Outpatient Trial Research Articles

Bulimia nervosa‐nonpurging subtype: Closer to the bulimia nervosa‐purging subtype or to binge eating disorder?

DSM-5 has dropped subtyping of bulimia nervosa (BN), opting to continue inclusion of the somewhat contentious diagnosis of BN-nonpurging subtype (BN-NP) within a broad BN category. Some contend however that BN-NP is more like binge eating disorder (BED) than BN-P. This study examines clinical characteristics, eating disorder symptomatology, and Axis I comorbidity in BN-NP, BN-P, and BED groups to establish whether BN-NP more closely resembles BN-P or BED. Women with BN-P (n = 29), BN-NP (n = 29), and BED (n = 54) were assessed at baseline in an outpatient psychotherapy trial for those with binge eating. Measures included the Structured Clinical Interviews for DSM-IV, Eating Disorder Examination, and Eating Disorder Inventory-2. The BN-NP subtype had BMIs between those with BN-P and BED. Both BN subtypes had higher Restraint and Drive for Thinness scores than BED. Body Dissatisfaction was highest in BN-NP and predicted BN-NP compared to BN-P. Higher Restraint and lower BMI predicted BN-NP relative to BED. BN-NP resembled BED with higher lifetime BMIs; and weight-loss clinic than eating disorder clinic attendances relative to the BN-P subtype. Psychiatric comorbidity was comparable except for higher lifetime cannabis use disorder in the BN-NP than BN-P subtype These results suggest that BN-NP sits between BN-P and BED however the high distress driving inappropriate compensatory behaviors in BN-P requires specialist eating disorder treatment. These results support retaining the BN-NP group within the BN category. Further research is needed to determine whether there are meaningful differences in outcome over follow-up.

DiAs Web Monitoring: A Real-Time Remote Monitoring System Designed for Artificial Pancreas Outpatient Trials

Developments in an artificial pancreas (AP) for patients with type 1 diabetes have allowed a move toward performing outpatient clinical trials. "Home-like" environment implies specific protocol and system adaptations among which the introduction of remote monitoring is meaningful. We present a novel tool allowing multiple patients to monitor AP use in home-like settings. We investigated existing systems, performed interviews of experienced clinical teams, listed required features, and drew several mockups of the user interface. The resulting application was tested on the bench before it was used in three outpatient studies representing 3480 h of remote monitoring. Our tool, called DiAs Web Monitoring (DWM), is a web-based application that ensures reception, storage, and display of data sent by AP systems. Continuous glucose monitoring (CGM) and insulin delivery data are presented in a colored chart to facilitate reading and interpretation. Several subjects can be monitored simultaneously on the same screen, and alerts are triggered to help detect events such as hypoglycemia or CGM failures. In the third trial, DWM received approximately 460 data per subject per hour: 77% for log messages, 5% for CGM data. More than 97% of transmissions were achieved in less than 5 min. Transition from a hospital setting to home-like conditions requires specific AP supervision to which remote monitoring systems can contribute valuably. DiAs Web Monitoring worked properly when tested in our outpatient studies. It could facilitate subject monitoring and even accelerate medical and technical assessment of the AP. It should now be adapted for long-term studies with an enhanced notification feature.

Artificial Pancreas: Model Predictive Control Design from Clinical Experience

The objective of this research is to develop a new artificial pancreas that takes into account the experience accumulated during more than 5000 h of closed-loop control in several clinical research centers. The main objective is to reduce the mean glucose value without exacerbating hypo phenomena. Controller design and in silico testing were performed on a new virtual population of the University of Virginia/Padova simulator. A new sensor model was developed based on the Comparison of Two Artificial Pancreas Systems for Closed-Loop Blood Glucose Control versus Open-Loop Control in Patients with Type 1 Diabetes trial AP@home data. The Kalman filter incorporated in the controller has been tuned using plasma and pump insulin as well as plasma and continuous glucose monitoring measures collected in clinical research centers. New constraints describing clinical knowledge not incorporated in the simulator but very critical in real patients (e.g., pump shutoff) have been introduced. The proposed model predictive control (MPC) is characterized by a low computational burden and memory requirements, and it is ready for an embedded implementation. The new MPC was tested with an intensive simulation study on the University of Virginia/Padova simulator equipped with a new virtual population. It was also used in some preliminary outpatient pilot trials. The obtained results are very promising in terms of mean glucose and number of patients in the critical zone of the control variability grid analysis. The proposed MPC improves on the performance of a previous controller already tested in several experiments in the AP@home and JDRF projects. This algorithm complemented with a safety supervision module is a significant step toward deploying artificial pancreases into outpatient environments for extended periods of time.

