Wellbutrin Withdrawal
The web site you are on now, The Road Back, offers
information on how to get off Strattera, prevent
Wellbutrin withdrawal side effects as well as
eliminating current Wellbutrin side effects.
You will find on this site the complete book, How
to Get Off Psychoactive Drugs Safely. Since
1999, over 50,000 people have now used this
information to get off their antidepressant or other
type of psychoactive medication.
Withdrawal off of Wellbutrin does not have to be
difficult and handling current Wellbutrin side
effects can be resolved quickly.
Note:
If you are taking Wellbutrin as well as an
anti-anxiety medication (benzodiazepine), the
anti-anxiety medication must be discontinued first.
If you are only discontinuing the Wellbutrin the
Wellbutrin must be reduced very slowly to prevent
withdrawal side effects from the anti-anxiety drug.
Wellbutrin slows the metabolism rate of anti-anxiety
drugs and when the Wellbutrin is removed from the
system the anti-anxiety medication will not take as
long to metabolize and this creates a withdrawal
effect from the anti-anxiety medication. See chapter
9 on the right side of each page for anti-anxiety
medication procedures.
In May 2013, our program made its next leap forward
and at this time; completely eliminating Wellbutrin
side effects is not only within our grasp, it is
here.
Anxiety in the daytime, insomnia at night, the
dreaded head symptoms common with Wellbutrin
withdrawal can now be a thing of the past.
There is quite a bit of information on our web site
and if the ill effects from Wellbutrin have you
unable to read very much text, we can make this very
quick and simple.
For head symptoms, even the brain zaps,
taking the right type of omega 3 fish oil will
eliminate them quickly. Take (1) Omega 3 Supreme TG in
the morning and (1) more at noon. Link is provided below
of where to find these..
If you have nausea, drink a couple cups of ginger
tea each day.
If you have insomnia, take a supplement called Neuro
Night. (You would take
1 capsule 15-minutes before bedtime)
If you have daytime anxiety, take Neuro Day. (Take 1
capsule twice a day)
These supplements are manufactured and sold by
Neuro Genetic Solutions.
If you are in the United States, Australia, Canada,
Europe and Great Britain the supplements are 50% off at the moment.
10% of the people wanting to get off Wellbutrin do
not make it because of the withdrawal side effects.
Of the 90% that are able to get off Wellbutrin, 50%
will still suffer during the Wellbutrin withdrawal.
There is no need to suffer.
Click How to Start located on the
top navigation menu for all of your answers.
Bupropion
Brand name (Wellbutrin)
Description
Antidepressant
Bupropion hydrochloride, an antidepressant of the
aminoketone class, is chemically unrelated to tricyclic,
tetracyclic, or other known antidepressant agents. Its
structure closely resembles that of diethylpropion; it is
related to phenylethylamines. It is designated as
(±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone
hydrochloride. The molecular weight is 276.2. The emperical
formula is C13H18CINO*HCl. Bupropion
powder is white, crystalline, and highly soluble in water.
It has a bitter taste and produces the sensation of local
anesthesia on the oral mucosa.
Bupropion is supplied for oral administration as 75 mg
(yellow-gold) and 100 mg (red) film-coated tablets. Each
tablet contains the labeled amount of bupropion
hydrochloride and the inactive ingredients: 75 mg tablet -
D&C Yellow No. 10 Lake, FD&C Yellow No. 6 Lake,
hydroxypropyl cellulose, hydroxypropyl methylcelluose,
microcrystalline cellulose, polyethylene glycol, talc, and
titanium dioxide; 100 mg tablet - FD&C Red No. 40 Lake, FD&C
Yellow No. 6 Lake, hydroxypropyl cellulose, hydroxypropyl
methylcellulose, microcrystalline cellulose, polyethylene
glycol, talc, and titanium dioxide.
Clinical Pharmacology
Pharmacodynamics and Pharmacological Actions:
The neurochemical mechanism of the antidepressant effect of
bupropion is not known. Bupropion does not inhibit monoamine
oxidase. Compared to classical tricyclic antidepressants, it
is a weak blocker of the neuronal uptake of serotonin and
norepinephrine; it also inhibits the neuronal re-uptake of
dopamine to some extent.
