BACKGROUND: For some adults with Attention-Deficit/Hyperactivity Disorder (ADHD), nonstimulants need to be considered either as a monotherapy or as an adjunct to stimulants.
OBJECTIVES: The objectives of this systematic review and meta-analysis were to assess the efficacy, acceptability, and tolerability of nonstimulants in adults with ADHD.
METHODS: Data sources, searches, and study selection were based on a previously published network meta-analysis of randomized clinical trials (RCTs) by Cortese at al. (Lancet Psychiatry 5(9):727-738, 2018), which we updated in March 2022. Specifically, we searched PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, OpenGrey, Web of Science Core Collection, ProQuest Dissertations and Theses (UK and Ireland), ProQuest Dissertations and Theses (abstracts and international), and the WHO International Trials Registry Platform, including ClinicalTrials.gov for double-blind RCTs with a placebo arm, lasting at least one week, including adults with a diagnosis of ADHD based on DSM-III, DSM-III-R, DSM-IV(TR), DSM-5 or ICD-9- or 10, and reporting data on efficacy, tolerability (drop-out due to side effects) and acceptability (drop-out due to any cause) of guanfacine, clonidine, or atomoxetine. Additionally, we searched for RCTs of viloxazine extended release (ER), approved for ADHD in 2021. Random-effects meta-analyses were conducted, and the risk of bias for individual RCTs was assessed using the Cochrane Risk of Bias tool.
RESULTS: We included 18 studies in the meta-analyses (4308 participants) plus one additional study in the narrative synthesis (374 participants). The meta-analysis showed that atomoxetine (15 RCTs) (Hedge's g = - 0.48, 95% CI [- 0.64; - 0.33]), guanfacine (two RCTs) (Hedge's g = - 0.66, 95% CI [- 0.94; - 0.38]) and viloxazine ER (one RCT) were significantly more efficacious than placebo. Atomoxetine was less well tolerated than placebo, while tolerability of guanfacine and viloxazine ER could not be meta-analysed, since only one study, for each medication, reported on it.
CONCLUSIONS: All investigated nonstimulants were more efficacious in the treatment of ADHD in adults, than placebo, while the placebo had better acceptability and tolerability.
PROTOCOL: https://osf.io/5vnmt/?view_only=2bf87ed12ba94645babedceeee4c0120 .
Naltrexone/Bupropion extended release (ER; Contrave) is an extended-release, fixed-dose combination medication of naltrexone (8 mg) and bupropion (90 mg) for patients with obesity or overweight with at least one weight-related comorbidity. Obese and overweight patients with or without comorbidities are at increased cardiovascular (CV) risk. Due to the increased CV risk profile in this patient population, this systematic literature review was conducted to assess human studies reporting major adverse CV events (MACE) and other CV events. A priori eligibility criteria included clinical studies (randomized and observational) published from January 1, 2012, to September 30, 2021, with data comparing users of naltrexone/bupropion ER, naltrexone with bupropion, bupropion without naltrexone, or naltrexone without bupropion versus comparator groups (placebo or other treatments), and with sufficient information to determine the frequency of MACE or other CV adverse events by treatment group. Among 2539 English-language articles identified, 70 articles met the eligibility criteria: seven studies of naltrexone/bupropion ER or naltrexone with bupropion, 32 studies of bupropion, and 31 studies of naltrexone. No studies reported an increased risk of MACE among users of naltrexone/bupropion ER, naltrexone with bupropion, or bupropion or naltrexone individually compared with nonusers. One-half of the available studies (n = 35) reported no (zero) CV events and the other half (n = 35) reported that a non-zero frequency of CV events occurred. Four studies reported data on MACE, including three studies of bupropion and one study of naltrexone/bupropion ER. For composite MACE and its components, the difference in proportions between naltrexone/bupropion ER-, bupropion-, or naltrexone-treated patients compared with active comparators or placebo-treated patients did not exceed 2.5%. In conclusion, the available human evidence does not indicate an increased risk of CV events or MACE following use of naltrexone/bupropion ER, naltrexone with bupropion, or the individual components.
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterised by inattention, hyperactivity, and impulsivity. ADHD can persist into adulthood and can affects individuals' social and occupational functioning, as well as their quality of life and health. ADHD is frequently associated with other mental disorders such as substance use disorders and anxiety and affective disorders. Amphetamines are used to treat adults with ADHD, but uncertainties about their efficacy and safety remain.
