fluvoxamine and Alcoholism

European Medicines Agency guidelines recognize two different treatment goals for alcohol dependence: abstinence and reduction in alcohol consumption. All currently approved agents are indicated for abstinence. This systematic review aimed to identify drugs in development for alcohol dependence treatment and to establish, based upon trial design, if any are seeking market authorization for reduction in consumption.. We searched PubMed and Embase (December 2001-November 2011) to identify agents in development for alcohol dependence treatment. Additional studies were identified by searching ClinicalTrials.gov and the R&D Insight and Clinical Trials Insight databases. Studies in which the primary focus was treatment of comorbidity, or n≤20, were excluded. Studies were then classified as 'abstinence' if they: described a detoxification/alcohol withdrawal period; enrolled patients who had undergone detoxification previously; or presented relapse/abstinence rates as the primary outcome. Studies in patients actively drinking at baseline were classified as 'reduction in consumption'.. Of 602 abstracts identified, 45 full-text articles were eligible. Five monotherapies were in development for alcohol dependence treatment: topiramate, fluvoxamine, aripiprazole, flupenthixol and nalmefene. Nalmefene was the only agent whose sponsor was clearly seeking definitive approval for reduction in consumption. Development status was unclear for topiramate, fluvoxamine, aripiprazole and flupenthixol. Fifteen agents were examined in published exploratory investigator-initiated trials; the majority focused on abstinence. Ongoing (unpublished) trials tended to focus on reduction in consumption.. While published studies generally focused on abstinence, ongoing trials focused on reduction in consumption, suggesting a change in emphasis in the approach to treating alcohol dependence.

Topics: Alcohol Abstinence; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Aripiprazole; Flupenthixol; Fluvoxamine; Fructose; Humans; Naltrexone; Piperazines; Psychotropic Drugs; Quinolones; Topiramate

Preclinical and clinical studies demonstrated an inverse relationship between serotonergic activity and alcohol consumption. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, citalopram, and fluvoxamine have subsequently been examined for their ability to reduce alcohol consumption in alcoholic subjects. Interindividual variability in response to SSRIs is large, with reductions in alcohol consumption ranging from 10% to more than 70%. Several factors, including gender, alcoholic subtype, and extent of drinking, appear to affect the treatment efficacy of the SSRIs. A significant challenge for researchers is to identify the subject variables that predict treatment response, providing a basis for guiding alcohol-dependent individuals to the treatment that is most likely to be effective for them. This article reviews the available clinical studies, discusses possible mechanisms of action for the SSRIs, and describes a model for predicting treatment responses in alcoholic subjects.

Topics: Alcohol Drinking; Alcoholism; Animals; Behavior, Addictive; Behavior, Animal; Citalopram; Clinical Trials as Topic; Comorbidity; Drinking Behavior; Drug Evaluation, Preclinical; Fluoxetine; Fluvoxamine; Humans; Mice; Rats; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

To review the respective pharmacologic profiles of the selective serotonin reuptake inhibitors (SSRIs), with particular emphasis placed on clinically relevant distinctions.. A MEDLINE search was conducted to identify English language literature published within the last five years on the four SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine). Previous review articles were scrutinized for additional citations, and manufacturers provided a contemporary bibliography of more recent material.. Studies were selected for specific citation on the basis of comparative research merit and the contribution of this original literature to the pharmacologic profile(s) described.. All SSRIs appear to be more efficacious than placebo for the acute treatment of major depressive disorder (MDD). Short-term (six-week) efficacy was comparable with that of tricyclic antidepressants for the amelioration of MDD regarded as moderate in severity. Further comparative trials are clearly indicated to demonstrate the therapeutic benefits of SSRIs in specific populations (e.g., geriatric, severely ill) and to demonstrate sustained benefit with long-term prophylaxis. Other potential indications for SSRIs include obsessive-compulsive disorder, panic disorder, bulimia, and chronic pain syndromes. Pharmacokinetic profiles of the four SSRIs reveal similar parametric values, and most quantitative differences are of limited clinical significance. Adverse effects are common but ordinarily mild and transient, primarily restricted to the gastrointestinal tract and central nervous system. Important differences in the prevalence or severity of these adverse effects await the accumulation of further clinical experience and the completion of additional comparative trials. Similarly, the relative propensity of SSRIs to inhibit the metabolism of other medications is currently under investigation.. The four SSRIs studied appear to be more similar than they are different. Slowly, important distinctions are beginning to emerge with regard to adverse effect profiles and potential drug interactions. Given that the costs of these respective medications are comparable, such differences may ultimately serve to establish the preferential selection of individual agents in specific clinical situations.