DiAs User Interface: A Patient-Centric Interface for Mobile Artificial Pancreas Systems

Recent in-hospital studies of artificial pancreas (AP) systems have shown promising results in improving glycemic control in patients with type 1 diabetes mellitus. The next logical step in AP development is to conduct transitional outpatient clinical trials with a mobile system that is controlled by the patient. In this article, we present the user interface (UI) of the Diabetes Assistant (DiAs), an experimental smartphone-based mobile AP system, and describe the reactions of a round of focus groups to the UI. This work is an initial inquiry involving a relatively small number of potential users, many of whom had never seen an AP system before, and the results should be understood in that light. We began by considering how the UI of an AP system could be designed to make use of the familiar touch-based graphical UI of a consumer smartphone. After developing a working prototype UI, we enlisted a human factors specialist to perform a heuristic expert analysis. Next we conducted a formative evaluation of the UI through a series of three focus groups with N = 13 potential end users as participants. The UI was modified based upon the results of these studies, and the resulting DiAs system was used in transitional outpatient AP studies of adults in the United States and Europe. The DiAs UI was modified based on focus group feedback from potential users. The DiAs was subsequently used in JDRF- and AP@Home-sponsored transitional outpatient AP studies in the United States and Europe by 40 subjects for 2400 h with no adverse events. Adult patients with type 1 diabetes mellitus are able to control an AP system successfully using a patient-centric UI on a commercial smartphone in a transitional outpatient environment.

Validation of the modified Vesikari score in children with gastroenteritis in 5 US emergency departments.

The burden of acute gastroenteritis (AGE) in US children is substantial. Research into outpatient treatment strategies has been hampered by the lack of easily used and validated gastroenteritis severity scales relevant to the populations studied. We sought to evaluate, in a US cohort, the reliability, construct validity, and generalizability of a gastroenteritis severity scale previously derived in a Canadian population, the modified Vesikari score (MVS). We conducted a prospective, cohort, clinical observational study of children 3 to 48 months of age with acute gastroenteritis presenting to 5 US emergency departments. A baseline MVS score was determined in the emergency department, and telephone follow-up 14 days after presentation was used to assign the follow-up MVS. We determined reliability using inter-item correlations; construct validity via principal component factor analysis; cross-sectional construct validity via correlations with the presence of dehydration, hospitalization, and day care and parental work absenteeism; and generalizability via score distribution among sites. Two hundred eighteen of 274 patients (80%) were successfully contacted for follow-up. Cronbach α was 0.63, indicating expectedly low internal reliability because of the multidimensional properties of the MVS. Factor analysis supported the appropriateness of retaining all variables in the score. Disease severity correlated with dehydration (P < 0.001), hospitalization (P < 0.001), and subsequent day care (P = 0.01) and work (P < 0.001) absenteeism. The MVS was normally distributed, and scores did not differ among sites. The MVS effectively measures global severity of disease and performs similarly in varying populations within the US health care system. Its characteristics support its use in multisite outpatient clinical trials.

Levomilnacipran for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?

