Abstract
Wellbutrin SR or bupropion hydrochloride is an antidepressant drug commonly used in patients with prolonged depression. It acts in such a way to restore the balance of natural chemicals in the human brain. It is important that the patient does not have problems such as seizure or severe hepatic cirrhosis or cranial trauma, or are taking any drugs that can interfere with bupropion. It is extremely vital to keep a watch on the patients with depression under bupropion therapy because there can be episodes where worsening of the depression symptoms may occur. In such cases there is a need to change the therapeutic regimen. This paper discusses the structure, mode of action, contraindications, side effects and risks of Wellbutrin SR.
Introduction
Wellbutrin SR also known as bupropion hydrochloride is drug belonging to the category of antidepressant and of the class of aminoketone. A structural analysis of the compound shows that the structure of bupropion hydrochloride is similar to the structure of diethylpropion. The chemical nomenclature is (±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride. Bupropion hydrochloride has a mol. wt. of 276.2 and its mol. formula is C13H18ClNO•HCl. It appears as white cristaline powder and is easily soluble in H2O. The compound tastes bitter and it gives a feeling or produces the sensation of local anesthesia inside the mouth.
The structural formula is:
What is the medicine used for?
Wellbutrin SR Tablets are in general an antidepressent drug. Suicide is a complex phenomenon that has attracted the attention of many over the centuries. This is a drug that is given to patients with suicidal tendency or the ones who are in depression phase. It is supplied for oral administration at various dosages as 100-mg which has a blue film coated tablet, 150-mg having a purple film coat, and 200-mg light pink film-coated sustained-release tablets. Each tablet in addition to the labeled amount (100, 150 or 200 mg) of bupropion hydrochloride have other inactive ingredients such as carnauba wax, cysteine hydrochloride, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, and titanium dioxide (John et al.,2005).
Wellbutrin is a prescription drug and is given to patients to help ease major depression. Though it is not given for short term depression, it is given if the symptoms are severe for about two or more weeks. The additional symptoms of this long term depression also include loss of concentration or happiness, sleep and appetite turbulence, anxiety or need of energy, feelings of guiltiness or insignificance, decreased sex drive, helplessness to give attention to any particular activity, and sometimes, suicidal thoughts or behavior (drugs.com, 2009).
Wellbutrin is also used for several other problems in addition to the treatment for depression. It is prescribed for Weight Loss, Bipolar Depression, attention-deficit hyperactivity disorder (ADHD), ADD, Fibromyalgia, Arthritis, Chronic Fatigue, Multiple Sclerosis, Lupus and Irritable Bowel Syndrome (IBS) (crazymeds.us, N.D.). When it is given for the treatment for depression, it is generally seen that it can improve the mood and give a feeling of well-being. Bipolar disorder also known as manic depression is another disorder where this drug has played a helping role. Bipolar disorder is a class of mood disorders in which the person experiences states or occurrence of depression or mania, hypomania, or mixed states which severely disable condition. Wellbutrin is administered in the depression phase of the bipolar disorder.
In fact the modern day treatments include mood stabilizer treatment that can dramatically halt the turbulent course of bipolar disorder, reduce the risk of suicide, increase life expectancy, increase productivity and functioning and 40-75% of patients who respond to mood stabilizers achieve a reasonable occupational status and ability to live independently (Goldberg et al, 1995; Tsuang et al, 1979). In recent years it is also seen that Bupropion is used to help people quit smoking by declining cravings and nicotine withdrawal effects (WebMD, 2009).
Depression is considered as a psychological situation that changes how an individual think and feel, and also affects the individual’s social behavior and sense of physical health (Franklin, 2002). Depression refers to any downturn in mood, which lead to various problems. A depressed mood is often reported as being miserable, sad, hopeless, discouraged, and irrational. Bipolar disorder involves cycles of depression and mania, or excitement. It is essential to give the patient Wellbutrin when in the depression phase.
Mode of Action
Pharmacodynamics
Wellbutrin SR is thought to bring back or restore the balance of natural chemicals or the neurotransmitters in the brain (WebMD, 2009). Specifically, Wellbutrin is consideration to work by varying the levels of the brain chemicals norepinephrine and dopamine (drugs.com, 2009). Studies have proven that Wellbutrin is a comparatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine.
Additionally, it also does not hinder monoamine oxidase or the re-uptake of serotonin. Though it is not much clear about the mechanism of action of bupropion, it is supposed that its mode of action is coordinated by noradrenergic and/or dopaminergic mechanisms (John et al.,2005). Wellbutrin SR Tablets were put to test to healthy volunteers and was found that bupropion reaches a peak concentration in the plasma in the initial three hours of oral administration. Further it was noted that intake of food amplified Cmax and AUC of bupropion by 11% and 17%, correspondingly. This result proves that there is no clinically noteworthy food effect.
Bupropion is widely metabolized in humans and the three metabolites that are found to be active are hydroxybupropion, which is created by hydroxylation of the tert-butyl group of bupropion. The other two metabolites are the amino-alcohol isomers threohydrobupropion and erythrohydrobupropion that are created by reduction of the carbonyl group. In vitro studies point out that cytochrome P450IIB6 (CYP2B6) is the main isoenzyme involved in the formation of hydroxybupropion. On the other hand cytochrome P450 isoenzymes aid in the creation of threohydrobupropion. Further, when the side chain bupropion undergoes the process of oxidation, it results in the formation of a glycine conjugate of meta-chlorobenzoic acid. This is then excreted as the main urinary metabolite.
As of now the strength and toxicity of the metabolites when compared to bupropion is still not much understood. According to the results of an antidepressant screening test in mice, it was found that hydroxybupropion is fifty percent as strong as bupropion, while threohydrobupropion and erythrohydrobupropion are five times less powerful than bupropion. It is of great significance as the plasma concentrations of the metabolites are high when compared to bupropion.
