Bupropion (also known as amfebutanone) is an atypical antidepressant whose structure closely resembles that of amphetamine, a powerful stimulant of the central nervous system.
Bupropion - Chemical Structure
However - despite the similarity with amphetamine - bupropion has a completely different pharmacological activity.
Indications
For what it uses
The use of bupropion is indicated for the treatment of major depressive disorder.
Warnings
Depression increases the risk of suicidal thoughts, self-harm and suicide attempts. These symptoms do not improve immediately after taking bupropion because the drug takes some time to show its therapeutic efficacy (generally two weeks, but sometimes even more). It is therefore necessary to keep patients under surveillance until significant remission occurs.
Bupropion should not be used for the treatment of depression in children and adolescents under the age of 18 years.
Caution should be exercised when administering bupropion in patients with pre-existing liver and / or renal disorders.
Bupropion lowers the seizure threshold, therefore, a lot of caution should be used in its administration in patients who have a history of convulsive disorders or who take other drugs capable of lowering the convulsive threshold, including, antipsychotic drugs, antimalarials, antihistamines, sedatives, stimulating or anorectic products. Even patients who have suffered head injuries, who abuse alcohol or who suffer from diabetes treated with insulin or hypoglycemic agents, are at risk of convulsions.
Administration of bupropion in hypertensive patients may cause worsening of hypertension.
Interactions
Bupropion metabolism may be decreased by concomitant administration of SSRIs (selective serotonin reuptake inhibitors), including:
- Paroxetine;
- fluvoxamine;
- sertraline;
- norfluoxetine;
- Fluoxetine;
- Vanlafaxina;
- Citalopram.
Since bupropion selectively inhibits dopamine reuptake, concomitant therapy with dopaminergic agonists or antagonists should be avoided.
The co-administration of bupropion and MAOIs (monoamine oxidase inhibitors) should be avoided due to the side effects that could arise from such an association.
Concomitant use of bupropion and the following drugs may increase the risk of seizures:
- Theophylline, used in the treatment of asthma;
- Other antidepressant drugs;
- Tramadol, an opioid painkiller;
- Sedatives;
- Mefloquine or chloroquine, drugs used to treat malaria;
- Drugs for controlling body weight or appetite;
- Steroids;
- Quinolones, drugs with antibiotic action;
- Antihistamines;
- Diabetes treatment drugs.
There may be an increase in the side effects induced by bupropion when it is given simultaneously with drugs, such as:
- Drugs for the treatment of Parkinson's disease (such as levodopa, amantadine or orphenadrine);
- Drugs used for the treatment of epilepsy, such as - for example - carbamazepine, phenytoin and valproate;
- Antitumorals, such as cyclophosphamide and ifosfamide;
- Β-blocker drugs, such as metoprolol;
- Antiplatelet agents, such as ticlopidine and clopidogrel;
- Antiarrhythmics, such as flecainide;
- Nicotine patches for smoking cessation;
- Drugs for the treatment of HIV, such as ritonavir.
Bupropion may reduce the therapeutic efficacy of tamoxifen (an anticancer medicine).
The combination of bupropion and alcohol should be avoided.
Side effects
Bupropion can induce various side effects that can occur differently and with different intensity in each patient. This happens due to the different sensitivity that each individual has towards the drug.
Below are the main side effects that may occur during bupropion therapy.
Nervous system disorders
Treatment with bupropion can cause headache, tremors, dizziness, concentration disorders, Parkinson's-like symptoms, lack of coordination, memory impairment, paresthesia and syncope.
Psychiatric disorders
Bupropion can cause various psychiatric disorders, including:
- Insomnia;
- agitation;
- Anxiety;
- Depression;
- Aggression;
- Hostility;
- Irritability;
- Hallucinations;
- Abnormal dreams and nightmares;
- depersonalization;
- Delirium;
- Psychosis;
- Paranoia;
- Suicidal conception and behavior.
Metabolism and nutrition disorders
Bupropion therapy can promote the onset of anorexia and weight loss. Furthermore, the drug can alter the blood glucose level.
Cardiovascular disorders
Treatment with bupropion can cause tachycardia and palpitations.
On the vascular level, on the other hand, the drug can cause an increase - even a serious one - in arterial pressure, vasodilation, redness and orthostatic hypotension, that is a sharp drop in blood pressure when passing from a sitting or lying position to an upright position.
