Efficacy In Preventing Relapse Research Articles

Paliperidone palmitate 6-month formulation for the treatment of schizophrenia: a 14-month follow-up study

IntroductionRelapse prevention is critical because psychopathology and functionality can worsen in patients with schizophrenia because the repeated episodes and we have strong evidence of antipsychotics efficacy for relapse prevention, but nonadherence rates in patients with schizophrenia are very high, even in comparison with other illness.There is extensive clinical trial evidence for the use of paliperidone palmitate 1-month (PP1M) and paliperidone palmitate 3-month (PP3M) formulations for maintaining treatment continuity and preventing relapses and risk of hospitalizations in patients with schizophrenia. (Najarian et al. Int J Neuropsychopharmacol 2022; 25(3) 238-251). Paliperidone palmitate 6-month (PP6M) formulation is a presentation that provides a dosing interval of once every six months.ObjectivesThe principal aim of this study was to evaluate the effectiveness, safety, and tolerability of the PP6M in patients with non-acute schizophrenia on an outpatient basisMethodsMethods: Sample: 22 patients diagnosed with schizophrenia (DSM 5 criteria) that started treatment with PP6M after being stabilized with PP1M (N:10) or PP3M (N:12) (the treatment dose was not changed in the four months before study inclusion)Bimonthly, the following evaluations were performed during a follow-up period of 14 months:The Clinical Global Impression-Schizophrenia scale (CGI-SCH)Treatment adherence, concomitant medication, adverse events and the number of hospitalizations and emergency visitsEfficacy values: Percentage of patients who remained free of admissions at the end of 14months of follow-up.Other evaluation criteria: Percentage of patients who never visited the emergency department at the end of 14 months of follow-up, average change from baseline visit to the final evaluation as assessed by score obtained on the following scale: GSI-SCH, treatment adherence rate and tolerability.ResultsThe percentage of patients who remained free of admission at the end of the 14 months follow-up was 90% in the total sample, 83% in the PP3M pre-treatment group and 100% in the PP1M pre-treatment group.The percentage of patients who never visited the emergency department at the end of 14 months follow-up was: 81% in the total sample, 75% in the PP3M pre-treatment group and 90% in the PP1M pre-treatment group.At the end of the study, a mean change of +0.12 (±0.11) on the ICG-SCH-SI scale in the total sample, +0.25 (±0.21) in the PP3M pre-treatment group and 0 in the PP1M pre-treatment group.The treatment persistence rate at the 14 month of follow-up was 100% in the total sample.Treatment was well tolerated, and no safety-related adverse events were collected. There were no tolerability-related withdrawals from treatment.ConclusionsIn our study, we found that long-term treatment with paliperidone palmitate 6-month formulation is effective and well tolerated in clinical practice conditions.Disclosure of InterestNone Declared

Current Updates on the Diagnosis and Management of Multiple Sclerosis for the General Neurologist.

Multiple sclerosis (MS) is an immune-driven disease that affects the central nervous system and is characterized by acute-on-chronic demyelination attacks. It is a major cause of global neurological disability, and its prevalence has increased in the United States. Conceptual understandings of MS have evolved over time, including the identification of B cells as key factors in its pathophysiology. The foundation of MS management involves preventing flares so as to avoid long-term functional decline. Treatments may be categorized into low-, middle-, and high-efficacy medications based on their efficacy in relapse prevention. With 24 FDA-approved treatments for MS, individual therapy is chosen based on distinct mechanisms and potential side effects. This review provides a detailed update on the epidemiology, diagnosis, treatment advances, and major ongoing research investigations in MS.

Tafenoquine exposure assessment, safety, and relapse prevention efficacy in children with Plasmodium vivax malaria: open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 trial