To describe the efficacy and safety of levomilnacipran (extended-release capsules) for the treatment of major depressive disorder (MDD). The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrialsregister.eu and http://www.clinicaltrials.gov for the search terms 'levomilnacipran' and 'F2695', and by obtaining posters presented at congresses. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information. Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin-norepinephrine reuptake inhibitor with greater potency for inhibition of norepinephrine relative to serotonin reuptake. Approval for the treatment of MDD was based on a clinical development program that included one 10-week Phase II and four 8-week Phase III randomised placebo-controlled clinical trials in outpatients with MDD where levomilnacipran was titrated to target doses ranging from 40 to 120mg taken once daily. Four of the five trials demonstrated efficacy as measured by the Montgomery Asberg Depression Rating Scale, with a NNT for response vs. placebo of 9 (95% CI 7-15), and for remission, 14 (95% CI 10-28). Levomilnacipran also demonstrated superiority over placebo as measured by improvement in the Sheehan Disability Scale functional impairment total score. NNH vs. placebo for discontinuation because an adverse event (AE) across all five trials was 19 (95% CI 14-28). The most commonly encountered AEs (incidence ≥5% and at least twice the rate of placebo) as identified in product labelling were nausea, hyperhidrosis, constipation, heart rate increased, erectile dysfunction in men, vomiting, tachycardia and palpitations, with NNH values vs. placebo of 10 (95% CI 8-12), 15 (95% CI 12-19), 17 (95% CI 13-24), 21 (95% CI 17-29), 20 (95% CI 14-36), 25 (95% CI 20-37), 25 (95% CI 19-40) and 30 (95% CI 22-49), respectively. Levomilnacipran was not associated with clinically relevant weight change in the short-term trials or in a 48-week open-label extension trial. Mean changes from baseline in systolic blood pressure (BP), diastolic BP and heart rate were +3.0mmHg, +3.2mm Hg and +7.4bpm for levomilnacipran, and -0.4mmHg, no change and -0.3bpm for placebo, respectively. Categorical shift in BP from normal or prehypertension at baseline to stage 1 or stage 2 hypertension at end of study was 10.4% for levomilnacipran vs. 7.1% for placebo, for a NNH of 31 (95% CI 18-94). Levomilnacipran represents another option for the treatment of MDD. Levomilnacipran appears to have a favourable weight-gain profile. Additional controlled data regarding long-term efficacy and comparative effectiveness will help characterise this new agent.

A Phase 2, Placebo-Controlled Study of the Opioid Receptor Antagonist LY2196044 for the Treatment of Alcohol Dependence

Endogenous opioid-mediated reward pathways may play a role in the development and maintenance of alcohol dependence. This study tested whether LY2196044, an opioid receptor antagonist, in combination with medical management would reduce drinking in alcohol-dependent patients. This was a multicenter, outpatient, randomized, double-blind, parallel, and placebo-controlled trial with a 16-week treatment period. Patients (N=375) were alcohol-dependent, treatment-seeking adults. Patients were randomly assigned to once-daily LY2196044 (final doses of 125 or 250mg/d) or placebo. DNA samples were collected at baseline. At each visit, patients underwent safety assessments, laboratory testing, efficacy measures, and medical management. Blood samples were also obtained for pharmacokinetic testing. The primary measure was the change from baseline in the percent heavy drinking days (HDD). Secondary efficacy measures were percent days abstinent per month and number of drinks per day. The treatment difference in change from baseline in % HDD between LY2196044 and placebo was not statistically significant (-43.02 vs. -38.72%, respectively; p=0.12). There was a trend toward greater change from baseline in the percent days abstinent per month for the LY2196044 group compared with the placebo group (33.49 vs. 28.12%, respectively; p=0.051). The decrease from baseline for mean number of drinks per day was statistically significantly greater in the LY2196044 group compared with the placebo group (-5.37 vs. -4.66drinks per day, respectively; p=0.013). LY2196044-treated patients who were dopamine receptor type 4-variable number tandem repeat L carriers had greater reductions in % HDD (p=0.0565), increased percent days abstinent (p=0.0496), and reduced drinks per day (p=0.0069) than placebo-treated L carriers. The safety profile for LY2196044 appeared similar to that of other opioid antagonists. The results from this proof-of-concept clinical trial warrant further evaluation of LY2196044 for the treatment of alcohol dependence.

