Wellbutrin

Wellbutrin is a psychoanaleptic from the category of other antidepressants.

Indications Wellbutrin

It is used in the treatment of severe depressive states.

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Release form

The release is made in tablets, in the amount of 10 pieces inside a blister plate. The box contains 6 such plates.

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Pharmacodynamics

Bupropion is a substance with a selective inhibitory effect on the processes of catecholamine (dopamine with norepinephrine) uptake by neurons. This component has a minimal effect on the processes of indolamine (serotonin) uptake, and does not suppress MAO activity.

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Pharmacokinetics

Suction.

When bupropion was administered to volunteers during studies, peak plasma levels of the substance were observed after 3 hours.

Information from 3 clinical tests suggests that bupropion values may be increased when the tablet is taken with food. Following administration with food, peak plasma levels of the component increased by 11%, 16%, and 35%, and AUC values increased by 17%, 17%, and 19% in 3 tests.

Bupropion and its metabolites exhibit linear pharmacokinetic properties with long-term use of the drug in doses of 150-300 mg/day.

Distribution processes.

Bupropion has a high distribution volume index – it is approximately 2000 l. The active element of the drug with its metabolic product (hydroxybupropion) is moderately synthesized with blood plasma proteins (84% and 77%, respectively). The degree of protein synthesis of threohydrobupropion is approximately half of the indicators characteristic of bupropion.

Metabolic processes.

Intensive metabolism of bupropion occurs inside the body. The presence of 3 pharmacoactive metabolic products is noted in the plasma: hydroxybupropion together with its amino alcohol isomers – threohydrobupropion, as well as erythrohydrobupropion.

Excretion.

About 87% of the active ingredient is excreted in the urine (less than 10% of the substance is in the form of active decay products), and up to 10% is excreted in the feces. During excretion, unchanged bupropion makes up only 0.5%.

The average clearance rate of the substance after using the drug is approximately 200 l/hour, and the average half-life is about 20 hours.

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Dosing and administration

The drug begins to affect the body at least 2 weeks after the start of therapy. The full effect of its use can be expected only after several weeks of the course, as in the case of taking other antidepressants.

The tablets should be swallowed whole, without chewing or crushing/dividing them, as this may increase the likelihood of developing side effects (eg, seizures).

Dose sizes for adults.

The maximum single serving size is 0.15 g. The tablets must be taken twice a day with intervals of at least 8 hours.

Quite often, patients taking the pills experience insomnia, which is often temporary. The frequency of this symptom can be reduced by refraining from taking the drug before bedtime (keeping an 8-hour interval between doses) or by reducing the portion size, if acceptable.

The initial dose size is a single dose of 150 mg per day.

For people who find that taking 0.15 g of the drug per day is not enough, it is possible to improve the condition by increasing the dose to the maximum value – 0.3 g/day (0.15 g twice a day).

When eliminating acute depressive episodes, antidepressants should be taken for at least six months. It has been determined that the medication in a dosage of 0.3 g/day will have a medicinal effect over a long therapeutic period (up to 12 months).

Dosages for the elderly.

Since it is impossible to exclude the possibility of intolerance to Wellbutrin in individual elderly patients, it may be necessary to reduce the frequency of use or the dose size of the drug.

Serving sizes for people with kidney problems.

Therapy begins with reduced dosages or with a lower frequency of administration, because bupropion and its metabolic products accumulate in this category of patients to a greater extent than under standard conditions.

Portions for people with liver dysfunction.

People with liver diseases should use the drug with caution. Due to the rather high variability of the pharmacokinetic properties of the drug, people with liver disorders of mild or moderate form should take the drug once a day in a portion of 0.15 g.

People with severe liver cirrhosis should take the tablets very carefully. For these patients, the maximum dose is 0.15 g, taken every other day.

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Use Wellbutrin during pregnancy

Separate epidemiological tests of the effect of Wellbutrin on pregnancy revealed an associated risk of intrauterine cardiovascular disease in the fetus when the drug was used in the first trimester. These findings were not consistent across tests.

The attending physician should consider the option of prescribing alternative therapy for a woman who is planning a pregnancy or who is already pregnant. The drug should be prescribed only in situations where the probable benefit from its use is higher than the risk of complications for the fetus.

Since bupropion and its breakdown products can be excreted in breast milk, treatment with Wellbutrin requires that breastfeeding be stopped for a while.

