelihood of positive emotions. Research has shown that modern antidepressants increase the concentrations of specific neurotransmitters by preventing reabsorption in the brain.5 the belief is that increasing concentrations of “feel-good” neurotransmitters such as serotonin will relieve depression symptoms. The most popular antidepressants9 created with this notion of a chemical imbalance include Zoloft, Lexapro, and Prozac. However, this theory is limited, and does not explain why multiple studies show no correlation regarding neurotransmitter concentrations in brain autopsies of depressed patients.2 For example, a patient could try numerous antidepressants every month before an effective one is determined. Such experimentation could possibly expose the patient to unanticipated side effects, which could be detrimental to his or her wellbeing in addition to depression. Neurotransmitters such as serotonin, norepinephrine, and dopamine may be involved in depression and happiness involvement is unclear.
Reexamining Publications and the Spread of Accurate Information
An advanced knowledge of depression relies on the dissemination of credible academic publications and properly funded research. Unfortunately, many studies are purposefully unpublished. In a 2010 meta-analysis, Irving Kirsch and his colleagues examined published and unpublished clinical trials using the Freedom of Information Act.10 They found that half of the trials showed no clinical difference between placebo and drug.10 Furthermore, the Federal Drug Administration’s guidelines support approval for antidepressant medication if one to two studies provide “substantial evidence” of a drug’s efficacy.11 Putting this regulation into perspective, a drug can receive FDA approval if two out of ten studies show a marginal benefit in taking the drug; Kirsch10 prudently notes that an antidepressant’s effect “[does not] have to be clinically significant [. . .] it just has to be statistically significant.” This system could help expedite the approval process for the sake of the patients it could benefit, but it may also propagate subpar performance of antidepressants, reducing consensus regarding their effectiveness.
Reforming Data Discrepancy
Requiring only statistical significance perpetuates a culture of approval based on the medication’s creator— not the medication’s user. The FDA’s method of anti-depressant support also allows patients to be prescribed drugs that might not even work. My first suggestion for reforming depression diagnosis and treatment rests in the publication of all research, studies, and clinical trials associated with the mental disorder. If not published, data and results should at the very least be made accessible to the public. The Freedom of Information Act12 is a solid foundation for open distribution of knowledge, but it only applies to federal agency records and requires a written request for specific information. The agencies are not required “to do research for you, analyze data, answer written questions, or create records in response to your request.”12 Additionally, there is no guarantee an individual can ask for or acquire the results of a pharmaceutical company’s private clinical trial conducted apart from a federal entity.
Why would pharmaceutical companies conduct such private trials, or refuse to publish certain studies? Consider GlaxoSmithKline’s (GSK) involvement in the largest healthcare fraud settlement in history. GSK failed to report safety data to the FDA, promoted unapproved uses for antidepressants Paxil and Wellbutrin, and bribed doctors to promote and prescribe these medications improperly.13 In 2012, GSK was required to pay $3 billion dollars and agree to monitor by the U.S. Government for five years.13 GSK was worried about its profits, not its patients. Transparency is the key to exposing which drugs work; it can be achieved through requiring higher standards for FDA approval, and mandating that all trials and studies are accessible. Without this openness, pharmaceutical companies will perpetuate a vicious cycle of insufficient drugs treating patients that never needed them in the first place.
Shifting From Qualitative to Quantitative Diagnosis
My second suggestion for reform emphasizes a quantitative format for diagnosis and treatment based on the neurobiological specificities of the individual. There is no reason for depressed patients to have the same medication if individuals respond differently based on their biological and genetic makeup. For example, assume advanced analysis of a person has shown that his specific neurobiological idiosyncrasies place strong emphasis on serotonin. Recall the long version of the 5-HTTLPR gene as one such idiosyncrasy. If his happiness inordinately depends on serotonin, existing antidepressants that are known to promote increased serotonin concentrations could be used with enhanced specificity. Knowing how happiness malfunctions in other individuals, which causes depression, can be instrumental in creating other patient-specific treatment plans. An analysis as described could be costly, especially since we currently lack the knowledge and ability to isolate specific neurobiological pathways in patients. However, individualized standards for diagnosis could be a crucial step towards quantitative and objective medical approaches to depression, giving doctors stronger foundational knowledge for treating patients with specific symptoms.
It is Wise to Invest
Reforming depression diagnosis and treatment as dictated above requires proper investment in brain research concerning human emotion. This must be accomplished by reconciling the relationship between academic and industrial research—my last suggestion for reform. Academic research in this sense pertains to independent studies usually funded by government grants. On the other hand, industrial research is done for pharmaceutical companies. UC Berkeley’s Understanding Science online resource elucidates how science can be used for a certain party’s benefit: “A pharmaceutical company paying for a study of a new depression medication, for example, might influence the study’s design or interpretation in ways that subtly favor the drug that they’d like to market.”14 A capitalistic model drives healthcare, but differing sources of funding can introduce predispositions based on motives. Therefore, possible regulations requiring unaffiliated academic research laboratories to conduct industrial studies could improve research as a whole by establishing another credible source as an academic proofreader. To make wise investments, we need to consider a system of checks and balances between academic and industrial research to prevent the dissemination of inaccurate information and faulty drugs.
Measurable Movements Forward
Investment in research based on the neurobiological and genetic networks linked to depression and the publication of all studies will usher in a quantitative reformation of diagnosis and treatment. Implementing these reforms could impact mental health globally by improving the way doctors and patients perceive depression. Doctor Siddhartha Mukherjee2 aptly explains the wonderment of the brain’s complexities with an analogy: “The painter Cézanne, confronting one of Monet’s landscapes, supposedly exclaimed: ‘Monet is just an eye, but, God, what an eye.’ The brain, by the same logic, is still a chemical soup—but, God, what a soup.” It is my hope that advancing neuroscience research through these proposals will elucidate the line between emotions and emotional disorders. Our brains, and the world’s wellbeing, deserve no less.
An earlier version of this article was published by the Stanford Journal of Public Health, Volume 6, Issue 2, Spring 2015.
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