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New Pharmacological Treatment Strategies for Relapse Prevention

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Book cover Behavioral Neurobiology of Alcohol Addiction

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 13))

Abstract

Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful—e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies—one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a “cocktail” of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the “treatment-seeking population” will benefit from those developments.

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Notes

  1. 1.

    In a few countries (e.g., Italy), γ-Hydroxybutyric acid (GHB) is a treatment option officially approved by the respective regulatory agencies and a large European trial has been initiated to further test the effectiveness of this drug. However, it should be emphasized that GBH is a street drug categorized as illegal in many countries. Clearly, GBH bears a strong potential to be abused and even in the context of being used as a substitution drug may produce multiple side effects, including the impairment of the immunological status of an abuser (Pichini et al. 2010).

  2. 2.

    Relapse-like behavior in animals is characterized by the ADE. Following a period of alcohol abstinence, animals considerably but temporally increase voluntary alcohol intake as compared to basal consumption levels. Following repeated deprivation phases, the ADE is characterized by an increased and compulsive demand for alcohol that clearly dissociates from normal drinking behavior (Spanagel and Hölter 1999; Vengeliene et al. 2009).

Abbreviations

ADE:

Alcohol deprivation effect

CRH:

Corticotropin-releasing hormone

D3R:

Dopamine D3 receptor

FDA:

Food and Drug Administration

fMRI:

Functional magnetic resonance imaging

GHB:

γ-Hydroxybutyric acid

GWAS:

Genome-wide association study

GlyT:

Glycine transporter

HPA:

Hypothalamic–pituitary–adrenal

KOR:

κ-Opioid receptor

MR:

Magnetic resonance

MOR:

μ-Opioid receptor

NMDA:

N-metlyl-D-aspartat

Per:

Period

RCT:

Randomized controlled trial

RR:

Relative risk

SNP:

Single nucleotide polymorphisms

Ent1:

Type 1 equilibrative nucleoside transporter

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Acknowledgments

This work was supported by the Bundesministerium für Bildung und Forschung (NGFN Plus; FKZ: 01GS08152, FKZ: 01GS08155 see under www.ngfn-alkohol.de and Spanagel et al. 2010; FKZ: 01GS08151) and the Deutsche Forschungsgemeinschaft (DFG): SFB636/Project B1 and D7, Reinhart-Koselleck Award SP 383/5-1, and The Deep Brain Stimulation project SP383/6-1.

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  1. Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Mannheim, Germany

    Rainer Spanagel & Valentina Vengeliene

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  1. Rainer Spanagel
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  2. Valentina Vengeliene
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Correspondence to Rainer Spanagel .

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  1. Abt. Psychopharmakologie, Zentralinstitut für Seelische Gesundheit, J 5, Mannheim, 68159, Germany

    Wolfgang H. Sommer

  2. Abt. Psychopharmakologie, Zentralinstitut für Seelische Gesundheit, J 5, Mannheim, 68159, Germany

    Rainer Spanagel

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Spanagel, R., Vengeliene, V. (2012). New Pharmacological Treatment Strategies for Relapse Prevention. In: Sommer, W., Spanagel, R. (eds) Behavioral Neurobiology of Alcohol Addiction. Current Topics in Behavioral Neurosciences, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28720-6_205

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