Perception of a New Prolonged-Release Buprenorphine Formulation in Patients with Opioid Use Disorder: The PREDEPO Study.

AIM: The aim of the study was to assess the acceptance of patients with opioid use disorder (OUD) to switching their opioid dependence treatment (ODT) for a prolonged-release buprenorphine (PRB) injection according to their prior ODT (buprenorphine/naloxone [B/N] or methadone). METHODS: This was an observational, retrospective/cross-sectional, multicentre study of adult patients diagnosed with OUD on ODT. Data collected from diaries were analysed to know their interest and opinion on PRB. Questions with fixed response options were included, and several Likert scales were used. RESULTS: A total of 98 patients were enrolled (B/N: 50.0%, methadone: 50.0%). The mean age was 46.9 ± 8.43 years and 79.6% were males. PRB was similarly perceived by both groups in most variables analysed, receiving a mean score of 7.2/10 (B/N: 7.4, methadone: 7.0; p = 0.520), and approximately 65% of patients said they were willing to switch to PRB (B/N: 63.3%, methadone: 65.3%; p = 0.833). Of these, a higher percentage in the B/N group considered that switching would be easy/very easy (B/N: 90.3%, methadone: 46.9%; p < 0.001) and that they would start PRB when available (B/N: 64.5%, methadone: 34.3%; p = 0.005). More than 90% would prefer the monthly injection (B/N: 93.6%, methadone: 100%; p = 0.514). One-third of patients in both groups were unsure/would not switch their ODT to PRB (B/N: 36.7%, methadone: 34.7%; p = 0.833). The main reason was administration by injection. CONCLUSION: Two-thirds of patients would switch their treatment for PRB, and most patients on B/N considered that switching would be easy. PRB could be a suitable alternative for OUD management.

Patients'satisfaction and experience in treatment with opioid substitution therapy in Spain. The PREDEPO study. / Satisfacción y experiencia de pacientes en tratamiento con sustitutivos opioides en España. Estudio PREDEPO.

The aim of this study was to compare patients' satisfaction, experience, objectives, and opinion based on their current opioid substitution therapy (OST) (buprenorphine/naloxone (B/N) or methadone). The PREDEPO study is an observational, cross-sectional, multicentric study performed in Spain. Adult patients diagnosed with opioid use disorder (OUD) receiving OST were included. They were asked to fill in a questionnaire regarding their current OST. A total of 98 patients were enrolled (B/N: 50%, methadone: 50%). Mean age was 47 ± 8 years old and 80% were male. Treatment satisfaction was similar between groups. The most frequently reported factor for being "very/quite satisfied" was "being able to distribute the dose at different times throughout the day" (44% B/N vs. 63% methadone; p = .122). A significantly lower proportion of patients in the B/N group versus the methadone group reported that having to collect the medication daily was "very/quite annoying" (19% vs. 52%, p = .032). Treatment objectives reported by the majority of patients were similar between groups ("not feeling in withdrawal anymore", "reduce/definitely stop drug use", "improve my health", and "stop thinking about using daily") except for "not having money problems anymore" (73% B/N vs. 92% methadone; p = .012).  These results suggest there are several unmet expectations regarding current OST. There is a need for new treatments that reduce the burden of OUD, avoid the need for daily dosing, and are less stigmatizing which in turn could improve patient management, adherence and, quality of life.

