In the 1960s a Danish company named Ferrosan began performing research on aspects of the central nervous system. Ferrosan was most interested in the relationship between the neurotransmitter serotonin and depressed mood in people. The original idea was that if a drug could be developed to increase serotonin levels in the brain it might lead to improvements in treating people with depression (DeGrandpre, 2006). The research resulted in the development of a formula for a compound then known as the "Buus-Lassen Compound" which allegedly had the capability to relieve the depression in people. The compound was patented in the United States in 1977 and the company later sold all rights and research surrounding this patent to SmithKline (now GlaxoSmithKline) in 1980 (DeGrandpre, 2006).
SmithKline put significant effort into developing the compound and much of this development occurred in the SmithKline plant in Harlow, England (DeGrandpre, 2006). Eventually SmithKline patented a formula for paroxetine in the United States on October 23, 1986. Following the patent for the new compound paroxetine went through years of clinical trials. SmithKline was able to gain FDA approval of the drug under the brand name Paxil on December 29, 1992 (DeGrandpre, 2006). The clinical trials for Paxil indicated that it was at least as effective as earlier tricyclic antidepressant drugs, but had fewer side effects (Anderson, 2001). It is the reduced side effect profile of Paxil and other selective serotonin reuptake inhibitors (SSRIs) along with their alleged ability to relieve depression that have made them popular in the treatment of depression. Generic versions of Paxil have been available since 2003 when the patent the original formula ran out.
Mechanism of Action and Side Effects
Paxil is one of the most potent and specific SSRIs. Paxil blocks the reuptake of serotonin and has been released into the synaptic space (or anywhere else in the body were serotonin is used) and this leads to an increased availability of serotonin (Mellerup & Plenge, 1986). Paxil has been marketed by GlaxoSmithKline for the treatment of depression, obsessive compulsive disorder (OCD), post traumatic stress disorder, social phobia, and premenstrual dysphoric disorder (Sadock & Sadock, 2007). Paxil was the first SSRI to be approved for the treatment of panic attacks and panic disorder (Sadock & Sadock, 2007). Paxil has also is been investigated regarding its efficacy to treat premature ejaculation (although the research on this does not always indicate that it is effective for premature ejaculation outside it's noted side effect of reducing sex drive; Waldinger, Zwinderman, & Olivier, 2004). Other investigational studies have suggested that Paxil can be efficacious in treating conditions such as chronic pain (Weitzner, Moncello, Jacobsen, & Minton, 2002), tension headache (Langemark & Olesen, 1994), compulsive gambling (Kim et al. 2002), and diabetic neuropathy (Vieta et al., 1999).
Although the side effect profile of SSRIs is not as extensive as tricyclic antidepressants and MAO inhibitors they often produce several side effects. A common side effect of SSRIs and of Paxil use is sexual dysfunction (Stahl, 2008). Sexual side effects most often in consist of difficulty becoming aroused, ejaculatory disturbance, and sometimes a total lack of interest in sex is also noted. Sexual side effects are typically reversible once the medication is been discontinued; however, in some people a post SSRI sexual dysfunction occurs where the side effects can last for months and even years following discontinuation (Stahl, 2008).
Nausea is one of the most common adverse side effects of treatment with Paxil (Stahl, 2008). Somnolence is another common side effect of Paxil use. Other common side effects include dry mouth, constipation, weight gain, agitation, dizziness, high blood pressure, headache, cognitive problems such as impaired memory, and paresthesia (Stahl, 2008). These side effects, if they occur, are typically are present during the first four weeks of use and most often decrease after four weeks of usage (Stahl, 2008). Side effects are also dose-dependent.
Other side effects that have been noted are hypomania, tremor, akathisia, and serotonin syndrome (Stahl, 2008). Although GlaxoSmithKline initially reported that discontinuation of Paxil did not produce any withdrawal symptoms, research has indicated that withdrawal symptoms do occur in individuals when SSRIs are discontinued (Stahl, 2008).