Single-dose tafenoquine 300 mg is approved for Plasmodium vivax malaria relapse prevention in patients at least 16 years old. We aimed to determine appropriate oral tafenoquine paediatric dosing regimens, including a dispersible formulation, and evaluated tafenoquine efficacy and safety in children infected with P vivax. This open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 study enrolled children (2-15 years) who weighed 5 kg or more, with glucose-6-phosphate dehydrogenase activity more than 70% of the local population median, and P vivax malaria infection, from three community health centres in Vietnam and one in Colombia. Patients received 3-day chloroquine plus oral single-dose tafenoquine as dispersible tablets (50 mg) or film-coated tablets (150 mg). Dosing groups were assigned by body weight, predicted to achieve similar median exposures as the approved 300 mg dose for adults: patients who weighed 5 kg or more to 10 kg received 50 mg, those who weighed more than 10 to 20 kg received 100 or 150 mg, those who weighed more than 20 to 35 kg received 200 mg, and patients who weighed more than 35 kg received 300 mg. Population pharmacokinetic analysis was done to develop a paediatric population pharmacokinetic model. The primary outcome was the tafenoquine area under the concentration-time curve extrapolated to infinity (AUC[0-∞]) by patient body weight in the pharmacokinetic population (all patients who received tafenoquine with at least one valid pharmacokinetic sample) estimated from a paediatric population pharmacokinetic model. A key prespecified secondary outcome was 4-month recurrence-free efficacy. This trial is registered with ClinicalTrials.gov, NCT02563496. Between Feb 6, 2017, and Feb 17, 2020, 60 patients were enrolled into the study: 14 (23%) received tafenoquine 100 mg, five (8%) 150 mg, 22 (36%) 200 mg, and 19 (32%) 300 mg. The paediatric population pharmacokinetic model predicted adequate tafenoquine exposure at all doses. The predicted median AUC(0-∞) was 73·8 (90% prediction interval [PI] 46·9-117·0) μg × h/mL with the 50 mg dose for patients who weighed 5 kg or more to 10 kg, 87·5 (55·4-139·0) μg × h/mL with the 100 mg dose for body weight more than 10 to 20 kg, 110·7 (70·9-174·0) μg × h/mL with the 200 mg dose for body weight more than 20 to 35 kg, and 85·7 (50·6-151·0) μg × h/mL with the 300 mg dose for body weight more than 35 kg. 4-month recurrence-free efficacy was 94·7% (95% CI 84·6-98·3). Adverse events were consistent with previous studies, except for the seven (12%) of 60 patients who had post-dose vomiting or spitting with the 50 mg dispersed tablet. Following mitigation strategies, there were no additional occurrences of this adverse event. There were no deaths during the study. For the prevention of P vivax relapse in children, single-dose tafenoquine, including a dispersible formulation, had exposure, safety, and efficacy consistent with observations in adolescents and adults, notwithstanding post-dose vomiting. GlaxoSmithKline and Medicines for Malaria Venture. For the Vietnamese and Spanish translations of the abstract see Supplementary Materials section.

Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review.

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.

Exercise is medicine… when you enjoy it: Exercise enjoyment, relapse prevention efficacy, and health outcomes for youth within a drug and alcohol treatment service

ObjectiveEvidence for the effectiveness of exercise as therapy for youth substance use disorder (SUD) is scarce. In this study, we investigated associations between exercise enjoyment and recovery outcomes for youth undergoing residential SUD treatment. MethodUsing ecological momentary assessment, each week participants reported perceptions of exercise enjoyment, relapse prevention efficacy, self-esteem, and physical health, and associations between these variables were assessed at both between- and within-person levels. There were 97 participants (age: M = 17.5, SD = 1.57, range = 14 to 21; 37 female, 60 male), with a final sample of 64 due to participants (n = 33) discontinuing treatment within 2 weeks of commencement. Of the remaining sample, 50% (n = 32) completed 3 or more assessments, 40% (n = 26) completed 5 or more, and 25% (n = 16) completed 7 or more. ResultsRelapse prevention efficacy, self-esteem, and perceived physical health increased over time in the program. Youth who, on average, enjoyed exercise more had higher self-esteem, perceived physical health, and relapse prevention efficacy than those who enjoyed it less. Additionally, on occasions when youth enjoyed exercise more (relative to their own average), they reported higher self-esteem, perceived physical health, and relapse prevention efficacy than on occasions when they reported enjoying it less. ConclusionParticipation in—and importantly, enjoyment of—exercise was linked to key health indices and predictors of relapse for youth during SUD treatment. These findings demonstrate that participation in enjoyable structured exercise may provide an important component of successful SUD treatment.

