What is wellbutrin?

Wellbutrin is the brand name for bupropion, a prescription drug that's used to treat depression.

It's also used to treat seasonal affective disorder (SAD), a type of depression that usually strikes in the fall and winter.

Under the brand name Zyban, bupropion has also been prescribed to help people quit smoking.

Wellbutrin belongs to the aminoketone class of antidepressants, which are chemically unrelated to the better-known selective-serotonin reuptake inhibitors (SSRIs), such as Prozac, Paxil, or Zoloft.

Wellbutrin moderates the levels and activity of the neurotransmitters norepinephrine and dopamine, but exactly how it works to treat depression is not known.

Doctors have also prescribed Wellbutrin off-label to treat attention deficit hyperactivity disorder (ADHD), and in tandem with other medications — particularly SSRIs — to treat bipolar disorder.

The Food and Drug Administration (FDA) originally approved Wellbutrin as a treatment for depression in 1985.

However, it was withdrawn from the market in 1986 amid findings that it increased the frequency of seizures in non-depressed bulimic patients at the originally recommended dose of 400 to 600 milligrams a day.

The FDA reapproved Wellbutrin in 1989 with a lowered daily dose and a warning about the increased risk of seizures.

It approved the sustained-release version (Wellbutrin SR) in 1996 and the extended-release version (Wellbutrin XL) in 2003.

In 2006, Wellbutrin was the first drug the FDA approved for the treatment of seasonal-affective disorder (SAD).

Wellbutrin Warnings

Wellbutrin, like other antidepressants, is required to carry a -box warning about an increased risk of suicidal thinking and behavior in children, teenagers, and young adults between the ages of 18 and 24.

The -box warning notes the need to monitor patients taking antidepressants for signs of any worsening of their depression, and for the emergence of suicidal thoughts, especially in the first few months of treatment or when the dose is either increased or decreased.

The warning also extended to Zyban, which contains the same ingredient as Wellbutrin and is made by the same company.

You should tell your doctor about all the prescription and over-the-counter (OTC) drugs, vitamins, illegal and recreational drugs, and dietary supplements you're taking, especially if you're on monoamine oxidase inhibitors (MAOIs), such as Marplan (isocarboxazid) or Nardil (phenelzine).

People who have had a seizure or epilepsy, an eating disorder such as bulimia or anorexia nervosa, or are using or withdrawing from alcohol or certain drugs used to treat anxiety, seizures, and insomnia such as Xanax, Valium, and Ativan, are generally not good candidates for Wellbutrin.

Also be aware that Wellbutrin can cause false-positive urine tests for amphetamines.

Your doctor also needs to know if you have liver or kidney disease, are taking insulin for diabetes, are taking other antidepressants, or are using a nicotine patch, which can increase the risk of high blood pressure.

Pregnancy and Wellbutrin

Wellbutrin may cause harm to a developing fetus.

Nonetheless, the drug's benefits to the mother may outweigh the potential risks to her developing fetus.

Data from population studies of pregnant women taking Wellbutrin in the first trimester indicated no increased risk of congenital malformations.

A 2010 study in the American Journal of Obstetrics and Gynecology suggested a link between Wellbutrin taken in the first trimester and congenital heart defects but found that more data was needed to confirm a connection.

Wellbutrin is present in breast milk, and there's some evidence that it may cause seizures in babies. It may also reduce the amount of breast milk a mother produces.

Talk with your doctor about the safety of breastfeeding while using Wellbutrin.

Wellbutrin and Weight Loss

Wellbutrin has been linked to weight loss, according to the Stanford School of Medicine, anecdotal reports, and other sources.

This distinguishes Wellbutrin from several other antidepressants, which are often associated with weight gain.

Studies have found that Wellbutrin, when combined with dietary recommendations, can result in significant weight loss.

Nonetheless, the FDA has not approved Wellbutrin for weight management.

Wellbutrin and Anxiety

Some doctors have prescribed Wellbutrin off-label for anxiety disorders, especially when a patient has anxiety and depression.