Affect regulation training (ART) for alcohol use disorders: Development of a novel intervention for negative affect drinkers

Although negative affect is a common precipitant of alcohol relapse, there are few interventions for alcohol dependence that specifically target negative affect. In this stage 1a/1b treatment development study, several affect regulation strategies (e.g., mindfulness, prolonged exposure, distress tolerance) were combined to create a new treatment supplement called affect regulation training (ART), which could be added to enhance cognitive–behavioral therapy (CBT) for alcohol dependence. A draft therapy manual was given to therapists and treatment experts before being administered to several patients who also provided input. After two rounds of manual development (stage 1a), a pilot randomized clinical trial (N=77) of alcohol-dependent outpatients who reported drinking often in negative affect situations was conducted (stage 1b). Participants received 12-weekly, 90-minute sessions of either CBT for alcohol dependence plus ART (CBT+ART) or CBT plus a healthy lifestyles control condition (CBT+HLS). Baseline, end-of-treatment, and 3- and 6-month posttreatment interviews were conducted. For both treatment conditions, participant ratings of treatment satisfaction were high, with CBT+ART rated significantly higher. Drinking outcome results indicated greater reductions in alcohol use for CBT+ART when compared to CBT+HLS, with moderate effect sizes for percent days abstinent, drinks per day, drinks per drinking day, and percent heavy drinking days. Overall, findings support further research on affect regulation interventions for negative affect drinkers.

Probiotics for preventing antibiotic-associated diarrhea

Probiotics for preventing antibiotic-associated diarrhea

A randomized double‐blind, placebo‐controlled trial of venlafaxine‐extended release for co‐occurring cannabis dependence and depressive disorders

To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. This was a randomized, 12-week, double-blind, placebo-controlled trial of out-patients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. The trial was conducted at two university research centers in the United States. One hundred and three cannabis-dependent adults participated in the trial. The primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. The proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (χ1 (2) = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (χ1 (2) = 7.46, P < 0.01; odds ratio = 4.51, 95% confidence interval: 1.53, 13.3). Mood improvement was associated with reduction in marijuana use in the placebo group (F1,179 = 30.49, P < 0.01), but not the VEN-XR group (F1,186 = 0.02, P = 0.89). For depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use.

Management of Hyperglycemia in Hospitalized Noncritical Patients

Randomized trials designed to determine optimum blood glucose (BG) levels among hospitalized noncritically ill patients are limited. In this group of patients, experts generally recommend premeal BG targets of 100 to 140 mg/dL, and random BG <180 mg/dL. Scheduled insulin is the mainstay therapy to control hyperglycemia in patients admitted to general wards and should include three components: basal, prandial, and correction insulin. Insulin doses should take into account the severity of hyperglycemia, weight, type of diabetes, age, caloric intake, renal function, and propensity for hypoglycemia. Limited data suggest that the traditional mixed-split insulin regimen formed of neutral protamine hagedorn-regular insulin is similar in efficacy and frequency of hypoglycemia to a more expensive and complex insulin analog regimen formed of twice-daily detemir and mealtime glulisine; however, based on extrapolation of data derived from trials of diabetic outpatients, basal insulin analogs such as glargine or detemir may be used instead of neutral protamine hagedorn insulin if there is concern about hypoglycemia. In patients with erratic meal intake, the use of short-acting insulin analogs may be preferred to regular insulin. Further studies are required to determine the ideal glycemic goals and insulin treatment strategies for control of hyperglycemia in hospitalized noncritically ill patients.

Sex Differences in Middle-of-the-Night Efficacy of Zolpidem Tartrate Sublingual Tablets in a 4-Week Insomnia Outpatient Trial (P05.013)

Sex Differences in Middle-of-the-Night Efficacy of Zolpidem Tartrate Sublingual Tablets in a 4-Week Insomnia Outpatient Trial (P05.013)

Low-n-6 and low-n-6 plus high-n-3 diets for use in clinical research

Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; #2·5% of energy (en%)) and arachidonic acid (#60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA a-linolenic acid (ALA; $1·5 en%) and EPA þ DHA ($1000 mg/d). Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to #2·5 en% (median LA 2·45 (2·1, 3·1); P,0·001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1·6 en%, (1·3, 2·0), P,0·001) and EPA þ DHA (1482 mg, (374, 2558), P,0·001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to #2·5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.