El objetivo es comparar la satisfacción, experiencia, objetivos y opinión de los pacientes con trastorno por consumo de opioides (TCO) en base a su tratamiento sustitutivo de opioides (TSO) actual (metadona o buprenorfina/naloxona (B/N)). El estudio PREDEPO es un estudio observacional, transversal, multicéntrico desarrollado en España que incluyó pacientes adultos, diagnosticados de TCO y en TSO, quienes contestaron una encuesta sobre su tratamiento actual. Se incluyeron 98 pacientes (B/N:50%, metadona:50%): edad media de 47 ± 8 años y el 80% varones. A nivel de la satisfacción con su tratamiento, los resultados fueron similares entre grupos. El factor "muy/bastante satisfactorio" que se reportó con mayor frecuencia fue "poder repartir las dosis en varios momentos del día" (44% B/N vs. 63% metadona; p = ,122). Se encontraron diferencias significativas en "tener que recoger la medicación diariamente" donde una menor proporción en el grupo B/N contestaron "muy/bastante molesto" versus el grupo metadona (19% vs. 52%, p = ,032). Los objetivos reportados por la mayoría de los pacientes fueron similares entre grupos ("no sentir más síndrome de abstinencia", "disminuir o dejar definitivamente mi consumo de drogas", "mejorar mi estado de salud" y "dejar de pensar en consumir todos los días") excepto en "no tener más problemas de dinero" (72% B/N vs. 92% metadona; p = ,012). Estos resultados evidencian que existen expectativas no cubiertas con los TSO actuales y la necesidad de nuevos tratamientos que disminuyan la carga de la enfermedad, eviten la necesidad de una dosificación diaria y reduzcan el estigma, mejorando así el manejo del paciente, su adherencia y calidad de vida.

Psychotic symptoms of cocaine self-injectors in a harm reduction program.

BACKGROUND: Psychotic symptoms are common among cocaine users. METHODS: An observational naturalistic study on the effects and events of intravenous cocaine use in a drug consumption room was carried out; the patients were diagnosed of cocaine dependence (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision). RESULTS: Twenty-one patients, 81% men self-injected cocaine 375 times. Psychotic symptoms were observed in 62% of the patients and 21% of the self-injections; delusions were observed in 9.3%, psychotic self-reference with insight in 9.1%, illusions in 6.4%, and hallucinations in 5.3%. A higher presence of psychotic symptoms was noted with cannabis used in the previous month (76.9% versus 44.4%; P = .001) (no psychotic symptoms group); also, a greater use of benzodiazepines was observed: 75.6% versus 63.6% (P = .046). Lower use of methadone in the group with psychosis was observed: 75.6% versus 97.3% (P = .001). Motor alterations were tremor 58%, stereotyped movements 24%, and behaviour alteration 6%, significantly more frequent in the psychotic group. CONCLUSIONS: Thus, there was a high frequency of psychotic symptoms after intravenous cocaine use; patients with psychotic symptoms reported higher use of cannabis and benzodiazepines in the previous month and lower use of methadone. More tremors and stereotyped movements were observed in the group with psychotic symptoms. It is necessary to give a special approach to cocaine intravenous users.

[Risk factors for relapse in drug-dependent patients after hospital detoxification]. / Factores de riesgo de recaída en pacientes drogodependientes tras desintoxicación hospitalaria.

This work describes the profile of patients with relapse after hospital detoxification at six months of outpatient follow-up. An observational and prospective study was carried out in patients with substance-dependence disorder who were in the Detoxification Unit of the Vall d'Hebron University Hospital (Barcelona) between June 2009 and October 2010. Demographic, clinical, diagnostic and therapeutic variables were assessed. The criterion for relapse was a return to use of the substance that had led to hospitalization, and relapse was assessed by means of anamnesis, breathalyzer and/or urine analysis. Study variables were compared between patients who relapsed and those who did not. Of the 165 patients included, 108 patients finished the study (75% males, age 37.7 ± 9.5 years). A total of 72.2% had relapsed at the 6-month follow-up. Profile of patients who relapsed was: hospitalized for heroin detoxification (91.7% vs 8.3%, p = .038), polyconsumers (71.4% vs 32%, p = .05), high substance use in the hours prior to admission as a "farewell" (61.5% vs 39.5%, p = .04), patients with comorbidity (44.9% vs 23.3%, p = .04) and patients with affective disorders (19.5% vs 3.2%, p = .005). Detoxification from opiates and use in the hours prior to admission were associated independently with relapse at 6 months. There is a high percentage of relapses after hospital detoxification. Patients most likely to relapse are those dependent on opiates and those with compulsive use immediately prior to hospitalization.

[Quality of life concept evolution: the subjective dimension as a relevant factor on drug addiction]. / Evolución del concepto de calidad de vida: la dimensión subjetiva como factor relevante en las drogodependencias.