However, some studies suggest that use of Wellbutrin has caused anxiety in people taking the drug for depression or other conditions.

A 2012 report in the journal Current Psychiatry finds that for people who have anxiety and depression, Wellbutrin "would not be a first-line choice because it is not FDA-approved to treat anxiety disorders."

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How to use wellbutrin?

Wellbutrin Dosage

Wellbutrin is available as a standard pill of 75 milligrams (mg) and 100 mg, as a sustained-release pill (100 mg), and as a long-acting extended-release tablet (150 and 300 mg).

The starting dose is usually 200 mg a day, given in two doses of 100 mg.

After three days, your doctor may increase the dose to 300 mg a day, given as 100 mg three times a day, with at least a six-hour interval between doses.

To minimize the risk of seizure, the dose must be increased gradually. The maximum dose is 450 mg a day.

The extended-release version is usually taken once a day in the morning within a 24-hour time frame.

Try to take Wellbutrin at the same time every day, and avoid taking it too close to bedtime.

Swallow the pills whole — do not split, chew, or crush them.

Be aware that it might take a month or more to feel improvement from the drug.

Continue to take it, and don't go off Wellbutrin without consulting your doctor.

Stopping the drug too abruptly can result in withdrawal or "discontinuation syndrome," which shows up as repetitive, uncontrollable twisting of a part of the body, irritability, anxiety, mania, and headaches.

Make sure you are not taking more than one product containing generic bupropion at one time, as that could result in an overdose.

Wellbutrin Overdose

An overdose of Wellbutrin is considered moderately dangerous. Deaths have been reported, but they're rare.

Symptoms of an overdose can include:

  • Hallucinations and delusions
  • Vomiting
  • Aggressive behavior
  • Rapid heart beat
  • Seizures

Call a poison control center or get to an emergency room if you believe you've overdosed.

If a person taking Wellbutrin has collapsed or is not breathing, call 911 immediately.

The safety and effectiveness of Wellbutrin has not been determined in children younger than 18.

No overall differences in Wellbutrin's safety or effectiveness were found in those older than 65.

Missed Dose of Wellbutrin

Skip any missed dose, and get back on schedule when it's time for the next dose.

You must allow the full six-hour interval between doses.

Do not double up on doses to recoup the missed one.



What are the side effects of wellbutrin?

Wellbutrin Side Effects

Common Side Effects of Wellbutrin

  • Agitation
  • Dry mouth
  • Constipation
  • Headache/migraine
  • Nausea/vomiting
  • Dizziness
  • Excessive sweating
  • Tremors
  • Insomnia
  • Blurred vision
  • Rapid heart beat
  • Nausea
  • Rash
  • Hostility
  • Irregular heart beat
  • Itchiness
  • Sweating
  • Hives
  • Visual disturbance
  • Taste disorders

Tell your doctor if any of those symptoms become severe or do not disappear.

Serious Side Effects of Wellbutrin

  • Chest pain
  • Flushing
  • Rapid, irregular heart
  • Rise in blood pressure
  • Confusion
  • Anorexia
  • Tinnitus (noise or ringing in the ears)
  • Seizures
  • Hallucinating
  • Irrational fears
  • Muscle or joint pain
  • Blisters
  • Swelling of the face, throat. tongue, lips, eyes, hands, feet, ankles, or lower legs
  • Hoarseness
  • Difficulty breathing or swallowing

If any of these serious side effects occur, stop taking Wellbutrin and call your doctor immediately or seek emergency medical care without delay.



What are the precautions of wellbutrin?

Suicidal Thoughts And Behaviors In Children, Adolescents, And Young Adults

Patients with MDD, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.

Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (selective serotonin reuptake inhibitors [SSRIs] and others) show that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with MDD and other psychiatric disorders. Short-term clinical trials did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24; there was a reduction with antidepressants compared with placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 subjects. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 subjects. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger subjects for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 subjects treated) are provided in Table 1.

