Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults

 

Abstract

Background

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset disorder that can persist into adulthood. Amphetamines are used to treat adult ADHD, but uncertainties persist about their efficacy and safety.

Objectives

To examine the efficacy and safety of amphetamines for adults with ADHD, as well as the influence of dose, drug type and release formulation type.

Search methods

We searched CENTRAL, PubMed, EMBASE, CINAHL, PsycINFO, clinicaltrials.gov, UK Clinical Trials Gateway and references obtained from articles and experts in the field. We conducted the electronic searches on 25 February 2010.

Selection criteria

Randomized controlled trials comparing the efficacy of amphetamine derivatives against placebo or an active intervention.

Data collection and analysis

Two authors extracted data from each included study. We used the standardized 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 the trials for risk of bias and drew a funnel plot to investigate the possibility of publication bias.

Main results

We included seven studies, which enrolled 1091 participants. All studies were placebo-controlled and three included an active comparator: guanfacine, modafinil and paroxetine. Most studies had short-term follow-up, with a mean study length of 8.1 weeks. Amphetamines improved ADHD symptom severity (SMD = -0.72; 95% CI -0.87 to -0.57) but did not improve retention in treatment overall and were associated with increased dropout due to adverse events (RR 3.03; 95% CI 1.52 to 6.05). The three amphetamine derivatives investigated (dextroamphetamine, lisdexamphetamine and mixed amphetamine salts (MAS)) were all efficacious for reducing ADHD symptoms, but MAS also increased retention in treatment. Different doses did not appear associated with differences in efficacy. We investigated immediate and sustained drug release formulations but found no difference between them on any outcome. When amphetamines were compared to other drug interventions, no differences were found. We did not find any study to be at low risk of bias overall, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment.

Authors' conclusions

Amphetamines improved short-term ADHD symptom severity. MAS also increased retention in treatment. Amphetamines were associated with higher attrition due to adverse events. The short study length and the restrictive inclusion criteria limit the external validity of these findings. Furthermore, the possibility that the results of the included studies were biased was high, which could have led to an overestimation of amphetamine efficacy.

 

Plain language summary

Amphetamines for Attention Deficit Hyperactivity Disorder in adults

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset psychiatric disorder that can persist into adulthood in up to 50% of patients. From a clinical point of view, ADHD is characterized by hyperactivity, mood instability, irritability, difficulties in maintaining attention, lack of organization and impulsive behaviours. The presence of other disorders occurring at the the same time is also common, especially mood disorders and substance abuse. It seems that amphetamines could reverse the underlying neurological problems that feature in ADHD, and so improve ADHD symptoms.

We found seven studies, which enrolled 1091 patients. These studies compared amphetamines to placebo and three of them also compared amphetamines with other drugs: guanfacine, modafinil and paroxetine. Three amphetamine derivatives were investigated: dexamphetamine, lisdexamphetamine and mixed amphetamine salts (MAS). Treatment length ranged from two to 20 weeks.

All amphetamines improved ADHD symptoms but overall they did not make people more likely to stay in treatment and were associated with a higher risk of treatment ending early due to adverse events. One type of amphetamine, mixed amphetamine salts, did, however, increase retention in treatment. We found no evidence that higher doses worked better than lower ones. We did not find any difference in effectiveness between immediate-release and sustained-release formulations. Therefore, it appears that short-term treatment with amphetamines reduces ADHD symptoms, but studies assessing the effects of amphetamines for longer periods of time are needed.

 

Resumen

Antecedentes

Anfetaminas para el trastorno de hiperactividad y déficit de atención (THDA) en adultos

El trastorno por hiperactividad y déficit de atención (THDA) es un trastorno que aparece en la niñez y puede persistir hasta la edad adulta. Las anfetaminas se utilizan para el tratamiento del THDA en adultos, pero todavía existen dudas con respecto a su eficacia y seguridad.

Objetivos

Examinar la eficacia y la seguridad de las anfetaminas en adultos con THDA, así como la influencia de la dosis, el tipo de fármaco y el tipo de formulación de liberación.

Estrategia de búsqueda

Se hicieron búsquedas en CENTRAL, PubMed, EMBASE, CINAHL, PsycINFO, clinicaltrials.gov, UK Clinical Trials Gateway y en referencias obtenidas de artículos y expertos en el tema. Las búsquedas electrónicas se realiaron el 25 de febrero de 2010.

Criterios de selección

Ensayos controlados aleatorios que compararan la eficacia de los derivados de la anfetamina con placebo o una intervención activa.

Obtención y análisis de los datos

Dos autores extrajeron los datos de cada estudio incluido. Se utilizó la diferencia de medias estandarizada (DME) y el cociente de riesgos (CR) para evaluar los resultados continuos y dicotómicos, respectivamente. Se realizó un análisis estratificado para determinar la influencia de las variables moderadoras. Se evaluó el riesgo de sesgo en los ensayos y se realizó un gráfico en embudo (funnel plot) para investigar la posibilidad de sesgo de publicación.

Resultados principales

Se incluyeron siete estudios que reclutaron a 1091 participantes. Todos los estudios fueron controlados con placebo y tres incluyeron un comparador activo: guanfacina, modafinilo y paroxetina. La mayoría de los estudios tuvo un seguimiento a corto plazo, con una duración media del estudio de 8,1 semanas. Las anfetaminas mejoraron la severidad de los síntomas del THDA (DME −0,72; IC del 95%: −0,87 a −0,57) pero no mejoraron la retención general en el tratamiento y se asociaron con una mayor tasa de abandonos debidos a los eventos adversos (CR 3,03; IC del 95%: 1,52 a 6,05). Los tres derivados de la anfetamina que se investigaron (dextroanfetamina, lisdexanfetamina y sales mixtas de anfetamina [SMA]) fueron eficaces para reducir los síntomas del THDA, pero las SMA también aumentaron la retención en el tratamiento. Dosis diferentes no parecieron asociarse con diferencias en la eficacia. Se investigaron formulaciones de liberación inmediata y sostenida del fármaco pero no se encontraron diferencias entre ellas en los resultados. Cuando las anfetaminas se compararon con otras intervenciones farmacológicas no se encontraron diferencias. No se encontraron estudios con bajo riesgo de sesgo general, principalmente porque las anfetaminas tienen efectos subjetivos potentes que pueden revelar el tratamiento asignado.

Conclusiones de los autores

Las anfetaminas mejoraron la severidad de los síntomas del THDA a corto plazo. Las SMA también aumentaron la retención en el tratamiento. Las anfetaminas se asociaron con un mayor desgaste debido a los eventos adversos. La corta duración del estudio y los criterios de inclusión restrictivos limitan la validez externa de estos hallazgos. Además, la posibilidad de que los resultados de los estudios incluidos estuvieran sesgados fue alta, lo que podría haber dado lugar a una sobrestimación de la eficacia de las anfetaminas.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano