nicotine + nicotine + bupropion

This combination therapy, often referred to as triple therapy or high-dose combination nicotine replacement therapy (NRT) plus bupropion, is a pharmacological strategy for smoking cessation, particularly studied in populations with high nicotine dependence or psychiatric comorbidities such as schizophrenia. It involves the concurrent administration of two NRT components—typically two transdermal patches to achieve a high-dose nicotine delivery (e.g., 30 mg/day) or a patch combined with an ad-libitum oral form—alongside bupropion, an atypical antidepressant. Nicotine acts as an agonist at neuronal nicotinic acetylcholine receptors (nAChRs), specifically the alpha-4 beta-2 subtype, to alleviate withdrawal symptoms and cravings by providing a controlled source of nicotine. Bupropion serves a dual role: it is a norepinephrine-dopamine reuptake inhibitor (NDRI) that increases synaptic levels of these neurotransmitters to reduce withdrawal-related dysphoria, and it acts as a non-competitive antagonist at nAChRs, which may block the reinforcing effects of any nicotine consumed through smoking. This multi-pronged approach was notably evaluated by Yu-Li Hospital in the PSIAARP trial to determine if higher nicotine replacement levels combined with bupropion could improve cessation outcomes and readiness to change in outpatients with schizophrenia.

Other names

Triple therapy for smoking cessationHigh-dose nicotine patch plus bupropionCombination NRT plus bupropionNicotine replacement therapy + nicotine replacement therapy + bupropion