Paxil is contraindicated in people less than 18 years of age and in women who are or may become pregnant in the future (Stahl, 2008). Paxil is also contraindicated in men who experience sexual side effects from the drug. Paxil may increase suicidal ideations in children and adolescents. Patients should not discontinue the use of Paxil unless under the care or supervision of a psychiatrist or physician as this can lead to a discontinuation syndrome (withdrawal symptoms; Stahl, 2008).
Description of presenting issue: Sam is a 32-year-old divorced Greek-American male. He was referred by a colleague at work was concerned about Sam's recent poor performance at work, marked by bouts of angry outbursts, moodiness, and sarcasm towards coworkers (Personal Communication, Dr. R. Seiken, April 14, 2013).
Sam is a bright articulate individual who works as a photographic editor and a large marketing firm. He complained that his major concern was the stress that he is feeling from his current position. He does not believe that his supervisor recognizes his efforts and is trying to keep him on the "back burner" to prevent his advancement in the organization. He is been very frustrated because initially supervisor was very supportive of him, but over the last month he has withdrawn his support.
Sam says that he has been feeling "down" for the past five or six weeks. He finds that he has been unmotivated to perform his duties at work, has been feeling "bored and empty," finds himself crying for no reason, and cannot sleep at night. He also reported that his appetite has decreased in the past four weeks and he eats about half as much as he used to.
Sam reported that he is considering making a career change but is not certain what he would like to do next. He reports that he has an active social life, going out several times per week to clubs and bars. Although Sam does not use recreational drugs, he does note that he sometimes "drinks too much when he is out partying." Recently, he was involved in a physical fight with another man at a bar.
Family History: Sam has one older (age 34) and one younger (age 28) sister. Both are married and live in the same town as Sam. Sam's parents are still married, but when Sam was a young boy his father suffered a "nervous breakdown" and left the family for 6 months. His parents are both retired, and travel frequently. He describes his father as a "serious, distant, hard-working man" and his mother as a "soft, warm, saint who put up with too much from everyone."
Sam was married twice previously (for 2 and 5 years, respectively). He described his second divorce as particularly painful, during which he was briefly hospitalized for a failed suicide attempt. He is very eager to be in a relationship now, and believes that he just has not found "the right woman."
Educational History: Sam attended college, but left midway through his senior year.
Medical History: Hospitalization at age 26 for suicide attempt, and at age 30 for gall bladder surgery. No current medications.
Alcohol/Substance Use: During adolescence, Sam experimented with a wide range of illegal drugs and prescription medications. Since his mid-20s, he has restricted his substance use to alcohol to 3 -- 6 drinks once or twice per week.
Treatment: Sam was diagnosed with major depressive disorder, recurrent. He was started on Paxil 20 mg daily. The psychiatrist noted his past suicide attempt and as a precaution scheduled weekly follow-up appointments for Sam for the first four weeks of treatment. The treating psychiatrist also explain the basic action of the medication, potential side effects to look out for, and discuss the use of the medication with him so that Sam knew that he should not drink alcohol while taking the medication.
Sam was seen weekly for reevaluation and he reported that the still felt the processed and a little jittery following the first week of usage. The psychiatrist increased the dosage to 30 mg a day and discussed common side effects (mild anxiety, jitteriness, etc.) and told Sam that if the jitteriness was not bothering him they could wait a week and see if he would habituate medication or he could prescribe an anxiolytic medication. Sam elected to wait.
The following week Sam reported that the jitteriness had subsided but that he was still somewhat depressed. The psychiatrist increased the dosage to 40 mg a day and discussed possible psychotherapy for Sam; however, Sam did not want to start psychotherapy at this time.
On his next appointment Sam reported that he was feeling somewhat better and was able to sleep at night. He also reported that he sat down and discussed his feelings with the supervisor and his supervisor told him that he felt…