The drug bupropion is assigned to the class of antidepressants. It is also used to treat nicotine dependence.
What is bupropion?
The drug bupropion is assigned to the antidepressant drug class. Bupropion is a selective dopamine and norepinephrine reuptake inhibitor (NDRI). It also marginally serves to inhibit the reuptake of serotonin. Prior to 2000, bupropion was known as amfebutamone. In the United States, the drug had been approved since 1984. Because reports of seizures, some of them fatal, after taking bupropion increased, approval was withdrawn in 1986 and then reissued in 1989 at a low dosage. Since 2003, bupropion has been approved in the United States for once-daily administration. In Germany, the drug received approval as an antidepressant in a sustained-release form in 2007. However, the drug was already used off-label as an antidepressant prior to this approval. In Switzerland, bupropion was for a long time approved only for smoking cessation. Since 2007, it has been administered there for the treatment of depressive episodes. In Switzerland, however, therapy with bupropion may only be initiated by a psychiatrist or a neurologist. From a chemical point of view, bupropion belongs to the phenethylamines and to the subgroup of cathinones and amphetamines. The drug is closely related to the neurotransmitters dopamine, epinephrine and norepinephrine. Bupropion is a selective norepinephrine and dopamine reuptake inhibitor. Thus, the drug inhibits the uptake of norepinephrine and dopamine in the synaptic cleft. Dopamine and norepinephrine are neurotransmitters. When an electrical impulse arrives at the synapse, which is located in front of a nerve cell, the presynaptic nerve cell releases the neurotransmitters into the so-called synaptic cleft. The synaptic cleft is a small gap between the two nerve cells. The neurotransmitters move from one nerve cell to the other. There, they dock onto a receptor on the postsynaptic neuron. This triggers an electrical impulse. In a healthy person, there is a balance between the neurotransmitters. In depressed people, the balance among the neurotransmitters is disturbed. Decreased activity of the nerve cells that transmit the neurotransmitters norepinephrine and dopamine develops. Bupropion inhibits the reuptake of norepinephrine and dopamine in the synaptic cleft. As a result, the neurotransmitters remain in the synapse longer and the concentration of neurotransmitters in the synaptic cleft is increased with longer-term use. Thus, bupropion has a mood-lifting and drive-enhancing effect. In addition, bupropion is also a so-called non-competitive antagonist at the cholinergic nicotinic receptors. Noncompetetive antagonists alter the corresponding receptor in such a way that the original substance can no longer trigger any effect or only a slight effect at the receptor.
Pharmacologic action
The main indication for bupropion is depression. Studies have shown that the effect of bupropion can be compared with the efficacy of antidepressants from the selective serotonin reuptake inhibitor (SSRI) class of drugs. In particular, in depression with psychological and physical fatigue, bupropion is more effective than SSRIs. In contrast, for depression with anxiety symptomatology, SSRIs work better than bupropion. While sexual dysfunction is more common with SSRI treatment, it is very rarely observed with bupropion therapy. After treatment failure of the antidepressant citalopram, bupropion is also used in second-line therapy. Its effect is similar to that of venlafaxine, sertraline or buspirone. One quarter of patients experience remission (temporary or permanent reduction of symptoms) during treatment with the drug. Bupropion is also used in smoking cessation. The effectiveness of the drug is comparable to the effectiveness of nicotine patches. However, it appears that the drug is inferior to varenicline in the treatment of nicotine addiction. Another indication for bupropion is attention deficit hyperactivity disorder (ADHD). However, the drug is not approved for this indication and has not been tested for efficacy or safety in patients under 18 years of age.Manufacturer-funded studies also showed that bupropion leads to a reduction in appetite and thus causes weight loss. It is not known whether body weight increases again after discontinuation of the substance. In combination with the drug naltrexone, bupropion has proven to be an effective preparation for weight reduction in obese patients. However, this combination drug has not yet been officially approved.
Risks and side effects
Common side effects of bupropion include insomnia and dry mouth. In addition, headache, muscle pain, loss of appetite, anxiety, difficulty concentrating, and confusion may occur. Bupropion may also cause priapism. Priapism is the term used to describe a painful permanent erection of the penis. This can lead to erectile dysfunction without treatment. Bupropion should not be given together with MAO inhibitors. Both drugs affect the catecholaminergic metabolic pathways, so serious interactions may occur. If alcohol is consumed at the same time, the drug may cause neuropsychiatric side effects. If bupropion and drugs that lower the seizure threshold are administered at the same time, seizures may occur. These drugs include antidepressants, tramadol, systemic steroids, sedative antihistamines, and antimalarials. The drug bupropion inhibits the CYP450-2D6 pathway. Since all tricyclics except doxepin are metabolized via this pathway, blood levels may increase when the substances are taken simultaneously. The effects of many analgesics, antipsychotics, beta-blockers, and antiarrhythmics may also be enhanced by bupropion. Despite a different metabolic pathway, citalopram levels also increase with concomitant use. Bupropion decreases the sedative effect of diazepam. If bupropion is used with nicotine patches for smoking cessation, blood pressure may rise sharply.