A Comparison of Aripiprazole, Methylphenidate, and Placebo for Amphetamine Dependence

Tiihonen, Jari; Kuoppasalmi, Kimmo; Föhr, Jaana; Tuomola, Pekka; Kuikanmäki, Outi; Vorma, Helena; Sokero, Petteri; Haukka, Jari; Meririnne, Esa

doi:10.1176/ajp.2007.164.1.160

Cited by 127 publications

(119 citation statements)

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“…However, a recent clinical trial for amphetamine dependence was terminated early because the aripiprazole group showed greater amphetamine use than those receiving placebo (Tiihonen et al 2007), which appears consistent with the human laboratory findings with cocaine.…”

Section: Clinical Trialmentioning

confidence: 60%

Controversies in translational research: drug self-administration

2008

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Rationale Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable. Objective The objective of this study was to track how antagonist, agonist, and partial agonist medication approaches influence heroin and cocaine self-administration by rodents, non-human primates, and humans and to compare these results to clinical outcomes. Results Across species, heroin self-administration was decreased by all three medication approaches, paralleling their demonstrated clinical utility. The heroin data emphasize the importance of assessing a medication's abuse liability preclinically to predict medication abuse and compliance and of considering subject characteristics (e.g., opioid dependence) when interpreting medication effects. For cocaine, the effects of ecopipam, modafinil, and aripiprazole were consistent in the laboratory and clinic, provided that the medications were administered repeatedly before self-administration sessions. Modafinil attenuated cocaine's reinforcing effects in the human laboratory and improved treatment outcome, while ecopipam and aripiprazole increased the reinforcing effects of cocaine and do not appear promising in the clinic. Conclusions The self-administration model has reliably identified medications to treat opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence. There have been numerous false positives when subjective effects are the primary outcome measure, but not when self-administration is the outcome. Factors relevant to the predictive validity of self-administration procedures include medication maintenance and the concurrent assessment of a range of behaviors to determine abuse liability and the specificity of effect.Keywords Cocaine . Opioid . Naloxone . Dopamine receptor . Drug abuse . Model . Monkey . Human . Reinforcement Laboratory testing of potential pharmacotherapies for drug abuse is an essential component of medication development. Although well-designed clinical trials are the standard by which the efficacy of a new medication is assessed, clinical trials test the effects of a potential treatment medication on a broad sample of patients, which is both costly and potentially risky. Before exposing a large number of treatment seekers to a medication, there needs to be both a strong scientific rationale for combining the medication with a drug of abuse as well as a demonstration that the co-administration of the medication and the abused drug is safe and selectively modifies the behavior of interest: drug taking.Models of drug self-administration in rodents, nonhuman primates, and humans have been used to evaluate the effects of candidate medications for the treatment of drug dependence. The self-administration model provides Psychopharmacology (2008) meaningful behavioral data on the safety and efficacy of potentia...

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Section: Clinical Trialmentioning

confidence: 60%

Controversies in translational research: drug self-administration

2008

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“…Preclinical data suggest that methylphenidate is capable of attenuating the effects of high doses of methamphetamine on the DA transporter (Sandoval et al, 2003). Indeed, early pilot clinical data on methylphenidate in heavy users of intravenous amphetamines showed promising results in reducing their amphetamine use (Tiihonen et al, 2007). Data from the interim analysis of a trial of D-amphetamine in Australia suggest that it may be beneficial for methamphetaminedependent patients (Wickes et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Bupropion for the Treatment of Methamphetamine Dependence

Elkashef

Rawson

Anderson

et al. 2007

Neuropsychopharmacol

199

188

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Bupropion was tested for efficacy in increasing weeks of abstinence in methamphetamine-dependent patients, compared to placebo. This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 30-day follow-up. Five outpatient substance abuse treatment clinics located west of the Mississippi participated in the study. One hundred and fifty-one treatment-seekers with DSM-IV diagnosis of methamphetamine dependence were consented and enrolled. Seventy-two participants were randomized to placebo and 79 to sustained-release bupropion 150 mg twice daily. Patients were asked to come to the clinic three times per week for assessments, urine drug screens, and 90-min group psychotherapy. The primary outcome was the change in proportion of participants having a methamphetamine-free week. Secondary outcomes included: urine for quantitative methamphetamine, self-report of methamphetamine use, subgroup analyses of balancing factors and comorbid conditions, addiction severity, craving, risk behaviors for HIV, and use of other substances. The generalized estimating equation regression analysis showed that, overall, the difference between bupropion and placebo groups in the probability of a non-use week over the 12-week treatment period was not statistically significant (p ¼ 0.09). Mixed model regression was used to allow adjustment for baseline factors in addition to those measured (site, gender, level of baseline use, and level of symptoms of depression). This subgroup analysis showed that bupropion had a significant effect compared to placebo, among male patients who had a lower level of methamphetamine use at baseline (po0.0001). Comorbid depression and attention-deficit/ hyperactivity disorder did not change the outcome. These data suggest that bupropion, in combination with behavioral group therapy, was effective for increasing the number of weeks of abstinence in participants with low-to-moderate methamphetamine dependence, mainly male patients, regardless of their comorbid condition.

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“…Grabowski and colleagues suggested that because methylphenidate had more peripheral than central nervous system effects, it may not have been an adequate reinforcer for cocaine. A recent study compared methylphenidate (54 mg/day sustained release), aripiprazole (a novel partial dopamine receptor agonist) and placebo in dependent amphetamine injectors [62]. The study was terminated early, as the aripiprazole study arm had significantly worse outcomes than the placebo arm.…”

Section: Indirect Dopamine Agonists For Psychostimulant Dependencementioning

confidence: 99%

The principles of agonist pharmacotherapy for psychostimulant dependence

Shearer

2008

Drug and Alcohol Review

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Issues. Psychostimulant dependence is a chronic, relapsing condition which is highly treatment refractory. No medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Agonist strategies have attracted limited attention. Approach. Successful examples of agonist pharmacotherapy in the treatment of heroin and nicotine dependence are first considered. Agonist pharmacological approaches to the treatment of psychostimulant dependence are then examined, based on the dopamine receptor agonist and indirect dopamine agonist strategies. Finally, the potential extension of the concept of agonist pharmacotherapy to include the novel non-amphetamine-type stimulant, modafinil, is discussed. Conclusions. Agonist approaches appear to be viable with risks outweighed by benefits in carefully selected, monitored and motivated patients. On the other hand, the effectiveness of indirect agonists such as dexamphetamine and methylphenidate are not established. Further research is required to determine optimal treatment models (whether maintenance or withdrawal), effective safe dosages and duration (short or long term). [Shearer J. The principles of agonist pharmacotherapy for psychostimulant dependence. Drug Alcohol Rev 2008;27:301-308]

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A Comparison of Aripiprazole, Methylphenidate, and Placebo for Amphetamine Dependence

Abstract: Methylphenidate is an effective treatment for reducing intravenous drug use in patients with severe amphetamine dependence.

Cited by 127 publications

References 6 publications

Controversies in translational research: drug self-administration

Controversies in translational research: drug self-administration

Bupropion for the Treatment of Methamphetamine Dependence

The principles of agonist pharmacotherapy for psychostimulant dependence

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