Wellbutrin

General information

Wellbutrin is an antidepressant with a unique mechanism of action that differs from most other drugs in this class. It is used to treat depressive disorders and help in smoking cessation by acting on neurotransmitters in the brain. The drug has a stimulant effect, making it suitable for patients with apathy and reduced energy.

Trade name

Wellbutrin

International Nonproprietary Name (INN)

Bupropion

Pharmaceutical formulation

The drug is available in the following forms:

• Immediate-release tablets: 75 mg and 100 mg.
• Prolonged-release (SR) tablets: 150 mg and 200 mg.
• Extended-release tablets (XL): 150 mg and 300 mg.

Composition

Acting substance

Bupropion (in the form of hydrochloride).

Auxiliary components

The composition varies depending on the form of release:

• Immediate-release tablets: microcrystalline cellulose, corn starch, magnesium stearate, crospovidone, hydroxypropyl methylcellulose (shell).
• SR tablets: polyvinyl alcohol, glyceryl behenate, silicon dioxide, ethylcellulose.
• XL tablets: polyethylene glycol, methacrylic acid (copolymer), titanium dioxide, talc.

Pharmacological properties

Pharmacodynamics

Bupropion, the active ingredient of Wellbutrin, is a norepinephrine and dopamine reuptake inhibitor. Its action is aimed at increasing the concentration of these neurotransmitters in the synaptic cleft, which improves the transmission of nerve impulses in certain areas of the brain responsible for the regulation of mood and motivation. Unlike selective serotonin reuptake inhibitors (SSRIs), bupropion minimally affects the serotoninergic system, making its action profile unique among antidepressants.

The drug has a moderate stimulant effect associated with dopaminergic activity, which helps patients with depression accompanied by lethargy, fatigue, and decreased energy. In addition, bupropion blocks nicotinic receptors, which explains its effectiveness as a smoking cessation aid. It has no significant effect on muscarinic, histamine, or adrenergic receptors, so it is less likely to cause sedative or anticholinergic side effects such as drowsiness or dry mouth.

Therapeutic effects usually appear 2 to 4 weeks after starting administration, although some patients report increased energy and improved concentration sooner. Maximum efficacy is maximized with regular use over several months.

Pharmacokinetics

Bupropion is well absorbed from the gastrointestinal tract after oral administration, reaching maximum plasma concentrations after 2 hours (for immediate release), 3 hours (SR), or 5 hours (XL). Bioavailability is about 5-20% due to extensive first-pass metabolism in the liver. Food intake slightly affects the rate of absorption but not the total absorption.

Binding to plasma proteins (mainly albumin) reaches 84% and the volume of distribution is about 20 L/kg, indicating wide penetration into tissues, including the central nervous system. Metabolism occurs in the liver with the participation of enzymes of the cytochrome P450 system, mainly CYP2B6, with the formation of three active metabolites: hydroxybupropion, triohydrobupropion and erythrohydrobupropion. These metabolites contribute significantly to the therapeutic effect, especially hydroxybupropion, the concentration of which is 2-5 times higher than the concentration of the parent substance.

The half-life of bupropion is about 21 hours, but metabolites are excreted more slowly (up to 30-50 hours), which provides prolonged action. Excretion is mainly through the kidneys (87% in the form of metabolites) and partially through the intestine (10%). In patients with impaired liver or kidney function, accumulation of active substances is possible, which requires dosage adjustment.

Indications for use

Wellbutrin is prescribed for the following conditions:

• Major depressive disorder (including seasonal depression for the XL form).
• Smoking cessation (maintenance therapy to reduce nicotine dependence).
• Depression with marked apathy, fatigue, or decreased concentration (as an alternative treatment).

Contraindications

The use of Wellbutrin is prohibited under the following conditions:

• Hypersensitivity to bupropion or any of the excipients.
• Convulsive disorders (epilepsy, history of seizures).
• Concurrent use of other drugs containing bupropion.
• Receipt of monoamine oxidase inhibitors (MAOIs) or a period of less than 14 days after their withdrawal.
• Bulimia or history of anorexia (due to risk of seizures).
• Severe hepatic insufficiency (cirrhosis).
• Children under 18 years of age.

Method of administration and dosage

How to take

The drug is taken orally, regardless of food intake. Tablets should be swallowed whole, without chewing or crushing, drinking enough water (100-150 ml). To minimize the risk of insomnia, it is recommended to take the drug in the morning or in the first half of the day.

Dosages for adults and children

Adults

Dosage depends on the form of release and indication:

• Wellbutrin (immediate release): 100 mg twice daily, with possible increase to 100 mg 3 times daily (maximum 450 mg).
• Wellbutrin SR: 150 mg once daily in the morning, after 3-7 days possibly increasing to 150 mg 2 times daily (maximum 400 mg).
• Wellbutrin XL: 150 mg once daily in the morning, with an increase to 300 mg after 1-2 weeks (maximum 450 mg).
• Smoking cessation (SR): 150 mg once daily for 3 days, then 150 mg 2 times daily (course 7-12 weeks).

Children

The drug is not used in children and adolescents younger than 18 years of age due to insufficient safety and efficacy data.

Dose adjustment for certain conditions

In moderate hepatic or renal impairment, the starting dose is reduced to 150 mg daily (XL) or 100 mg daily (immediate release), with a maximum dose of 300 mg. In elderly patients, it is recommended to start at the lowest dose (150 mg XL or 100 mg SR), taking into account the general health status.

Side Effects

The following adverse reactions may occur while taking Wellbutrin:

• Nervous system side: insomnia, headache, tremor, irritability, anxiety.
• Cardiovascular system: tachycardia, increased blood pressure.
• Digestive system: dry mouth, nausea, constipation, decreased appetite.
• Skin reactions: increased sweating, rash, itching.
• Other: decrease in body weight, ringing in the ears, seizures (at high doses).

Overdose

Symptoms of overdose

If the recommended dose is exceeded, the following may be observed:

• Convulsions (most common symptom).
• Tachycardia, arrhythmias, hypertension
• Nausea, vomiting, confusion.
• Hallucinations, somnolence or coma (in severe cases).

First aid measures

In case of overdose it is necessary:

1. Stop taking the drug.
2. Call an ambulance immediately.
3. Rinse the stomach (if it has been less than 1 hour).
4. Give activated charcoal (1 g/kg body weight).
5. Support cardiac and respiratory control until the arrival of a doctor.

Interaction with other drugs

Effects on the effects of other drugs

Wellbutrin may increase the effects of:

• Drugs that lower the seizure threshold (antipsychotics, tricyclic antidepressants).
• Beta-blockers and antiarrhythmic drugs (increase in their concentration).

The drug is metabolized by CYP2B6, and its effect may be weakened by inducers of this enzyme (e.g., carbamazepine) or enhanced by inhibitors (e.g., fluconazole).

Compatibility with alcohol and food

Alcohol increases the risk of seizures and increases side effects, so its use is contraindicated. Food does not affect the absorption of the drug.

Special instructions

Use in pregnancy and breastfeeding

The use of Wellbutrin during pregnancy is possible only in strict indications, as safety data are limited. Bupropion penetrates the placental barrier and is excreted with breast milk, therefore, in lactation it is recommended to discontinue feeding or choose an alternative treatment.

Effects on driving and mechanisms

The drug may cause dizziness, tremor or decreased concentration, especially at the beginning of therapy. Patients should refrain from driving or operating machinery until individual reaction is evaluated.

Particularities of use in the elderly and children

Elderly patients are more likely to experience side effects such as hypertension or insomnia, so careful dose selection and monitoring of the condition is required. In children under 18 years of age, the drug is not used due to the high risk of seizures and insufficient data.