Studies also point out that since bupropion is easily metabolized, there are high risks for drug-drug interactions especially those agents that are metabolized by the cytochrome P450IIB6 (CYP2B6) isoenzyme. Even though cytochrome P450IIB6 (CYP2B6) is not involved in bupropion metabolism, studies have found that drug-drug interactions occur when bupropion taken along with drugs metabolized by this isoenzyme.
There was also a study that was conducted using radioactive 14C-bupropion to specifically study the fate of this drug in the human body. This study pointed out that with an oral administration of 200 mg of 14C-bupropion, ninety seven percent in total of the radioactive dose was excreted through urine and feces. It was also observed that the part of the oral dose of bupropion was excreted without any change and accounted for only 0.5%. This shows that bupropion is a highly metabolic compound (GlaxoSmithKline, 2008).
Dosage and Administration
Seizure is one of the most common risks when Wellbutrin SR tablets are administered. Hence it is especially important to administer Wellbutrin SR Tablets in such a manner to minimize the risk of seizure. Steady increase in dosage is also significant if anxiety, motor agitation, and sleeplessness are encountered during the initial days of treatment. It is also possible to manage these effects by momentary decrease of dose or the short-term administration of a transitional to long-acting sedative hypnotic which is usually not required beyond the first week of treatment. Sleeplessness may also be overcome by skipping out bedtime doses. In any case if there is no reduction of depression symptoms then dose escalation should be stopped.
In general, the dose for adults is 300 mg/day, administered as 150 mg twice daily. It is necessary to note that Wellbutrin SR Tablets should always be given at the lowest dose of 150 mg/day single daily dose in the morning in the initial phase and then it should be gradually increased depending up on the tolerance. However it is important to give a gap of a minimum of eight hours in between the successive doses of 150 mg. Unlike the other antidepressant drugs Wellbutrin SR shows its full antidepressant effect only after a long period (probably w weeks or more).
The 300 mg/day dosage can be increased to the maximum of 400 mg/day administered as 200 mg twice daily, if an adequate clinical improvement is noted with several weeks of treatment using 300 mg/day. It is important to note that the patient health history should be studied before using Wellbutrin SR. For instance, extreme caution in patients with severe hepatic cirrhosis need to be taken as it can lead to serious complications and in such cases the dose must not go beyond 100 mg/day or 150 mg alternate day in these patients. Since Bupropion is linked with a dose-related risk of seizures, it is also important to note the contradictions with other concomitant medications (GlaxoSmithKline, 2008).
It is essential to study the factors or conditions that may alter the metabolic capacity in a patient. For instance, if the patient has liver disease, congestive heart failure [CHF], or any other conditions, it is important to be cautious in administering Bupropion. It is important to take into account the factor of what will happen if elimination influence the degree and extent of accumulation of the active metabolites of bupropion. Before the moderately polar metabolites of bupropion are excreted through urine, they undergo additional metabolism in the liver.
Studies have shown that there is an impact of age on the pharmacokinetics of bupropion and its metabolites. However, it is still not fully characterized. An examination of steady-state bupropion concentrations from various efficacy studies including patients dosed between 300 to 750 mg/day, on a 3 times daily schedule, discovered no association among age (18 to 83 years) and plasma concentration of bupropion. In yet another study, a single-dose pharmacokinetic study established that the character of bupropion and its metabolites in elderly people was comparable to that of younger people (GlaxoSmithKline, 2008).
Side Effects of Wellbutrin SR
There are several side effects that were noticed in subjects using Wellbutrin SR. for instance, Wellbutrin SR 300 mg/day resulted in subjects suffering from Anorexia, dry mouth, rash, sweating, tinnitus, and tremor. On the other hand there were more side effects with higher doses. Wellbutrin SR 400 mg/day produced side effects such as abdominal pain, disturbance, nervousness, giddiness, dry mouth, sleeplessness, myalgia, vomiting, tremor, pharyngitis, sweating, tinnitus, and increased urinary frequency (John et al.,2005).
Studies also can out with sever contradictions when Wellbutrin SR is administered. There are also studies that suggest contraindication of Wellbutrin SR in patients who abruptly stop their alcoholic nature or even if the stop any sedatives such as benzodiazepines. Wellbutrin SR has also shown serious contraindication in patients who have an allergic reaction to bupropion or any of the other ingredients that make up the tablet.
Conclusion
Wellbutrin SR is a psychotropic drug and in recent years has come up with several new applications. Patients suffering from prolonged depressive disorder may experience worsening of their depression that may lead to suicidal ideation and behavior. Wellbutrin SR is an effective and proven antidepressant drug that can be administered in doses that is recommended by the physician.
However, it takes time to show considerable improvement and need to be continuously administered over several weeks before any good results can be noted. It is extremely important to keep a watch on the patients with depression who are taking this drug because there can be episodes where there can be worsening of the depression symptoms. And in such cases it is important to change the therapeutic regimen. Wellbutrin SR should be given with great care to patients with a history of seizure, cranial trauma, or other inclination(s) to seizure, or patients medicated with other drugs that minimizes seizure threshold (GlaxoSmithKline, 2008).
References
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John D. P., John H.O’Neal, and Mary C.T. (2005) Handbook of Clinical Psychopharmacology for Therapsits, 4th ed. New Harbinger Publications, Oakland, Calif.
Tsuang, M.T, Woolson, R.F, Fleming, M. (1979). Long-Term Outcome Of Major Psychosis – I. Schizophrenia and Affective Disorders Compared with Psychiatrically Symptom-Free Surgical Conditions.