Contraindications

Main contraindications:

• patients who are intolerant to bupropion or other components of the drug;
• people suffering from seizures;
• persons who have suddenly stopped taking sedatives or drinking alcohol;
• administration to people who are taking any other medication containing bupropion at the same time, because the frequency of seizures is determined by the dosage of this substance;
• the patient has a history of or currently has anorexia or bulimia of a nervous nature, since this category of patients has been shown to frequently experience seizures when using bupropion with a rapid release phase;
• Combined use with MAOIs. The interval between discontinuing irreversible MAOIs and starting Wellbutrin therapy should be at least 2 weeks.

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Side effects Wellbutrin

The use of the medication may cause the following side effects:

• lesions affecting the immune system: signs of intolerance, such as urticaria, often appear. More severe symptoms of hypersensitivity are occasionally noted, including bronchospasm/dyspnea, Quincke's edema or anaphylaxis. Myalgia with arthralgia, as well as fever, occur together with rash and other manifestations of intolerance of a delayed nature. Such symptoms are somewhat similar to serum sickness;
• Metabolic manifestations and digestive disorders: anorexia is often observed. Sometimes weight loss occurs. A disorder of blood glucose values occurs occasionally;
• Mental disorders: insomnia is often observed. Sleep disorders may develop. Quite often, a feeling of anxiety or excitement arises. Sometimes, a state of disorientation, dysphoria or depression is observed. Feelings of anxiety, aggression, irritability, and hostility appear sporadically; strange dreams or hallucinations arise, and in addition, paranoid thoughts, delusions, and a state of depersonalization develop. Psychoses, suicidal thoughts, and suicidal behavior may be observed. Mania, euphoria, hypomania, and changes in the state of the psyche may develop;
• disorders affecting the central nervous system: headaches are often observed. Dizziness, memory problems, tremor, myoclonus, migraine, dystonia, as well as anxiety and taste disorders are quite common. Vertigo, dysarthria, problems with attention and concentration, and akathisia may sometimes develop. Rarely, ECG abnormalities and seizures occur. Paresthesia, ataxia, problems with motor coordination, dystonia, fainting, and shaking palsy are observed isolatedly. Delirium, dyskinesia, coma, and problems with sensitivity may develop;
• lesions in the visual organs: visual impairment is often observed. Diplopia occasionally develops. Mydriasis is sometimes observed. An increase in IOP values is possible;
• disorders affecting the auditory organs: tinnitus often occurs;
• symptoms in the heart area: sometimes there are disturbances in the heart rhythm, tachycardia and changes in the ECG values. Rarely, myocardial infarction develops. It is also possible that blood pressure indicators increase and swelling appears. Increased heartbeat is noted occasionally;
• reactions of the vascular system: often there is an increase in blood pressure (sometimes significant), and in addition to this, redness. Orthostatic collapse or vasodilation develops occasionally;
• signs of digestive disorders: problems with the gastrointestinal tract (including vomiting with nausea) and dry mouth mucosa are often noted. Dyspeptic symptoms, constipation and abdominal pain often appear. Sometimes irritation in the gum area and toothache occur. Intestinal perforation is also possible;
• disorders of the hepatobiliary system: hepatitis or jaundice occurs occasionally, and in addition, the liver enzyme level increases;
• lesions of the subcutaneous layers and skin: hyperhidrosis, rash and itching are often observed. Stevens-Johnson syndrome or erythema multiforme appear sporadically, and psoriasis also worsens. Alopecia may develop;
• Respiratory system damage: pulmonary embolism occasionally occurs. Bronchitis may develop;
• dysfunction of the musculoskeletal system and connective tissues: muscle twitching is observed sporadically. The development of rhabdomyolysis or arthritis may be expected;
• problems with the urogenital system and kidneys: most often, infections affecting the urinary organs are noted. Sometimes there is a weakening of libido. Urination increases in frequency or, on the contrary, is delayed. Menstrual cycle disorders, the development of glucosuria, impotence, nocturia, gynecomastia, as well as the appearance of swelling in the testicles are possible;
• systemic disorders: often there is pain in the sternum, fever and asthenia;
• problems with hematopoietic processes: thrombocytopenia or leukopenia, as well as leukocytosis, may occur.

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Overdose

In addition to the symptoms listed among the side effects, intoxication leads to such manifestations as loss of consciousness, a feeling of drowsiness and changes in ECG readings (conduction disorder, for example, prolongation of QRS interval values) or arrhythmia. There are also reports of death.

To treat an overdose, the victim must be hospitalized and monitored for ECG and vital signs. It is important to ensure that the airways are clear and that there are no problems with ventilation and oxygenation. Activated charcoal should also be given. Induction of vomiting is not necessary. Bupropion has no specific antidote.

