Background: The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short-term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
Objectives: To assess the evidence for the efficacy, harms, and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes.
Search methods: We searched the Cochrane Tobacco Addiction Group Specialised Register, most recently on 29 April 2022.
Selection criteria: We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow-up from efficacy analyses. We included trials with any follow-up length for our analyses of harms.
Data collection and analysis: We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow-up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropouts due to treatment. We carried out meta-analyses where appropriate.
Main results: We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I2 = 16%; 50 studies, 18,577 participants). There was moderate-certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I2 = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I2 = 43%; 15 studies, 4117 participants; low-certainty evidence). There was moderate-certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I2 = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I2 = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I2 = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high-certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I2 = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I2 = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I2 = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I2 = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I2 = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single-form NRT (RR 1.03, 95% CI 0.93 to 1.13; I2 = 0%; 10 studies, 7613 participants). We also found evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I2 = 16%; 6 studies, 975 participants), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I2 = 0%; 3 studies, 417 participants), although this result was subject to imprecision. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression.
Authors' conclusions: There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion may increase SAEs (moderate-certainty evidence when compared to placebo/no pharmacological treatment). There is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single-form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. Further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability.
Antecedentes: Los perfiles farmacológicos y los mecanismos de los antidepresivos son variados. Sin embargo, existen varios motivos por los que podrían ayudar a las personas a abandonar el tabaquismo: la abstinencia de nicotina puede producir un estado de ánimo bajo a corto plazo que los antidepresivos pueden aliviar; y algunos antidepresivos pueden tener un efecto específico sobre las vías o receptores neuronales que subyacen a la adicción a la nicotina.
Objetivos: Evaluar la evidencia de la eficacia, los efectos perjudiciales y la tolerabilidad de los fármacos con propiedades antidepresivas para ayudar en el abandono del hábito de fumar a largo plazo en personas que fuman cigarrillos. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en el Registro especializado del Grupo Cochrane de Tabaquismo (Cochrane Tobacco Addiction Group), la más reciente el 29 de abril de 2022. CRITERIOS DE SELECCIÓN: Se incluyeron los ensayos controlados aleatorizados (ECA) en personas que fumaban, que compararon fármacos antidepresivos con placebo o ningún tratamiento farmacológico, una farmacoterapia alternativa o el mismo fármaco utilizado de forma diferente. Se excluyeron de los análisis de eficacia los ensayos con menos de seis meses de seguimiento. Para los análisis de los efectos perjudiciales se incluyeron ensayos con cualquier duración del seguimiento. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se extrajeron los datos y se evaluó el riesgo de sesgo mediante los métodos Cochrane estándar. El desenlace principal de esta revisión fue el abandono del hábito de fumar tras al menos seis meses de seguimiento. Se utilizó la definición más rigurosa de abstinencia disponible en cada ensayo, y las tasas bioquímicamente validadas, si estaban disponibles. Los desenlaces secundarios fueron los efectos perjudiciales y los desenlaces de tolerancia, incluidos los eventos adversos (EA), los eventos adversos graves (EAG), los EA psiquiátricos, las convulsiones, las sobredosis, los intentos de suicidio, la muerte por suicidio, la mortalidad por todas las causas y los abandonos del ensayo debidos al tratamiento. Cuando fue apropiado se realizaron metanálisis.
