Clinical Global Impression Scores Research Articles

Electroconvulsive Therapy and Clozapine in Adolescents With Schizophrenia Spectrum Disorders

To evaluate the safety and effectiveness of the combination of electroconvulsive therapy (ECT) and clozapine compared to ECT with other antipsychotics or benzodiazepines in a sample of adolescents diagnosed with schizophrenia spectrum disorders. Data regarding 28 adolescent subjects aged 13 to 18 with diagnoses of schizophrenia spectrum disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and treated with ECT were retrospectively collected. Twelve subjects were also treated with clozapine and 16 with other antipsychotics or benzodiazepines during ECT course and follow-up. Electroconvulsive therapy parameters and adverse effects were assessed using a systematic protocol. Positive and Negative Syndrome Scale and Clinical Global Impression scores before ECT and after acute ECT, and rate of rehospitalization during 1-year follow-up were used to assess effectiveness. Response was defined as a 20% decrease in Positive and Negative Syndrome Scale scores. No differences were observed in the mean charge needed to induce seizure and electroencephalographic duration, but there was a slight difference in the current used. The nonclozapine group showed greater restlessness and agitation, although no differences were found in other adverse effects. The percentage of responders was similar: 66.7% in the clozapine group and 68.8% in the nonclozapine group. However, the rate of rehospitalization was lower in the patients treated with clozapine during 1-year follow-up (7.1%) compared to that of the nonclozapine group (58.3%) (P = 0.009). The main findings of this study were that combining ECT with clozapine, compared to ECT with other antipsychotics or benzodiazepines, was safe and that both treatments were equally effective. Charges needed to induce seizure were similar in both groups. Patients treated with clozapine during 1-year follow-up had a lower rate of rehospitalization.

Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes

Alcoholism is a chronic psychiatric disorder affecting neural pathways that regulate motivation, stress, reward and arousal. Brain-derived neurotrophic factor (BDNF) regulates mood, response to stress and interacts with neurotransmitters and stress systems involved in reward pathways and addiction. Aim of the study was to evaluate the association between a single nucleotide polymorphism (BDNF Val66Met or rs6265) and alcohol related phenotypes in Caucasian patients. In ethnically homogenous Caucasian subjects of the Croatian origin, the BDNF Val66Met genotype distribution was determined in 549 male and 126 female patients with alcohol dependence and in 655 male and 259 female healthy non-alcoholic control subjects. Based on the structured clinical interview, additional detailed clinical interview, the Brown-Goodwin Scale, the Hamilton Rating Scale for Depression and the Clinical Global Impression scores, alcoholic patients were subdivided into those with or without comorbid depression, aggression, delirium tremens, withdrawal syndrome, early/late onset of alcohol abuse, prior suicidal attempt during lifetime, current suicidal behavior, and severity of alcohol dependence. The results showed no significant association between BDNF Val66Met variants and alcohol dependence and/or any of the alcohol related phenotypes in either Caucasian women, or men, with alcohol dependence. There are few limitations of the study. The overall study sample size was large (N=1589) but not well-powered to detect differences in BDNF Val66Met genotype distribution between studied groups. Healthy control women were older than female alcoholic patients. Only one BDNF polymorphism (rs6265) was studied. In conclusion, these data do not support the view that BDNF Val66Met polymorphism correlates with the specific alcohol related phenotypes in ethnically homogenous medication-free Caucasian subjects with alcohol dependence.