AIM: to analyze the Quality of Life Concept, is which currently used in drug addiction. We reviewed the studies published until April 2010, using two international databases: PubMed (key words: quality of life, addiction, drug dependence and dual diagnosis) and the Web of Knowledge (search by author). We identified 479 papers on quality of life and drugs abuse, of which were on: quality of life and addictions (433) and quality of life and dual pathology (37). RESULTS: the quality of life concept has evolved, from the forties decade till the present time, remains controversial and still subject to change. Most authors accept the multidimensionality of the quality of life concept, that includes the physical/biological, psychological and social dimension. Currently the patient's satisfaction concept is emerging. On the other hand, it is known that there are discrepancies in the patient's and therapist's view on the patient's quality of life, especially in dually diagnosed patients. CONCLUSIONS: The conceptual study of the quality of life is important. Quality of life components, as the perception of the disease, have been associated with treatment adherence and the disease's progress. For the previous reasons we believe. Quality of Life should be included in the regular evaluation.

[Initiation cocaine use in elderly patients: a case report]. / Inicio del consumo de cocaína en edades tardías: a propósito de un caso.

INTRODUCTION: Cocaine use is an uncommon condition in older people, a population in which cocaine use is probably overlooked. Cases initiation of use in late adulthood as well as elderly relapsing to use from youth drug use have been reported. CLINICAL CASE: We report a woman of 61 years of age hospitalized in the detoxification unit for cocaine dependence tratment (used 1-1,5g/ day). She did not begin cocaine use until she was 60 years old. Some risk factors include retirement, chronic pain, and affective symptoms are related with loneliness and increased cocaine use in elderly, and account for the underreporting of abuse or dependence. Old people have more medical conditions related to cocaine use and have greater health deterioration than young people. DISCUSION: Cocaine use should be evaluated in every patient, and elderly patients should be checked particularly when presenting atypical medical or psychiatric conditions.

Larger Gray Matter Volume in the Basal Ganglia of Heavy Cannabis Users Detected by Voxel-Based Morphometry and Subcortical Volumetric Analysis.

Background: Structural imaging studies of cannabis users have found evidence of both cortical and subcortical volume reductions, especially in cannabinoid receptor-rich regions such as the hippocampus and amygdala. However, the findings have not been consistent. In the present study, we examined a sample of adult heavy cannabis users without other substance abuse to determine whether long-term use is associated with brain structural changes, especially in the subcortical regions. Method: We compared the gray matter volume of 14 long-term, heavy cannabis users with non-using controls. To provide robust findings, we conducted two separate studies using two different MRI techniques. Each study used the same sample of cannabis users and a different control group, respectively. Both control groups were independent of each other. First, whole-brain voxel-based morphometry (VBM) was used to compare the cannabis users against 28 matched controls (HC1 group). Second, a volumetric analysis of subcortical regions was performed to assess differences between the cannabis users and a sample of 100 matched controls (HC2 group) obtained from a local database of healthy volunteers. Results: The VBM study revealed that, compared to the control group HC1, the cannabis users did not show cortical differences nor smaller volume in any subcortical structure but showed a cluster (p < 0.001) of larger GM volume in the basal ganglia, involving the caudate, putamen, pallidum, and nucleus accumbens, bilaterally. The subcortical volumetric analysis revealed that, compared to the control group HC2, the cannabis users showed significantly larger volumes in the putamen (p = 0.001) and pallidum (p = 0.0015). Subtle trends, only significant at the uncorrected level, were also found in the caudate (p = 0.05) and nucleus accumbens (p = 0.047). Conclusions: This study does not support previous findings of hippocampal and/or amygdala structural changes in long-term, heavy cannabis users. It does, however, provide evidence of basal ganglia volume increases.

Cocaine-induced Psychosis and Brain-derived Neurothrophic Factor in Patients with Cocaine Dependence: Report of Two Cases.