Evaluating lurasidone as a treatment option for bipolar disorder

ABSTRACTIntroduction: Lurasidone has been approved in the United States as a monotherapy and adjunct for acute bipolar I depression, as well as an antipsychotic for patients with schizophrenia.Areas covered: Herein, the authors review the pharmacodynamics and pharmacokinetics of lurasidone as well and the major randomized clinical trials. The authors also provide their expert opinion.Expert opinion: Lurasidone has not been studied in patients with mania or bipolar psychosis. It has been studied, both as a monotherapy and adjunctive treatment to lithium or valproate, in acute depression and in prevention of recurrence of any mood episode in patients with bipolar disorder initially treated for bipolar depression or mania. It is approved in the United States for acute bipolar I depression. It has clinically meaningful treatment effect sizes for improvement in depression compared to placebo (0.51 monotherapy, 0.34 adjunct). The number needed to treat (NNT) for response with monotherapy was 5 (for both lower and higher dose groups), and for remission was 6 and 7 (for lower dose and higher dose groups, respectively); the NNT for adjunctive therapy was 7. It has not demonstrated efficacy in relapse prevention when added to a mood stabilizer but is safe in combination with other medications.

Immunomodulators use in a treatment of lower urogenital tract infections in women

Relevance. Women’ immune system indexes are dependent on cyclic hormonal influences. They decrease in the ovulation and in luteal phase of the menstrual cycle forming a “window of vulnerability” when there is an increased risk of infection with pathogenic and opportunistic microorganisms. Infected tissues inflammatory reaction in its turn aggravates these disorders. For these reasons, one should not only use empirical regimens of antimicrobial therapy covering wide spectrum of pathogens, but also to consider the possibility and need of a comprehensive approach with use of adjuvant treatment methods (detoxification, immunomodulatory, supportive therapy). Aim. To determine immunological changes in the body of women with lower genital tract infectious and inflammatory diseases and to justify a role of immunomodulators in increasing of treatment and relapse prevention efficacy. Materials and methods. In order to write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, eLIBRARY, etc.) for the last 2-22 years. The review included articles from peer-reviewed literature. Results. Due to its immunomodulatory, anti-inflammatory and detoxifying effects azoximer bromide contributes to an increase in treatment efficacy: elimination of pathogenic flora increases by 30%, clinical manifestations resolution occurs 2 times faster, a relapse risk reduces. Conclusion. To activate anti-infective immunity a comprehensive treatment with immunomodulators use is advisable.

S229. CAN LONG-ACTING INJECTABLE PALIPERIDONE DOSING BE OPTIMIZED WITH PLASMA LEVEL MEASUREMENTS?

BackgroundMost people with schizophrenia respond robustly to antipsychotic medication but are at very high risk of relapse if these medications are stopped. Long-term maintenance treatment with antipsychotic medication can dramatically reduce the risk of relapse. With long-acting injectable antipsychotic medication (LAI), adherence is documented which may account for superior efficacy in relapse prevention reported in some studies. It is known that plasma antipsychotic levels vary greatly across individuals with standard doses of LAIs. Establishing the lowest effective plasma levels for relapse prevention may also help in minimizing side effects that may contribute to problems with adherence. This study was carried out to describe the plasma paliperidone levels associated with clinical stability in patients receiving the LAI, paliperidone palmitate. We predicted that higher paliperidone plasma levels would be associated with lower subjective well-being and greater levels of sexual dysfunction.MethodsPatients with clinical diagnoses of schizophrenia and schizoaffective disorder attending specialized schizophrenia outpatient clinics at St. Joseph’s Healthcare Hamilton were invited to participate if they were receiving maintenance treatment with paliperidone palmitate. The study involved two visits, 3 to 4 weeks apart, on days that subjects were scheduled to receive consecutive injections of paliperidone palmitate. Plasma paliperidone levels and prolactin levels were drawn prior to the injection at Visit 1 and a second paliperidone levels was drawn at Visit 2. At Visit 1, a series of rating scales were also completed including the Subjective Well-being under Neuroleptic scale – Short version (SWN), the Changes in Sexual Functioning Questionnaire (CSFQ) and the Drug Attitude Inventory (DAI).ResultsTwenty-one subjects (11F/10M) provided informed consent for this study and had plasma paliperidone levels measured. Patients had been receiving LAI paliperidone for a mean of 18 months (SD = 11.4). Mean paliperidone levels at Visit 1 (n=21) and Visit 2 (n=18) were 34.9 ng/ml (SD = 20.0 ng/ml; range = 5.1–73.9 ng/ml) and 35.1 ng/ml (SD = 17.2 ng/ml; range = 9.0–67.5 ng/ml), respectively. Plasma paliperidone levels measured at Visit 2 were highly correlated with levels from Visit 1 (n=18; r = .89, p <.001). Plasma prolactin levels were correlated with levels of plasma paliperidone (n=21, r=0.56, p < .01). Lower scores on the CSFQ – Sexual Desire factor were associated with higher levels of paliperidone (n=19, r =-.61, p<.01) and prolactin (n=19, r=-.56, p <.01). Higher paliperidone levels were associated with more negative scores on the Drug Attitude Inventory (n=19, r=-0.49, p < .05). Plasma paliperidone levels were not associated with scores on the SWN (n=21, r=-.-02).DiscussionIn patients receiving maintenance treatment with paliperidone palmitate, plasma paliperidone levels varied approximately 15-fold. Higher paliperidone levels were associated with more negative attitudes towards medication and more severe deficits in sexual desire but not with subjective well-being. Many stable patients had plasma level close to the 20ng/ml level which in PET studies leads to 65% dopamine D2 receptor occupancy, a level reported to be associated with antipsychotic response. Our findings raise the possibility that maintaining patients at levels just above the 20ng/ml level may be sufficient for relapse prevention but may spare the adverse effects such as sexual dysfunction associated with higher plasma levels. These results suggest that measuring plasma levels in patients receiving paliperidone as a LAI may be of value in identifying the minimum effective dose for prevention of relapse and side effects.