Topics: 1-Naphthylamine; Alcoholism; Antidepressive Agents; Anxiety Disorders; Clinical Trials as Topic; Depressive Disorder; Drug Interactions; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline

There has been much recent interest in the pharmacological manipulation of alcohol intake and alcohol seeking behaviour. An effective drug treatment could form an important part of a multi-modal treatment programme and could make controlled drinking more of a reality. In animal models the serotonin reuptake inhibitors, including fluvoxamine, have been consistently shown to reduce alcohol consumption, even in alcohol-preferring rat strains. Clinical studies have shown that these specific serotonin reuptake inhibitors may also be useful in significantly reducing the alcohol intake of a group of early stage problem drinkers. Although there are many possible mechanisms, the most likely mechanism to explain this mode of action of these specific serotonin antidepressants is that the serotonin enhancement they produce reduces the positive reinforcement properties of alcohol and thereby produces an anti-craving effect. These studies now need to be replicated, with particular attention being given to those patients who fulfil the criteria of the alcohol dependence syndrome. Such an ongoing study with fluvoxamine will be described.

Topics: Alcohol Drinking; Alcoholism; Combined Modality Therapy; Fluvoxamine; Follow-Up Studies; Humans

Alcoholism is a multifaceted medicosocial problem. Recent literature discusses a common dyad, alcoholism and anxiety. Both disorders are interdigitated with the brain amine serotonin (5-hydroxytryptamine, 5-HT). Direct 5-HT activation reportedly attenuates alcohol consumption, whereas depletion enhances use patterns. Acute alcohol consumption has also been associated with a transient rise, albeit eventual diminished 5-HT turnover. A variety of 5-HT models have confirmed this observation, e.g., reduced platelet 5-HT content, uptake, and cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid. Such altered characteristics of 5-HT secondary to chronic alcohol use may explain the frequent morbidity of anxiety and/or depression. Acute alcohol consumption is also associated with accumulation of the 5-HT aldehyde derivative 5-hydroxymethtryptoline. Thus, alcohol may induce the in vivo formation of aldehydes, e.g., beta-carbolines, that themselves possess high lipophilicity and psychotropic activity. Future investigation into 5-HT-specific pharmacologic probes in alcoholism will be interesting. Preliminary research has consistently demonstrated that 5-HT-enhancing agents (e.g., zimelidine or fluvoxamine) decrease alcohol consumption, preference, and short-term memory decrements. Thus, 5-HT appears to represent at least one common denominator for a spectrum of behavioral disorders including anxiety and alcoholism.

Topics: Alcohol Drinking; Alcoholism; Animals; Anti-Anxiety Agents; Anxiety Disorders; Arousal; Brain; Fluvoxamine; Humans; Oximes; Receptors, Serotonin; Serotonin; Zimeldine

