Article

A systematic review of modafinil: Potential clinical uses and mechanisms of action.

Department of Psychiatry, University of California, San Diego, CA, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.14). 05/2006; 67(4):554-66. DOI: 10.4088/JCP.v67n0406
Source: PubMed

ABSTRACT Modafinil is a novel wake-promoting agent that has U.S. Food and Drug Administration approval for narcolepsy and shift work sleep disorder and as adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. Modafinil has a novel mechanism and is theorized to work in a localized manner, utilizing hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate. It is a well-tolerated medication with low propensity for abuse and is frequently used for off-label indications. The objective of this study was to systematically review the available evidence supporting the clinical use of modafinil.
The search term modafinil OR Provigil was searched on PubMed. Selected articles were mined for further potential sources of data. Abstracts from major scientific conferences were reviewed. Lastly, the manufacturer of modafinil in the United States was asked to provide all publications, abstracts, and unpublished data regarding studies of modafinil.
There have been 33 double-blind, placebo-controlled trials of modafinil. Additionally, numerous smaller studies have been performed, and case reports of modafinil's use abound in the literature.
Modafinil is a promising drug with a large potential for many uses in psychiatry and general medicine. Treating daytime sleepiness is complex, and determining the precise nature of the sleep disorder is vital. Modafinil may be an effective agent in many sleep conditions. To date, the strongest evidence among off-label uses exists for the use of modafinil in attention-deficit disorder, postanesthetic sedation, and cocaine dependence and withdrawal and as an adjunct to antidepressants for depression.

Full-text

Available from: Jacob Seth Ballon, Jun 27, 2014
1 Follower
 · 
328 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cocaine, already a significant drug problem in North and South America, has become a more prominent part of the European drug scene. Cocaine dependence has major somatic, psychological, psychiatric, socio-economic, and legal implications. No specific effective pharmacological treatment exists for cocaine dependence. Recent advances in neurobiology have identified various neuronal mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Data were obtained from Medline, EMBASE, and PsycINFO searches of English-language articles published between 1985 and June 2007 using the key words: cocaine, addiction, cocaine dependence, clinical trials, pharmacotherapy(ies) singly and in combination. Large well-controlled studies with appropriate statistical methods were preferred. Pharmacological agents such as GABA agents (topiramate, tiagabine, baclofen and vigabatrin) and agonist replacement agents (modafinil, disulfiram, methylphenidate) seem to be the most promising in treatment of cocaine dependence. The results from trials of first- and second-generation neuroleptics are largely negative. Aripiprazole, a partial dopaminergic agonist that may modulate the serotonergic system, shows some promise. Preliminary results of human studies with anti-cocaine vaccine, N-acetylcysteine, and ondansetron, are promising, as are several compounds in preclinical development. While no medication has received regulatory approval for the treatment of cocaine dependence, several medications marketed for other indications have shown efficacy in clinical trials. An anti-cocaine vaccine and several compounds in preclinical development have also shown promise. Findings from early clinical trials must be confirmed in larger, less selective patient populations.
    The International Journal of Neuropsychopharmacology 06/2008; 11(3):425-38. DOI:10.1017/S1461145707008097 · 5.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nicotine deprivation symptoms, including fatigue and attentional deficits, predict relapse following smoking cessation. Modafinil (Provigil), a wakefulness medication shown to have efficacy for the treatment of cocaine addiction, was tested as a novel therapy for nicotine dependence in a double-blind placebo-controlled trial. One hundred and fifty-seven treatment-seeking smokers received brief smoking cessation counseling and were randomized to: (1) 8 weeks of modafinil (200mg/day), or (2) 8 weeks of placebo. The primary outcome was biochemically verified 7-day point prevalence abstinence at the end of treatment (EOT). Secondary outcomes included cigarette smoking rate and post-quit nicotine deprivation symptoms (e.g., negative affect, withdrawal). In this interim study analysis, EOT quit rates did not differ between treatment arms (42% for placebo vs. 34% for modafinil; OR=0.67 [0.34-1.31], p=0.24). Further, from the target quit date to EOT, the daily smoking rate was 44% higher among non-abstainers in the modafinil arm, compared to non-abstainers in the placebo arm (IRR=1.44, CI95=1.09-1.89, p<0.01). Modafinil-treated participants also reported greater increases in negative affect and withdrawal symptoms, vs. participants randomized to placebo (ps<0.05). These data do not support the use of modafinil for the treatment of nicotine dependence and, as a consequence, this trial was discontinued. Cigarette smoking should be considered when modafinil is prescribed, particularly among those with psychiatric conditions that have high comorbidity with nicotine dependence.
    Drug and Alcohol Dependence 06/2008; 98(1-2):86-93. DOI:10.1016/j.drugalcdep.2008.04.008 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cocaine is more and more used and abused in France. Cocaine dependence is quite serious and is associated with numerous adverse health consequences. No effective pharmacotherapy for cocaine dependence is yet available. Recent advances in neurobiology, brain imaging and some clinical trials suggest that certain medications that modulate GABAergic, dopaminergic, and glutamatergic systems, as well as immunotherapy, show promise in the treatment of cocaine addiction. Recent controlled clinical studies have tested some of these drugs, which act on the various neurobiological circuits modified by cocaine exposure and clinically improve patients' symptoms. Pharmacological agents such as modafinil, GABAergic agents (baclofen, topiramate, tiagabin, and vigabatrin), disulfiram, aripiprazole, N-acetylcysteine and cocaine vaccine seem very promising in the treatment of cocaine dependence. However, this must be confirmed in larger patient populations.
    La Presse Médicale 05/2008; 37(4 Pt 2):689-98. DOI:10.1016/j.lpm.2007.08.015 · 1.17 Impact Factor