Subsequent therapy is determined by the condition of the victim or the recommendations of a special institution dealing with the treatment of intoxications (if any).

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Interactions with other drugs

The metabolic process leads to the transformation of bupropion into its main active decay product, the substance hydroxybupropion. This process occurs mainly with the participation of the hemoprotein P450 IIB6 (type CYP2B6). Because of this, caution is required when combining the drug with drugs that affect the CYP2B6 isoenzyme (such as ifosfamide with clopidogrel, cyclophosphamide with orphenadrine, and ticlopidine).

Although bupropion is not metabolized by CYP2D6, in vitro 450 tests have shown that this element, together with hydroxybupropion, inhibits the metabolic process of CYP2D6. In pharmacokinetic tests, bupropion administration increased plasma desipramine values. This effect was observed for at least 7 days after taking the last dose of bupropion. When combined with drugs that are primarily metabolized by this isoenzyme (eg, antiarrhythmics, SSRIs, antipsychotics, tricyclics, and some β-blockers), it is necessary to initiate treatment with minimal doses of such a drug. When Wellbutrin is included in the treatment regimen of a person who is already taking a drug metabolized by CYP2D6, it is necessary to evaluate the option of reducing the dosage of this drug, especially for drugs with a narrow drug index.

Medicines that require metabolic activation by CYP2D6 to be effective (such as tamoxifen) may have their medicinal effect reduced when combined with drugs that inhibit the activity of CYP2D6 (bupropion).

Although citalopram does not undergo first-pass metabolism via CYP2D6, data from one test showed that bupropion increased peak and AUC levels of citalopram by 30% and 40%, respectively.

Due to the fact that bupropion undergoes intensive metabolism, the combination of the substance with drugs that potentiate metabolism (including phenytoin, carbamazepine, efavirenz with phenobarbital, and also ritonavir) or inhibit it, can lead to a change in the medicinal effect of the drug.

Results of a series of clinical trials involving volunteers showed that ritonavir (with twice daily administration of 0.1 g or 0.6 g of the drug) or 0.1 g of ritonavir with 0.4 g of lopinavir (twice daily administration), depending on the dose size, reduced the levels of bupropion with its main metabolic products by approximately 20-80%.

Similarly, a single dose of efavirenz 0.6 g daily for 14 days reduces bupropionol levels by approximately 55%.

This effect of ritonavir with lopinavir, as well as efavirenz, is due to the induction of metabolic effects on bupropion. People using any of these drugs in combination with medications that contain bupropion may need to use increased doses of bupropion, but it is prohibited to exceed the maximum permissible limits of the recommended doses.

Although the results of clinical tests did not show any pharmacokinetic interaction of the active element of the drug with alcoholic beverages, there is some data that negative manifestations developed from the central nervous system or a decrease in tolerance to alcohol was observed in individuals who consumed such beverages during therapy with Wellbutrin. Alcohol consumption during the therapy period should be reduced to a minimum or stopped completely.

There is evidence of an increased incidence of toxic effects on the central nervous system when the drug is combined with amantadine and levodopa. The drug should be used with caution by people taking amantadine or levodopa.

The combined use of the drug and NTS may lead to an increase in blood pressure values.

Impact on laboratory test results.

There are reports of drug interactions with tests used to quickly detect the presence of medications in urine. The tests may give false positive results, especially for amphetamines. To confirm a positive result, a chemical method must be used as an alternative.

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Storage conditions

Wellbutrin should be kept out of reach of children. Temperature values are maximum 25°C.

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Shelf life

Wellbutrin can be used for 2 years from the date of manufacture of the drug.

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Reviews

Wellbutrin receives quite a lot of reviews, and the patients' opinions in them are quite polar. The drug is used quite successfully in eliminating depression. In addition, it is often written that the drug helps alleviate the condition during the process of quitting smoking.

The drug copes with the task of treating depression very effectively, but it has a significant disadvantage - the presence of unpleasant side effects that develop during the 1-2 weeks of use. Among the advantages for men, it can be noted that the drug does not suppress erectile function.

To achieve the desired medicinal effect, as well as to minimize the risk of side effects, therapy should be started with a dose of 0.15 g of Wellbutrin. Sometimes it is also necessary to select the optimal time for taking the drug for the patient - there are people for whom taking a pill before bed is most suitable, but there are also those who need to take the drug early in the morning (at 5-6 o'clock).

Also among the disadvantages of the drug:

• To purchase it, you need a prescription;
• too many negative symptoms;
• quite a high price.