Sodium Oxybate for Narcolepsy with Cataplexy: Systematic Review and Meta-Analysis

To assess the efficacy and safety of sodium oxybate (SXB) in narcolepsy-cataplexy patients. Systematic review and meta-analysis. Adults with narcolepsy-cataplexy. SXB. Electronic databases (e.g., MEDLINE) and references of included studies were searched to identify randomized controlled trials (RCTs) assessing the efficacy and safety of SXB for patients with narcolepsy-cataplexy. Risk of bias was appraised using the Cochrane risk of bias tool. Meta-analysis was conducted in Review Manager Version 5. Six RCTs and 5 companion reports were included after screening 14 full-text articles and 483 citations. All were private-industry funded. SXB (usually 9 g/night) was superior to placebo for reducing mean weekly cataplexy attacks (n = 2 RCTs, mean difference [MD]: -8.5, 95% CI: -15.3, -1.6), increasing maintenance wakefulness test (MWT) (n = 2, MD: 5.18, 95% CI: 2.59-7.78), reducing sleep attacks (n = 2, MD: -9.65, 95% CI: -17.72, -1.59), and increasing Clinical Global Impression scores (n = 3, relative risk, RR: 2.42, 95% CI: 1.77-3.32). SXB did not significantly increase REM sleep versus placebo (n = 2, MD: -0.49, 95% CI: -3.90, 2.92). Patients receiving SXB had statistically more adverse events versus placebo, including nausea (n = 3, relative risk [RR]: 7.74, 95% CI: 3.2, 19.2), vomiting (n = 2, RR: 11.8, 95% CI: 1.6, 89.4), and dizziness (n = 3, RR: 4.3, 95% CI: 1.1, 16.4). Enuresis was not significantly different from placebo (n = 2, RR: 2.6, 95% CI: 0.8, 9.8). All meta-analyses had minimal statistical heterogeneity (p-value > 0.1). Narcolepsy patients on SXB have significant reductions in cataplexy and daytime sleepiness. SXB is well tolerated in patients with narcolepsy, and most adverse events were mild to moderate in severity.

How can we measure endometriosis-associated pelvic pain?

Purpose The aim of our work was to explore which of the most commonly used pain scales is best suited to assess treatment success in endometriosis therapy and, therefore, qualifies best to be used as primary endpoint for clinical studies in this indication. Methods We compared patient's responses on the different pain scales Visual Analog Scale, Biberoglu and Behrman Score, and SF-36 Bodily Pain Subscale with the Clinical Global Impression score. Parametric and non-parametric correlation coefficients and effect sizes were calculated. Results A total of 428 patients with endometriosis-associated pelvic pain from three studies were included in our analyses. Their mean age was 31.4±6.3 years and their mean pain score on the visual analog scale was 58.1±21.9 at baseline. The highest correlation with the Clinical Global Impression score was observed for the visual analog scale followed by the B&B pelvic pain item. The highest effect sizes were found for dysmenorrhea and SF-36 bodily pain subscale followed by the visual analog scale. Conclusions A general measure of endometriosis-related pain can be recommended as primary endpoint in clinical trials to assess painful symptoms of endometriosis. In addition, a disease-specific quality of life tool is recommended to help interpret impact on patients’ daily activities.

Improvement of Apathy After Levofloxacin Treatment

Apathy is common in various neurological conditions. A caregiver of a patient with normal pressure hydrocephalus and cognitive decline repeatedly reported improvement in apathy, social interaction, and ability to perform activities of daily living after treatment with levofloxacin for upper respiratory infections. We sought to determine whether this effect could be objectively supported and replicated outside the context of infection. An n-of-1 study was performed using 2 treatment and 2 nontreatment phases during an infection-free interval. Treatment arms consisted of 10-day courses of levofloxacin 500 mg daily. The evaluating investigator, caregiver, and patient were blind to treatment assignments. Measures included the Apathy Evaluation Scale (clinician and caregiver), Apathy Inventory (clinician and caregiver), Northwestern University Disability Scale, Disability Assessment for Dementia, and caregiver clinical global impression score. The patient had less apathy and disability during 2 periods of treatment with levofloxacin 500 mg daily compared with periods without levofloxacin treatment. Caregiver clinical global impression scores were significantly better during days on treatment compared with off treatment (P=0.0007). Evaluation of a single patient suggests that improvement in apathy may be a previously undescribed effect of levofloxacin. Further study is warranted.