Resultados principales: En esta revisión se incluyó un total de 124 estudios (48 832 participantes) y se agregaron 10 estudios nuevos a esta versión actualizada. La mayoría de los estudios reclutaron adultos de la comunidad o de clínicas para dejar de fumar; cuatro estudios se centraron en adolescentes (con participantes entre 12 y 21 años). Se consideró que 34 estudios tenían un alto riesgo de sesgo; sin embargo, restringir los análisis solo a los estudios con un riesgo de sesgo bajo o incierto no cambió la interpretación clínica de los resultados. Hubo evidencia de certeza alta de que el bupropión aumentó las tasas de abandono del hábito de fumar en comparación con placebo o ningún tratamiento farmacológico (RR 1,60; IC del 95%: 1,49 a 1,72; I 2 = 16%; 50 estudios, 18 577 participantes). Hubo evidencia de certeza moderada de que una combinación de bupropión y vareniclina podría haber dado lugar a tasas de abandono superiores a las de la vareniclina sola (RR 1,21; IC del 95%: 0,95 a 1,55; I 2 = 15%; tres estudios, 1057 participantes). Sin embargo, no hubo evidencia suficiente para establecer si una combinación de bupropión y terapia de reemplazo de nicotina (TRN) dio lugar a tasas de abandono superiores a la TRN sola (RR 1,17; IC del 95%: 0,95 a 1,44; I 2 = 43%; 15 estudios, 4117 participantes; evidencia de certeza baja). Hubo evidencia de certeza moderada de que los participantes que tomaron bupropión tenían más probabilidades de notificar EAG que los que tomaron placebo o ningún tratamiento farmacológico. Sin embargo, los resultados fueron poco precisos y el IC tampoco abarcó diferencias (RR 1,16; IC del 95%: 0,90 a 1,48; I 2 = 0%; 23 estudios, 10 958 participantes). Los resultados también fueron poco precisos al comparar los EAG entre las personas asignadas al azar a una combinación de bupropión y TRN versus TRN sola (RR 1,52; IC del 95%: 0,26 a 8,89; I 2 = 0%; cuatro estudios, 657 participantes) y asignadas al azar a bupropión más vareniclina versus vareniclina sola (RR 1,23; IC del 95%: 0,63 a 2,42; I 2 = 0%; cinco estudios, 1268 participantes). En ambos casos, la evidencia se consideró de certeza baja. Hubo evidencia de certeza alta de que el bupropión dio lugar a más abandonos del ensayo debido a EA que el placebo o ningún tratamiento farmacológico (RR 1,44; IC del 95%: 1,27 a 1,65; I 2 = 2%; 25 estudios, 12 346 participantes). Sin embargo, no hubo evidencia suficiente de que el bupropión combinado con TRN versus TRN sola (RR 1,67; IC del 95%: 0,95 a 2,92; I 2 = 0%; tres estudios, 737 participantes) o el bupropión combinado con vareniclina versus vareniclina sola (RR 0,80; IC del 95%: 0,45 a 1,45; I 2 = 0%; cuatro estudios, 1230 participantes) tuvieran un impacto sobre el número de abandonos debidos al tratamiento. En ambos casos, la imprecisión fue sustancial (se consideró que la evidencia fue de certeza baja en ambas comparaciones). El bupropión produjo tasas de abandono del hábito de fumar inferiores a la vareniclina (RR 0,73; IC del 95%: 0,67 a 0,80; I 2 = 0%; nueve estudios, 7564 participantes) y a la TRN combinada (RR 0,74; IC del 95%: 0,55 a 0,98; I 2 = 0%; dos estudios; 720 participantes). Sin embargo, no hubo evidencia clara de una diferencia en la eficacia entre el bupropión y la TRN como monoterapia (RR 1,03; IC del 95%: 0,93 a 1,13; I 2 = 0%; 10 estudios, 7613 participantes). También se encontró evidencia de que la nortriptilina ayudó a dejar de fumar en comparación con el placebo (RR 2,03; IC del 95%: 1,48 a 2,78; I 2 = 16%; seis estudios, 975 participantes) y alguna evidencia de que el bupropión produjo tasas de abandono del hábito de fumar superiores a la nortriptilina (RR 1,30; IC del 95%: 0,93 a 1,82; I 2 = 0%; tres estudios, 417 participantes), aunque este resultado estuvo sujeto a imprecisión. Los hallazgos en cuanto a si los antidepresivos, principalmente el bupropión y la nortriptilina, tuvieron un efecto beneficioso particular en las personas con depresión actual o previa fueron escasos e inconsistentes.