Brain-derived neurotrophic factor (BDNF) is linked to numerous brain functions. In addition, BDNF alterations contribute to neurological, mental, and addictive disorders. Cocaine dependence has received much attention recently due to its prevalence and psychological effects. Symptoms of psychosis are one of the most serious adverse events precipitated by cocaine use. It is particularly important to identify patients at risk of developing cocaine-induced psychosis (CIP). We described two cases of patients with cocaine dependence who presented with CIP and had changes in their BDNF levels during the psychotic episode. BDNF levels were initially low in both patients, and then decreased by more than 50% in association with CIP. The relationship between BDNF and psychosis is described in the literature. These cases revealed that BDNF levels decreased during a CIP episode and, thus, it is necessary to investigate BDNF and its relationship with CIP further.

Observational study on medications prescribed to dual-diagnosis outpatients.

OBJECTIVES: To quantify the number of medications used for treating psychiatric and addictive disorders in a cohort of dual diagnosis with substance dependence outpatients and report the most frequent pharmacological groups used. METHODS: A descriptive, cross-sectional study was conducted. Demographic data, Axis I comorbidity diagnosis with substance dependence, and the medications prescribed were recorded. Diagnosis was assessed by the Structured Clinical Interview for DSM-IV (SCID). RESULTS: One hundred seven patients (mean age 37.7 years; SD = 10.2 years) were evaluated (76.6% men). On average, patients took 4.0 (SD = 1.8) medications. The pharmacological groups prescribed were antipsychotics (69.2%) followed by antidepressants (65.4%), antiepileptics (58.9%), anxiolytics (37.4%), alcohol-aversive drugs (15.9%), methadone (15.9%), lithium (3.7%), and naltrexone (2.8%). Older patients (>45 years old) were found to have a higher number of prescribed medications. Patients diagnosed with a dual psychotic disorder were prescribed a larger number of pharmacological agents (mean = 4.4; SD = 2.1) than patients with a mood disorder (mean = 3.7; SD = 1.3) or an anxiety disorder (mean = 2.9; SD = 1.2), K = 10.5, P = 0.005. CONCLUSIONS: Because polypharmacy is frequent in patients with mental illness and a co-occurring substance use disorder, specialized approaches need to be developed.

Cocaine-induced psychosis and impulsivity in cocaine-dependent patients.

Cocaine-dependent patients have high impulsiveness. Cocaine-induced psychosis is common among cocaine-dependent patients. Different risk factors associated with cocaine-induced psychosis have been reported. The aim of this study is to analyze the relationship between psychotic symptoms in cocaine-dependent patients and impulsivity and mental disorders characterized by impulsivity. This descriptive study included 287 outpatients with cocaine dependence according to the DSM-IV-TR criteria. The Structured Clinical Interview for DSM-IV Axis I and II, the Barratt Impulsiveness Scale, and a specific questionnaire on the presence of cocaine-induced psychosis were used to assess patients. Symptoms were observed in 59.9% of the study population. Total and cognitive impulsiveness scores obtained from the Barratt Impulsiveness Scale were significantly higher in patients with cocaine-induced psychosis. Individuals from this group reported more overdose incidents, initiated more treatments during their lifetime, and had a significantly greater prevalence of attention deficit hyperactivity disorder. Patients with cocaine-induced psychosis have a greater degree of impulsivity and a higher prevalence of attention deficit hyperactivity disorder. Thus, if these disorders are observed in cocaine-dependent participants, the presence of psychotic symptoms should be evaluated to prevent further occurrence and their consequences.

Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence.