Greater Responsiveness to Donepezil in Alzheimer Patients With Higher Levels of Acetylcholinesterase Based on Attention Task Scores and a Donepezil PET Study

The aim of the study was to predict donepezil responders among patients with Alzheimer disease (AD) based on cognitive tests and positron emission tomography. The Mini-Mental State Examination, Digit Symbol subtest (DigSm) of Wechsler Adult Intelligence Scale Revised, and Trail-Making Test A were administered for 80 patients with AD to assess global function, attention, and executive function, respectively. The same tests and the Clinical Global Impression (CGI) scale were conducted after treatment with oral donepezil (5 mg/d) for 6 months (study 1). [C]-Donepezil positron emission tomography examinations were conducted before and after treatment for 30 randomly selected patients. The distribution volume (DV), which indicates the density of donepezil-binding sites, was calculated using Logan graphical analysis (study 2). In study 1, 35 patients were identified as responders based on the CGI and Mini-Mental State Examination changes. These patients had higher baseline DigSm scores compared with nonresponders. In study 2, 15 patients were responders. DigSm correlated with DV at baseline. DV at baseline and %DV change in responders were higher than in nonresponders, and these variables correlated with ΔDigSm and CGI scores. Higher baseline attention may predict responsiveness to donepezil in patients with AD, and higher acetylcholinesterase levels result in a greater clinical effect.

Effects of Paroxetine on Plasma Concentrations of Aripiprazole and Its Active Metabolite, Dehydroaripiprazole, in Japanese Patients With Schizophrenia

The effects of paroxetine coadministration on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, were studied in 14 Japanese patients with schizophrenia. The patients had been treated with aripiprazole (24 mg/d in 5 cases, 12 mg/d in 5 cases, and 6 mg/d in 4 cases) for at least 2 weeks. Paroxetine 10 mg/d was coadministered during the first week, and the dose was increased to 20 mg/d during the second week. Blood samples were taken 3 times, before the start of paroxetine and then 1 and 2 weeks after paroxetine coadministration. On the same days, the severity of illness and extrapyramidal adverse effects were evaluated by the clinical global impressions and the Drug-Induced Extra-Pyramidal Symptoms Scale, respectively. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection. Plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole during coadministration of paroxetine 10 and 20 mg/d were significantly (P < 0.05) higher (1.5-fold and 1.7-fold; 1.4-fold and 1.5-fold) than those before paroxetine coadministration. Those values during coadministration of paroxetine 20 mg/d were also significantly (P < 0.05) higher (1.1-fold and 1.1-fold) than those during coadministration of paroxetine 10 mg/d. Plasma concentrations of dehydroaripiprazole were unchanged throughout the study period. The mean clinical global impression score was significantly (P < 0.05) higher during the paroxetine 10 mg/d than that before coadministration, whereas the Drug-Induced Extra-Pyramidal Symptoms Scale scores remained unchanged during the study. This study suggests that lower doses (10-20 mg/d) of paroxetine coadministration increase plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole.

Efficacy and safety of combination of risperidone and haloperidol with divalproate in patients with acute mania

Objective. The current study evaluated the efficacy and safety of risperidone and haloperidol as an adjunctive agent in combination with divalproate in patients with an episode of acute mania. Methods. This 6-week randomized, single-blind study was conducted in psychiatric wards of a mental hospital. A total of 41 patients were randomly assigned to the risperidone (risperidone plus divalproate) or haloperidol groups (haloperidol plus divalproate). Efficacy was assessed by changes in symptom rating scales [Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) scores]. Safety and tolerability were assessed by monitoring the Extrapyramidal Symptom Rating Scale (ESRS) and Hamilton Rating Scale for depression. Results. Mean doses at baseline, and at weeks 4 and 6 were 3.77, 4.95 and 5.00 mg/day of risperidone and 5.89, 9.95 and 8.58 mg/day of haloperidol, respectively. Risperidone was shown to have significant anti-manic effects which was observed as early as week 1, following start of treatment. The BPRS scores were in favor of risperidone at week 2. Patients receiving risperidone exhibited significant greater global improvement on the CGI, as early as week 2 and over the entire treatment period, than haloperidol after 4 weeks of treatment. The ESRS at endpoint were significantly higher in the haloperidol patients. Conclusions. Risperidone plus divalproate was more efficacious than haloperidol plus divalproate for treatment of acute mania, and was well tolerated due to its evidence showing rapid anti-manic action, effective and sustained control of manic and psychotic symptoms and a favorable safety and tolerability profile in acute mania.

