The Mechanics of Happiness: Antidepressants Demystified

Whether it is the best of times or the worst of times, you do not need Charles Dickens to tell you that life is an emotional roller coaster. But when the feeling of dreary monotony does not subside and the cloudy skies of apathy never clear up, it is probably time to get professional help, perhaps even pharmaceutical help. According to a 2005-2008 study conducted by the Centers for Disease Control (CDC), the rate of antidepressant use in the United States has risen over 400% in the past twenty years [1]. This rather dramatic spike raises some questions: Are antidepressants so commonly prescribed because of their effectiveness? How do they actually treat depression?

The biochemical basis of depression lies in the activity of neurotransmitters, which are the chemicals that neurons, in the brain and elsewhere, use to relay information to one another. A message is sent from the pre-synaptic cell to the post-synaptic cell when neurotransmitters travel across the synapses between neurons and bind to their specific receptors located on the postsynaptic cell receiving the message [2]. Once neurotransmitters are released into the synaptic cleft, they eventually must be reabsorbed back into the pre-synaptic neuron in a process termed reuptake[3].

Enter antidepressants. Most of today’s medications are designed to interfere with the reuptake process so as to maintain higher levels of neurotransmitter activity in those experiencing emotional imbalance, which is oftentimes caused by abnormally low levels of certain neurotransmitters. Antidepressants generally target specific neurotransmitters such as serotonin, which is involved in modulating mood, emotion, sleep, and appetite [4]. Low levels of serotonin activity in the brain have been linked to depression and other mood disorders [5],  leading to a category of antidepressant called selective serotonin reuptake inhibitors (SSRIs) that inhibit the body’s reuptake and deactivation of serotonin. In theory, the neurotransmitter accumulation increases synaptic activity and improves mood. Other examples include serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine reuptake inhibitors (NRIs) such as Reboxetine, the first commercially available NRI.

The validity of antidepressants has been called into question because in some studies, placebos have been shown to be just as effective as the antidepressants in dealing with depression. Can it truly be said that antidepressants have superior efficacy?

In 2009, research psychologist Aimee Hunter and her colleagues at UCLA examined individual responses to antidepressants to assess the effectiveness of antidepressants in treating depression. They found that the same antidepressant can trigger varying side effects from patient to patient, and they discovered one serious possible side effect: the risk for suicidal tendencies. However, they also discovered a possible diagnostic tool for the risk of suicidal ideation. Hunter et al. concluded that depressed patients who developed suicidal thoughts while taking the drug showed different brain activity patterns from those of patients who were taking the placebo and also had suicidal thoughts.

Quantitative electroencephalography [7] localized the difference in brain pattern activity to the midline and right frontal area (MRF) in the brain. The right frontal lobe of the brain is associated with a person’s sense of self, ability to appreciate humor, and social behavior. Damage to this region can lead to a drastic change in personality, pseudodepression, or pseudopsychopathic behavior [8,9,10]. Patients who developed suicidal thoughts while taking antidepressants had a six-fold decrease in MRF activity, while patients who were taking the placebo had slightly increased MRF activity [7]. The medial frontal cortex of the brain is involved in motivation, and lesions to this area sometimes cause patients to become apathetic, inattentive, and slow to respond [11]. An artificial decrease in activity within these two areas is likely to foreshadow the development of suicidal ideation, reflecting the possibility of antidepressants actually worsening depression in some patients

Although a patient on antidepressants typically doesn’t experience a change in mood until he or she has taken the medication for at least a few weeks or months [6], changes in MRF activity appear quickly, sometimes as soon as 48 hours after the initial dose. This brief window of opportunity before the occurrence of behavioral changes provides a chance for medical professionals to monitor the risk for suicidal tendencies [7]. Hunter’s findings suggest that while not all patients will exhibit a drastic change in MRF activity, those who do are at a higher risk for suicidal ideation. If further studies confirm Hunter’s findings, it is very likely that QEEG tests can help ascertain whether a patient is prone to a detrimental side effect of antidepressant consumption. Such tests will also determine if a particular antidepressant is effective and non-detrimental for a given patient.

The prevalence of antidepressants in America is an undeniable reality, which is why it is important to achieve progress in improving their efficacy and safety for all patients. Extensive knowledge concerning the mechanisms and dangers of antidepressant consumption will prove crucial so that findings like Hunter’s can be applicable on the clinical level.

References
1. Pratt LA, Brody DJ, Gu Q. Antidepressant use in persons aged 12 and over: United States, 2005–2008. NCHS data brief, no 76. Hyattsville, MD: National Center for Health Statistics. 2011.
2. Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 21.1, Overview of Neuron Structure and Function. Available from: http://www.ncbi.nlm.nih.gov/books/NBK21535/
3. Nazario, B. MD. “How Different Antidepressants Work.” http://www.webmd.com/depression/how-different-antidepressants-work?page=3. Date accessed: April 30, 2013.
4. Schloss, W. P. “The serotonin transporter: a primary target for antidepressant drugs.” http://www.biopsychiatry.com/serotonin.htm. Date accessed: April 30, 2013.
5. Encyclopædia Britannica Online, s. v. “serotonin,” accessed April 30, 2013, http://www.britannica.com/EBchecked/topic/535741/serotonin.
6. Perlstein, E. O. “How do antidepressants actually work?” http://www.perlsteinlab.com/featured/how-do-antidepressants-actually-work. Date accessed: April 30, 2013.
7. Szalavitz, M. “Antidepressants: Are They Effective or Just a Placebo?” http://www.time.com/time/health/article/0,8599,1991841-1,00.html. Date accessed: April 30, 2013.
8. “Frontal Lobes.” Centre for Neuro Skills. http://www.neuroskills.com/brain-injury/frontal-lobes.php Date accessed: May 19, 2013.
9. Shammi, P, Struss, D.T. Humor appreciation: a role of the right frontal lobe. BRAIN: A Journal of Neurology. 1998. 122(4): 657-666. http://brain.oxfordjournals.org/content/122/4/657.full Date accessed: May 19, 2013.
10. Lawson, W. “Brain Area Affects Sense of ‘Self.’” 2013. ABC News. http://abcnews.go.com/Technology/story?id=98580&page=1#.UZl0lrXihyw Date accessed: May 19, 2013.
11. Auchus, A.“Overview of Cerebral Function.” 2012. The Merck Manual for health care professionals. http://www.merckmanuals.com/professional/neurologic_disorders/function_and_dysfunction_of  _the_cerebral_lobes/overview_of_cerebral_function.html Date accessed: May 19, 2013.

Sarah Watanaskul is a first year student at the University of Chicago majoring in Biological Sciences with a specialization in Immunology.

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