Bupropion hydrochloride is an antidepressant in the aminoketone class and is chemically unrelated to tricyclic, selective serotonin reuptake inhibitor (SSRI), or other known antidepressants. The drug is commonly sold under the Wellbutrin and Zyban brand names. Bupropion is a chemical derivative of diethylpropion, an amphetamine-like substance used as an anorectic (appetite suppressant). The drug is both a norepinephrine reuptake inhibitor and a dopamine reuptake inhibitor.
Bupropion was developed by Burroughs Research in 1966 and patented by Burroughs-Wellcome (which later became Glaxo-Wellcome, and, as of 2000, GlaxoSmithKline) in 1974. In 1989, the FDA approved it for marketing under the brand name Wellbutrin as an antidepressant. The drug was quickly recalled due to a risk of seizures, but it was discovered that the risk could be substantially reduced by cutting the dosage in half.
Glaxo went on to develop a sustained-release (SR) version of Wellbutrin to reduce the drug into the system at a slower rate. The SR version is taken twice a day, and is also available in a generic form (Bupropion SR). As well, there is an extended-release formulation of the drug, Wellbutrin XL, which is the most recent version of the drug.
In 1997 the FDA approved bupropion to aid smokers in quitting. Glaxo subsequently marketed the drug under the name Zyban to help tobacco smokers stop by reducing the severity of craving and the addiction/withdrawal symptoms. It can be used in combination with nicotine replacement therapies. The drug is being investigated for yet more uses for disorders such as weight loss, ADHD, prevention ofseasonal affective disorder (SAD), Restless Leg Syndrome and a possibility of increasing sexual functioning in women.
antidepressant, smoking deterrent
Bupropion is a selective catecholamine (norepinephrine and dopamine) reuptake inhibitor. It has only a minor effect on serotonin reuptake and does not inhibit MAO. The drug’s antidepressant effects are considered to be mediated by its dopaminergic and noradrenergic action.
Indications and Dosage:
Wellbutrin is indicated for the treatment of depression. A doctor considering this as a first-line defense for an initial episode of depression should be aware that the drug may cause generalized seizures in a dose-dependent in some patients. The incidence of seizures may exceed that of other antidepressants by as much as four-fold. The relative risk is only an approximate estimate because no comparative studies have been conducted.
The usual dose for depression is 300mg/day, given 3 times a day in 100mg increments, beginning with 200mg in the initial few days. For tobacco cessation, 150mg/day initially is fine, with possible increases to 300mg if indicated and directed by a physician. In patients receiving insulin, sympathomimetic anorectic drugs, or anti-malaria agents, the daily dose of Wellbutrin should not exceed 150mg.
It is particularly important to administer Wellbutrin in a way so as to minimize the risk of seizure. Increases in dosage should not exceed 100mg/day in a 3-day period. Gradual increases in dosage is also important if motor restlessness, insomnia, or agitation are to be minimized. If indicated, these effects may be managed by temporarily reducing the dosage or by the short-term introduction of an intermediate to long-lasting sedative hypnotic. A sedative hypnotic is normally not required beyond the first week of treatment. Insomnia may also be reduced or minimized by avoiding bedtime dosage. If adverse effects continue, increases in dosage should be stopped. No single dose of Wellbutrin should exceed 150mg. It should be taken 3 times a day, preferably with at least 6 hours between doses.
For persons with impaired hepatic function (including mild to moderate hepatic cirrhosis) the dose should not exceed 75/mg once a day.
As with other antidepressant drugs, the full effects of Wellbutrin may not be noted for approximately 4 weeks after treatment begins, possibly longer. An increase in dosage, up to a maximum of 450mg/day may be considered for individuals when no clinical improvement is seen after several weeks of treatment at the standard 300mg/day dosage. If no improvement is noted at the 450mg/day dosage after an appropriate amount of time, Wellbutrin should be discontinued.
Adverse side effects common to Wellbutrin include dry mouth, agitation, insomnia, headache/migraine, constipation, nausea/vomiting, and tremor.
An advantage of bupropion over most other traditional antidepressants is that it causes no sexual dysfunction in men and may even increase sex drive in both men and women. According to a recent study, bupropion may also increase libido in women with “hypoactive sexual desire disorder” but without signs of depression. Studies also suggest that the drug may increase sexual functioning in minority women suffering from depression, but it is too early for treatment to be indicated in these women, and further controlled trials are needed to establish conclusive evidence.
GlaxoSmithKline withdrew the licensing application from the MHRA before completion of the process in Britain, following serious concerns over the drug’s safety. As such, Wellbutrin remains unlicensed in the UK. At one point Zyban accounted for 25% of all MHRA yellow card adverse drug reactions in the UK, and it has allegedly been connected with suicides and severe, sometimes permanent, psychological disorders including depression, personality change, anger and memory control issues, general psychological disturbance/abnormality, and psychosis and mania. Stroke, sometimes leading to death, and suicidality have been noted as well.
Its use is also banned or restricted in other developed nations. In the UK 66 people (or their survivors) alleged Zyban was responsible for their cardiovascular, allergic or psychiatric problems. The drug’s use in the UK is limited to a smoking cessation aid, and can be obtained only one time, with subsequent prescription illegal.
Little data has been collected on the metabolism of Wellbutrin with concomitant use of other drugs or, alternatively, the effect of concomitant administration of Wellbutrin on the metabolism of other drugs.