Rasagiline

Rasagiline (Azilect®), a selective, irreversible, monoamine oxidase-B inhibitor, is available in the EU, the US and in several other countries worldwide, including Canada and Israel. It is indicated for the treatment of idiopathic Parkinson's disease as monotherapy or as adjunctive therapy to levodopa in patients [corrected]with end-of-dose fluctuations in the EU and for the treatment of adult patients with the signs and symptoms of idiopathic Parkinson's disease in the US. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of rasagiline as monotherapy or as adjunctive therapy to levodopa in patients with Parkinson's disease. Oral rasagiline as monotherapy or as adjunctive therapy to levodopa was effective in the symptomatic treatment of adult patients with Parkinson's disease participating in double-blind, placebo-controlled, multinational studies. In patients with early Parkinson's disease, monotherapy with rasagiline 1 mg/day (recommended dosage) significantly slowed the rate of worsening (i.e. an increase in the Unified Parkinson's Disease Rating Scale [UPDRS] score) in the ADAGIO and TEMPO studies, with the results from the ADAGIO study for rasagiline 1 mg/day suggesting a slowing of clinical progression. However, at the higher dosage of 2 mg/day, rasagiline met the primary endpoint in the TEMPO study and the first, but not the second, of three hierarchical primary endpoints in the ADAGIO study. Compared with delayed-start rasagiline monotherapy, early initiation was associated with a slower long-term progression of the clinical signs and symptoms of Parkinson's disease in the TEMPO study. As adjunctive therapy to levodopa in the LARGO and PRESTO studies, rasagiline 0.5 and/or 1 mg/day significantly reduced the total daily 'off' time (primary efficacy endpoint) and significantly improved the Clinical Global Impression score, the UPDRS activities of daily living subscale score during 'off' time and the UPDRS motor subscale score during 'on' time compared with placebo in patients with advanced Parkinson's disease. Although rasagiline showed neuroprotective properties both in vitro and in vivo, identifying its potential to slow clinical progression in the clinical setting has been elusive to date and was not definitively demonstrated in the studies discussed in this article. Additional rasagiline studies specifically designed to assess the clinical progression of Parkinson's disease while addressing the potentially confounding factors of the delayed-start study design would therefore be of interest. As monotherapy or as adjunctive therapy to levodopa, rasagiline was generally well tolerated, with the frequency and nature of treatment-emergent adverse events generally similar across clinical studies and between rasagiline and placebo groups. Therapy with rasagiline appears to be associated with a low incidence of cognitive and behavioural adverse events. Thus, oral rasagiline as monotherapy or as adjunctive therapy to levodopa provides a useful option in the treatment of adult patients with Parkinson's disease.

A randomized, double-blind, placebo-controlled clinical trial of acamprosate in alcohol-dependent individuals with bipolar disorder: a preliminary report

Alcohol use disorders commonly co-occur with bipolar disorder and are associated with a more severe course of bipolar illness, yet treatment research in this important clinical population is scarce. The current study assessed the effects of acamprosate on alcohol use and mood symptoms in subjects with co-occurring bipolar disorder and active alcohol dependence. Thirty-three adults meeting criteria for bipolar I or bipolar II disorder and current alcohol dependence were randomized to receive add-on acamprosate (1998 mg/day) or placebo while concurrently maintained on mood stabilizing medications. Participants were assessed weekly for frequency and quantity of alcohol consumption and general clinical severity for eight weeks. Depressive symptoms, manic symptoms, and alcohol craving were assessed biweekly. Biomarkers of alcohol use were assessed at study baseline and endpoint. Of the 33 subjects randomized, 23 (69.7%) completed all active phase visits. Over the trial as a whole, no statistically significant treatment differences were detected in drinking outcomes. Post-hoc analysis revealed lower Clinical Global Impression scores of substance use severity in acamprosate-treated participants in weeks 7-8 of the trial. No significant differences in depressive symptoms, manic symptoms, or adverse events were observed between groups. Acamprosate was well-tolerated, with no worsening of depressive or manic symptoms, and appeared to confer some clinical benefit in study completers in the last two weeks of the trial. Larger studies of longer duration are required to fully explore the utility of acamprosate in this population.