OBJECTIVES: To examine the efficacy and safety of amphetamines for adults with ADHD.
SEARCH METHODS: In August 2017, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and two trials registers, and we ran citation searches for included studies. We also contacted the corresponding authors of all included studies, other experts in the field, and the pharmaceutical company, Shire, and we searched the reference lists of retrieved studies and reviews for other published, unpublished, or ongoing studies. For each included study, we performed a citation search in Web of Science to identify any later studies that may have cited it.
SELECTION CRITERIA: We searched for randomised controlled trials comparing the efficacy of amphetamines (at any dose) for ADHD in adults aged 18 years and over against placebo or an active intervention.
DATA COLLECTION AND ANALYSIS: Two review authors extracted data from each included study. We used the standardised mean difference (SMD) and the risk ratio (RR) to assess continuous and dichotomous outcomes, respectively. We conducted a stratified analysis to determine the influence of moderating variables. We assessed trials for risk of bias and drew a funnel plot to investigate the possibility of publication bias. We rated the quality of the evidence using the GRADE approach, which yielded high, moderate, low, or very low quality ratings based on evaluation of within-trial risk of bias, directness of evidence, heterogeneity of data; precision of effect estimates, and risk of publication bias.
MAIN RESULTS: We included 19 studies that investigated three types of amphetamines: dexamphetamine (10.2 mg/d to 21.8 mg/d), lisdexamfetamine (30 mg/d to 70 mg/d), and mixed amphetamine salts (MAS; 12.5 mg/d to 80 mg/d). These studies enrolled 2521 participants; most were middle-aged (35.3 years), Caucasian males (57.2%), with a combined type of ADHD (78.8%). Eighteen studies were conducted in the USA, and one study was conducted in both Canada and the USA. Ten were multi-site studies. All studies were placebo-controlled, and three also included an active comparator: guanfacine, modafinil, or paroxetine. Most studies had short-term follow-up and a mean study length of 5.3 weeks.We found no studies that had low risk of bias in all domains of the Cochrane 'Risk of bias' tool, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment, but also because we noted attrition bias, and because we could not rule out the possibility of a carry-over effect in studies that used a cross-over design.Sixteen studies were funded by the pharmaceutical industry, one study was publicly funded, and two studies did not report their funding sources.Amphetamines versus placeboSeverity of ADHD symptoms: we found low- to very low-quality evidence suggesting that amphetamines reduced the severity of ADHD symptoms as rated by clinicians (SMD -0.90, 95% confidence interval (CI) -1.04 to -0.75; 13 studies, 2028 participants) and patients (SMD -0.51, 95% CI -0.75 to -0.28; six studies, 120 participants).Retention: overall, we found low-quality evidence suggesting that amphetamines did not improve retention in treatment (risk ratio (RR) 1.06, 95% CI 0.99 to 1.13; 17 studies, 2323 participants).Adverse events: we found that amphetamines were associated with an increased proportion of patients who withdrew because of adverse events (RR 2.69, 95% CI 1.63 to 4.45; 17 studies, 2409 participants).Type of amphetamine: we found differences between amphetamines for the severity of ADHD symptoms as rated by clinicians. Both lisdexamfetamine (SMD -1.06, 95% CI -1.26 to -0.85; seven studies, 896 participants; low-quality evidence) and MAS (SMD -0.80, 95% CI -0.93 to -0.66; five studies, 1083 participants; low-quality evidence) reduced the severity of ADHD symptoms. In contrast, we found no evidence to suggest that dexamphetamine reduced the severity of ADHD symptoms (SMD -0.24, 95% CI -0.80 to 0.32; one study, 49 participants; very low-quality evidence). In addition, all amphetamines were efficacious in reducing the severity of ADHD symptoms as rated by patients (dexamphetamine: SMD -0.77, 95% CI -1.14 to -0.40; two studies, 35 participants; low-quality evidence; lisdexamfetamine: SMD -0.33, 95% CI -0.65 to -0.01; three studies, 67 participants; low-quality evidence; MAS: SMD -0.45, 95% CI -1.02 to 0.12; one study, 18 participants; very low-quality evidence).Dose at study completion: different doses of amphetamines did not appear to be associated with differences in efficacy.Type of drug-release formulation: we investigated immediate- and sustained-release formulations but found no differences between them for any outcome.Amphetamines versus other drugsWe found no evidence that amphetamines improved ADHD symptom severity compared to other drug interventions.
