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Biological Approaches
Published in Tricia L. Chandler, Fredrick Dombrowski, Tara G. Matthews, Co-occurring Mental Illness and Substance Use Disorders, 2022
Tricia L. Chandler, Mary C. Hoke, Tara G. Matthews, Elizabeth Reyes-Fournier
Acamprosate is prescribed for alcohol dependence treatment: namely, the maintenance of alcohol abstinence. Acamprosate works by reducing excitatory glutamate neurotransmission and increases inhibitory gamma-aminobutyric acid (GABA) neurotransmission. Because alcohol withdrawal can lead to excessive glutamate activity and deficient GABA activity, Acamprosate can act as an ‘artificial alcohol’ to mitigate these effects (Stahl, 2017). Side effects, though uncommon, can include nausea, anxiety, and depression. Acamprosate has been found to be effective primarily when used to decrease cravings for alcohol following detoxification (Schatzberg & Nemeroff, 2013).
Improving the Old, Embracing the New: Implications of Alcohol Research for Future Practice
Published in Gary Rosenberg, Weissman Andrew, Behavioral and Social Sciences in 21st Century Health Care: Contributions and Opportunities, 2021
Acamprosate is a drug that was first developed in Europe. Although it appears to accomplish the same end, it works on a very different principle than naltrexone. In a very interesting rat model, rats are allowed to drink alcohol for a number of months (usually 6–8). These rats are then deprived of alcohol for different periods of time. When the rats are allowed to resume drinking alcohol, the animals double and triple their consumption. (These animals are “standard issue” in that they are not bred for alcohol preference or any other known effect.) In Europe they call this effect the “Alcohol Deprivation Effect.” This kind of an effect is blocked by acamprosate. Unlike naltrexone, acamprosate does not work on the opiate receptor. Acamprosate was originally thought to work on the gamma-aminobutyric acid (GABA) receptor, the brain’s major inhibitory neurotransmitter. Evidence now suggest that it actually works in the glutamate receptor, the brain’s major excitatory receptor and on the NMDA receptor. The European results on Acamprosate were very similar to those found in the U.S. with naltrexone; about twice as many people did well with Acamprosate as they did with placebo. They also found, as with naltrexone in the U.S., that the medication’s effectiveness was as an adjunct to competent behavioral therapy, not as a single treatment. Lipha pharmaceuticals has just completed a national trial in the U.S., which involved many of our top-notch clinical research grantees. Lipha will use the results of this trial to apply for an FDA approval for acamprosate.
Alcohol Pharmacology and Pharmacotherapy of Alcoholism
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Aman Upaganlawar, Sindhu Ramesh, Ellery Jones, Vishnu Suppiramaniam, Timothy Moore, Muralikrishnan Dhanasekaran
Acamprosate is an analog of GABA (Plosker, 2015), which mainly acts by stabilizing the neurotransmitters equilibrium in the brain, which is altered in chronic alcoholics (Williams, 2005). The primary mechanism is through a weak NMDA-receptor antagonist activity as its bind to polyamine site and as a GABAA activator (Naassila et al., 1998). Additionally, it decreases the elevated glutamate levels as well as inhibits metabotropic glutamate receptor 5 (mGlur5). Acamprosate at a dose of 1.3–2 g/day reduces rate of drinking as well as relapse in those abstinent. Most common side effect is diarrhea, yet abuse liability is not noted. Acamprosate with psychosocial interventions have shown potential improvements in alcohol consumption outcomes (Plosker, 2015). Increase efficacy of acamprosate is demonstrated when given besides disulfiram with no adverse drug interactions (Besson et al., 1998).
Resveratrol impairs acquisition, reinstatement and precipitates extinction of alcohol-induced place preference in mice
Published in Neurological Research, 2021
The current treatment approaches commonly used for chronic alcoholism include psychotherapy (e.g. counseling) and pharmacotherapy (i.e. disulfiram, naltrexone, and acamprosate) [21]. Acamprosate is the United States Food and Drug Administration approved drug for the treatment of alcohol addiction that is only effective in certain patients, unfortunately [25]. Acamprosate probably affects the NMDA receptor antagonist and acts as an agonist of GABA receptors [26,27]. However, the most common side effects were listed in patients receiving acamprosate involving headache, diarrhea, nausea, and flatulence [26]. Hence, there is a need to develop new pharmacological agents with low side effect profiles for the treatment of alcohol addiction. Taking into account the considerable side effect potentials of the current drugs, resveratrol could be considered as an adjunct agent for the treatment of alcohol addiction.
Pharmacotherapeutic management of co-morbid alcohol and opioid use
Published in Expert Opinion on Pharmacotherapy, 2020
Lauren E. Hood, Jonna M. Leyrer-Jackson, M. Foster Olive
A review by Rosner and colleagues found acamprosate to be drug to a safe and effective treatment for maintaining abstinence in dependent patients after alcohol detoxification [110]. This meta-analysis showed that acamprosate significantly increased the duration of abstinence and decreased drinking levels across the trials in this review and others [110,111]. Acamprosate has also been found to ameliorate alcohol-induced disturbances in sleep patterns [112], and has no documented abuse potential or ill effects from overdoses [113]. The most common side effects associated with acamprosate use include gastrointestinal distress, headaches and dizziness. Acamprosate is not metabolized and is excreted via the kidneys, and is thus contraindicated in patients with renal insufficiency [113]. When comparing the efficacy of acamprosate to other AUD treatments such as naltrexone, specific outcome measures and recovery circumstances appear to play an important role. A meta-analysis investigating when a particular treatment is most helpful found that while naltrexone was more successful in reducing cravings and occurrences of heavy drinking, acamprosate was more efficacious for promoting abstinence [111]. However, the large multi-site COMBINE study revealed that acamprosate was not superior to placebo in reducing average number of drinking days or time to first heavy drinking day [114]. Thus, the clinical efficacy of acamprosate in treating AUD should be considered moderate at best.
Management of insomnia in alcohol use disorder
Published in Expert Opinion on Pharmacotherapy, 2020
Pierre A. Geoffroy, Michel Lejoyeux, Benjamin Rolland
Acamprosate shows efficacy in maintaining abstinence in newly detoxified patients by a suggested modulation of neuronal hyperexcitability mainly by actions on the glutamate excitatory neurotransmission [76]. A first RCT study assessed by polysomnographic recordings, in 24 men with AUD, effects of 2 tablets of 333 mg acamprosate vs placebo, three times daily [77]. Acamprosate was initiated 8 days before alcohol withdrawal and continued during the 15 days following alcohol withdrawal. Acamprosate, compared to placebo, improved sleep architecture by decreasing wake time after sleep onset and increasing stage 3 and REM sleep latency. Regarding withdrawal effects, whereas no significant treatment x withdrawal effect was observed, acamprosate improved sleep efficiency and total sleep time [77]. A later large RCT in 592 patients with AUD (292 completed the 6-month trial), authors observed that 40.2% of them had sleep disturbances at baseline, decreasing to 26.1% after 6 months in the placebo group and 19.5% in the acamprosate group, with a significant difference between groups. Finally, a recent individual patient data meta-analysis, selecting all the randomized trials of acamprosate in which insomnia was documented, found 12 studies including 3508 patients and concluded that, after 6-month follow-up, insomnia symptoms decrease spontaneously with abstinence but more frequently with acamprosate treatment (decrease of −26% for placebo versus −45% for acamprosate) [78]. Taken as a whole, acamprosate seems to be efficient as a preventive treatment to lessen sleep disturbances during alcohol withdrawal.