Reduction of Tinnitus Severity by the Centrally Acting Muscle Relaxant Cyclobenzaprine: An Open-Label Pilot Study

Tinnitus, the phantom perception of sounds, is a highly prevalent disorder. Although a wide variety of drugs have been investigated off label for the treatment of tinnitus, there is no approved pharmacotherapy. We report an open-label exploratory pilot study to assess the effect of muscle relaxants acting on the central nervous system on tinnitus patients. Cyclobenzaprine at high (30 mg) and low doses (10 mg), orphenadrine (100 mg), tizanidine (24 mg) and eperisone (50 mg) were administered to a maximum of 20 patients per group over a 12-week period. High-dose cyclobenzaprine resulted in a significant reduction in the Tinnitus Handicap Inventory (THI) score between baseline and week 12 in the intention-to-treat sample. On the other hand, other treatments were not effective. These results were confirmed in an explorative analysis where baseline corrected THI and Clinical Global Impression scores at week 12 were compared between groups. The present open trial presents a new promising pharmacotherapy for tinnitus that should be validated in placebo-controlled double-blind trials.

P-771 - The use of new generation antipsychotics in people with intellectual disability

The New Generation Antipsychotics (NGAs) are frequently used in People with Intellectual Disability (PWID), especially for treating aggressive behaviour. However there is very limited research to fully establish evidence-based approaches for their use in this population. Aim To evaluate the effectiveness of NGAs, in particular olanzapine and risperidone, in treating aggressive behaviour in PWID for who previous medication with First Generation Antipsychotics (FGAs) were not effective. Method 62 subjects with intellectual disability underwent to a two-arm, parallel group pragmatic trial of olanzapine and risperidone with balanced randomisation and blind assessment of outcomes after a switch from a treatment with FGAs. Psychiatric disorders were evaluated by Diagnostic Assessment for the Severely Handicapped (DASH). Aggressive behaviour was assessed by Overt Aggression Scale (OAS) and clinical outcome by Clinical Global Impression (CGI) Scale. Side effects were assessed with specific scales, laboratory and instrumental tests. Results Both risperidone and olanzapine resulted to be more effective than FGAs in reducing aggressive behavior and in treating concurrent psychiatric disorders. The degree of improvement in our sample was very high for OAS and CGI scores. Both compounds resulted to be well tolerated, with side-effects similar to those encountered in other patient populations. Conclusion Our findings seem to confirm previous literature on that olanzapine and risperidone can be effective in reducing aggressive behaviour in PWID. Although NGAs have shown greater efficacy and safety than FGAs, there is still a need for controlled trial and more methodically researches to confirm their benefit.

O-35 - Agomelatine versus venlafaxine in the treatment of anhedonia in major depressive subjects: a pilot study

The primary aim of the present study was to compare the effects of agomelatine and venlafaxine XR on anhedonia in patients with Major Depressive Disorder. Secondary endpoints were to test its antidepressant and anxiolytic efficacy. Sixty patients received randomly agomelatine (25–50 mg/day; N = 30) or venlafaxine XR (75-150 mg/day, N = 30). Psychopathological assessment was performed at baseline and over eight weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impression (CGI). Both groups showed an overall significant reduction in times for SHAPS, HAM-D and HAM-A. A significant difference between times was observed for SHAPS scores in Agomelatine group: from baseline of 6.5 (T0) to 4 at week 1 (−2.5) (T1), 3.5 at week 2 (−3.0) (T2), and 3.4 at week 8 (−2.9) (T3). In the venlafaxine group, the reduction on SHAPS scores was not significant between visits (p = .08). At the last observation a significant difference between groups in favour of agomelatine was observed for SHAPS scores (D = 2.2; p < 0.05); moreover, only patients treated with agomelatine showed a significant improvement in CGI scores from baseline (D = 2.94, p < 0.05). Agomelatine showed significantly greater efficacy on anhedonia and at least similar antidepressant efficacy to venlafaxine in patients with Major Depressive Disorder, with a better clinical improvement. Therefore, the efficacy of agomelatine on anhedonia, a potential trait marker of vulnerability for depression, holds particular importance in the treatment of patients with depressive features.