AUTHORS' CONCLUSIONS: Amphetamines improved the severity of ADHD symptoms, as assessed by clinicians or patients, in the short term but did not improve retention to treatment. Amphetamines were associated with higher attrition due to adverse events. The short duration of studies coupled with their restrictive inclusion criteria limits the external validity of these findings. Furthermore, none of the included studies had an overall low risk of bias. Overall, the evidence generated by this review is of low or very low quality.
Introducción: El trastorno por déficit de atención / hiperactividad (TDAH) es uno de los trastornos neuropsiquiátricos más frecuentes de la infancia y la adolescencia. Los estimulantes son generalmente la primera opción del fármaco; Sin embargo, hasta el 20% de los pacientes no responden a ellos. Los estimulantes también pueden empeorar el sueño comórbido, el estado de ánimo y los trastornos de ansiedad, y están asociados con problemas de mal uso y desvío. El bupropión, un inhibidor de la recaptación de dopamina y norepinefrina, es una alternativa no estimulante prometedora con reportes de resultados positivos para el manejo del ADHD en poblaciones adolescentes y adultas. Este estudio revisa sistemáticamente los ensayos clínicos sobre el tema. Métodos: Utilizando las palabras clave bupropión o Wellbutrin o Zyban o Elontril y trastorno de déficit de atención con hiperactividad o TDAH o ADDH, una búsqueda preliminar en las bases de datos PubMed y Ovid produjo 25,455 artículos publicados en inglés entre el 1 de enero de 1988 y el 1 de mayo de 2016. De estos , Hubo sólo seis artículos sobre ensayos clínicos con niños. También se revisaron artículos completos para referencias de interés. Resultados Todos los ensayos abiertos, controlados y aleatorios disponibles demostraron la eficacia del bupropion en la mejora de los síntomas del TDAH. Los tres ensayos de cabeza a cabeza encontraron que el bupropión tenía una eficacia comparable a la del metilfenidato (p> 0,05). Sin embargo, un estudio multicéntrico doble ciego controlado por placebo de bupropión encontró tamaños de efecto más pequeños para el bupropión, tal como se cuantificaron utilizando las calificaciones de los síntomas del TDAH por parte del profesor y los padres, que el metilfenidato. En términos de tolerabilidad, un ensayo de cabeza a cabeza encontró que la cefalea se observó con más frecuencia en el grupo tratado con metilfenidato que en el grupo tratado con bupropión, mientras que la frecuencia de otros efectos secundarios no difirió significativamente. CONCLUSIÓN: Los hallazgos actuales deben ser interpretados con precaución debido a la base de datos muy limitada. El bupropión debe considerarse para el manejo farmacológico del ADHD infantil y adolescente, pero se justifican más ensayos controlados aleatorios con tamaños de muestra más grandes. También hay evidencia de sus beneficios en niños con TDAH comórbido y conducta, uso de sustancias o trastornos depresivos.
Motivation is an integral factor in substance use treatment and long-term recovery. However, it is unclear what role intrinsic and extrinsic motivation play across different treatment modalities. A meta-analysis (N = 84) was performed to estimate the pooled effect size of Motivational Interviewing (MI; primarily targeting intrinsic motivation) and contingency management (CM; primarily targeting extrinsic motivation) at different follow-up periods. Collapsed across all substance types, CM had a significant effect at 3-month follow-up, only. In contrast, MI had a significant effect at 6-month follow-up, only. CM had small and medium effects on multiple substances at 3-month follow-up (i.e., tobacco, marijuana, stimulants, polysubstances), but not at 6-month follow-up. MI had 1 significant medium effect at 3-month follow-up (i.e., marijuana), but several significant small effects at 6-month follow-up (i.e., alcohol, tobacco, polysubstances). This meta-analysis suggests that both CM and MI promote reductions in a range of substances, even several months after the intervention concludes. Further, these results provide some evidence that extrinsically focused CM may produce medium follow-up effects in the short run, but intrinsically focused MI may produce small but durable follow-up effects. However, this interpretation is complicated by the differences between the MI and CM studies that preclude statistical tests comparing effect sizes, and few studies assessed motivation itself. Future researchers should investigate how motivational dynamics impact lasting outcomes in substance use treatment. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurobiological condition, characterised by behavioral and cognitive symptoms such as inattention, impulsivity and/or excessive activity. The syndrome is commonly accompanied by psychiatric comorbidities and is associated with educational and occupational underachievement.Although psychostimulant medications are the mainstay of treatment for ADHD, not all adults respond optimally to, or can tolerate, these medicines. Thus, alternative non-stimulant treatment approaches for ADHD have been explored. One of these alternatives is bupropion, an aminoketone antidepressant and non-competitive antagonism of nicotinic acetylcholine receptors. Bupropion is registered for the treatment of depression and smoking cessation, but is also used off-label to treat ADHD.
