Bupropion Side Effects
- agitation
- akathisia
- anaphylactoid reactions
- angioedema
- anorexia
- anxiety
- arrhythmia exacerbation
- blurred vision
- confusion
- constipation
- depression
- diaphoresis
- dizziness
- dysgeusia
- dyspepsia
- dyspnea
- ecchymosis
- erythema multiforme
- flatulence
- hallucinations
- headache
- hostility
- hypertension
- insomnia
- irritability
- libido decrease
- maculopapular rash
- mania
- menstrual irregularity
- nausea/vomiting
- neonatal abstinence syndrome
- oral ulceration
- palpitations
- paranoia
- pruritus
- psychosis
- rash (unspecified)
- restlessness
- seizures
- serum sickness
- sinus tachycardia
- Stevens-Johnson syndrome
- stomatitis
- Tourette’s syndrome
- tremor
- urticaria
- weakness
- weight loss
- xerosis
- xerostomia
Bupropion Adverse Reactions
Bupropion exhibits a greater potential for causing seizures than other antidepressants.[505] The incidence of seizures occurring with bupropion is dose-dependent. Seizures occur in roughly 0.1% of patients receiving up to 300 mg/day (sustained-release) and 0.5% of patients receiving up to 450 mg/day (immediate-release) of bupropion. According to the manufacturer, the incidence of seizures in patients taking Wellbutrin® XL as a single dose of 450 mg is 0.4%. Although seizure incidence has not been evaluated in clinical trials of the extended-release formulation of bupropion, its bioequivalence with the immediate-release and sustained-release formulations suggests that the risk may be similar to that encountered with use of these products. The incidence of seizures rises disproportionately at dosages >450 mg/day (immediate-release).[505] In patients receiving a 600-mg/day immediate-release regimen of bupropion, the risk of seizures was estimated to be 10-fold that of patients administered the 450-mg maximum daily recommended dose. To limit the risk of seizures, recommended single or maximum daily dosages of of any dosage form of bupropion should not be exceeded. Some patients may be more at risk of experiencing seizures with bupropion therapy (see Precautions). The use or withdrawal of some medication regimens, including ethanol, may lower seizure threshold; these should be utilized cautiously with bupropion (see Drug Interactions). When possible, concomitant use of these medications with bupropion should be avoided.
In clinical trials of bupropion for either the treatment of depressive symptoms or for smoking cessation, the most common side effects reported are headache/migraine (26%) and insomnia (roughly 29%). A substantial number of patients taking bupropion experience increased agitation, anxiety, CNS stimulation, irritability, and restlessness. Some symptoms may be dose-related and may respond to dosage reduction. To limit insomnia, do not give doses close to bedtime. In some cases these symptoms may require treatment with sedative/hypnotic therapy. Depression has been reported frequently in smoking cessation studies (incidence >/= 1/100 patients). In roughly 2% of patients treated, CNS symptoms will necessitate drug discontinuation. While causality with bupropion has not been determined, CNS symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (severe restlessness), hypomania, and mania may be an indication of worsening depression or suicidal tendencies, and should be immediately reported to the health care provider.
Treatment with any antidepressant can activate psychosis in susceptible patients, with the possibility of manic episodes in patients with bipolar illness. Bupropion has been associated with a number of other neuropsychiatric signs and symptoms, such as confusion, delusions, hallucinations, psychotic episodes, and paranoia. Infrequent (0.1-1%) or rare (<1%) neurological side effects reported include abnormal coordination, amnesia; gait impairment or ataxia; coma; delirium; depersonalization; derealization; dyskinesia; euphoria; extrapyramidal reactions; EEG changes; emotional lability; hostility; hypesthesia; hyperkinesia; hypertonia; hypomania; memory impairment; neuralgia; paresthesia; tardive dyskinesia; tinnitus; suicidal ideation; and vertigo. Causal effect may be uncertain as trials were not always conducted with adequate controls. Some events have mimicked symptoms of cerebrovascular accidents (CVA) or trans-ischemic attacks (TIA). Causal effect may be uncertain as adequate controls are not always available. However, some effects are found to resolve upon dose reduction or discontinuation of therapy. Abnormal EEGs, akinesia, aphasia, dysarthria, dystonia, extrapyramidal syndrome, hypokinesia, increased libido, manic reaction, and unmasking tardive dyskinesia have also been noted, but the incidence and causal association with bupropion have not been reported.
Frequent neurological adverse events of bupropion include tremor. The incidence of tremor is high; roughly 20% of patients reported tremor during trials, compared to approximately 8% taking placebo. Patients with Gilles de la Tourette’s syndrome or a family history of this syndrome may have motor or phonetic tics unmasked or exacerbated by the use of bupropion for ADHD symptoms. Exacerbation of tics may respond to dosage reduction; in some cases bupropion may need to be discontinued.