Effectiveness and tolerability of transdermal rivastigmine in the treatment of Alzheimer&amp;rsquo;s disease in daily practice

BackgroundOral cholinesterase inhibitors at doses efficacious for the treatment of Alzheimer’s disease (AD) are often prematurely discontinued due to gastrointestinal side effects. In controlled clinical trials, transdermal rivastigmine demonstrated less such effects at similar efficacy. The current study aimed to verify the validity of this data in daily practice.MethodsThis was a prospective, multicenter, observational study on transdermal rivastigmine in Germany. Eligible patients were those with AD who had not yet been treated with rivastigmine. Outcome measures were changes in clock-drawing test, Mini-Mental State Examination (MMSE), Caregiver Burden Scale, Clinical Global Impression (CGI), physicians’ assessments of tolerability, and the incidence of adverse events (AEs) over 4 months of treatment.ResultsIn 257 centers 1113 patients were enrolled; 614 women and 499 men, mean age 76.5 years. In 58% of patients AD was treated for the first time and in 42% therapy was switched to transdermal rivastigmine, mostly due to lack of tolerability (13.6%) or effectiveness (26.9%). After 4 months, 67.4% of patients were on the target dose of 9.5 mg/day and 21.8% were still on 4.6 mg/day. MMSE significantly improved in patients with and without pretreatment (ΔMMSE, 0.9 ± 3.4 and 0.8 ± 3.4, respectively, both P < 0.001); the CGI score improved in 60.9% and 61.3% of patients, respectively. Overall 11.7% of patients had AEs, mainly affecting the skin or the gastrointestinal tract; in 1.1% of cases AEs were serious; 14.7% of patients discontinued therapy, 6.0% due to AEs. With rivastigmine treatment the percentage of patients taking psychotropic comedication decreased, particularly in first-time treated rivastigmine patients (from 27.1% to 22.6%; P < 0.001).ConclusionResults were in line with data from controlled clinical trials. Switching from any other oral acetylcholinesterase inhibitor to transdermal rivastigmine may improve cognition.

Supervised team management, with or without structured psychotherapy, in heavy users of a mental health service with borderline personality disorder: a two-year follow-up preliminary randomized study

BackgroundIndividuals affected by severe Borderline Personality Disorder (BPD) are often heavy users of Mental Health Services (MHS). Short-term treatments currently used in BPD therapy are useful to target disruptive behaviors but they are less effective in reducing heavy MHS use. Therefore, alternative short-term treatments, less complex than long-term psychodynamic psychotherapies but specifically oriented to BPD core problems, need to be developed to reduce MHS overuse. This study aimed to evaluate the efficacy of adding Sequential Brief Adlerian Psychodynamic Psychotherapy (SB-APP) to Supervised Team Management (STM) in BPD treatment compared to STM alone in a naturalistic group of heavy MHS users with BPD. Effectiveness was evaluated 6 times along a two-year follow-up.MethodsThirty-five outpatients who met inclusion criteria were randomly assigned to two treatment groups (STM = 17; SB-APP = 18) and then compared. Clinical Global Impression (CGI) and CGI-modified (CGI-M) for BPD, Global Assessment of Functioning (GAF), State-Trait Anger Expression Inventory (STAXI), and Symptom Checklist-90 Revised (SCL-90-R) were administered at T1, T3, T6, T12, T18 and T24. At T12 the Working Alliance Inventory-Short Form (WAI-S) was also completed. At the one-year follow-up, SB-APP group did not receive any additional individual psychological support. MHS team was specifically trained in BPD treatment and had regular supervisions.ResultsAll patients improved on CGI, GAF, and STAXI scores after 6 and 12 months, independently of treatment received. SB-APP group showed better outcome on impulsivity, suicide attempts, chronic feelings of emptiness, and disturbed relationships. We found a good stabilization at the one year follow-up, even after the interruption of brief psychotherapy in the SB-APP group.ConclusionsAlthough STM for BPD applied to heavy MHS users was effective in reducing symptoms and improving their global functioning, adding a time-limited and focused psychotherapy was found to achieve a better outcome. In particular, focusing treatment on patients' personality with a specific psychotherapeutic approach (i.e. SB-APP) seemed to be more effective than STM alone.Trial RegistrationClinicalTrials.gov: NCT1356069