OBJECTIVES: To assess the effects and safety of bupropion for the treatment of adults with ADHD.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and seven other databases in February 2017. We also searched three trials registers and three online theses portals. In addition, we checked references of included studies and contacted study authors to identify potentially relevant studies that were missed by our search.
SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that evaluated the effects (including adverse effects) of bupropion compared to placebo in adults with ADHD.
DATA COLLECTION AND ANALYSIS: Two review authors (WV, GB) independently screened records and extracted data using a data extraction sheet that we tested in a pilot study. We extracted all relevant data on study characteristics and results. We assessed risks of bias using the Cochrane 'Risk of bias' tool, and assessed the overall quality of evidence using the GRADE approach. We used a fixed-effect model to pool the results across studies.
MAIN RESULTS: We included six studies with a total of 438 participants. Five studies were conducted in the USA, and one in Iran. All studies evaluated a long-acting version of bupropion, with the dosage ranging from 150 mg up to 450 mg daily. Study intervention length varied from six to 10 weeks. Four studies explicitly excluded participants with psychiatric comorbidity and one study included only participants with opioid dependency. Four studies were funded by industry, but the impact of this on study results is unknown. Two studies were publicly funded and in one of these studies, the lead author was a consultant for several pharmaceutical companies and also received investigator-driven funding from two companies, however none of these companies manufacture bupropion. We judged none of the studies to be free of bias because for most risk of bias domains the study reports failed to provide sufficient details. Using the GRADE approach, we rated the overall quality of evidence as low. We downgraded the quality of the evidence because of serious risk of bias and serious imprecision due to small sample sizes.We found low-quality evidence that bupropion decreased the severity of ADHD symptoms (standardised mean difference -0.50, 95% confidence interval (CI) -0.86 to -0.15, 3 studies, 129 participants), and increased the proportion of participants achieving clinical improvement (risk ratio (RR) 1.50, 95% CI 1.13 to 1.99, 4 studies, 315 participants), and reporting an improvement on the Clinical Global Impression - Improvement scale (RR 1.78, 95% CI 1.27 to 2.50, 5 studies, 337 participants). There was low-quality evidence that the proportion of participants who withdrew due to any adverse effect was similar in the bupropion and placebo groups (RR 1.20, 95% CI 0.35 to 4.10, 3 studies, 253 participants). The results were very similar when using a random-effects model and when we analysed only studies that excluded participants with a psychiatric comorbidity.
AUTHORS' CONCLUSIONS: The findings of this review, which compared bupropion to placebo for adult ADHD, indicate a possible benefit of bupropion. We found low-quality evidence that bupropion decreased the severity of ADHD symptoms and moderately increased the proportion of participants achieving a significant clinical improvement in ADHD symptoms. Furthermore, we found low-quality evidence that the tolerability of bupropion is similar to that of placebo. In the pharmacological treatment of adults with ADHD, extended- or sustained-release bupropion may be an alternative to stimulants. The low-quality evidence indicates uncertainty with respect to the pooled effect estimates. Further research is very likely to change these estimates. More research is needed to reach more definite conclusions as well as clarifying the optimal target population for this medicine. Treatment response remains to be reported in a DSM5-diagnosed population. There is also a lack of knowledge on long-term outcomes.