Assess the efficacy and safety of fluvoxamine, sertraline, citalopram, paroxetine, fluoxetine.. The study included 175 patients with alcohol dependence and depressive disorders. 161 had a diagnosis Alcohol Dependence Syndrome (ADS); 14 patients had a «dual diagnosis». All patients were randomized into 5 groups according to the drugs received. To assess the therapeutic efficacy of drugs, the following scales were used: visual analogue scale (VAS), Montgomery-Asberg Depression Rating Scale (MADRS), Hospital Anxiety and Depression Scale (HADS). The safety of drugs was assessed by the incidence of adverse events (AEs) or serious adverse events (SAEs).. The drugs relieve depressive disorders: fluvoxamine by the 7th day of treatment, sertraline, paroxetine, citalopram by the 14th day, fluoxetine by the 30th day of therapy. A significant decrease in the level of anxiety when taking fluvoxamine and citalopram occurs by the 7th day, when taking sertraline and paroxetine - by the 14th day, and when taking fluoxetine - by the 30th day. The presence of an anticraving effect in SSRIs is confirmed by the obtained strong and average correlation coefficients between affective disorders and craving for alcohol. The correlation analysis allowed drawing the conclusions about the close connection of presenting features of the affective disorders (depression and anxiety) and craving. The anticraving effect is more expressive in fluvoxamine, sertraline, citalopram and paroxetine. The most common adverse reactions (increased insomnia and anxiety) are observed in: fluoxetine, citalopram, sertraline, paroxetine. Fluvoxamine has the most favorable safety profile.. SSRIs can be effectively used for the treatment of depressive disorders in alcohol dependence.. Оценить эффективность и безопасность флувоксамина в сравнении с флуоксетином, циталопрамом, сертралином, пароксетином.. В исследование были включены 175 пациентов с синдромом зависимости от алкоголя и депрессивными расстройствами. 161 пациент имел диагноз «синдром зависимости от алкоголя»; 14 — «двойной диагноз». Все пациенты были рандомизированы на 5 групп в соответствии с получаемым препаратом. Для оценки терапевтической эффективности препаратов использовались шкалы визуальная аналоговая (ВАШ), оценки депрессии Монтгомери—Асберг (MADRS), госпитальная оценки тревоги и депрессии (HADS). Безопасность препаратов оценивалась по частоте развития нежелательных явлений (НЯ) или серьезных нежелательных явлений (СНЯ).. Флувоксамин купирует депрессивные расстройства к 7-му дню терапии, сертралин, пароксетин, циталопрам — к 14-му дню, флуоксетин — к 30-му дню. Достоверное снижение уровня тревоги при приеме флувоксамина и циталопрама происходит к 7-му дню, при приеме сертралина и пароксетина — к 14-му дню, а при приеме флуоксетина — к 30-му дню. Полученные сильные и средние коэффициенты корреляции между аффективными расстройствами и влечением к алкоголю подтверждают наличие антикрейвингового эффекта СИОЗС. Антикрейвинговый эффект больше выражен у флувоксамина, сертралина, циталопрама и пароксетина. Наиболее часто побочные реакции в виде усиления бессонницы и беспокойства наблюдаются (в порядке убывания) у флуоксетина, циталопрама, сертралина, пароксетина. Флувоксамин обладает наиболее благоприятным профилем безопасности.. СИОЗС могут эффективно использоваться для лечения депрессивных расстройств при алкогольной зависимости.

Topics: Alcoholism; Citalopram; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline

Patients with a diagnosis of alcohol dependence, detoxified and abstinent for 10-30 days, were randomly allocated to placebo or the serotonin reuptake inhibitor, fluvoxamine (up to 300 mg per day), plus counselling and support. In the intention to treat sample of 493, there was a trend for the fluvoxamine group to do worse than the placebo group on the primary outcome criteria: abstinence; and relapse defined as drinking > or =5 units on an occasion and > or =4 such occasions in a week, or > or =12 units on an occasion (1 unit = 9g ethanol). When typology of alcoholism was assigned by scores on the Tridimensional Personality Questionnaire, Types I and II had similar rates of survival without relapse on placebo (PLC I: 19.3%, n = 135; PLC II: 18.2%, n = 110), but on fluvoxamine Type II did worse than Type I (FLU I: 13.7%, n = 131; FLU II: 6.14%, n = 114) (P < 0.01). When typology was assigned on the basis of age of onset of alcohol problems (< or = age 25, or > age 25), early-onset patients in the fluvoxamine group relapsed more frequently than late-onset patients in that group (no longer significant after adjustment for gender), as did those who commenced regular drinking before age 25 (both with and without adjustment for gender). One explanation for our finding could be that impulsivity in early-onset or Type II patients may be accentuated by serotonin enhancement.

Topics: Adult; Aged; Alcoholism; Analysis of Variance; Double-Blind Method; Female; Fluvoxamine; Humans; Logistic Models; Male; Middle Aged; Prospective Studies; Secondary Prevention

Compliance with the medication regimen in treatment trials for alcoholism appears to be a key determinant of treatment outcome. However, there is no consensus as to the best method to assess medication compliance. This study examines the feasibility of using ultraviolet light detection of a urinary riboflavin tracer to determine compliance with medication therapy. Six sets of urine specimens (with n ranging from 15 to 38) were rated independently by two judges. Test-retest reliability was high: 90 and 95% agreement for two judges. Inter-rater reliability ranged from 73 to 95% agreement between judges (mean = 88%), with correspondence kappa values ranging from 0.46 to 0.85 (mean = 0.69). Diaries, capsule counts, and spectrofluorimetric data were used to validate judges' ratings in four trials, including one in which subjects were alcohol-dependent participants in one of three pharmacotherapy trials. Rating accuracy was influenced by dosage, time interval between ingestion and urine collection, and previous dosing. Overall, ratings tended to be accurate, with incorrect judgments limited to specimens with low concentrations of urinary riboflavin. The results indicate that ultraviolet light detection of urinary riboflavin is a useful method for the assessment of patient compliance with medication regimens, including compliance of patients assigned to receive placebo in clinical trials of medications for alcoholism treatment.