Do antipsychotic drugs lose their efficacy for relapse prevention over time?

There is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review.

Levomilnacipran, the more active enantiomer of the serotonin and norepinephrine reuptake inhibitor (SNRI) milnacipran, was recently approved in the US for the treatment of major depressive disorder (MDD). The drug was developed as an extended release (ER) capsule formulation to allow for once-daily administration, thereby improving patient adherence. This agent differs from other available SNRIs in having a greater potency for inhibition of norepinephrine relative to serotonin reuptake. The efficacy of levomilnacipran ER has been evaluated in seven randomised, double-blind clinical trials (one Phase II and four Phase III trials, and two long-term efficacy studies). These studies documented that levomilnacipran is generally more effective than placebo for the treatment of MDD in the short-term, whereas no firm evidence exists on long-term efficacy for relapse prevention. Preliminary evidence suggests that levomilnacipran ER may be effective in improving not only depressive symptoms but also symptoms related to functioning (social life, work, and family life). Short-and longer-term studies found that the rate of withdrawal from levomilnacipran therapy due to adverse events was rather low. Moreover the drug appeared to be generally well tolerated. The most common adverse effects included nausea, hyperhidrosis, constipation, tachycardia, palpitations, erectile dysfunction and ejaculation disorder. As hypertension or orthostatic hypotension may occur in a few patients, the cardiovascular safety of levomilnacipran needs to be more extensively investigated especially on long-term treatment. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of levomilnacipran ER in the treatment of MDD in relation to currently available antidepressants including other SNRIs.

Impact of long-acting injectable antipsychotics on the illness progression in schizophrenia

Several data suggest an association between repeated psychotic episodes in patients with schizophrenia and poor outcomes on the course of the illness, including worse psychosocial functioning and quality of life, deterioration and stigma. However, there is strong evidence showing antipsychotic efficacy for relapse prevention in chronic and first-episode patients. Non-adherence and partial adherence to antipsychotic treatment is a common feature that has been detected in half or more patients with schizophrenia. The use of long-acting injectable antipsychotics (LAIs) is a valuable treatment option in order to prevent non-adherence rates and the risk of relapse in patients with schizophrenia. Nevertheless, LAIs are an underutilized, yet efficacious, treatment option. This underutilization is due, at least in part, to patients and clinicians reluctance to use LAIs because of needle pain, time constraints, stigmatization, and cost. However, results from recent meta-analytic evidences including randomized control trials (RCTs) are in contrast with those from naturalistic cohort studies or mirror-image studies in showing superiority of LAIs versus oral antipsychotics (OAPs) in preventing relapse in patients with schizophrenia. After a review of updated data, guidance will be offered concerning the appropriate use of LAIs in patients with schizophrenia.

Practitioner review: Long-term pharmacological treatment of pediatric bipolar disorder.