Bupropion may cause weight loss. A weight loss of more than 5 pounds occurred in 28% of patients taking immediate-release bupropion, approximately double that seen for patients on tricyclic antidepressants or placebo. Approximately 15% of patients on sustained-release formulations lose weight. It is not known if bupropion, like other ADHD therapies, causes growth inhibition in pediatric patients. Weight gain is rare with bupropion treatment. The incidence of anorexia reported during trials was similar for patients taking bupropion and patients on placebo (roughly 18% in each group) and may represent a symptom of the depressive illness rather than an adverse event.
Cardiac toxicity is relatively uncommon for bupropion when compared with tricyclic antidepressants. Hypertension occurs in roughly 4.3% of patients taking bupropion as an antidepressant, compared to 1.6% taking placebo. New onset or worsening of existing hypertension occurs in a higher percentage of patients (i.e., 6.1%) taking bupropion concurrently with nicotine transdermal systems (NTS) for smoking cessation. In some cases hypertension has been severe. Many patients on bupropion experience dizziness (21%), compared to 16.2% taking placebo. Roughly 1.2% of patients on bupropion experience episodes of palpitations or sinus tachycardia. Infrequent and rare cardiovascular side effects include arrhythmia exacerbation, AV block, chest pain (unspecified); postural hypotension; premature ventricular contractions (PVCs), syncope, ventricular tachycardia, or other arrhythmias.
Bupropion has some anticholinergic effects. In a placebo-controlled trial, 27.6% of patients experienced xerostomia, compared to 18.4% taking placebo. Constipation is another frequent adverse reaction. Blurred vision affected 14.6% of patients, compared to 10.3% taking placebo. Rarely, diplopia, mydriasis, or xerophthalmia occur.
Dyspepsia and nausea/vomiting may occur fairly frequently (>1%) during therapy with bupropion but these symptoms require medical attention only if they persist or are troublesome. Some patients report flatulence or dysgeusia. Adverse GI reactions occurring in roughly 0.1-1% of patients include oral ulceration or stomatitis. Rare events in 0.1-1% or less of patients have included elevated hepatic enzymes, excessive thirst (polydipsia), gastric reflux, GI bleeding, glossitis, hepatitis, and jaundice. In some cases, causality is unknown.
Twice as many patients taking bupropion reported libido decrease (3.1%) compared to patients taking placebo (1.6%). Menstrual irregularity was reported as unspecified menstrual complaints by 4.7% of patients. Impotence is rare with bupropion use, and does not occur at a rate higher than placebo.
Excessive diaphoresis occurs in roughly 20% of patients taking bupropion, compared to 14% of patients taking placebo. Rash (unspecified) and pruritus occurs in roughly 2% of patients taking bupropion. Skin reactions occurring in up to 1% of patients include acneiform rash and xerosis. Alopecia, maculopapular rash, and exfoliative dermatitis have also occurred rarely with bupropion use. Musculoskeletal events reported in roughly 1% of patients include arthralgia and myalgia.
Rarely, anaphylactoid reactions characterized by symptoms such as urticaria, angioedema, and dyspnea requiring medical treatment have been reported in clinical trials with bupropion. These events occur in 0.1-0.3% or less of patients treated. In addition, there have been rare spontaneous postmarketing reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion. One case of a serum sickness reaction has also been reported in the literature. These serum-sickness-like reactions consist of delayed hypersensitivity reactions, consisting of arthralgia, myalgia, fever and rash.
Rarely, other side effects have been reported with bupropion use (<= 0.1%); causality is uncertain in some cases. Rare endocrine-related side effects have included hyperglycemia, hypoglycemia, and syndrome of inappropriate antidiuretic hormone (SIADH). Hematologic effects reported with bupropion include infrequent cases of ecchymosis. Anemia, leukocytosis, leukopenia, thrombocytopenia, and pancytopenia have been noted; the incidence has not been reported. Rare or infrequent musculoskeletal adverse reactions have included leg cramps or twitching, arthritis, rhabdomyolysis, and muscle weakness. rare urogenital reactions have included abnormal ejaculation or painful erections; cystitis; dysuria; incontinence; urinary retention; and vaginitis. Causal effect may be uncertain as trials were not always conducted with adequate controls.
While not reported for bupropion, a neonatal abstinence syndrome has been reported in infants exposed to certain antidepressants in utero. After birth, symptoms consistent with withdrawal (i.e., poor feeding, hypoglycemia, hypothermia, lethargy or irritability, vomiting, etc.) were noted. Such complications can arise immediately upon delivery. In some reports, serum concentrations of the agent were measurable in the infants affected, so the symptoms may have been due to a direct adverse effect of the antidepressant. The physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, and taking the drug half-life into consideration, appropriate tapering of the agent prior to delivery may be considered as an alternative.
[ Last revised: 1/25/2005 4:42:00 PM ]
References
505. Skowron DM, Stimmel GL. Antidepressants and the risk of seizures. Pharmacotherapy 1992;12:18-22.
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