Bupropion produces dose-related CNS stimulant effects in
animals, as evidenced by increased locomotor activity,
increased rates of responding in various schedule-controlled
operant behavior tasks, and, at high doses, induction of
mild stereotyped behavior.
Bupropion causes convulsions in rodents and dogs at doses
approximately tenfold the dose recommended as the human
antidepressant dose.
Absorption, Distribution, Pharmacokinetics, Metabolism, and
Elimination:
Oral bioavailability and single-dose pharmacokinetics:
In humans, following oral administration of bupropion, peak
plasma bupropion concentrations are usually achieved within
2 hours, followed by a biphasic decline. The average
half-life of the second (post-distributional) phase is
approximately 14 hours, with a range of 8 to 24 hours. Six
hours after a single dose, plasma bupropion concentrations
are approximately 30% of peak concentrations. Plasma
bupropion concentrations are dose-proportional following
single doses of 100 to 250 mg; however, it is not known if
the proportionality between dose and plasma level is
maintained in chronic use.
The absolute bioavailability of bupropion tablets in humans
has not been determined because an intravenous formulation
for human use is not available.
However, it appears likely that only a small proportion of
any orally administered dose reaches the systemic
circulation intact. For example, the absolute
bioavailability of bupropion in animals (rats and dogs)
ranges from 5% to 20%.
Metabolism:
Following oral administration of 200 mg of 14C-bupropion,
87% and 10% of the radioactive dose were recovered in the
urine and feces, respectively. However, the fraction of the
oral dose of bupropion excreted unchanged was only 0.5%, a
finding documenting the extensive metabolism of bupropion.
Several of the known metabolites of bupropion are
pharmacologically active, but their potency and toxicity
relative to bupropion have not been fully characterized.
However, because of their longer elimination half-lives, the
plasma concentrations of at least two of the known
metabolites can be expected, especially in chronic use, to
be very much higher than the plasma concentration of
bupropion. This is of potential clinical importance because
factors or conditions altering metabolic capacity (e.g.,
liver disease, congestive heart failure, age, concomitant
medications, etc.) or elimination may be expected to
influence the degree and extend of accumulation of these
active metabolites.
Furthermore, bupropion has been shown to induce its own
metabolism in three animal species (mice, rats, and dogs)
following subchronic administration. If induction also
occurs in humans, the relative contribution of bupropion and
its metabolites to the clinical effects of bupropion may be
changed in chronic use.
Plasma and urinary metabolites so far identified include
biotransformation products formed via reduction of the
carbonyl group and/or hydroxylation of the tert-butyl group
of bupropion. Four basic metabolites have been identified.
They are the erythro- and threo-amino alcohols of bupropion,
the erythro-amino diol of bupropion, and a morpholinol,
metabolite (formed from hydroxylation of the tert-butyl
group of bupropion).
The morpholinol metabolite appears in the systemic
circulation almost as rapidly as the parent drug following a
single oral dose. Its peak level is three times the peak
level of the parent drug; it has a half life on the order of
24 hours; and its AUC 0 to 60 hours is about 15 times that
of bupropion.
The threo-amino alcohol metabolite has a plasma
concentration time profile similar to that of the
morpholinol metabolite. The erythro-amino alcohol and the
erythro-amino diol metabolites generally cannot be detected
in the systemic circulation following a single oral dose of
the parent drug. The morpholinol and the threo-amino alcohol
metabolites have been found to be half as potent as
bupropion in animal screening tests for antidepressant
drugs.
During a chronic dosing study in 14 depressed patients with
left ventricular dysfunction, it was found that there was
substantial interpatient variability (two- to five-fold) in
the trough steady-state concentrations of bupropion and the
morpholinol and threo-amino alcohol metabolites. In
addition, the steady-state plasma concentrations of these
metabolites were 10 to 100 times the steady-state
concentrations of the parent drug.
