Baclofen in the treatment of alcohol use disorder: tailored doses matter.

Aims: To address the question of tailored baclofen prescribing in alcohol use disorder (AUD) in relation to dose-dependent efficacy and the potential danger of high doses and to provide suggestions for the use of high doses of baclofen in the treatment of AUD. The context is the approvement in France of baclofen in the treatment of AUD without dose limitation, making French physicians, who usually prescribe baclofen in a tailored manner, often use high or very high doses.

Methods: A narrative review of the results of randomized controlled trials (RCTs) and observational studies that used tailored baclofen prescribing and of the severe adverse effects of baclofen that have been reported in the literature.

Baclofen in alcohol use disorder: An analysis of the data provided by the French "Temporary Recommendation for Use" 2014-2017 cohort.

Alcohol use disorder (AUD) is a devastating illness for which effective treatments are lacking. Studies over the last two decades have shown that baclofen, a GABA-B agonist, could be a promising treatment for AUD. However, the efficacy of baclofen is still controversial, and studies have shown that it may be associated with an excess of hospitalizations and deaths.

Binge Eating Disorders in Antipsychotic-Treated Patients With Schizophrenia: Prevalence, Antipsychotic Specificities, and Changes Over Time.

Background: Excessive energy intake likely favors metabolic dysfunction in patients with schizophrenia and may be, in part, the consequence of antipsychotic treatments. However, previous studies on the prevalence of bulimia and binge eating symptoms in antipsychotic-treated patients are contradictory and not sufficiently informative.

Methods: The prevalence of bulimia nervosa, binge eating disorder, and subsyndromal binge eating disorder was studied using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria in 156 patients with schizophrenia or schizoaffective disorder treated with antipsychotic monotherapy.

The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective.

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety.

A Review of the Potential Mechanisms of Action of Baclofen in Alcohol Use Disorder.

Baclofen, a GABA-B receptor agonist, is a promising treatment for alcohol use disorder (AUD). Its mechanism of action in this condition is unknown. GABA-B receptors interact with many biological systems potentially involved in AUD, including transduction pathways and neurotransmitter systems.

Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors.

Alcohol and nicotine are the most widely co-abused drugs. Both modify the activity of dopaminergic (DA) neurons of the Ventral Tegmental Area (VTA) and lead to an increase in DA release in the Nucleus Accumbens, thereby affecting the reward system. Evidences support the hypothesis that distinct nicotinic acetylcholine receptors (nAChRs), the molecular target of acetylcholine (ACh) and exogenous nicotine, are also in addition implicated in the response to alcohol.

Striatal and Extrastriatal Dopamine Transporter Availability in Schizophrenia and Its Clinical Correlates: A Voxel-Based and High-Resolution PET Study.

Neuroimaging studies investigating dopamine (DA) function widely support the hypothesis of presynaptic striatal DA hyperactivity in schizophrenia. However, published data on the striatal DA transporter (DAT) appear less consistent with this hypothesis, probably partly due to methodological limitations. Moreover, DAT in extrastriatal regions has been very poorly investigated in the context of schizophrenia.

Colitis possibly induced by quetiapine.

A 39-year-old man with bipolar disorder was hospitalised for depression. He was started on quetiapine (titrated up to 300 mg), lactulose (a laxative) and tropatepine (an anticholinergic). Valpromide (a mood stabiliser) and prazepam were later added and rapidly withdrawn.

The use of very high-doses of baclofen for the treatment of alcohol-dependence: a case series.

Baclofen, particularly high-dose baclofen, has recently emerged as a treatment of major interest for alcohol-dependence. However, baclofen has many potentially dangerous side effects, and the maximal dose of baclofen that may be used is a matter of discussion. Here, the author analyses the medical charts of the last 100 patients seen in his clinic, 17 of whom have been taking a very high dose of baclofen, which is to say, more than 300 mg/day.

[Off-label prescriptions in public psychiatric hospital practice].

Aim: Analyze prescriptions in public hospital psychiatric practice.

Methods: Psychiatric and somatic prescriptions were analyzed a given day regarding their indication, dosage, treatment duration, and prescription scheme. Consultants were individually asked for the reasons of off-label prescriptions.

Suppression of alcohol dependence using baclofen: a 2-year observational study of 100 patients.

Aims: The purpose of this study was to examine the long-term effects of baclofen in a large cohort of alcohol-dependent patients compliant to baclofen treatment.

Methods: A hundred patients with alcohol dependence, resistant to usual treatments, were treated with escalating doses of baclofen (no superior limit). Alcohol consumption (in grams) and craving for alcohol were assessed before treatment and at 3, 6, 12, and 24 months.

Abstinence and 'low-risk' consumption 1 year after the initiation of high-dose baclofen: a retrospective study among 'high-risk' drinkers.