Although long-term treatment is a core aspect of the management of children and adolescents with bipolar disorder (BD), most clinical recommendations are based on results from short-term studies or adult data. In order to guide clinical practice, we review the efficacy and safety profile of mood stabilizers, antipsychotics, and other pharmacological strategies for the long-term treatment of BD in pediatric patients. A MEDLINE, EMBASE, Cochrane and PsycInfo search (inception through November 2013) was performed to identify prospective studies longer than 12weeks assessing the use of pharmacological strategies for the long-term treatment of BD in pediatric patients (0-18years of age). Four randomized controlled trials (RCT) [three placebo-controlled (assessing aripiprazole (2) and flax oil), and one head-to-head comparison of lithium vs. divalproex], and thirteen noncontrolled studies (six open-label studies assessing lithium or anticonvulsants, five assessing second-generation antipsychotics (SGAs) and four assessing combination strategies) were included in the review. Aripiprazole has shown efficacy for relapse prevention in children with pediatric bipolar disorder (PBD) 4-9years of age in one placebo-controlled RCT. Positive results have been reported in noncontrolled studies with quetiapine and lithium for relapse prevention, as well as with lithium, quetiapine, ziprasidone, and the combination of risperidone and divalproex or lithium for long-term symptom reduction in PBD. The most frequently reported adverse events in children and adolescents treated with lithium and anticonvulsants are gastrointestinal and neurological, whereas use of SGAs is mainly related to weight gain and sedation. According to the limited empirical evidence, aripiprazole can be useful for relapse prevention in children with PBD. Given the lack of consistent efficacy data, clinical decision making should be based on individual clinical aspects and safety concerns.

A randomized clinical trial of self-help intervention for smoking cessation: Research design, interventions, and baseline data

Tobacco smoking is the leading preventable cause of mortality and morbidity. Although behavioral counseling combined with pharmacotherapy is the most effective approach to aiding smoking cessation, intensive treatments are rarely chosen by smokers, citing inconvenience. In contrast, minimal self-help interventions have the potential for greater reach, with demonstrated efficacy for relapse prevention, but not for smoking cessation. This paper summarizes the design and methods used for a randomized controlled trial to assess the efficacy of a minimal self-help smoking cessation intervention that consists of a set of booklets delivered across time. Baseline participant recruitment data are also presented. Daily smokers were recruited nationally via multimedia advertisements and randomized to one of three conditions. The Usual Care (UC) group received a standard smoking-cessation booklet. The Standard Repeated Mailings (SRM) group received 8 booklets mailed over a 12-month period. The Intensive Repeated Mailings (IRM) group received 10 booklets and additional supplemental materials mailed monthly over 18months. A total of 2641 smokers were screened, 2349 were randomized, and 1874 provided data for analyses. Primary outcomes will be self-reported abstinence at 6-month intervals up to 30months. If the self-help booklets are efficacious, this minimal, low cost intervention can be widely disseminated and, hence, has the potential for significant public health impact with respect to reduction in smoking-related illness and mortality.

Antipsychotics, mood stabilisers, and risk of violent crime

SummaryBackgroundAntipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden.MethodsWe used linked Swedish national registers to study 82 647 patients who were prescribed antipsychotics or mood stabilisers, their psychiatric diagnoses, and subsequent criminal convictions in 2006–09. We did within-individual analyses to compare the rate of violent criminality during the time that patients were prescribed these medications versus the rate for the same patients while they were not receiving the drugs to adjust for all confounders that remained constant within each participant during follow-up. The primary outcome was the occurrence of violent crime, according to Sweden's national crime register.FindingsIn 2006–09, 40 937 men in Sweden were prescribed antipsychotics or mood stabilisers, of whom 2657 (6·5%) were convicted of a violent crime during the study period. In the same period, 41 710 women were prescribed these drugs, of whom 604 (1·4 %) had convictions for violent crime. Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics (hazard ratio [HR] 0·55, 95% CI 0·47–0·64) and by 24% in patients prescribed mood stabilisers (0·76, 0·62–0·93). However, we identified potentially important differences by diagnosis—mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder. The rate of violence reduction for antipsychotics remained between 22% and 29% in sensitivity analyses that used different outcomes (any crime, drug-related crime, less severe crime, and violent arrest), and was stronger in patients who were prescribed higher drug doses than in those prescribed low doses. Notable reductions in violent crime were also recorded for depot medication (HR adjusted for concomitant oral medications 0·60, 95% CI 0·39–0·92).InterpretationIn addition to relapse prevention and psychiatric symptom relief, the benefits of antipsychotics and mood stabilisers might also include reductions in the rates of violent crime. The potential effects of these drugs on violence and crime should be taken into account when treatment options for patients with psychiatric disorders are being considered.FundingThe Wellcome Trust, the Swedish Prison and Probation Service, the Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare.