Gastrointestinal disorders
Taking bupropion can cause abdominal pain, nausea, vomiting, constipation and dry mouth.
Hepatobiliary disorders
Bupropion therapy can promote the occurrence of hepatitis, jaundice and alteration of liver enzyme values in the blood.
Skin and subcutaneous tissue disorders
Following treatment with bupropion, skin rashes, erythema, pruritus, Stevens-Johnson syndrome (a variant of polymorphic erythema) and increased sweating may occur. Furthermore, an exacerbation of psoriasis may occur in patients with psoriasis.
Other side effects
Other side effects that may occur following bupropion are:
- Allergic reactions in sensitive subjects and - in some cases - anaphylactic shock;
- Angioedema;
- Temperature;
- Dyspnoea;
- bronchospasm;
- Arthralgia and myalgia;
- Muscle contractions;
- Asthenia;
- Chest pain;
- Alteration of the sense of taste;
- Vision disorders;
- Tinnitus.
Overdose
The symptoms of bupropion overdose consist of an exacerbation of side effects, but cases of unconsciousness have also been reported. Death has rarely occurred due to overdosing.
No specific antidote is known, therefore the treatment is only symptomatic. The use of activated charcoal may be useful. However, if an overdose is taken, it is necessary to go immediately to a hospital.
Action mechanism
Bupropion is a selective dopamine (DA) reuptake inhibitor at presynaptic level and has a mild action also against the reuptake of serotonin (5-HT) and noradrenaline (NA).
Dopamine, serotonin and noradrenaline are neurotransmitters that are synthesized within specific presynaptic nerve endings and released based on certain stimuli. Once in the synaptic space (the space present between the presynaptic and postsynaptic nerve endings), these interact with their postsynaptic receptors to carry out their biological action. After that, they are recaptured by specific transporters and returned to the presynaptic termination.
Bupropion mainly inhibits the re-uptake of dopamine, thus allowing it to remain in the synaptic space for a prolonged period. Dopamine, therefore, interacts with its postsynaptic receptors for a longer time, producing a consequent increase in the dopaminergic signal.
Mode of Use - Posology
Bupropion is available for oral administration as tablets. As the drug can cause sleep disturbances, taking the tablets before bedtime is not recommended.
The bupropion dosage must be established by the doctor on an individual basis.
In any case, the dose of drug normally used is 150 mg of active ingredient, to be taken once a day. The dose can be increased up to 300 mg.
In patients with hepatic and / or renal insufficiency a reduction in the dose of bupropion administered may be necessary.
Although no cases of withdrawal symptoms have been reported, abrupt termination of therapy is not recommended; instead, a gradual reduction of the dose is recommended.
Pregnancy and breastfeeding
Some studies have reported an increased risk of cardiovascular malformations in newborns whose mothers took bupropion during pregnancy, especially during the first trimester of gestation. Therefore, bupropion should not be given to pregnant women, unless the doctor considers it absolutely necessary.
Bupropion and its metabolites are excreted in breast milk, so the drug should not be used by mothers who are breast-feeding.
Contraindications
The use of bupropion is contraindicated in the following cases:
- Known hypersensitivity to bupropion;
- In patients suffering from convulsive pathologies or with a history of convulsive disorders;
- In patients taking other bupropion-based medicines;
- In patients suffering from tumors involving the central nervous system;
- In patients with severe liver cirrhosis;
- In patients who suffer - or who have suffered - from bulimia or anorexia nervosa;
- In patients already on MAOI therapy.
Bupropion and smoking
To learn more: Bupropion for smoking cessation
Bupropion is a drug that is not only used for the treatment of major depression, but is also used in smoking cessation therapy.
In fact, in addition to inhibiting dopamine reuptake (a mechanism responsible for the antidepressant action), the drug also has an antagonistic action against nicotinic receptors already at therapeutic concentrations.
Bupropion - thanks to its mechanism of action - is able to reduce nicotine cravings in patients, also reducing discomfort and symptoms induced by abstinence. Furthermore, the drug is able to reduce the risk of relapse.
Generally, the recommended starting dose of bupropion is 150 mg per day, which can be increased up to a maximum of 300 mg.