The effect of other disease states and altered organ
function on the metabolism and/or elimination of bupropion
has not been studied in detail. However, the elimination of
the major metabolites of bupropion may be affected by
reduced renal or hepatic function because they are
moderately polar compounds and are likely to undergo
conjugation in the liver prior to urinary excretion. The
preliminary results of a comparative single-dose
pharmacokinetic study in normal versus cirrhotic patients
indicated that half-lives of the metabolites were prolonged
by cirrhosis and that the metabolites accumulated to levels
two to three times those in normals.
The effect of age on plasma concentrations of bupropion and
its metabolites has not been characterized.
In vitro tests show that bupropion is 80% or more bound to
human albumin at plasma concentrations up to 800 micromolar
(200 mcg/mL).
Indications And Usage
Bupropion is indicated for the treatment of depression. A
physician considering bupropion for the management of a
patient's first episodes of depression should be aware that
the drug may cause generalized seizures with an approximate
incidence of 0.4% (4/1000). This incidence of seizures may
exceed that of other marketed antidepressants by as much as
fourfold. This relative risk is only an approximate estimate
because no direct comparative studies have been conducted.
The efficacy of bupropion has been established in three
placebo-controlled trials, including two of approximately 3
weeks duration in depressed inpatients, and one of
approximately 6 weeks duration in depressed outpatients. The
depressive disorder of the patients studied corresponds most
closely to the Major Depression category of the APA
Diagnostic and Statistical Manual III.
Major Depression implies a prominent and relatively
persistent depressed or dysphoric mood that usually
interferes with daily functioning (nearly every day for at
least 2 weeks); it should include at least four of the
following eight symptoms: change in appetite, change in
sleep, psychomotor agitation or retardation, loss of
interest in usual activities or decrease in sexual drive,
increased fatigability, feelings of guilt or worthlessness,
slowed thinking or impaired concentration, and suicidal
ideation or attempts.
Effectiveness of bupropion in long-term use, that is, for
more than 6 weeks, has not been systematically evaluated in
controlled trials. Therefore, the physician who elects to
use bupropion for extended periods should periodically
re-evaluate the long-term usefulness of the drug for the
individual patient.
Contraindications
Bupropion is contraindicated in patients with a seizure
disorder. Bupropion is also contraindicated in patients with
a current or prior diagnosis of bulimia or anorexia nervosa
because of a higher incidence of seizures noted in such
patients treated with bupropion. The concurrent
administration of bupropion and a monoamine oxidase (MAO)
inhibitor is contraindicated. At least 14 days should elapse
between discontinuation of an MAO inhibitor and initiation
of treatment with bupropion. Bupropion is contraindicated in
patients who have shown an allergic response to it.
Warnings
Seizures:
Bupropion is associated with seizures in approximately 0.4%
(4/1000) of patients treated at doses up to 450 mg/day. This
incidence of seizures may exceed that of other marketed
antidepressants by as much as fourfold. This relative risk
is only an approximate estimate because no direct
comparative studies have been conducted. The estimate
seizure incidence for bupropion increases almost tenfold
between 450 and 600 mg/day, which is twice the usually
required daily dose (300 mg) and one and one-third the
maximum recommended daily dose (450 mg). Given the wide
variability among individuals and their capacity to
metabolize and eliminate drugs, this disproportionate
increase in seizure incidence with dose incrementation calls
for caution in dosing.
During the initial development, 25 among approximately 2400
patients treated with bupropion experienced seizures. At the
time of seizure, seven patients were receiving daily doses
of 450 mg or below for an incidence of 0.33% (3/1000) within
the recommended dose range. Twelve patients experienced
seizures at 600 mg per day (2.3% incidence); six additional
patients has seizures at daily doses between 600 and 900 mg
(2.8% incidence).
A separate, prospective study was conducted to determine the
incidence of seizure during an 8-week treatment exposure in
approximately 3200 additional patients who received daily
doses of up to 450 mg. Patients were permitted to continue
treatment beyond 8 weeks if clinically indicated. Eight
seizures occurred during the initial 8-week treatment period
and five seizures were reported in patients continuing
treatment beyond 8 weeks, resulting in a total seizure
incidence of 0.4%.