A comparative study using Disulfiram and Naltrexone in alcohol-dependent adolescents

Aims: There are currently three agents approved by US-FDA for the pharmacotherapy of alcohol dependence, namely Naltrexone, Disulfiram and Acamprosate. The present study aimed to clinically compare Disulfiram (DSF) and Naltrexone (NTX) and their efficacy in relapse prevention in adolescents in a routine clinical setting.Design: Fifty-two adolescents with alcohol dependence with supportive family members that would ensure medical compliance and follow up were randomized to 6 months of treatment with DSF or NTX. Weekly group psycho-education was also provided. The psychiatrist, patient and family member were not blind to the treatment prescribed. Measurements: Alcohol consumption, craving and adverse events were recorded weekly for 4 months and then fortnightly. Serum gamma glutamyl transferase (GGT) was measured at the start and end of the study.Results: At the end of the study, 46 patients were still in contact. Relapse occurred at a mean of 93 days with DSF compared to 63 days for NTX. 84.61% patients on DSF remained abstinent compared to 53.85% with NTX.Conclusions: DSF was superior to NTX in promoting abstinence in adolescents with alcohol dependence having good family support.

Effectiveness of lurasidone vs. quetiapine XR for relapse prevention in schizophrenia: A 12-month, double-blind, noninferiority study

ObjectiveTo evaluate the relapse prevention efficacy of lurasidone compared with quetiapine XR (QXR) in adults patients with schizophrenia. MethodThis double-blind study evaluated the relapse prevention efficacy of 12months of flexible-dose treatment with lurasidone (40–160mg/day) compared with QXR (200–800mg/day), in outpatients with an acute exacerbation of chronic schizophrenia who had recently completed a 6-week placebo-controlled trial of treatment with either lurasidone or QXR. The primary endpoint, time-to-relapse, was analyzed using a Cox proportional hazards model in this noninferiority trial. ResultsThe Kaplan–Meier estimate of the probability of relapse over 12months was 23.7% for subjects receiving lurasidone vs. 33.6% for QXR. The hazard ratio [95% CI] for probability of relapse was 0.728 [0.410, 1.295] (log-rank p=0.280). Since the upper limit of the hazard ratio (1.295) was smaller than the prespecified noninferiority margin (1.93), noninferiority of lurasidone compared with QXR was demonstrated in this study. The probability of hospitalization at 12months was lower for the lurasidone group compared with the QXR group (9.8% vs. 23.1%; log-rank p=0.049). A significantly higher proportion of lurasidone subjects achieved remission at study endpoint compared with the QXR group (61.9% vs. 46.3%; p=0.043). Discontinuation rates due to AEs were similar for lurasidone and QXR (7% vs. 5%). Treatment with lurasidone was not associated with clinically significant changes in weight or metabolic parameters. ConclusionsTwelve months of treatment with lurasidone met noninferiority criteria, and was associated with higher rates of remission, and reduced risk of hospitalization compared with QXR. No clinically significant effects on weight or metabolic parameters were observed during maintenance treatment with lurasidone.

The Effect of a Multifaceted Efficacy Intervention on Exercise Behavior in Relatives of Colon Cancer Patients

