Comparison of Amantadine and Desipramine Combined with Psychotherapy for Treatment of Cocaine Dependence

Weddington, William W.; Brown, Barry S.; Haertzen, Charles A.; Hess, Judith M.; Mahaffey, Joan R.; Kolar, Anne F.; Jaffe, Jerome H.

doi:10.3109/00952999108992817

Cited by 129 publications

(43 citation statements)

References 29 publications

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“…For example, cocaine withdrawal in humans in the outpatient setting is characterized by severe depressive symptoms combined with irritability, anxiety, and anhedonia lasting several hours to several days (i.e., the "crash") and may be one of the motivating factors in the maintenance of the cocaine-dependence cycle (Gawin and Kleber, 1986). Inpatient studies have shown similar changes in mood and anxiety states, but they generally are much less severe (Weddington et al, 1991 ). Opiate withdrawal is characterized by severe dysphoria, and ethanol withdrawal produces dysphoria and anxiety.…”

Section: Neural Substrates For the Negative Reinforcement Associated mentioning

confidence: 82%

Drug addiction: Functional neurotoxicity of the brain reward systems

Weiss

Koob

2001

neurotox res

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Drug addiction is a chronic relapsing brain disorder characterized by a compulsion to take a drug with loss of control over drug intake. The hypothesis under discussion here is that chronic drug use produces long-lasting dysfunctions in neurons associated with the brain reward circuitry, and this "functional neurotoxicity" of drugs of abuse leads to vulnerability to relapse and continued drug dependence. Several sources of reinforcement are associated with various components of the drug addiction cycle and much progress has been made in identifying the midbrain-basal forebrain neural elements involved in the positive reinforcing effects of drugs of abuse and more recently in the neural elements involved in the negative reinforcement associated with drug addiction. Key elements for the acute reinforcing effects of drugs of abuse include a macrostructure in the basal forebrain called the extended amygdala that contains parts of the nucleus accumbens and amygdala and involves key neurotransmitters such as dopamine, opioid peptides, serotonin, GABA, and glutamate. Withdrawal from drugs of abuse is associated with subjective symptoms of negative affect and dysregulation of brain reward systems involving some of the same neurochemical systems implicated in the acute reinforcing effects of drugs of abuse. In addition, the functional toxicity of acute withdrawal is accompanied by recruitment of the brain stress neurotransmitter system corticotrophin-releasing factor. During more prolonged abstinence, post-acute withdrawal, evidence is accumulating of continued dysregulation of the neural systems associated with drug reinforcement and stress, regulation that may represent more subtle but persistent functional neurotoxic effects of chronic drug use and could be responsible for long-lasting vulnerability to relapse. Such functional neurotoxicity could be hypothesized to lead to a change in set point for drug reward that may represent an allostatic state contributing to vulnerability to relapse and re-entry into the addiction cycle. Elucidation of the specific neuropharmacological changes contributing to this prolonged functional neurotoxicity will be the challenge of future research on the neurobiology of drug addiction.

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Section: Neural Substrates For the Negative Reinforcement Associated mentioning

confidence: 82%

Drug addiction: Functional neurotoxicity of the brain reward systems

Weiss

Koob

2001

neurotox res

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“…For example, cocaine withdrawal in humans in the outpatient setting is characterized by severe depressive symptoms combined with irritability, anxiety, and anhedonia lasting several hours to several days (i.e., the "crash") and may be one of the motivating factors in the maintenance of the cocaine-dependence cycle (Gawin and Kleber 1986). Inpatient studies of cocaine withdrawal in cocaine-dependent subjects have shown similar changes in mood and anxiety states, but they generally are much less severe (Weddington et al 1991). Opiate withdrawal is characterized by severe dysphoria, and alcohol withdrawal produces pronounced dysphoria and anxiety.…”

Section: Motivational Components Of Withdrawalmentioning

confidence: 99%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,541

1,962

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This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drugtaking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop. The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to BACKGROUNDDrug addiction is a chronically relapsing disorder that is defined by two major characteristics: a compulsion to take the drug with a narrowing of the behavioral repertoire toward excessive drug intake, and a loss of control in limiting intake (American Psychiatric Association 1994; World Health Organization 1992). An important challenge for neurobiological research is to understand the neuroadaptive differences between controlled drug use and loss of control, and by extension, the molecular, cellular and system processes that lead to addiction (Koob and Le Moal 1997).Animal models are critical for understanding the neuropharmacological mechanisms involved in the development of addiction. While there are no complete animal models of addiction, animal models do exist for many elements of the syndrome. These elements can be derived from symptoms or diagnostic criteria for addiction or conceptual frameworks such as different sources of reinforcement (American Psychiatric Association 1994; World Health Organization 1992). Linking neu- 24 , NO . 2 ropharmacological events to animal models can occur at multiple levels of analysis -molecular, cellular and system -and it will only be the integration of these changes across dimensions of analysis that will allow a full understanding of the neurobiology of drug addiction.Advances in neuroscience research are rapidly unr...

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“…Therapeutic effects of antidepressants in cocainedependent patients have been examined in several trials, with mostly disappointing results. [10][11][12][13][14][15][16][17][18] Nevertheless, compelling reasons exist to consider such agents. Although cocaine is a potent dopamine reuptake blocker, longterm use is associated with down-regulation of dopaminergic systems.…”

Section: Discussionmentioning

confidence: 99%

Six-Month Trial of Bupropion With Contingency Management for Cocaine Dependence in a Methadone-Maintained Population

Poling¹,

Oliveto²,

Petry³

et al. 2006

Arch Gen Psychiatry

155

142

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Context:No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy.Objective: To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals.Design: This 25-week, placebo-controlled, doubleblind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB).Setting: Outpatient clinic at the Veterans Affairs Connecticut Healthcare System. Participants: A total of 106 opiate-dependent, cocaineabusing individuals.Interventions: All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study.Main Outcome Measure: Thrice-weekly urine toxicologic test results for cocaine and heroin.Results: Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (PϽ.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (PϽ.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (PϽ.001). In contrast, by treatment end, the VCB and VCP groups showed no significant improvement in cocaine use. Conclusion:These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone.

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Comparison of Amantadine and Desipramine Combined with Psychotherapy for Treatment of Cocaine Dependence

Cited by 129 publications

References 29 publications

Drug addiction: Functional neurotoxicity of the brain reward systems

Drug addiction: Functional neurotoxicity of the brain reward systems

Drug Addiction, Dysregulation of Reward, and Allostasis

Six-Month Trial of Bupropion With Contingency Management for Cocaine Dependence in a Methadone-Maintained Population

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