Divalproex Loading in the Treatment of Cocaine Dependence
Medical University of South Carolina, Charleston, South Carolina, United States Journal of psychoactive drugs
(Impact Factor: 1.1).
09/2001; 33(3):283-7. DOI: 10.1080/02791072.2001.10400575
The current pilot project was designed to evaluate the safety and tolerability of a loading dose of divalproex (DVPX) in subjects with cocaine dependence. Seventeen cocaine-dependent subjects were enrolled in an eight-week, open-label trial of 20 mg/kg/day DVPX. Subjects were seen weekly and urine drug screens were obtained at each visit. Over the eight-week trial, craving intensity and frequency as well as reported time using cocaine decreased significantly. Retention in the current study was 79% at week four and 50% at week eight. The medication and dosing strategy was well tolerated. This pilot study indicates that DVPX loading is well tolerated and may be efficacious in the treatment of cocaine dependence. A placebo-controlled trial would be of interest.
Available from: Michael P Bogenschutz
- "Its efficacy in preventing withdrawal seizures and DTs is not well established, however. CBZ lacks the abuse potential of benzodiazepines and does not potentiate the depressant effects of alcohol on the central nervous system  . Dizziness, nausea, and vomiting, however, are common side effects, particularly at higher doses . "
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ABSTRACT: Physicians have a growing array of pharmacotherapies available for the treatment of substance use disorders. These medications are of central importance in the treatment of opioid and nicotine dependence and are of growing importance in the treatment of alcohol and stimulant dependence. Pharmacotherapy alone is rarely sufficient treatment for substance use disorder; appropriate psychosocial treatment or mutual help (eg, 12-step) participation is almost always indicated whether or not pharmacotherapy is used. Specialized facilities, licensing, and training are necessary for the use of some of the pharmacotherapies discussed in this article. The obstetrician gynecologist must determine the scope of his or her own practice in this area (ie, when to treat and when to refer) based on interest, training and experience, and available resources.
Available from: José Francisco Navarro
- "Marcada mejoría de los signos y síntomas del síndrome de abstinencia y de la conducta de craving Margolin et al 110 1991 Pemolina 10 (EA) Ausencia de efectos clínicamente relevantes (C + MET) Jenkins et al 111 1992 Gepirona 41 (DC, P) Discreta mejoría tras el tratamiento con gepirona (dosis media de 16,25 mg/día) durante 12 semanas Carroll et al 79 1993 Disulfiram 26 (DC, P) Reducción del consumo de cocaína y alcohol tras el tratamiento con disulfiram Higgins et al 105 1993 Disulfiram 12 (EA) Reducción significativa del consumo de cocaína y alcohol (C + Alc) tras el tratamiento con disulfiram (250 mg) Cornish et al 91 1995 Carbamazepina 82 (DC, P) Ausencia de efectos clínicamente relevantes tras 10 semanas de tratamiento Kranzier et al 92 1995 Carbamazepina 40 (DC, P) Ausencia de efectos clínicamente relevantes tras el tratamiento con carbamazepina (600 mg/día) durante 3 meses Montoya et al 93 1995 Carbamazepina 62 (DC, P) Ausencia de efectos clínicamente relevantes tras el tratamiento con el fármaco durante 8 semanas Grabowski et al 96 1997 Metilfenidato 24 (DC, P) Ausencia de diferencias significativas. Porcentajes de (48 frente a 42%) retención similares en los sujetos tratados con metilfenidato y placebo Johnson et al 112 1997 Ritanserina 65 (DC, P) Ausencia de efectos clínicamente relevantes tras el tratamiento con ritanserina (10 mg/día) durante 10 semanas Carroll et al 104 1998 Disulfiram 40 (DC, P) Reducción del consumo de cocaína y alcohol tras el tratamiento con disulfiram Levin et al 95 1998 Metilfenidato 12 (EA) Reducción significativa del consumo de cocaína y del craving (C+HIP) tras 8 semanas de tratamiento (40-80 mg) McCance et al 103 1998 Disulfiram 7 (DC, P) El disulfiram incrementó las concentraciones plasmáticas de cocaína de 3 a 6 veces, así como las respuestas cardiovasculares asociadas al consumo de cocaína, sin modificar significativamente las respuestas conductuales a la cocaína Myrick et al 88 1998 Ácido valproico 17 (EA) 79% de retención a la cuarta semana y 50% a la octava semana, sin efectos colaterales "
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ABSTRACT: Cocaine abuse is a serious health problem in many areas of the world, yet there are no proven effective medications for the treatment of cocaine dependence. Preclinical studies suggest that the reinforcing effect of cocaine that promotes its abuse is mediated by blockade of the presynaptic dopamine transporter. This results in increased dopamine activity in the mesolimbic or meso-accumbens dopamine reward system of brain. Development of new medications to treat cocaine dependence has focused on manipulation of this dopamine system, either by direct action on dopamine binding sites (transporter or receptors) or indirectly by affecting other neurotransmitter systems that modulate the dopamine system. In principle, a medication could act via one of three mechanisms: (i) as a substitute for cocaine by producing similar dopamine effects; (ii) as a cocaine antagonist by blocking the binding of cocaine to the dopamine transporter; or (iii) as a modulator of cocaine effects by acting at other than the cocaine binding site. The US National Institute on Drug Abuse has a Clinical Research Efficacy Screening Trial (CREST) programme to rapidly screen existing medications. CREST identified four medications warranting phase II controlled clinical trials: cabergoline, reserpine, sertraline and tiagabine. In addition, disulfiram and selegiline (deprenyl) have been effective and well tolerated in phase II trials. However, selegiline was found ineffective in a recent phase III trial. Promising existing medications probably act via the first or third aforementioned mechanisms. Sustained-release formulations of stimulants such as methylphenidate and amfetamine (amphetamine) have shown promise in a stimulant substitution approach. Disulfiram and selegiline increase brain dopamine concentrations by inhibition of dopamine-catabolising enzymes (dopamine-beta-hydroxylase and monoamine oxidase B, respectively). Cabergoline is a direct dopamine receptor agonist, while reserpine depletes presynaptic stores of dopamine (as well as norepinephrine and serotonin). Sertraline, baclofen and vigabatrin indirectly reduce dopamine activity by increasing activity of neurotransmitters (serotonin and GABA) that inhibit dopamine activity. Promising new medications act via the second or third aforementioned mechanisms. Vanoxerine is a long-acting inhibitor of the dopamine transporter which blocks cocaine binding and reduces cocaine self-administration in animals. Two dopamine receptor ligands that reduce cocaine self-administration in animals are also undergoing phase I human safety trials. Adrogolide is a selective dopamine D(1) receptor agonist; BP 897 is a D(3) receptor partial agonist.A pharmacokinetic approach to treatment would block the entry of cocaine into the brain or enhance its catabolism so that less cocaine reached its site of action. This is being explored in animals using the natural cocaine-metabolising enzyme butyrylcholinesterase (or recombinant versions with enhanced capabilities), catalytic antibodies, and passive or active immunisation to produce anti-cocaine binding antibodies. A recent phase I trial of a "cocaine vaccine" found it to be well tolerated and producing detectable levels of anti-cocaine antibodies for up to 9 months after immunisation.
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