A randomised controlled trial of sublingual buprenorphine–naloxone film versus tablets in the management of opioid dependence

BackgroundBuprenorphine–naloxone sublingual film was introduced in 2011 in Australia as an alternative to tablets. This study compared the two formulations on subjective dose effects and equivalence, trough plasma levels, adverse events, patient satisfaction, supervised dosing time, and impact upon treatment outcomes (substance use, psychosocial function). Methods92 buprenorphine–naloxone tablet patients were recruited to this outpatient multi-site double-blind double-dummy parallel group trial. Patients were randomised to either tablets or film, without dose changes, over a 31 day period. ResultsNo significant group differences were observed for subjective dose effects, trough plasma buprenorphine or norbuprenorphine levels, adverse events and treatment outcomes. Buprenorphine–naloxone film took significantly less time to dissolve than tablets (173±71 versus 242±141s, p=0.007, F=7.67). ConclusionsThe study demonstrated dose equivalence and comparable clinical outcomes between the buprenorphine–naloxone film and tablet preparations, whilst showing improved dispensing times and patient ratings of satisfaction with the film.

Repurposed Medications Show Promise in Stimulant Dependence

Back to table of contents Previous article Next article From the ExpertsFull AccessRepurposed Medications Show Promise in Stimulant DependencePublished Online:4 Jan 2013https://doi.org/10.1176/appi.pn.2013.1a12Stimulant dependence is a substance use disorder (SUD) that continues to affect society on many levels. The economic temptation of producing or bringing stimulants or their precursors (methamphetamine and cocaine) across the U.S. border to sell is continuing as certain South American countries now allow full-fledged coca plant cultivation. Containing the flow of illicit drugs within state lines and across U.S. borders is an insurmountable task for any agency, and demand reduction from effective treatments is desperately needed.Stimulant dependence is a substance use disorder (SUD) that continues to affect society on many levels. The economic temptation of producing or bringing stimulants or their precursors (methamphetamine and cocaine) across the U.S. border to sell is continuing as certain South American countries now allow full-fledged coca plant cultivation. Containing the flow of illicit drugs within state lines and across U.S. borders is an insurmountable task for any agency, and demand reduction from effective treatments is desperately needed.Research for these addiction treatments has benefited greatly from neuroimaging studies and “repurposed” medications. Neuroimaging studies have been essential to understanding central deficits and altered neurotransmission linked to stimulant dependence. For example, recent evidence dispels the widely held misconception that stimulant-dependent individuals are more sensitive to these drugs than the average person, and this is why they become dependent. In fact, the opposite is true. They are less sensitive to the positive euphoric effects of stimulants. This also extends to natural rewards such as food. In contrast, these same individuals are often hypersensitive to stress and overly influenced by environmental cues associated with drug taking that can trigger relapse. Environmental cues that control behavior are influenced by usurped memory circuits. SUDs are often accompanied by comorbid negative mood states that may also contribute to continued drug use through self-medication. Neuroimaging has revealed that abnormally low dopaminergic neurotransmission is paired with orbitofrontal hypoactivation in stimulant dependence and limits impulse control, executive functioning, and working memory. Medications that modulate dopamine, glutamate, and norepinephrine (NE) neurotransmission that show promise for impulse control and enhance cognition may also be used to treat stimulant dependence. Doxazosin is a repurposed NE blocker used for hypertension that Newton et al. (2012) recently found blocks cocaine’s positive subjective effects and the feeling “likely to use cocaine” in cocaine-dependent volunteers after a cocaine infusion. An outpatient clinical trial is presently examining this medication for decreasing cocaine use. Another repurposed medication, the angiotensin-converting enzyme inhibitor and antihypertensive perindopril blocks the cardiovascular and positive subjective effects of methamphetamine. The commonly prescribed antidepressant bupropion has also shown some efficacy in decreasing methamphetamine use in moderate users. Rivastigmine, used in the treatment of dementia, significantly decreased “likely to use methamphetamine” in dependent volunteers. Finally, the atypical stimulant modafinil, used to treat narcolepsy, blocks cocaine’s positive subjective effects and has decreased cocaine use in a select subpopulation.Psychiatric addiction research has benefited from repurposing a wide range of medications. The science behind using these medications is based on understanding from neuroimaging of damaged and reinforcing human neural circuits due to addictive stimulants. For the most part, the development of effective treatments for this pernicious disorder appears promising. ■References are posted at http://www.psychnews.org/update/experts_2_32.html.Thomas Kosten, M.D., is the J.H. Waggoner Professor of Psychiatry, Pharmacology and Neuroscience, vice chair for psychiatry, and codirector of the Institute for Clinical and Translational Research at Baylor College of Medicine. Colin Haile, M.D., Ph.D., is an assistant professor at Baylor College of Medicine, Menninger Department of Psychiatry and Michael E. DeBakey VA Medical Center. He and Kosten are the coauthors of "Cocaine and Methamphetamine Dependence: Advances in Treatment" from American Psychiatric Publishing. APA members may purchase the book at a discount at http://www.appi.org/SearchCenter/Pages/SearchDetail.aspx?ItemId=62407. ISSUES NewArchived