Table 1: Risk Differences in the Number of Suicidality Cases by Age Group in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Subjects

Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Subjects Treated
Increases Compared with Placebo
<18 14 additional cases
18-24 5 additional cases
Decreases Compared with Placebo
25-64 1 fewer case
≥65 6 fewer cases

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases [see BOXED WARNING].

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.

Families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for WELLBUTRIN should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Neuropsychiatric Adverse Events And Suicide Risk In Smoking Cessation Treatment

WELLBUTRIN is not approved for smoking cessation treatment; however, it contains the same active ingredient as the smoking cessation medication ZYBAN. Serious neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation. These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide [see ADVERSE REACTIONS]. Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these adverse events occurred in patients taking bupropion who continued to smoke.

Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses. Observe patients for the occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should stop taking WELLBUTRIN and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many postmarketing cases, resolution of symptoms after discontinuation of bupropion was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

Seizure

WELLBUTRIN can cause seizure. The risk of seizure is dose-related. The dose should not exceed 450 mg/day. Increase the dose gradually. Discontinue WELLBUTRIN and do not restart treatment if the patient experiences a seizure.

The risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment with WELLBUTRIN. WELLBUTRIN is contraindicated in patients with a seizure disorder, current or prior diagnosis of anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see CONTRAINDICATIONS, DRUG INTERACTIONS]. The following conditions can also increase the risk of seizure: severe head injury; arteriovenous malformation; CNS tumor or CNS infection; severe stroke; concomitant use of other medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids); metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia); use of illicit drugs (e.g., cocaine); or abuse or misuse of prescription drugs such as CNS stimulants. Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or insulin; use of anorectic drugs; and excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates.

Incidence Of Seizure With Bupropion Use

Bupropion is associated with seizures in approximately 0.4% (4/1,000) of patients treated at doses up to 450 mg/day. The estimated seizure incidence for WELLBUTRIN increases almost 10-fold between 450 and 600 mg/day.

The risk of seizure can be reduced if the dose of WELLBUTRIN does not exceed 450 mg/day, given as 150 mg 3 times daily, and the titration rate is gradual.

Hypertension

Treatment with WELLBUTRIN can result in elevated blood pressure and hypertension. Assess blood pressure before initiating treatment with WELLBUTRIN and monitor periodically during treatment. The risk of hypertension is increased if WELLBUTRIN is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity [see CONTRAINDICATIONS].

Data from a comparative trial of the sustained-release formulation of bupropion HCl, nicotine transdermal system (NTS), the combination of sustained-release bupropion plus NTS, and placebo as an aid to smoking cessation suggest a higher incidence of treatment-emergent hypertension in patients treated with the combination of sustained-release bupropion and NTS. In this trial, 6.1% of subjects treated with the combination of sustained-release bupropion and NTS had treatment-emergent hypertension compared with 2.5%, 1.6%, and 3.1% of subjects treated with sustained-release bupropion, NTS, and placebo, respectively. The majority of these subjects had evidence of pre-existing hypertension. Three subjects (1.2%) treated with the combination of sustained-release bupropion and NTS and 1 subject (0.4%) treated with NTS had study medication discontinued due to hypertension compared with none of the subjects treated with sustained-release bupropion or placebo. Monitoring of blood pressure is recommended in patients who receive the combination of bupropion and nicotine replacement.

In a clinical trial of bupropion immediate-release in MDD subjects with stable congestive heart failure (N = 36), bupropion was associated with an exacerbation of pre-existing hypertension in 2 subjects, leading to discontinuation of bupropion treatment. There are no controlled trials assessing the safety of bupropion in patients with a recent history of myocardial infarction or unstable cardiac disease.

Activation Of Mania/Hypomania

Antidepressant treatment can precipitate a manic, mixed, or hypomanic manic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. Prior to initiating WELLBUTRIN, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression). WELLBUTRIN is not approved for use in treating bipolar depression.

Psychosis And Other Neuropsychiatric Reactions

Depressed patients treated with WELLBUTRIN have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. Some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated upon dose reduction and/or withdrawal of treatment. Instruct patients to contact a healthcare professional if such reactions occur.