Bupropion is extensively metabolized, and as such, the co-administration of other drugs may affect its clinical activity. Depending on the drug, the effects of either when taken together could be increase, decreased or altered. It is especially important to talk to your doctor before combining Wellbutrin and the following:
- Beta blockers (used for high blood pressure and heart conditions) (Inderal, Lopressor, Tenormin)
- Carbamazepine (Tegretol)
- Levodopa (Larodopa)
- Cimetidine (Tagamet)
- Cyclophosphamide (Cytoxan)
- MAOIs (such as Nardil and Parnate)
- Major tranquilizers such as Haldol, Thorazine, Mellaril and Risperdal
- Nicotine patches
- Orphenadrine (Norgesic)
- Other antidepressants such as Norpramin, Pamelor, Zoloft and Prozac
- Steroid medications such as Prednisone
- Theophylline (Theo-Dur)
- Phenytoin (Dilantin)
Wellbutrin Information for Parents and Kids:
The safety and efficacy of bupropion in children under the age of 18 is not well-established. As with all antidepressants, there is some indication that children and teenagers taking them may be more likely to develop suicidality or self-harming thoughts. Children and adolescents taking medications such as bupropion should be carefully monitored, especially in the initial stage of treatment and anytime the dosage is increased or decreased. If the child develops depression, harmful thoughts, extreme worry or agitation, panic attacks, sleep difficulties, irritability, aggressive behavior, extreme restlessness, frenzied/abnormal excitement, or any sudden or unusual changes in behavior, the child’s physician should be contacted right away.
Wellbutrin Warnings and Precautions:
Persons with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression of the development of suicidality or unusual behavioral changes, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.
A major depressive episode may actually be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled studies) that treating such an event with an antidepressant along may increase the likelihood of a precipitated mixed/manic episode in patients at risk for bipolar disorder. Therefore, prior to beginning antidepressant therapy, patients with depressive symptoms should be properly screened to determine if they are at risk for bipolar disorder. Wellbutrin, it should be noted, is not approved as a bipolar disorder treatment option.
Patients should be made aware that Wellbutrin contains the same active ingredient as Zyban (used to aid in quitting smoking) and as such, Wellbutrin should not be used in conjunction with Zyban or any other bupropion-containing medications.
Some precautions to consider with Wellbutrin therapy include the following:
A good number of patients treated with bupropion experience some degree of increased agitation, anxiety, insomnia and restlessness, especially shortly after beginning treatment. In clinical trials, these symptoms were sometimes severe enough to require treatment with sedative/hypnotic drugs. In around 2% of patients, symptoms were of sufficient magnitude to warrant discontinuation of Wellbutrin treatment altogether.
Some patients taking Wellbutrin have reportedly shown a variety of neuropsychiatric signs and symptoms including psychotic episodes, hallucinations, delusions, paranoia and confusion. Due to the uncontrolled nature of many trials, it is nearly impossible to know the true extent of risk imposed by bupropion treatment.
A loss in weight of greater than 5 lbs occurred in 28% of patients receiving Wellbutrin. This incidence is approximately double that seen in patients treated with placebo or tricyclics. Further, while 34.5% of tricyclic patients gained weight, the same can be said in only 9.4% of Wellbutrin patients. Thus, if weight loss is a major sign of an individual’s depressive illness, the anorectic and/or weight-loss potential of Wellbutrin treatment should be taken into consideration.
Hypertension, in some cases severe, has been reported by some patients taking bupropion alone and in combination with nicotine replacement therapy. This has been observed in patients with and without pre-existing hypertension. Care should be exercised in treating persons with a recent history of unstable heart disease or myocardial infarction, as there is no clinical evidence of the safety of Wellbutrin in these individuals.
As with any medication, it is important to consult a physician before discontinuing Wellbutrin treatment. An estimated 30% of patients who discontinue Wellbutrin experience withdrawal symptoms. The symptoms are frequently attributed to “flu like” effects such as muscle aches, headaches, nausea etc. These usually last 1 to 2 weeks.
Over-dosage & Contraindications:
Since Wellbutrin’s introduction, overdoses of up to 17,500mg have been reported. Seizure was reported in around one-third of all overdoses. Other severe reactions reported with overdose of bupropion alone included loss of consciousness, sinus tachycardia and hallucinations. In multiple-drug overdoses, adverse reactions reported include muscle rigidity, respiratory failure, fever, rhabdomyolysis, hypotension, stupor and coma.
Though most individuals recovered without secondary reactions to their overdoses, deaths associated with overdoses of Wellbutrin alone have rarely been observed in patients ingesting massive amounts of bupropion. Multiple uncontrolled seizures, cardiac failure, bradycardia and cardiac arrest prior to death were reported in these individuals.
Persons with hypersensitivity to bupropion or any of its active agents should not take Wellbutrin.
Wellbutrin is contraindicated in patients with a seizure disorder or those treated with Zyban Sustain-Release tablets, or any other medications containing bupropion because the incidence of seizure is dose dependent.
Wellbutrin should not be used by patients with a current or prior diagnosis of anorexia or bulimia due to the higher incidence of seizures noted in such patients. Bupropion is not for use in persons undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines).
The concurrent use of Wellbutrin and an MAOI is not recommended. At least 14 days should pass between discontinuing an MAOI and beginning treatment with Wellbutrin. As well, a two week time period should elapse between cessation of Wellbutrin therapy and initiation of an MAOI.
Generic Name: bupropion
Chemical Formula: C13H18ClNO
Routes of Administration: oral
Elimination Half Life: 20 hours
Legal Status: by prescription only