Depressive Disorder, Research Paper Example

An Analysis of SSRIs used to Treat Major Depressive Disorder and how thy Effect the Brain and Central Nervous System

Mood disorders are characterized by periods of intense elation or chronic bouts of sadness or a combination of both. The National Institute of Mental Health (NIMH) website provides national data on mental health disorders. The NIMH estimates that approximately twenty-one million Americans or 9.5% of the U.S. population eighteen years of age and older suffer from mood disorders and millions more probably go undiagnosed. Although mood disorders have been prevalent for centuries, Kendler et al (2010) note that these major debilitating mental diseases have only been the subject of significant clinical research for about the past twenty years (p. 460).

This paper provides an analysis of a major category of drugs know as Selective Serotonin Reuptake Inhibitors (SSRIs) used in the treatment of Major Depressive Disorder (MDD). In many patients with high levels of cortisol in their blood, additional drugs must be taken in combination with an SSRI in order to effectively control the symptoms associated with depression.  The paper also discusses how these drugs affect the brain and central nervous system and provides information on how long the drugs remain in the body.

Major Depressive Disorder: An Overview

Major Depressive Disorder is the primary cause of disability in the U.S. population between the ages of fifteen and forty-four years. Steiner (2009) indicates that more women suffer from the illness than men (p. 61). All humans experience normal emotions related to the daily events in our lives. We experience joy when we successfully accomplish an important personal goal and we feel sadness at the loss of a loved one. The MDD individual exhibits emotional behaviors that are disproportionate to the event that has occurred and can often exhibit intense emotions even when nothing out of the ordinary appears to have happened ( Belmaker & Agam, 2008, pp.56-57). Several studies have also linked severe depression to the genetic make-up that individuals inherit from their parents. In these cases, multiple family members exhibit MDD behaviors.

Drug Therapies used to Treat Major Depressive Disorder

Serotonin is one of the fifty or so neurotransmitters found in the central nervous system, the digestive system and the brain. Serotonin (5 HT) is a monoamine neurotransmitter that is centralized within the central nervous system. Researchers now know that Serotonin is involved in almost all human behavioral functions including the regulation of sleep patterns, body temperature, appetite, sexual behavior, muscular functions, endocrinal functions and for our purposes, depression (Lacivita et al, 2011, p. 122). The chemical is synthesized in the brain from an amino acid called L-tryptophan. Serotonin is pervasive throughout the body transmitted from the brain to all parts of the central nervous system. Serotonin is triggered by groups of cells in the brainstem called the raphe nucleus. A single Serotonin brain cell is capable of activating up to 500,000 neurons. Vesticles within the Serotonin neuron act as storage receptacles. In addition, Serotonin molecules adhere to reuptake transporters located on the axon membrane of the neuron. The drug therapies discussed below affect the reuptake process. (Hyttel, 2004, pp.20-21).

A neurotransmitter is a chemical that transmits information between neurons or nerve cells.   In patients with Major Depressive Disorder, levels of Serotonin within the brain are lower than the levels found in patients without the disorder. A classification of drugs known as Selective Serotonin Reuptake Inhibitors (SSRIs) can be administered to counteract the depleted levels of Serotonin in the brain. When a SSRI such as Zoloft is taken by the patient, it prevents the reuptake of Serotonin back into the neurons that produced it. This results in an increase in the amount of Serotonin throughout the central nervous system. In other words, these drugs “suppress” or “inhibit” the natural breakdown of Serotonin thereby causing increased levels of the chemical to remain in the brain.  (Bjork et al, 2010, pp. 1351-1353).

Three of the most widely prescribed SSRIs are Sertraline (Zoloft), Fluoexetine (Prozac) and Paraoexetine (Paxil). Although it depends upon the dosage, body weight, rates of metabolism and other factors, a 50 milligram dose of each of these drugs has the following half life:

Zoloft 12 hour half life

Prozac 24 hour half life

Paxil 8 hour half life (nimh.gov).

One issue that has confounded clinical researchers is that not all individuals with MDD have a defective Serotonin transmitter gene. Obviously, there are other factors that contribute to the development of the disorder. Kendler et al (2010) hypothesize that prolonged levels of severe stress can also lead to the development of major depression. Their study shows that MDD patients under severe stress had elevated levels of the hormone cortisol in their blood (pp. 65-66). The depression was controlled by administering drugs that affect the adrenal gland’s production of this hormone. Three of the more widely used medications to regulate the production of cortisol are Mitotane  (Lysodren), Metyrapone (Metopirone) and Ketoconazole (Nizoral). The half life of these drugs based upon a dosage of 200 milligrams is approximately 10 to 12 hours (nimh.gov).

Two other drugs are often used in combination with the medications described above to treat MDD. Lithiam affects the concentrations of Tryptophan and Serotonin in the brain and has a half life of 12 hours. Lithiam, taken in combination with an SSRI, can be effective in controlling suicidal tendencies in severely depressed patients. Valproic Acid increases the level of another neurotransmitter within the brain called Gama-Aminobutyric Acid and has a half life of up to 27 hours (Kessler et al, 2003, p. 3099).

Conclusion

This paper examined how a category of drug therapies known as Selective Serotonin Reuptake Inhibitors are used to treat severe depression and how these drugs affect the brain and central nervous system. A considerable body of research has been developed over the past twenty years in an attempt to better understand the causes of depression. Clinical researchers have demonstrated success in developing a series of drugs called SSRIs that slow the breakdown of Serotonin in the central nervous system and the brain and help to relieve the symptoms associated with depression. Advances in drug therapies make it possible for individuals who suffer from depression to lead a normal life.  The pharmaceutical industry continues to invest millions of dollars in clinical trials to develop even more effective drugs that can be used to combat this disorder.

References

Belmaker, R.H. & Agam, Galila (2008). Major Depressive Disorder. The New England Journal of Medicine, 358, 55-68.

Bjork, Karl, Sjogren, Benita & Svenningson, Per. (2010). Regulation of serotonin receptor function in the nervous system by lipid rafts and adaptor proteins. Experimental Cell Research, 316(8), 1351-1356.

Hyttel, J. (2004). Pharmacological characterization of selective serotonin reuptake inhibitors. International Clinical Psychopharmacology, 9(1), 19-26.

Kendler, Kenneth S., Kessler, Ronald C., Walters, Ellen E., Heath, Andrew C., & Eaves, & Eaves, Lindon J. (2010). Stressful Life Events, Genetic Liability, and Onset of an Episode of Major Depression in Women. Focus, 8, 459-470.

Lacivita, Enza, Bernardi, Francesco, Perrone, Roberto & Hedlund, Peter B. (2011). Serotonin 5-HT receptor agents: Structure—activity relationships and potential therapeutic applications in central nervous system disorders. Pharmacology and Therapeutics, 129(2), 120-148.

Kessler, Ronald C., Berglund, Patricia, Demler, Olga, Jin, Robert, Kortz, Doreen, Merikangas, Kathleen R., Rush, A. John, Walters, Ellen P., & Wang, Philip S. (2003). The Epidemiology of Major Depressive Disorder. The Journal of the American Medical Association, 289(23), 3095-3105.

National Institute of Mental Health website retrieved on November 14, 2011 from http://www.nimh.nih.gov

Steiner, Meir. (2009). Female-specific mood disorders. Psychiatry, 8(2), 61-66.