Conclusiones de los autores: Hay evidencia de certeza alta de que el bupropión puede ayudar en el abandono del hábito de fumar a largo plazo. Sin embargo, el bupropión podría aumentar los EAG (evidencia de certeza moderada en comparación con placebo/ningún tratamiento farmacológico). Existe evidencia de certeza alta de que las personas que toman bupropión tienen más probabilidades de interrumpir el tratamiento en comparación con las que reciben placebo o ningún tratamiento farmacológico. La nortriptilina también parece tener un efecto beneficioso sobre las tasas de abandono del hábito de fumar en relación con el placebo, aunque el bupropión podría ser más eficaz. La evidencia también indica que el bupropión podría ser tan eficaz como la TRN sola para ayudar a las personas a dejar de fumar, pero menos que la TRN combinada con vareniclina. En la mayoría de los casos, la escasez de datos dificultó establecer conclusiones sobre los efectos perjudiciales y la tolerabilidad. Es poco probable que estudios adicionales que investiguen la eficacia del bupropión versus placebo cambien la interpretación del efecto, lo que no proporciona una justificación clara para seguir utilizando el bupropión para dejar de fumar frente a otros tratamientos autorizados para dejar de fumar; en particular, la TRN y la vareniclina. Sin embargo, es importante que los futuros estudios de antidepresivos para el abandono del hábito de fumar midan e informen sobre los efectos perjudiciales y la tolerabilidad.
ВВЕДЕНИЕ И АКТУАЛЬНОСТЬ: The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short‐term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction. ЗАДАЧИ: To assess the evidence for the efficacy, harms, and tolerability of medications with antidepressant properties in assisting long‐term tobacco smoking cessation in people who smoke cigarettes. МЕТОДЫ ПОИСКА: We searched the Cochrane Tobacco Addiction Group Specialised Register, most recently on 29 April 2022. КРИТЕРИИ ОТБОРА: We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow‐up from efficacy analyses. We included trials with any follow‐up length for our analyses of harms. СБОР И АНАЛИЗ ДАННЫХ: We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow‐up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all‐cause mortality, and trial dropouts due to treatment. We carried out meta‐analyses where appropriate. ОСНОВНЫЕ РЕЗУЛЬТАТЫ: We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results. There was high‐certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I 2 = 16%; 50 studies, 18,577 participants). There was moderate‐certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I 2 = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I 2 = 43%; 15 studies, 4117 participants; low‐certainty evidence). There was moderate‐certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I 2 = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I 2 = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I 2 = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high‐certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I 2 = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I 2 = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I 2 = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I 2 = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I 2 = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single‐form NRT (RR 1.03, 95% CI 0.93 to 1.13; I 2 = 0%; 10 studies, 7613 participants). We also found evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I 2 = 16%; 6 studies, 975 participants), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I 2 = 0%; 3 studies, 417 participants), although this result was subject to imprecision. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression. ВЫВОДЫ АВТОРОВ: There is high‐certainty evidence that bupropion can aid long‐term smoking cessation. However, bupropion may increase SAEs (moderate‐certainty evidence when compared to placebo/no pharmacological treatment). There is high‐certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single‐form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. Further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability.
Trial registration: ClinicalTrials.gov NCT00738595 NCT00507728 NCT00322205 NCT00666978 NCT00689611 NCT00307203 NCT00142831 NCT00086411 NCT00124683 NCT00141206 NCT00044434 NCT00330187 NCT00628225 NCT00143364 NCT00439413 NCT00304707 NCT00218647 NCT00006170 NCT01621009 NCT00344695 NCT00150241 NCT01621022 NCT00332644 NCT00018148 NCT00181818 NCT00894166 NCT00129272 NCT00261170 NCT00405912 NCT00722124 NCT00018174 NCT00129311 NCT00176449 NCT00063323 NCT00033592 NCT00087880 NCT00000457 NCT01875172 NCT00390923 NCT00770666 NCT00218231 NCT00104598 NCT00484692 NCT05205811.
Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.