Topics: Alcoholism; Anti-Anxiety Agents; Buspirone; Dose-Response Relationship, Drug; Double-Blind Method; Fluoxetine; Fluvoxamine; Humans; Patient Compliance; Riboflavin; Selective Serotonin Reuptake Inhibitors; Sensitivity and Specificity; Ultraviolet Rays

A combination of depression and alcohol use disorder (AUD) is a typical and most common example of a dual diagnosis at the intersection of general psychiatry and addiction psychiatry. A comorbidity of depression and AUD is more common than it can be brought about by mere coincidence, which might be explained to some extent by the synergetic effect of both diseases, with each of them complicating the course and worsening the prognosis of the other. Treatment protocols for patients with depression and comorbid AUD include antidepressants, specific medications for alcohol dependence, and psychotherapy. The first-line antidepressants in the treatment of patients with a comorbid combination of depression and alcohol use disorder, as in other clinical situations implying use of antidepressants, are selective serotonin reuptake inhibitors (SSRIs). Fluvoxamine has certain advantages over the other SSRIs in the treatment of patients with a depression and comorbid AUD.. Сочетание депрессии и расстройства употребления алкоголя представляет собой типичный и наиболее распространенный пример двойного диагноза —коморбидной пары, соединяющей психиатрию и наркологию. Коморбидность депрессии и расстройства употребления алкоголя встречается чаще, чем это может определяться простым совпадением, что объясняется синергизмом обоих заболеваний, каждое из которых осложняет течение и ухудшает прогноз другого. Протоколы лечения пациентов с двойным диагнозом включают антидепрессанты, средства лечения алкогольной зависимости и психотерапию. Антидепрессантами первой линии в лечении пациентов с сочетанием депрессии и расстройства употребления алкоголя, как и в других клинических ситуациях, представляющих показания для применения антидепрессантов, служат селективные ингибиторы обратного захвата серотонина (СИОЗС). Определенными преимуществами в лечении пациентов с двойным диагнозом в сравнении с другими СИОЗС обладает флувоксамин.

Topics: Alcoholism; Antidepressive Agents; Depression; Fluvoxamine; Humans; Selective Serotonin Reuptake Inhibitors

Fluvoxamine is commonly administered to patients with recurrent depressive disorder. Some of these patients do not show adequate response to the therapy with fluvoxamine, whereas many of them experience dose-dependent adverse drug reactions. Previous research revealed that CYP2D6 is involved in the metabolism of fluvoxamine, the activity of which is highly dependent on the polymorphism of the gene encoding it.. The objective of this study was to investigate the effect of polymorphisms of the CYP3A4, CYP2C9, CYP3A5, ABCB1, CYP2C19, SCL6A4, and 5-HTR2A genes on the concentration/dose indicator of fluvoxamine and on the CYP3A expression level obtained by measuring the miR-27b plasma concentration levels in patients suffering from a recurrent depressive disorder.. Our study included 105 patients with recurrent depressive disorder (average age - 37.5 ± 13.2 years). The treatment regimen included fluvoxamine in an average daily dose of 117.6 ± 44.3 mg per week. Therapy efficacy was assessed using the international psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6b-HC/cortisol). Therapeutic drug monitoring has been performed using HPLC-MS/MS.. Our study didn't reveal any statistically significant results in terms of the treatment efficacy and safety of the therapy. We also didn't reveal a statistical significance for the concentration/dose indicator of fluvoxamine in patients with different genotypes. Analysis of the results of the pharmacotranscriptomic part of the study didn't demonstrate the statistically significant difference in the miR-27b plasma levels in patients with different genotypes. At the same time, correlation analysis didn't reveal a statistically significant relationship between the fluvoxamine efficacy profile evaluated by changes in HAMD scale scores and the miR-27b plasma concentration: r. Thus, the effect of genetic polymorphism of the CYP3A4, CYP2C9, CYP2C9, CYP3A5, ABCB1, CYP2C19, CYP2C19, CYP2C19, SCL6A4, 5-HTR2A gene on the efficacy and safety profiles of fluvoxamine was not demonstrated in a group of 105 patients with depressive disorder and alcohol use disorder.