Efficacy and tolerability of quetiapine versus haloperidol in first-episode schizophrenia: a randomized clinical trial

BackgroundSchizophrenia is a chronic disease of global importance. The second-generation antipsychotic quetiapine has a favorable side-effect profile, however, its clinical effectiveness has been called into question when compared with first-generation antipsychotics such as haloperidol. This study evaluates the efficacy and tolerability of quetiapine versus haloperidol for first-episode schizophrenia in the outpatient setting.Methods156 adult patients with first-episode schizophrenia participated in an outpatient clinical trial and were randomized to quetiapine (200 mg/d; n = 78) or haloperidol (5 mg/d; n = 78). The study medications were titrated to a mean daily dose of 705 mg for quetiapeine and 14 mg for haloperidol. The patients were assessed at baseline, six weeks, and twelve weeks. The primary outcome measures were positive and negative scores of the Positive and Negative Syndrome Scale (PANSS). Secondary measures were Global Assessment of Functioning (GAF) scale for overall psychosocial functioning, and Simpson-Angus Scale (SAS) for extra-pyramidal symptoms.ResultsAt twelve weeks, the quetiapine group had a greater decrease in PANSS positive (18.9 vs. 15.3, p = 0.013) and negative scores (15.5 vs. 11.6, p = 0.012), however, haloperidol showed a greater decrease in general psychopathology score (23.8 vs. 27.7, p = 0.012). No significant difference between groups were found for total PANSS (58.3 vs. 54.8, p = 0.24) and GAF (45.7 vs. 46.2, p = 0.79).ANOVA identified significant group interactions on PANSS positive (F = 18.72, df = 1.6,52.4, p < 0.0001), negative (F = 5.20, df = 1.1,35.7, p < 0.0001), depression/anxiety (F = 106.49, df = 1.14,37.8, p < 0.0001), and total scores (F = 7.51, df = 1.4,45.6, p = 0.001).SAS (8.62 vs. 0.26, p < 0.0001) and adverse events of akathisia (78% vs. 0%, p = 0.000), parkinsonism (66.6% vs. 0%, p < 0.0001), and fatigue (84.6% vs. 66.6%, p = 0.009) were greater in haloperidol compared to quetiapine, whereas headache was more common in quetiapine treated patients (11.5% vs. 35.9%, p < 0.0001).ConclusionsQuetiapine has greater efficacy for positive and negative symptoms with less extra-pyramidal symptoms than haloperidol when used for first-episode schizophrenia in the outpatient setting.

Novel epidural baclofen infusion trial for intractable spasticity with long-term follow-up observation and a focused review of the literature

Background Intrathecal baclofen (ITB) infusion has been increasingly used in patients with intractable spasticity. Prior to the implantation of the permanent pump, a trial is usually conducted to document efficacy. Intrathecal bolus injection of baclofen, followed by serial evaluations to confirm the improvement of spasticity, has been most commonly used during such trials. However, for patients who refused to undergo ITB trial injection due to previous untoward complications such as intractable headache, there has been no other alternatives. Objective To report the first case of a successful epidural baclofen infusion trial, conducted as outpatient in a lady with severe spasticity due to multiple sclerosis; to report the long term follow-up observation (3 years) following the permanent intrathecal pump placement; and to conduct a focused review of the literature pertaining to epidural baclofen. Design Case report. Setting: Tertiary-care pain clinic. Case Report: A 62-year-old female with progressive spasticity of bilateral lower extremities and left upper extremity due to multiple sclerosis, not responding to multiple oral antispasticity drugs, was referred to clinic for ITB therapy. The patient adamantly declined ITB bolus trial due to previous episode of severe headache following lumbar puncture. Thus an outpatient epidural baclofen infusion was performed and was successful. Based on the positive response from the epidural infusion trial, a permanent IT pump was subsequently placed and the patient has had sustained reduction of her spasticity since pump implantation 3 years ago. Limitation: Single center case report. Conclusion In patients who are reluctant to the ITB bolus trial due to previous complication such as headache, an outpatient epidural baclofen infusion trial, when done properly, can serve as an alternative approach to the ITB trial and provides needed information

