Medications Acting on the Serotonergic System for the Treatment of Alcohol Dependent Patients

Purpose of the review This article addresses the question of “best treatment options,” which clinicians face when treating pregnant women with alcohol and/or opioid dependence. Recent findings Alcohol Studies show that alcohol consumption is associated with fetal abnormalities and long-term cognitive problems depending on amount consumed, drinking pattern, and time of gestation. Screening and evaluation of specific interventions are important to reduce alcohol consumption during pregnancy and associated problems in infants. Opioids Withdrawal-induced fetal distress and the risk of relapse are the primary reasons why opioid detoxification is only recommended in the second or third trimesters and only in those pregnant women who refuse opioid maintenance therapy (OMT). Methadone is the most established treatment of pregnant opioid-dependent women, but recent investigations suggest that substitution with buprenorphine may have advantages over methadone in terms of neonatal abstinence syndrome (NAS). Promising results have been also reported for slow-release oral methadone and the heroin equivalent diamorphin. Summary Data regarding the pharmacological treatment of alcohol abuse and/or dependence is limited in pregnant women. So far, benzodiazepines seem to be the most recommendable option for managing alcohol withdrawal, and psychosocial interventions succeed in reducing alcohol consumption or in maintaining abstinence in alcohol-dependent pregnant women. Recent data, albeit preliminary, support the use of naltrexone in the treatment of alcohol-dependent pregnant women. Regarding opioid dependence meta-analyses do not clearly support the superiority of one substitute over the other during pregnancy owing to the presence of interfering factors (such as illicit drug use) in the studies conducted. Current results suggest that factors like the health status of the mother, the need for additional medications (e.g. treatment for HIV), comorbid drug dependence, and concurrent drug use need to be considered in order to find the “best opioid substitute”. Further considerations include the expectant mother’s compliance level to the treatment and the degree to which she tolerates the respective substitute.

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“…disulfiram [59], naltrexone (tablets and intramuscular) [Garbutt, 2010], acamprosate [60], topiramate [61], baclofen [62] and ondansetron [63]. …”

Section: The Treatment Of Alcohol/opioid-dependent Pregnant Womenmentioning

confidence: 99%

The treatment of alcohol and opioid dependence in pregnant women

Heberlein

Leggio

Stichtenoth

et al. 2012

Current Opinion in Psychiatry

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“…Results obtained with 5-HTT inhibitor in alcohol-dependent patients are mixed. These mixed results may be explained by the sub-type of alcohol-dependent patient who is treated and by the fact that alcohol intake is concurrently regulated by interactions of multiple neurotransmitter systems (Kenna, 2010;Pettinati, 2001). The ability to modify the levels of multiple monoamine neurotransmitters may be the key to treating alcoholism in a broader population.…”

Section: Introductionmentioning

confidence: 99%

Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats

O'Brien

Legastelois

Houchi

et al. 2011

Neuropsychopharmacol

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A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5-40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment.

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“…topiramate, ondansetron, baclofen, and others) are also under investigation and hold significant promise. While other articles in this special issue review many of these medications [10][11][12][13][14][15][16] the aim of this review is to summarize recent research, which attempts to identify new future neuropharmacological targets. These novel targets may eventually lead to the development of new medications for AD.…”

Section: Introductionmentioning

confidence: 99%

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Leggio¹,

Cardone²,

Ferrulli³

et al. 2010

curr pharm des

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Treating alcohol use disorders represents a main goal in public health, but the effect of current medications is modest. Thus, in the last few years, research has been focusing on identifying new neuropharmacological targets for alcohol dependence. This review will summarize recent research, which has identified new targets to treat alcohol dependence. A variety of systems have been investigated, such as the endocannabinoid system, modulators of glutamatergic transmission, corticotropin-releasing factor (CRF), neuropeptide Y (NPY), nociceptin, glial cell line-derived neurotrophic factor (GDNF), acetaldehyde (ACD), substance P and Neurokinin 1 (NK1) receptor, nicotinic acetylcholine receptors (nAchRs), alpha-adrenergic receptor, and many others. Compared to preclinical studies, only a few clinical studies have been conducted so far. Thus, there is a critical need to translate successful preclinical results into human clinical trials. However, since some clinical studies have failed to replicate preclinical findings, future research will have not only to identify more efficacious medications, but also delineate the best match between a particular pharmacotherapy with a specific alcoholic subtype.

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Medications Acting on the Serotonergic System for the Treatment of Alcohol Dependent Patients

Cited by 51 publications

References 83 publications

The treatment of alcohol and opioid dependence in pregnant women

The treatment of alcohol and opioid dependence in pregnant women

Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

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