Preclinical studies indicate that brain-derived neurotrophic factor (BDNF) is involved in neuroplastic changes underlying enduring cocaine-seeking following withdrawal. However, little is known about temporal changes in serum BDNF levels or the involvement of BDNF in craving and abstinence in early-abstinent cocaine-dependent patients. Twenty-three cocaine-dependent individuals (aged 33.65 ± 6.85 years) completed a two-week detoxification program at an inpatient facility. Two serum samples were collected for each patient at baseline and at the end of the protocol. Serum samples were also collected for 46 healthy controls (aged 35.52 ± 9.37 years). Demographic, consumption and clinical data were recorded for all patients. Significantly lower serum BDNF levels (p<.0001) were observed for cocaine-dependent patients at baseline compared to healthy controls. Serum BDNF levels increased significantly across 12 days of early abstinence (p=.030). Baseline BDNF levels correlated with craving (p=.034). Post-detoxification BDNF levels correlated with craving (p=.018), loss of control (p<.000), abstinence measures (p=0.031), depression (p=0.036), and anxiety (p=0.036). Post-detoxification BDNF levels also had predictive value for the loss of control measure of craving. Chronic cocaine use is associated with decreased serum BDNF. A progressive increase in serum BDNF levels during early abstinence correlates with cocaine craving and abstinence symptoms and may reflect increasing BDNF levels in different brain regions. These findings suggest that serum BDNF may be a biomarker for cocaine addiction.

Driving and legal status of Spanish opioid-dependent patients.

BACKGROUND: Opioid dependent patients have legal problems, driving violations and accidents more frequently than the general population. We have hypothesized that those patients currently driving may have better legal outcomes than those who do not possess a valid driving license. With this aim we have analyzed the information gathered in the PROTEUS study regarding the legal and driving statuses and assessed the possible association between them. The PROTEUS study was an observational, cross-sectional, descriptive, multicenter nationwide representative study, conducted in Spanish healthcare centers for opioid dependent patients. FINDINGS: The driving and legal statuses of a population of opioid dependent patients ≥ 18 years and enrolled in Opioid Agonist Therapy treatment centers in Spain, were assessed using a short specific questionnaire and the EuropASI questionnaire to highlight distinct individual clinical needs. 621 patients were evaluable (84% men, 24.5% active workers). 321 patients (52%) drove on a regular basis. Nineteen percent of patients had some problem with the criminal justice system. There was a significant difference (p = 0.0433) in status, according to the criminal justice system, between patients who drove on a regular basis and those who did not, with a higher percentage of patients with non-pending charges among usual drivers. CONCLUSIONS: Regular drivers showed fewer legal problems than non-regular drivers, with the exception of those related to driving (driving violations and drunk driving). Driving is a good prognostic factor for the social integration of the patients and policies should be implemented to enable these patients to drive safely under medical authorization. The legal description will be useful to assess treatment efficacy.

Candidate pathway association study in cocaine dependence: the control of neurotransmitter release.

OBJECTIVES: Cocaine is the second most used illegal drug in Europe. The transition from use to dependence involves both genetic and environmental factors. Genetic variation in neurotransmitter systems is involved in the susceptibility to cocaine dependence. We examined the possible contribution to cocaine dependence of 16 genes involved in the cellular machinery that controls neurotransmitter release: genes encoding proteins of the SNARE complex (STX1A, SNAP25, VAMP1 and VAMP2), fusion control elements (SYT1, SYT2, CPLX1, CPLX2, CPLX3 and CPLX4) and regulatory elements (STXBP1, SYP, SNPH, NSF, NAPA and RAB3A). METHODS: We genotyped 121 SNPs, selected according to genetic coverage criteria, in 360 cocaine-dependent patients and 360 controls from Spain. RESULTS: Single and multiple-marker analyses revealed a strong association between cocaine dependence and the NSF gene, encoding the N-ethylmaleimide-sensitive factor (P = 5.1e-04, OR = 2.44 (1.45-4.00) and P = 0.001, OR = 1.82 (1.28-2.59), respectively). The presence and absence of psychotic symptoms were also studied. Interestingly, when we considered the time between initial consumption and the onset of cocaine dependence, we observed that the association was mainly restricted to the group of patients that rapidly developed drug dependence (≤ 2 years; P = 2.98e-06, OR = 1.33 (1.20-1.47)). CONCLUSIONS: Our data show preliminary evidence that NSF may predispose not only to cocaine dependence, but also to an early onset of the dependence.

A double-blind, placebo-controlled, randomized pilot study comparing quetiapine with placebo, associated to naltrexone, in the treatment of alcohol-dependent patients.