Long-term efficacy and safety of gabapentin enacarbil in Japanese restless legs syndrome patients

Several short- and long-term studies conducted in Europe/North America have demonstrated good efficacy and tolerability of 600-1800 mg gabapentin enacarbil (GEn). However, no studies have evaluated the efficacy of long-term treatment with GEn in Asian patients. Therefore, the objective of this study was to evaluate the efficacy and safety of long-term treatment with GEn in Japanese patients with restless legs syndrome (RLS) in a multicenter open-label study. RLS patients aged 20-80 years were allocated to receive oral GEn 1200 mg/day for a treatment period of 52 weeks. International Restless Legs Syndrome Scale (IRLS) score, investigator- and patient-rated Clinical Global Impression (CGI) scores, Pittsburgh Sleep Quality Index (PSQI) total scores and subscores, and short form (SF)-36 subscores were assessed, and adverse events (AEs) were monitored. In 181 patients (mean age, 54.9±12.2 years; BMI, 23.0±2.6 kg/m²) IRLS score decreased from 24.4±0.4 at baseline to 6.3±0.6 at week 52, with a reduction of -18.0±0.6. The IRLS responder rate was 80.3% at week 52. ICGI and PCGI responder rates were 87.1% and 87.1%, respectively. PSQI and SF-36 also showed significant improvements. AEs were reported in 96.2% of patients but remained mild-to-moderate in nearly all the cases. Serious AEs occurred in 1.6%. Dizziness and somnolence were noted in 46.2% and 41.2% of patients, respectively, and mostly occurred during the first 4 weeks. No episodes of augmentation were reported. In conclusion, long-term treatment with GEn improved RLS symptoms as well as investigator- and patient-reported outcomes in Japanese patients with moderate-to-severe RLS, with an acceptable safety profile. Randomized, double-blind, placebo/active-controlled trials are desirable to confirm these preliminary results.

Follow-up study on refractory schizophrenia with brain stereotaxis therapy

To determine the long-term effect and security of refractory schizophrenia with brain stereotaxis multi-target therapy technique. A total of 87 patients with refractory schizophrenia were treated with brain stereotaxis multi-target therapy and were followed up over 2 years. The scores of Clinical Global Impression, Brief Psychiatric Rating Scale, Positive and Negative Symptom Scale, Wechsler Adult Intelligence Scale, Wechsler Memory Scale, Actives of Daily Living, and Social Disability Screening Schedule were compared before and after the operation. Of the 87 patients, 40 obviously improved, 24 improved, 12 improved little, 7 did not change. None grew worse, 1 died, and 3 shed. There was a significant difference in the scales before and after the operation (P<0.01). No severe complications and sequelae occurred. Stereotaxic multi-target therapy is effective and safe for refractory schizophrenia. After the operation, drug therapy should be maintained and recovery of social function is helpful.