Angle-Closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs including WELLBUTRIN may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Hypersensitivity Reactions

Anaphylactoid/anaphylactic reactions have occurred during clinical trials with bupropion. Reactions have been characterized by pruritus, urticaria, angioedema, and dyspnea requiring medical treatment. In addition, there have been rare, spontaneous postmarketing reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion. Instruct patients to discontinue WELLBUTRIN and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction (e.g., skin rash, pruritus, hives, chest pain, edema, and shortness of breath) during treatment.

There are reports of arthralgia, myalgia, fever with rash and other serum sickness-like symptoms suggestive of delayed hypersensitivity.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts And Behaviors

Instruct patients, their families, and/or their caregivers to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Advise families and caregivers of patients to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or healthcare professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.

Neuropsychiatric Adverse Events And Suicide Risk In Smoking Cessation Treatment

Although WELLBUTRIN is not indicated for smoking cessation treatment, it contains the same active ingredient as ZYBAN which is approved for this use. Inform patients that some patients have experienced changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation and suicide when attempting to quit smoking while taking bupropion. Instruct patients to discontinue bupropion and contact a healthcare professional if they experience such symptoms [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS].

Severe Allergic Reactions

Educate patients on the symptoms of hypersensitivity and to discontinue WELLBUTRIN if they have a severe allergic reaction.

Seizure

Instruct patients to discontinue and not restart WELLBUTRIN if they experience a seizure while on treatment. Advise patients that the excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizure. Advise patients to minimize or avoid use of alcohol.

Angle-Closure Glaucoma

Patients should be advised that taking WELLBUTRIN can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible [see WARNINGS AND PRECAUTIONS].

Bupropion-Containing Products

Educate patients that WELLBUTRIN contains the same active ingredient (bupropion hydrochloride) found in ZYBAN, which is used as an aid to smoking cessation treatment, and that WELLBUTRIN should not be used in combination with ZYBAN or any other medications that contain bupropion (such as WELLBUTRIN SR, the sustained-release formulation and WELLBUTRIN XL or FORFIVO XL, the extended-release formulations, and APLENZIN, the extended-release formulation of bupropion hydrobromide). In addition, there are a number of generic bupropion HCl products for the immediate-, sustained-, and extended-release formulations.

Potential For Cognitive And Motor Impairment

Advise patients that any CNS-active drug like WELLBUTRIN may impair their ability to perform tasks requiring judgment or motor and cognitive skills. Advise patients that until they are reasonably certain that WELLBUTRIN does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. WELLBUTRIN may lead to decreased alcohol tolerance.

Concomitant Medications

Counsel patients to notify their healthcare provider if they are taking or plan to take any prescription or over-the-counter drugs because WELLBUTRIN and other drugs may affect each others’ metabolisms.

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy with WELLBUTRIN. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to WELLBUTRIN during pregnancy [see Use In Specific Populations].

Storage Information

Instruct patients to store WELLBUTRIN at room temperature, between 68°F and 77°F (20°C to 25°C) and keep the tablets dry and out of the light.

Administration Information

Instruct patients to take WELLBUTRIN in equally divided doses 3 or 4 times a day, with doses separated by at least 6 hours to minimize the risk of seizure. Instruct patients if they miss a dose, not to take an extra tablet to make up for the missed dose and to take the next tablet at the regular time because of the dose-related risk of seizure. Instruct patients that WELLBUTRIN tablets should be swallowed whole and not crushed, divided, or chewed. WELLBUTRIN can be taken with or without food.

WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, and ZYBAN are trademarks owned by or licensed to the GSK group of companies. The other brands listed are trademarks owned by or licensed to their respective owners and are not owned by or licensed to the GSK group of companies. The makers of these brands are not affiliated with and do not endorse the GSK group of companies or its products.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Lifetime carcinogenicity studies were performed in rats and mice at bupropion doses up to 300 and 150 mg/kg/day, respectively. These doses are approximately 6 and 2 times the MRHD, respectively, on a mg/m2 basis. In the rat study there was an increase in nodular proliferative lesions of the liver at doses of 100 to 300 mg/kg/day (approximately 2 to 6 times the MRHD on a mg/m2 basis); 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 positive response (2 to 3 times control mutation rate) in 2 of 5 strains in the Ames bacterial mutagenicity assay. Bupropion produced an increase in chromosomal aberrations in 1 of 3 in vivo rat bone marrow cytogenetic studies.

There were no effects on male and female fertility when rats were administered oral doses of bupropion up to 300 mg/kg/day (approximately 6 times the MRHD on a mg/m2 basis) to females prior to mating and either through Day 13 of gestation or through lactation, and to males for 60 days prior to and through mating. However, doses of 200 mg/kg/day (approximately 4 times the MRHD on a mg/m2 basis) or greater, caused transient ataxia or behavioral changes in adult female rats. There were also no adverse effects on fertility, reproduction, or growth and development of male or female offspring.

Use In Specific Populations

Pregnancy

Pregnancy Exposure Registry

There is an independent pregnancy exposure registry that monitors pregnancy outcomes in women exposed to any antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-4056185 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants.

Risk Summary

Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see Data). There are risks to the mother associated with untreated depression in pregnancy (see Clinical Considerations). When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (MRHD) of 450 mg/day. When given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater. Decreased fetal weights were seen at doses twice the MRHD and greater (see Animal Data).

The estimated background risk for major birth defects and miscarriage is unknown for the indicated population. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal And/Or Embryo/Fetal Risk

A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.

Data

Human Data

Data from the international bupropion Pregnancy Registry (675 first trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. The Registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations.

No increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). Data from the United Healthcare database, which had a limited number of exposed cases with cardiovascular malformations, and a case-control study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) of self-reported bupropion use from the National Birth Defects Prevention Study (NBDPS) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester.

Study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding a possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI: 1.2, 5.7), and the Slone Epidemiology case control study did not find increased risk for LVOTO.

Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0) but did not find increased risk for any other cardiovascular malformations studied (including LVOTO as above). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD.

For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies.

Animal Data

In studies conducted in pregnant rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively (approximately 10 and 6 times the MRHD, respectively, on a mg/m2 basis). There was no evidence of fetal malformations in rats. When given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately equal to the MRHD on a mg/m2 basis) and greater. Decreased fetal weights were observed at doses of 50 mg/kg/day (approximately 2 times the MRHD on a mg/m2 basis) and greater. No maternal toxicity was evident at doses of 50 mg/kg/day or less.

In a pre-and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 3 times the MRHD on a mg/m2 basis) from embryonic implantation through lactation had no effect on pup growth or development.

Lactation

Risk Summary

Data from published literature report the presence of bupropion and its metabolites in human milk (see Data). There are no data on the effects of bupropion or its metabolites on milk production. Limited data from postmarketing reports have not identified a clear association of adverse reactions in the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for WELLBUTRIN and any potential adverse effects on the breastfed child from WELLBUTRIN or from the underlying maternal condition.

Data

In a lactation study of 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Postmarketing reports have described seizures in breastfed infants. The relationship of bupropion exposure and these seizures is unclear.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established [see BOXED WARNING, WARNINGS AND PRECAUTIONS].

Geriatric Use

Of the approximately 6,000 subjects who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation trials), 275 were aged ≥65 years and 47 were aged ≥75 years. In addition, several hundred subjects aged ≥65 years participated in clinical trials using the immediate-release formulation of bupropion (depression trials). No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function [see DOSAGE AND ADMINISTRATION, Use In Specific Populations, CLINICAL PHARMACOLOGY].

Renal Impairment

Consider a reduced dose and/or dosing frequency of WELLBUTRIN in patients with renal impairment (Glomerular Filtration Rate: less than 90 mL/min). Bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].

Hepatic Impairment

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose of WELLBUTRIN is 75 mg daily. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].