The objective of this study was to determine whether quetiapine plus naltrexone is more effective than naltrexone alone for the treatment of alcohol-dependent patients. This was a double-blind, randomized clinical trial where eligible alcohol-dependent patients were randomized to receive naltrexone (50mg/day) plus quetiapine (25-200mg/day) or naltrexone (50mg/day) plus placebo for 12 weeks, and afterwards patients received naltrexone alone during 4 additional weeks. The primary efficacy measures were percent days abstinent, drinks per drinking day, and the relapse rate. Sixty-two patients received a single-blind treatment with placebo plus naltrexone, and they were thereafter randomly assigned to quetiapine plus naltrexone (n=30) or placebo plus naltrexone (n=32). Eleven (36.7%) patients in the quetiapine-treated group and 4 (12.5%) patients in the placebo-treated group withdrew before they completed 12 weeks of treatment. There were no statistically significant differences for any primary drinking outcomes between treatment groups. Both regimens were well tolerated. This study failed to demonstrate any additional benefit from the combination of quetiapine and naltrexone compared to naltrexone alone on drinking outcomes.

[Ambulatory group treatment for cocaine dependent patients combining cognitive behavioral therapy and motivational interviewing]. / Tratamiento ambulatorio grupal para dependientes de cocaína combinando terapia cognitivo conductual y entrevista motivacional.

Psychological interventions in cocaine dependent patients have demonstrated efficacy. Remarkable approaches are Contingency Management (CM) and Cognitive Behavioral Therapy (CBT). Lack of treatment adherence is the most important limitation. Motivational Interview (MI) has been shown to be an adherence enhancer. The objective of this study is to evaluate retention and abstinence in a combined CM and CBT group treatment in patients who have reached maintenance stage according to Prochaska and DiClemente's transtheoretical model (1982). Therefore, a longitudinal study was carried out with cocaine dependent patients with or without concomitant mental health disease. A 12-session open group was conducted weekly. Nineteen patients were included (78.9% men, mean age 36.6 years), 95% consumed intranasally and 47% had another psychiatric comorbidity. Treatment retention was 84%. During treatment and the first month of follow-up, all patients remained abstinent whereas at three months, 3 patients relapsed. These data confirm that using combined CM and CBT group therapy in cocaine dependents undergoing maintenance treatment enhances adherence and is effective to achieve abstinence.

Association study between the DAT1, DBH and DRD2 genes and cocaine dependence in a Spanish sample.

Drug addiction is a complex neuropsychiatric disorder involving the environmental and genetic factors. Genetic and physiological evidences suggest that the dopaminergic system may play an important role in cocaine abuse and dependence. Several association studies have focused on dopaminergic genes. We genotyped the Int8 and 3'UTR variable number of tandem repeats of the dopamine transporter gene (DAT1/SLC6A3), the TaqIA (rs1800497) and TaqIB (rs1079597) SNP polymorphisms within the dopamine receptor D2 gene and the 19-bp insertion/deletion and c.444G>A (rs1108580) polymorphisms of the dopamine ß-hydroxylase gene (DBH) in a Spanish sample of 169 patients with cocaine addiction and 169 sex-matched controls. The case-control study showed a nominal overrepresentation of the 5R/5R genotype of the Int8 variable number of tandem repeats within DAT1 in cocaine abusers (P=0.016). However, no significant associations were detected when DAT1 haplotype frequencies or polymorphisms within the other dopaminergic genes were considered. Sample size is limited and further studies should be performed in a larger cohort.

[Users' perception of a harm reduction program in an outpatient drug dependency treatment center]. / Valoración de los usuarios de un programa de reducción de daños integrado en un ambulatorio de drogodependencias.