Topics: Alcoholism; Biomarkers; Comorbidity; Cytochrome P-450 CYP3A; Fluvoxamine; Humans; MicroRNAs; Mood Disorders; Tandem Mass Spectrometry

Low serotonin function is associated with alcoholism, leading to speculation that increasing serotonin function could decrease ethanol consumption. Mice with one or two deletions of the serotonin transporter (SERT) gene have increased extracellular serotonin. To examine the relationship between SERT genotype and motivation for alcohol, we compared ethanol self-administration in mice with zero (knockout, KO), one (HET) or two copies (WT) of the SERT gene. All three genotypes learned to self-administer ethanol. The SSRI, fluvoxamine, decreased responding for ethanol in the HET and WT, but not the KO mice. When tested under a progressive ratio schedule, KO mice had lower breakpoints than HET or WT. As work requirements were increased across sessions, behavioral economic analysis of ethanol self-administration indicated that the decreased breakpoint in KO as compared to HET or WT mice was a result of lower levels of unconstrained demand, rather than differences in elasticity, i.e. the proportional decreases in ethanol earned with increasing work requirements were similar across genotypes. The difference in unconstrained demand was unlikely to result from motor or general motivational factors, as both WT and KO mice responded at high levels for a 50% condensed milk solution. As elasticity is hypothesized to measure essential value, these results indicate that KO value ethanol similarly to WT or HET mice despite having lower break points for ethanol.

Topics: Alcoholism; Animals; Ethanol; Fluvoxamine; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motivation; Selective Serotonin Reuptake Inhibitors; Self Administration; Serotonin Plasma Membrane Transport Proteins

Clinical studies indicate that selective serotonin-reuptake inhibitors (SSRIs) may decrease alcohol intake and craving in particular subgroups of alcoholics. The aim of the present study was to compare the behavioral profile of various SSRIs in alcohol-preferring cAA rats, a genetic model of alcoholism. The effects of acute IP administration of fluoxetine (doses in mg/kg 1-10), citalopram (3-30), fluvoxamine (3-30) and paroxetine (1-10) on ethanol (EtOH) intake and preference, as well as food and total fluid intake, were determined in a 12-h access, water vs. 10% v/v EtOH two-bottle choice paradigm. Each compound reduced EtOH intake [Minimal Effective Doses (MEDs) 5, 10, 30 and 1 mg/kg for fluoxetine, citalopram, fluvoxamine, and paroxetine, respectively]. The degree of selectivity, that is, the extent to which reductions in EtOH intake could be separated from reductions in food and/or total fluid intake varied across the compounds. Thus, whereas EtOH intake was more markedly affected than food intake by fluoxetine, both parameters were equally affected by citalopram, and food intake was more markedly affected than EtOH intake by fluvoxamine and paroxetine. The anti-alcohol effect also differed with respect to specificity, that is, the degree to which effects on EtOH intake coincided with effects on EtOH preference. Whereas fluoxetine showed the highest level of specificity, followed by citalopram and fluvoxamine, the effect of paroxetine was nonspecific. The observed variation in the degree of selectivity and specificity of the anti-alcohol effect of SSRIs suggests that reductions in EtOH intake are not merely a consequence of a general suppressive effect on consummatory behavior. It is hypothesized that differences between the behavioral profiles of these compounds reflect a differential involvement of 5-HT receptor subtypes.

Topics: Alcohol Drinking; Alcoholism; Animals; Citalopram; Disease Models, Animal; Eating; Ethanol; Female; Fluoxetine; Fluvoxamine; Food Preferences; Male; Paroxetine; Rats; Rats, Mutant Strains; Selective Serotonin Reuptake Inhibitors

Korsakoff's psychosis (Wernicke-Korsakoff-Syndrome) following severe, long-term alcoholism is considered to be widely resistant to treatment. We report two cases with beneficial effects of treatment by a combination of clonidine and fluvoxamine.

Topics: Adrenergic alpha-Agonists; Adult; Alcohol Withdrawal Delirium; Alcoholism; Anti-Anxiety Agents; Brain; Clonidine; Drug Therapy, Combination; Fluvoxamine; Humans; Korsakoff Syndrome; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors; Treatment Outcome