Aims: The aim of the study was to assess the proportions of 'high-risk' drinkers' abstinent or with 'low-risk' consumption levels 1 year after the initiation of high-dose baclofen.

Methods: This is a retrospective 'open' study; the outcome of this study was to assess the level of alcohol consumption in the 12th month of treatment.

Results: Of the 181 patients included, a follow-up evaluation was possible in 132 patients.

Is smoking linked to positive symptoms in acutely ill psychiatric patients?

Background: The self-medication hypothesis is commonly put forward to explain the high prevalence of smoking in psychiatric patients. However, studies supporting the self-medication hypothesis have most often been carried out on chronic patients stabilized by antipsychotics.

Aim: Given that antipsychotics tend to erase psychiatric symptoms, the present study was undertaken on acutely ill patients usually receiving no medications, or on whom medications are ineffective.

Smoke extracts and nicotine, but not tobacco extracts, potentiate firing and burst activity of ventral tegmental area dopaminergic neurons in mice.

Nicotine prominently mediates the behavioral effects of tobacco consumption, either through smoking or when taking tobacco by snuff or chew. However, many studies question the exclusive role of nicotine in these effects. The use of preparations containing all the components of tobacco, such as tobacco and smoke extracts, may be more suitable than nicotine alone to investigate the behavioral effects of smoking and tobacco intake.

Olanzapine-induced accumulation of adipose tissue is associated with an inflammatory state.

Second-generation antipsychotics are widely used in the treatment of all forms of psychoses, but they often produce undesirable side effects, among which are weight gain and other elements of metabolic syndrome. The mechanisms of these adverse effects are not known. The liver and adipose tissue are the principal candidate organs implicated in the development of antipsychotic-induced metabolic adverse effects.

Electrophysiological characterization of harmane-induced activation of mesolimbic dopamine neurons.

It has been suggested that the beta-carbolines harmane and norharmane may be involved in the pathophysiology of Parkinson's disease, psychosis and addiction, but the mechanisms of these possible effects remain to be elucidated. In the present study, the effects of the two compounds were examined by using in vivo extracellular recordings of ventral tegmental dopamine neurons. The effects of harmane (2mg/kg) and norharmane (2mg/kg), were compared to those of nicotine (11microg/kg), of cotinine (0.

"Where do auditory hallucinations come from?"--a brain morphometry study of schizophrenia patients with inner or outer space hallucinations.

Auditory verbal hallucinations are a cardinal symptom of schizophrenia. Bleuler and Kraepelin distinguished 2 main classes of hallucinations: hallucinations heard outside the head (outer space, or external, hallucinations) and hallucinations heard inside the head (inner space, or internal, hallucinations). This distinction has been confirmed by recent phenomenological studies that identified 3 independent dimensions in auditory hallucinations: language complexity, self-other misattribution, and spatial location.

Early perturbation in feeding behaviour and energy homeostasy in olanzapine-treated rats.

Rationale: The antipsychotic drug, olanzapine, often induces weight gain and glucose metabolism disturbances, which may result from feeding pattern abnormalities.

Objectives: The objectives of the study were to examine the effects of a chronic olanzapine treatment on feeding patterns in the rat and to investigate a potential time-related association between feeding patterns and the appearance of glucose metabolism abnormalities and adiposity.

Methods: Male rats were treated with olanzapine (2 mg/kg/day), haloperidol (1 mg/kg/day) or a control solution (drugs mixed with the food).

Chronic intermittent nicotine treatment dose-dependently alters serotonergic neurons response to citalopram in the rat.

Acetylcholine nicotinic systems and serotonergic systems are known to interact. In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons. One hypothesis is that states of functioning of DRN 5-HT neurons (firing rate and sensitivity) vary as a function of nicotine dose and mode of administration during chronic nicotine treatment.

Cortical folding abnormalities in schizophrenia patients with resistant auditory hallucinations.

Gray matter volume and functional abnormalities have been reported in language-related cortex in schizophrenia patients with auditory hallucinations. Such abnormalities might denote abnormal cortical folding development, which can now be investigated using gyrification measures. Anatomic magnetic resonance images (MRIs) were obtained from 30 schizophrenia patients screened for resistant auditory hallucinations and 28 control subjects.

Comparison of self-reports and biological measures for alcohol, tobacco, and illicit drugs consumption in psychiatric inpatients.

Background: Asking psychiatric in-patients about their drug consumption is unlikely to yield reliable results, particularly where alcohol and illicit drug use is involved. The main aim of this study was to compare spontaneous self-reports of drug use in hospitalized psychiatric patients to biological measures of same. A secondary aim was to determine which personal factors were associated with the use of tobacco, alcohol, and illicit drugs as indicated by these biological measures.