OBJECTIVES: We analyzed the perspective of users enrolled in a harm reduction program that provides syringe exchange, an educational room for «warmth and coffee¼, a methadone maintenance program, a room for supervised drug consumption, a place for personal hygiene, and medical and psychosocial follow-up. The particularity of this program lies in its integration within an outpatient drug treatment center forming part of a general hospital. METHODS: We performed a descriptive study using qualitative methods. Theoretical sampling was conducted. Twelve in-depth interviews and one focus group composed of eight users were carried out. Information analysis was based on grounded theory. Literal transcriptions were coded and subsequently sorted into broad categories. Three researchers participated in this process and finally a fourth researcher triangulated the results. RESULTS: Five dimensions were identified in the users' discourse: accessibility, service, relationship, localization, and identity. Each consisted of several topics that were evaluated based on the participants' experiences and expectations. The dimension of identity emerged as a distinctive element in patient-program bonding. CONCLUSIONS: The users' overall evaluation of the program was positive. Facilitators and barriers influencing patient-program bonding were identified and participants suggested ways to remove barriers. The coexistence among users of the harm reduction program and patients treated conventionally provoked ambivalence but the team's management was deemed helpful in easing the difficulties arising from this situation.

A double-blind, placebo-controlled study of olanzapine in the treatment of alcohol-dependence disorder.

BACKGROUND: A 12-week, double-blind, randomized, parallel-group clinical trial, comparing olanzapine and placebo treatment together with cognitive-behavioral psychotherapy, was carried out to determine the efficacy, safety, and tolerability of olanzapine in the treatment of alcoholism. METHODS: A total of 60 alcohol-dependent patients were assigned to 12 weeks' treatment with either olanzapine or placebo. The primary variable relapse to heavy drinking rate was evaluated by means of intention-to-treat analyses. Alcohol consumption, craving, adverse events, and changes in the biochemical markers of heavy drinking and possible toxicity were also evaluated. RESULTS: We did not find significant differences in the survival analysis between placebo and olanzapine-treated patients (Kaplan-Meier log rank = 0.46, df = 1, p = 0.50). Eleven (37.9%) patients treated with olanzapine relapsed compared with 9 (29%) of those receiving placebo (chi = 0.53, df = 1, p = 0.5). Although some adverse events (weight gain, increased appetite, drowsiness, constipation, and dry mouth) were found more frequently in the olanzapine group, differences did not reach statistical significance in comparison with the placebo group. CONCLUSIONS: Olanzapine was well tolerated, as the rate of adverse events was low, and it was safe, because it did not interfere with the normalization of biochemical markers of heavy drinking or alter liver function markers. Alcohol-dependent patients showed good adherence and compliance with the treatment protocol, but we found no differences in relapse rate or other drinking variables when comparing olanzapine with placebo-treated patients.

A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial.

BACKGROUND: A 12-week, multicenter, double-blind, randomized, parallel-group clinical trial to compare naltrexone and placebo was carried out to determine the efficacy, safety, and tolerability of naltrexone together with a psychosocial intervention in the treatment of alcoholism. METHODS: A total of 202 alcohol-dependent patients were assigned to 12 weeks' treatment with either naltrexone or placebo. The relapse rate was evaluated by means of intention-to-treat analyses. Alcohol consumption, craving, adverse events, and changes in the biochemical markers of heavy drinking and possible toxicity were evaluated in the 192 patients who were considered to be assessable. RESULTS: The survival function for patients who were treated with naltrexone was significantly better than that of the patients who were treated with placebo (Kaplan-Meier log rank = 4, df = 1, p < 0.05). In addition, 7.9% of patients who were treated with naltrexone relapsed as compared with 18.8% of those who received placebo [chi = 5.89, df = 2, p = 0.050]. In comparing naltrexone with placebo-treated patients, the most common adverse events were abdominal pain [8.6% vs. 1%; (chi = 6.1, df = 1, p < 0.05)] and headache [7.5% vs. 1% (chi = 5.1, df = 1, p < 0.05)]. CONCLUSIONS: Naltrexone was well-tolerated, as the rate of adverse events was low, and safe, as it did not interfere with the normalization of biochemical markers of heavy drinking or alter liver function markers. Naltrexone seemed to reduce relapse rate to heavy drinking, but we found no differences in other alcohol consumption variables between naltrexone- and placebo-treated groups. Although the naltrexone group showed a tendency to consume fewer drinks per drinking day and had a longer time to first drink, differences were not statistically significant.