The risk of seizure appears to be strongly associated with
dose and the presence of predisposing factors. A significant
seizure, CNS tumor, concomitant medications that lower
seizure threshold, etc.) was present in approximately
one-half of the patients experiencing a seizure. Sudden and
large increments in dose may contribute to increased risk.
While many seizures occurred early in the course of
treatment, some seizures did occur after several weeks at
fixed dose.
Recommendations for reducing the risk of seizure:
Retrospective analysis of clinical experience gained during
the development of bupropion suggests that the risk of
seizure may be minimized if (1) the total daily dose of
bupropion does not exceed 450 mg, (2) the daily dose is
administered t.i.d., with each single dose not to exceed 150
mg to avoid high peak concentrations of bupropion and/or its
metabolites, and (3) the rate of incrementation of dose is
very gradual. Extreme caution should be used when bupropion
is (1) administered to patients with a history of seizure,
cranial trauma, or other predisposition(s) toward seizure,
or (2) prescribed with other agents (e.g., antipsychotics,
other antidepressants, etc.) or treatment regimens (e.g.,
abrupt discontinuation of a benzodiazepine) that lower
seizure threshold.
Potential for Hepatotoxicity:
In rats receiving large doses of bupropion chronically,
there was an increase in incidence of hepatic hyperplastic
nodules and hepatocellular hypertrophy. In dogs receiving
large doses of bupropion chronically, various histologic
changes were seen in the liver, and laboratory tests
suggesting mild hepatocellular injury were noted. Although
scattered abnormalities in liver function tests were
detected in patients participating in clinical trials, there
is no clinical evidence that bupropion acts as a hepatotoxin
in humans.
Precautions
General:
Agitation and Insomnia: A substantial proportion of patients
treated with bupropion experience some degree of increased
restlessness, agitation, anxiety, and insomnia, especially
shortly after initiation of treatment. In clinical studies,
these symptoms were sometimes of sufficient magnitude to
require treatment with sedative/hypnotic drugs. In
approximately 2% of patients, symptoms were sufficiently
severe to require discontinuation of treatment with
bupropion.
Psychosis, Confusion, and Other Neuropsychiatric Phenomena:
Patients treated with bupropion have been reported to show a
variety of neuropsychiatric signs and symptoms including
delusions, hallucinations, psychotic episodes, confusion,
and paranoia. Because of the uncontrolled nature of many
studies, it is impossible to provide a precise estimate of
the extent of risk imposed by treatment with bupropion. In
several cases, neuropsychitric phenomena abated upon dose
reduction and/or withdrawal of treatment.
Activation of Psychosis and/or Mania: Antidepressants can
precipitate manic episodes in Bipolar Manic Depressive
patients during the depressed phase of their illness and may
activate latent psychosis in other susceptible patients.
Bupropion is expected to pose similar risks.
Altered Appetite and Weight: A weight loss of greater than 5
pounds occurred in 28% of patients receiving bupropion. This
incidence is approximately double that seen in comparable
patients treated with tricyclics or placebo. Furthermore,
while 34.5% of patients receiving tricyclic antidepressants
gained weight, only 9.4% of patients treated with bupropion
did. Consequently, if weight loss is a major presenting sign
of a patient's depressive illness, the anorectic and/or
weight reducing potential of bupropion should be considered.
Suicide:
The possibility of a suicide attempt is inherent in
depression and may persist until significant remission
occurs. Accordingly, prescriptions for bupropion should be
written for the smallest number of tablets consistent with
good patient management.
Use in Patients with Systemic Illness:
There is no clinical experience establishing the safety of
bupropion in patients with a recent history of myocardial
infarction or unstable heart disease. Therefore, care should
be exercised if it is used in these groups. Bupropion was
well tolerated in patients who has previously developed
orthostatic hypotension while receiving tricyclic
antidepressants.
Because bupropion HCl and its metabolites are almost
completely excreted through the kidney and metabolites are
likely to undergo conjugation in the liver prior to urinary
excretion, treatment of patients with renal or hepatic,
impairment should be initiated at reduced dosage as
bupropion and its metabolites may accumulate in such
patients beyond concentrations expected in patients without
renal or hepatic impairment. The patient should be closely
monitored for possible toxic effects of elevated blood and
tissue levels of drug and metabolites.