Regular physical activity (PA) provides health benefits; however, at least 60% of the population fails to engage in the recommended amount of PA required to produce these health benefits. The primary purpose of the study was to examine over a 12-week structured exercise program the effect of a multifaceted efficacy intervention (MEI-i.e., task and specific types of self-regulatory efficacy) on objectively measured exercise behavior. Secondary purposes were to examine the effect of the MEI on both task and self-regulatory efficacy levels; and to determine whether efficacy beliefs could predict exercise behavior. Relatives of colon cancer patients (N = 140) were enrolled in an exercise program, and were randomized to either a MEI or attention control condition, and took part in classroom sessions. Behavior was assessed throughout the 12-week program using objective measures of frequency, duration, and intensity of exercise, and dropout rates, while self-reported task, barrier, scheduling, goal-setting, and relapse prevention efficacy were assessed at baseline and weeks4, 8, and 12. The MEI group exercised for longer duration in the early phase of the program (i.e., 0-4weeks); however, no significant differences were noted for exercise frequency and intensity. Differential dropout was found favoring the MEI group at weeks8 and 12. No treatment condition differences were found for reported efficacy beliefs. Proceeding self-efficacious beliefs were associated with objective measures of behavior. A MEI grounded in Social Cognitive Theory was partially effective in influencing colon cancer relatives' exercise behavior.

Drs. Nelson and Papakostas Reply

Drs. Nelson and Papakostas Reply

Supervised Disulfiram in Relapse Prevention in Alcohol-Dependent Patients Suffering From Comorbid Borderline Personality Disorder--A Case Series

Disulfiram is widely used to prevent alcoholic relapse. However, due to the intended adverse reaction with ethanol, some believe that its use is dangerous for patients with personality disorders or psychiatric comorbidities because of their increased risk of impulsivity or suicidal behaviour. We examined the safety and efficacy in relapse prevention of a series of alcoholics with borderline personality disorder (BPD). Case history study of patients diagnosed with BPD, prescribed disulfiram in a dose of 1.5-2.5 g/week, supervised by a physician in up to three brief contacts per week. Two out of eight patients remained completely abstinent during the supervised disulfiram therapy over a mean period of 9.25 months. Adherence to treatment was 18.44 +/- 21.78 months. The first relapse occurred after 1.38 +/- 1.41 months. The cumulated time of abstinence was 16.88 +/- 20.48 months. The overall tolerability was considered to be high; dizziness and fatigue appeared in all patients at the beginning of the therapy but did not persist. No serious adverse events or ethanol-disulfiram interactions were observed. No suicidal behaviour was reported. Although case observations should be interpreted with caution, supervised disulfiram seems to deserve further investigation in patients with comorbid BPD, for whom it appears to help prevent alcoholic relapse.

Evaluation of subjective effects of aripiprazole and methamphetamine in methamphetamine-dependent volunteers

A variety of neuropharmacological strategies are being pursued in the search for an effective treatment for methamphetamine (Meth) addiction. In this study, we investigated the safety and potential efficacy of aripiprazole, an antipsychotic agent acting on both dopamine and serotonin systems. We conducted a double-blind in-patient clinical pharmacology study to assess potential interactions between intravenous (i.v.) Meth (15 mg and 30 mg) and oral aripiprazole (15 mg). In addition, the effects of aripiprazole treatment on abstinence-related craving and cue-induced craving were evaluated. Participants included non-treatment-seeking, Meth-dependent patients (n=16), aged 18-45 yr, currently using Meth. Following baseline Meth dosing (15 mg and 30 mg), participants received 2 wk treatment with aripiprazole (n=8) or placebo (n=8). Participants then completed cue exposure sessions using neutral and Meth-related cues. Meth dosing (15 mg and 30 mg) was then repeated. Aripiprazole treatment had no effect on cue-induced Meth craving, or on daily baseline craving assessed over the course of medication treatment, although aripiprazole treatment was associated with increased craving independent of Meth dosing. Aripiprazole treatment was associated with significantly higher ratings on Addiction Research Center Inventory (ARCI) subscales reflecting euphoria and amphetamine-like effects following Meth dosing. Aripiprazole treatment was also associated with significant reductions in ratings of 'bad effects' and reductions on the ARCI subscale for sedation effects following Meth dosing. Aripiprazole treatment reduced the increase in systolic blood pressure following Meth dosing, but had no other effects on cardiovascular responses to Meth. Aripiprazole treatment did not alter the pharmacokinetics of Meth. These findings indicate that aripiprazole treatment appears to be safe in volunteers with Meth dependence, although the finding that aripiprazole increased some of the rewarding and stimulatory effects produced by acute Meth suggests that 15 mg aripiprazole is unlikely to be efficacious for the treatment of Meth dependence. Further research with lower doses of aripiprazole, possibly using study designs aimed at evaluating efficacy for relapse prevention, are needed before ruling out aripiprazole as a treatment for Meth dependence.