By: Michelle Rosenstein, B.Sc. Pharmacology, McGill University
Depression is the second leading cause of disability worldwide after heart disease. In other words, depression is a very common illness that is difficult to manage. The main struggle in treating depression lies in the uncertainty about its precise cause. Currently, and ever since the marketing of antidepressant drugs in the 1990s, the “Chemical Imbalance” theory represents the culturally dominant model for depression. In turn, this theory significantly influences pharmaceutical drug development and public expectations. Although the association between “chemical imbalance” and mental illness is widely accepted, the public is generally unaware of its origins, meaning, and impact. What is the “Chemical Imbalance” theory and what led to its popularization? How has this theory affected drug development? What are the different classes of antidepressant drugs and how do they work? Are these drugs sufficient for the treatment of depression? Medications are generally designed to fit a pre-existing disease model. To the contrary, mood-elevating compounds were first discovered serendipitously. Only after the studying of these compounds were they found to increase levels of neurotransmitters (chemicals in the brain). Thus, the “Chemical Imbalance” Theory stemmed from the assumption that these two actions – the elevation of mood and the facilitation of chemical transmission – are linked. According to this theory, depression is caused by a deficit of specific neurotransmitters at key sites in the brain and is therefore treatable with the right medication. Unfortunately, the antidepressants available in the mid20th century were not very specific, leading to a vast array of severe adverse effects.
However, in 1987, Prozac was approved by the Food and Drugs Administration to treat depression. Prozac was designed to selectively increase serotonin levels in the brain, resulting in fewer side effects. (Serotonin is a chemical associated with appetite, sleep, and mood.) In many ways, Prozac and its direct-to-consumer marketing led to the popularization of the “Chemical Imbalance” Theory. The pharmaceutical industry advertised depression as a common “problem of living”, whereby every person would benefit from antidepressant medications. These advertisements blurred the line between depression and normal sadness, boosting antidepressant sales. Further, the “Chemical Imbalance” Theory was described as the definitive cause of depression, when in reality, its precise role (a cause, symptom, or neither) remains unknown. Nevertheless, hundreds of drugs were designed under the paradigm of the “Chemical Imbalance” Theory. Their main purpose is to facilitate chemical transmission in the brain by enhancing the amount of specific neurotransmitters within neural connections. Each drug class (TCAs, MAOIs, SSRIs, SNRIs, NaSSAs, and atypical antidepressants) tackles this task in a different way. These medications continue to be prescribed due to their observed capacity to reduce depressive symptoms. It is important to note that individuals respond differentially to different antidepressants, and in turn, may need to try several medications before being satisfied. Several psychosocial factors – such as the doctor-patient relationship, the patient’s desire for pharmacological intervention, and the patient’s willingness to adhere to therapy – may influence the treatment outcome. In addition, the therapeutic effect of these antidepressant drugs is generally delayed for 2-6 weeks. Since antidepressants increase neurotransmitter levels on a much quicker timescale (relative to the observed therapeutic effect), it is believed that these compounds alter chemical transmission via additional mechanisms. These distinct mechanisms are accounted for by newer publications, in which other potential causes of depression (apart from “chemical imbalance”) are discussed. Generally, the theories most supported by the scientific community – whether involving inflammation, hormones, or neurogenesis (the formation of new connections in the brain) – tend to emphasize the dynamic interaction between biological and psychosocial components. According to these biopsychosocial models, an individual’s susceptibility to depression is dependent on their genetic vulnerability, past life events (traumas, abuse, bereavement, etc.), access to social support networks, and their knowledge of effective coping styles. Therefore, depression is a multi-factorial illness. To that respect, Health Canada’s guidelines for treating depression recommend psychological counseling in conjunction with antidepressant drugs. How might psychological interventions contribute to the management of depressive symptoms and the prevention of their onset? Firstly, psychotherapy provides patients with an opportunity to express their experiences and emotions, address the underlying psychosocial triggers of their depressive episode(s). In addition, patients attain the coping skills necessary to deal with unforeseen life stressors, reducing the likelihood of relapse. Unlike medications, patients generally continue to benefit from psychotherapy even after its completion or cessation. However, it is important to remember that patient treatment preference, patient expectations, and the experience of the therapist may significantly influence the effectiveness of any psychotherapeutic approach. Several studies have analyzed the efficacy of monotherapies (prescription antidepressants or psychotherapy independently) in comparison to combined therapies. In a recent publication of the Canadian Journal of Psychiatry (2013), Dr. J. Spijker and colleagues conclude that combining antidepressants with psychotherapy (cognitive-behavioral therapy, interpersonal psychotherapy, etc.) is preferential when treating chronic major depressive disorder. In a different study that focused on mild to moderate depression, both patients and therapists deem combined therapy to be more effective than pharmacotherapy alone at reducing symptoms and improving quality of life. Generally, psychiatrists evaluate disease severity, disease chronicity, availability of treatments, and patient preference prior to recommending treatment options. In conclusion, depression is very individualistic in terms of how someone may develop the disease, experience symptomatology, and respond to proposed interventions. Successful treatments generally account for the biological, psychological, and social processes of the mood disorder. Thus, if your loved one is depressed, it is important that they understand the full range of tools available to support their recovery. “Antidepressants are but one element available in the treatment of depression.”- Professor I. Reid
If you would like to learn more about depression, antidepressant drugs, and/or how neurons normally communicate, please refer to: 1) Health Canada (2009). It’s Your Health: Depression. http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/diseases-maladies/ depression-eng.php 2) Neuroscientifically Challenged (2014). Video: 2-Minute Neuroscience: Synaptic Transmission. https://www.youtube.com/watch?v=WhowH0kb7n0 3) Anthony, R. (2015). How Antidepressants Work in the Brain: A Comprehensive Guide. Medical Daily. http:// www.medicaldaily.com/how-antidepressants-workbrain-comprehensive-guide-336250 4) Mayo Clinic. Video: Antidepressants – How they help relieve depression: http://www.mayoclinic.org/diseases-conditions/depression/multimedia/antidepressants/vid-20084764