Information for Patients:
Physicians are advised to discuss the following issues with
patients:
Patients should be instructed to take bupropion in equally
divided doses three or four times a day to minimize the risk
of seizure.
Patients should be told that any CNS-active drug like
bupropion may impair their ability to perform tasks
requiring judgment or motor and cognitive skills.
Consequently, until they are reasonably certain that
bupropion does not adversely affect their performance, they
should refrain from driving an automobile or operating
complex, hazardous machinery.
Patients should be told that the use and cessation of use of
alcohol may alter the seizure threshold, and, therefore,
that the consumption of alcohol should be minimized, and, if
possible, avoided completely.
Patients should be advised to inform their physician if they
are taking or plan to take any prescription or
over-the-counter drugs. Concern is warranted because
bupropion and other drugs may affect each others metabolism.
Patients should be advised to notify their physician if they
become pregnant or intend to become pregnant during therapy.
Drug Interactions:
No systematic data have been collected on the consequences
of the concomitant administration of bupropion and other
drugs.
However, animal data suggest that bupropion may be an
inducer of drug metabolizing enzymes. This may be of
potential clinical importance because the blood levels of
co-administered drugs may be altered.
Alternatively, because bupropion is extensively metabolized,
the co-administration of other drugs may affect its clinical
activity. In particular, care should be exercised when
administering drugs known to affect hepatic
drug-metabolizing enzyme systems (e.g., carbamazepine,
cimetidine, phenobarbital, phenytoin).
Studies in animals demonstrate that the acute toxicity of
buproprion is enhanced by the MAO inhibitor phenelzine (see
CONTRAINDICATIONS).
Limited clinical data suggest a higher incidence of adverse
experiences in patients receiving concurrent administration
of bupropion and L-dopa. Administration of bupropion to
patients receiving L-dopa concurrently should be undertaken
with caution, using small initial doses and small gradual
dose increases.
Concurrent administration of bupropion and agents which
lower seizure threshold should be undertaken only with
extreme caution (see WARNINGS). Low initial dosing and small
gradual dose increases should be employed.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Lifetime carcinogenicity studies were performed in rats and
mice at doses up to 300 and 150 mg/kg/day, respectively. In
the rat study there was an increase in nodular proliferative
lesions of the liver at doses of 100 to 300 mg/kg/day; lower
doses were not tested. The question of whether or not such
lesions may be precursors of neoplasms of the liver is
currently unresolved. Similar liver lesions were not seen in
the mouse study, and no increase in malignant tumors of the
liver and other organs was seen in either study.
Bupropion produced a borderline positive response (2 to 3
times control mutation rate) in some strains in the Ames
bacterial mutagenicity test, and a high oral dose (300, but
not 100 or 200 mg/kg) produced a low incidence of
chromosomal aberrations in rats. The relevance of these
results in estimating the risk of human exposure to
therapeutic doses is unknown.
A fertility study was performed in rats; no evidence of
impairment of fertility was encountered at oral doses up to
300 mg/kg/day.
Pregnancy: Teratogenic Effects:
Pregnancy Category B: Reproduction studies have been
performed in rabbits and rats at doses up to 15 to 45 times
the human daily dose and have revealed no definitive
evidence of impaired fertility or harm to the fetus due to
bupropion. (In rabbits, a slightly increased incidence of
fetal abnormalities was seen in two studies, but there was
no increase in any specific abnormality.) There are no
adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always
predictive of human response, this drug should be used
during pregnancy only if clearly needed.
Labor and Delivery:
The effect of bupropion on labor and delivery in humans is
unknown.
Nursing Mothers:
Because of the potential for serious adverse reactions in
nursing infants from bupropion, a decision should be made
whether to discontinue nursing or to discontinue the drug,
taking into account the importance of the drug to the
mother.
Pediatric Use:
The safety and effectiveness of bupropion in individuals
under 18 years old have not been established.
Use in the Elderly:
Bupropion has not been systematically evaluated in older
patients.
|