Atención e Hiperactividad por Déficit de adulto (TDAH) es un trastorno psiquiátrico frecuente asociado con la discapacidad y la alta comorbilidad frecuente. farmacoterapia estándar actual (metilfenidato y la atomoxetina) mejora los síntomas de TDAH en el corto plazo, pero se han publicado datos pobres sobre el tratamiento a largo plazo. Además, un número de pacientes que presentan respuesta parcial o no a metilfenidato y la atomoxetina. La investigación de las principales fuentes de bases de datos se ha llevado a cabo para obtener una visión general de los enfoques farmacológicos alternativos en pacientes adultos con TDAH. Entre los compuestos alternativos, anfetaminas (sales de anfetamina mezcladas y lisdexamfetamine) tienen la evidencia más robusta de la eficacia, sino que pueden estar asociados con efectos secundarios graves (por ejemplo, síntomas psicóticos o hipertensión). Los antidepresivos, especialmente aquellos que actúan como potenciadores de noradrenalina o dopamina, tienen evidencia de eficacia, pero deben evitarse en pacientes con trastorno bipolar comórbido. Finalmente metadoxine y el litio pueden ser particularmente adecuadas en caso de uso indebido de alcohol comórbida o el trastorno bipolar.
ANTECEDENTES: La dependencia de cocaína es un problema de salud pública que se caracteriza por la reincidencia y una serie de complicaciones médicas y psicosociales. La dependencia de cocaína sigue siendo un trastorno para el cual no existe un tratamiento farmacológico de eficacia comprobada.
Objetivos: Evaluar la eficacia y la aceptabilidad de los medicamentos antipsicóticos para la dependencia a la cocaína.
ESTRATEGIA DE BÚSQUEDA: Esta revisión es una actualización de una revisión Cochrane anterior publicado en 2007. Se realizaron búsquedas hasta el 15 de julio de 2015, de Cochrane Drugs and Alcohol registro especializado del Grupo (búsqueda en CRSLive); la Cochrane Library (incluyendo el Registro Cochrane Central de Ensayos Controlados (CENTRAL); la Base de Datos de Resúmenes de Revisiones de Efectos (DARE)); PubMed; EMBASE; CINAHL y Web of Science. Todas las búsquedas incluyeron literatura en idiomas no-Inglés.
Criterios de selección: Todos los ensayos controlados aleatorios y ensayos clínicos controlados con especial atención en el uso de cualquier medicación antipsicótica para el tratamiento de la dependencia a la cocaína.
Recopilación y análisis de datos: Se utilizaron procedimientos metodológicos estándar que se esperan por Cochrane.
Resultados principales: Se incluyeron 14 estudios (719 participantes). Los fármacos antipsicóticos estudiados fueron la risperidona, olanzapina, quetiapina, lamotrigina, aripiprazol, haloperidol y reserpina. La comparación de los fármacos antipsicóticos versus placebo, se encontró que los antipsicóticos reducen la deserción: ocho estudios, 397 participantes, riesgo relativo (RR) 0,75 (intervalo de confianza del 95% (IC) 0,57 a la 0,97), calidad de evidencia moderada. No se encontraron diferencias significativas para ninguno de los otros resultados primarios considerados: número de participantes que usaron cocaína durante el tratamiento, dos estudios, 91 participantes: RR 1,02 (IC del 95%: 0,65 a 1,62); abstinencia continua, tres estudios, 139 participantes: RR 1,30 (IC del 95%: 0,73 a 2.32); efectos secundarios, seis estudios, 291 participantes: RR 1,01 (IC del 95%: 0,93 a 1,10); y el deseo, cuatro estudios, 240 participantes: RR 0,13 (-1.08 a 1.35). Por todas estas comparaciones se calificó la calidad de la evidencia tan bajo.Las comparaciones de un solo fármaco versus placebo o versus otro fármaco se llevan a cabo en pocos ensayos con muestras de pequeño tamaño, lo que limita la fiabilidad de los resultados. Entre estas comparaciones, sólo se parecía quetiapina para superar a placebo en la reducción del consumo de cocaína, medido por gramos por semana: diferencia de medias (DM) (IC del 95% -0.92 -0.16 a) -0.54, por dólares estadounidenses gastados por semana: MD -53,80 ( IC del 95%: -97,85 a -9,75), y por el deseo: MD -1,23 (IC del 95%: -2,19 a -0,27), pero los resultados provienen de un estudio con 60 participantes.Las principales limitaciones de los estudios fueron el alto riesgo de sesgo de deserción (40% de los estudios incluidos) y la baja calidad de la información, principalmente para el riesgo de sesgo de selección, el rendimiento y el sesgo de detección, que nos clasificado como de riesgo claro para el 75 % a 80% de los estudios. Por otra parte, la mayoría de los estudios incluidos no informaron resultados en resultados importantes como los efectos secundarios, o el uso de la cocaína durante el tratamiento y el deseo, lo que impidió la posibilidad de incluirlos en la síntesis estadística.