Measuring psychopathology by HAMD and CGI ratings to guide antidepressant treatment under naturalistic conditions

Introduction: Clinical trials have shown that early improvement on the Hamilton Depression Rating (HAMD) scale is highly predictive for later response. The aim of this study was to find out if psychopathological rating using either the HAMD or Clinical Global Impression (CGI) scale is also predictive under every day conditions. Methods: Inpatients with a major depressive disorder were included and rated using the HAMD scale at baseline and on days 14 and 35 and by the CGI scale on day 14. On day 35, HAMD sum score reduction by at least 50% was defined as response. Results: 55 patients were included. An HAMD score reduction of ≥ 20% on day 14 was highly predictive (p = 0.01) for both response and non-response on day 35. HAMD sum scores correlated well on the CGI scale (p = 0.000). Patients with “much” or “minimal” improvement on the CGI scale on day 14 exhibited a more pronounced reduction on the HAMD scale on day 35 than patients who were “unchanged” or “worse” according to CGI (42 or 32% vs. 31 or 8%, respectively). CGI rating on day 14 predicted response on day 35 with only 44% specificity (p = 0.255). Regression analysis revealed that CGI explained only 5.1% of the variance of response on day 35 (chix2 = 1,5; df = 1; p = 0.209). Conclusion: From the findings that HAMD score changes from baseline to day 14 but not CGI scores on day 14 are predictive for later response it is concluded that HAMD but not CGI rating can be used under every day conditions to guide antidepressant pharmacotherapy.

What is the optimal dose of escitalopram for the treatment of obsessive–compulsive disorder? A naturalistic open-label study

This study explored the efficacy and tolerability of very high doses (maximum dose of >40 mg/day), high doses (maximum dose of 25-40 mg/day), and standard doses (maximum dose of ≤20 mg/day) of escitalopram (ESC) as an anti-obsessive-compulsive disorder treatment in a naturalistic clinical setting. We reviewed the medical records of all patients with obsessive-compulsive disorder (n=246) who had taken ESC between May 2006 and September 2009, and assigned Clinical Global Impression (CGI) scores, retrospectively. Of the total sample, 24.4, 38.2, and 37.4% patients received very high, high, and standard doses of ESC, and the mean daily maximum doses of ESC were 57.3±12.0 mg, 33.9±5.4 mg, and 13.4±5.8 mg, respectively. The CGI-Severity scores in each group decreased significantly after treatment with ESC, as evidenced by response rates (i.e. CGI-Improvement scores of 1 or 2) of 46.3, 43.2, and 26.2%, respectively. Although some adverse events increased in a dose-dependent manner, most could be managed with an ESC dose adjustment. These results imply that doses less than or equal to 40 mg/day ESC are sufficient for symptomatic improvement with good tolerability for most patients. Very high doses of ESC, on the other hand, can be considered for patients with inadequate therapeutic responses to the administration of 40 mg/day ESC.

A 25-year follow-up of patients admitted to methadone treatment for the first time: Mortality and gender differences

Introduction We conducted a follow-up study to evaluate the outcome of a heroin-dependent population 25 years after their first enrollment in methadone maintenance treatment (MMT). We assessed mortality in the sample plus actual drug use, treatment, and medical factors associated with drug dependence, focusing on possible gender differences. Methods Prospective follow-up study of 214 heroin-dependent patients consecutively admitted for MMT between 1980 and 1984 in the Asturias Public Health Service. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated. An ad-hoc protocol on drug misuse and treatment, drug-related morbidity and Clinical Global Impression (CGI) scores were assessed in the survivors' sample. Results Information was received on 159 subjects, 106 of whom were deceased. Men accounted for 76.2% of the study cohort. Over the 25-year follow-up period, the SMR was 22.51 (95% CI = 22.37–22.64). In the survivors sample, 39.6% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 47.2% and hepatitis B/C in 81.1%; current heroin use was reported by 22.6%. There were no gender differences in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 25-year follow-up compared with 31.1% of males. Conclusions This study confirms the high mortality of heroin addicts even after enrollment in MMT. Severity of the addiction in terms of mortality was similar in both genders. Women who survived the 25-year follow-up were more likely to have stopped using heroin than men.