Conclusiones de los revisores: En la actualidad, no existen pruebas que apoyen el uso de medicamentos antipsicóticos en el tratamiento de la dependencia de la cocaína, aunque los resultados provienen de sólo 14 ensayos, con pequeños tamaños de muestra y de moderada a baja calidad de las pruebas.
Antecedentes: La dependencia de la cocaína es un trastorno grave para el cual no se ha aprobado ninguna medicación. Al igual que los opioides para la dependencia de heroína, la terapia de reemplazo con psicoestimulantes podría ser una terapia eficaz para el tratamiento. OBJETIVOS: Evaluar los efectos de los psicoestimulantes en el abuso y la dependencia de cocaína. Los resultados específicos incluyen la abstinencia sostenida de cocaína y la retención en el tratamiento. También estudiamos la influencia del tipo de fármaco y trastornos comórbidos sobre la eficacia de los psicoestimulantes. MÉTODOS DE BÚSQUEDA: Esta es una actualización de la revisión publicada anteriormente en 2010. Para esta revisión actualizada, buscamos en el Registro de Ensayos del Grupo Cochrane de Drogas y Alcohol, CENTRAL, MEDLINE, Embase y PsycINFO hasta el 15 de febrero de 2016. Buscamos búsquedas de artículos obtenidos Y consultó a expertos en la materia. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos clínicos controlados aleatorios de grupos paralelos que compararon la eficacia de un fármaco psicoestimulante versus placebo. Recopilación y análisis de datos: Se utilizaron procedimientos metodológicos estándar esperados por Cochrane. Se incluyeron 26 estudios con 2366 participantes. Los estudios incluidos evaluaron nueve fármacos: bupropión, dexanfetamina, lisdexamfetamina, metilfenidato, modafinilo, mazindol, metanfetamina, sales mixtas de anfetamina y selegilina. No consideramos que ningún estudio tuviera un bajo riesgo de sesgo en todos los dominios incluidos en la herramienta Cochrane de riesgo de sesgo. El sesgo de desgaste fue la fuente potencial de sesgo más frecuentemente sospechada de los estudios incluidos. Se encontró evidencia de muy baja calidad de que los psicoestimulantes mejoraron la abstinencia sostenida de cocaína (RR 1,36, intervalo de confianza 95% 1,05 a 1,77, P = 0,02), pero no redujeron el uso de cocaína (diferencia de medias estandarizada) 0,16, IC del 95%: -0,02 a 0,33) entre los participantes que continuaron utilizando el mismo. Además, se encontró una evidencia de calidad moderada de que los psicoestimulantes no mejoraron la retención en el tratamiento (RR 1,00; IC del 95%: 0,93 a 1,06). La proporción de deserciones inducidas por eventos adversos y de deserciones inducidas por eventos adversos cardiovasculares fue similar en psicoestimulantes y placebo (RD 0,00, IC del 95%: -0,01 a 0,01; RD 0,00, IC del 95%: -0,02 a 0,01, respectivamente). Cuando se incluyó el tipo de fármaco como variable moderadora, la proporción de pacientes que lograron una abstinencia sostenida de cocaína fue mayor con bupropión y dexanfetamina que con placebo. Los psicoestimulantes también parecían aumentar la proporción de pacientes que alcanzaban la abstinencia sostenida de cocaína y heroína entre los adictos a la heroína y la cocaína doblemente administrados con metadona. Sin embargo, la retención al tratamiento fue baja, por lo que nuestros resultados pueden verse comprometidos por el sesgo de desgaste. No encontramos evidencia de sesgo de publicación. CONCLUSIONES DE LOS AUTORES: Esta revisión encontró resultados mixtos. Los psicoestimulantes mejoraron la abstinencia de cocaína en comparación con el placebo en algunos análisis, pero no mejoraron la retención del tratamiento. Dado que el abandono del tratamiento fue alto, no podemos descartar la posibilidad de que estos resultados estuvieran influenciados por el sesgo de desgaste. Las pruebas existentes no demuestran claramente la eficacia de ningún tratamiento farmacológico para la dependencia de la cocaína, pero el tratamiento de sustitución con psicoestimulantes parece prometedor y merece más investigación.
ANTECEDENTES: La dependencia de drogas es frecuente en los pacientes con trastorno de hiperactividad y déficit de atención (TDAH). Sin embargo, la eficacia y seguridad de los tratamientos farmacológicos en esta población no están claros.
MÉTODOS: Una revisión sistemática con meta-análisis se llevó a cabo. Se incluyeron los ensayos clínicos controlados con placebo aleatorios que investigan la eficacia del tratamiento farmacológico en pacientes con co-produciendo el TDAH y trastorno por uso de sustancias (TUS). Gravedad de los síntomas del TDAH, la abstinencia de drogas y tratamiento de todas las causas de discontinuación fueron los puntos finales primarios del estudio. Los efectos de las covariables pacientes-, intervencionismo y las relacionadas con el estudio sobre los resultados primarios fueron investigados por medio de meta-regresión.
RESULTADOS: Se incluyeron trece estudios, que reclutaron a un total de 1.271 pacientes. Una pequeña a moderada reducción de los síntomas del TDAH se encontró. Análisis Meta-regresión identificó la presencia de un período inicial como covariable asociados con la eficacia reducida. Por el contrario, ningún efecto beneficioso se observó tanto en la abstinencia de drogas o la interrupción del tratamiento. La eficacia de los síntomas del TDAH fue menor en los estudios con un período lead-in. Se encontró una correlación positiva entre la eficacia para el TDAH y que para SUD.
CONCLUSIONES: La eficacia de las intervenciones farmacológicas para la co-produciendo el TDAH y SUD ha sido poco investigado. Se obtuvieron resultados mixtos: mientras que las intervenciones farmacológicas mejoran los síntomas del TDAH, ningún efecto beneficioso sobre la abstinencia de drogas o al interrumpir el tratamiento se señaló. La fuerza de la recomendación del tratamiento farmacológico para la co-produciendo el TDAH y SUD tanto, es modesto. El estudio se ha registrado en el registro prospectivo internacional de las revisiones sistemáticas (PROSPERO): CRD 4212003414.
For some adults with Attention-Deficit/Hyperactivity Disorder (ADHD), nonstimulants need to be considered either as a monotherapy or as an adjunct to stimulants.
OBJECTIVES:
The objectives of this systematic review and meta-analysis were to assess the efficacy, acceptability, and tolerability of nonstimulants in adults with ADHD.
METHODS:
Data sources, searches, and study selection were based on a previously published network meta-analysis of randomized clinical trials (RCTs) by Cortese at al. (Lancet Psychiatry 5(9):727-738, 2018), which we updated in March 2022. Specifically, we searched PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, OpenGrey, Web of Science Core Collection, ProQuest Dissertations and Theses (UK and Ireland), ProQuest Dissertations and Theses (abstracts and international), and the WHO International Trials Registry Platform, including ClinicalTrials.gov for double-blind RCTs with a placebo arm, lasting at least one week, including adults with a diagnosis of ADHD based on DSM-III, DSM-III-R, DSM-IV(TR), DSM-5 or ICD-9- or 10, and reporting data on efficacy, tolerability (drop-out due to side effects) and acceptability (drop-out due to any cause) of guanfacine, clonidine, or atomoxetine. Additionally, we searched for RCTs of viloxazine extended release (ER), approved for ADHD in 2021. Random-effects meta-analyses were conducted, and the risk of bias for individual RCTs was assessed using the Cochrane Risk of Bias tool.
RESULTS:
We included 18 studies in the meta-analyses (4308 participants) plus one additional study in the narrative synthesis (374 participants). The meta-analysis showed that atomoxetine (15 RCTs) (Hedge's g = - 0.48, 95% CI [- 0.64; - 0.33]), guanfacine (two RCTs) (Hedge's g = - 0.66, 95% CI [- 0.94; - 0.38]) and viloxazine ER (one RCT) were significantly more efficacious than placebo. Atomoxetine was less well tolerated than placebo, while tolerability of guanfacine and viloxazine ER could not be meta-analysed, since only one study, for each medication, reported on it.
CONCLUSIONS:
All investigated nonstimulants were more efficacious in the treatment of ADHD in adults, than placebo, while the placebo had better acceptability and tolerability.