Radiofrequency volumetric thermal ablation of fibroids: a prospective, clinical analysis of two years’ outcome from the Halt trial

BackgroundAlthough most myomas are asymptomatic, quality of life is compromised for many women with uterine fibroid disease. Twelve-month outcomes from the Halt Trial have been reported in the literature. Here we analyze the clinical success of radiofrequency volumetric thermal ablation (RFVTA) of symptomatic uterine fibroids at two years of follow up.MethodsProspective, multicenter, outpatient interventional clinical trial of fibroid treatment by RFVTA in 124 premenopausal women (mean age, 42.4 ± 4.4 years) with symptomatic uterine fibroids and objectively confirmed heavy menstrual bleeding (≥160 to ≤500 mL).Outcome measures included: subject responses to validated questionnaires, treatment-emergent adverse events, and surgical re-intervention for fibroids at 24 months postprocedure. Continuous and categorical variables were summarized using descriptive statistics and means and percentages. Comparisons between visits were based on t-tests using repeated measures models. P-values < 0.05, adjusted for multiplicity, were statistically significant.ResultsOne hundred twelve subjects were followed through 24 months. Change in symptom severity from baseline was –35.7 (95% CI, –40.1 to –31.4; p<.001). Change in health-related quality of life (HRQL) was 40.9 (95% CI, 36.2 to 45.6; p < .001). HRQL subscores also improved significantly from baseline to 24 months in all categories (concern, activities, energy/mood, control, self-consciousness, and sexual function) [p<.001]. Six patients underwent surgical re-intervention for fibroid-related bleeding between 12 and 24 months providing a re-intervention rate of 4.8% (6/124).ConclusionRadiofrequency volumetric thermal ablation of myomas significantly reduces symptom severity and improves quality of life with low surgical re-intervention through 24 months of follow up.Trial registrationClinicalTrials.gov: NCT00874029

Are Antipsychotics Useful in the Treatment of Anorexia Nervosa? A Review of the Literature

A review of the literature on the use of second generation antipsychotics (SGA) in adolescent and adult patients with anorexia nervosa (AN) is presented. Open-label studies and case reports suggested beneficial effects of variable doses of olanzapine, quetiapine, risperidone and aripiprazole in AN subjects. Randomized, double-blind, controlled studies conducted mainly with olanzapine demonstrated its efficacy on specific psychopathological aspects of AN. Moreover, although not consistently, increases in Body Mass Index (BMI) or appetite with no significant side effects were also reported. Taken together, the data of olanzapine studies, even if with a number of different limitations, show that this pharmacological treatment can be effective in improving specific aspects of AN in adult but not in adolescent patients. Further studies are warranted to consolidate these findings. Quetiapine and aripiprazole seem to be potentially promising options in the treatment of severe adult and adolescent AN patients because of their lower propensity to induce weight gain, revealing positive psychopathological effects and good tolerability. Given the inherent cardiac risks associated with the treatment of low weight AN patients, care should be taken when SGA use is being considered. Moreover, although SGA use might be associated to several other side effects (increasing weight, developing glucose intolerance and/or diabetes, metabolic disturbances) little has been published on this topic in AN patients and only few of the analyzed studies have reported adverse reactions. The different mechanisms underlying these effects are therefore discussed. Future directions for pharmacologic treatment research in AN should include randomized controlled trials with different antipsychotic medications, inpatient versus outpatient trials and the assessment of medication effect for relapse prevention in weight-restored patients.

Are Antipsychotics Useful in the Treatment of Anorexia Nervosa? A Review of the Literature

A review of the literature on the use of second generation antipsychotics (SGA) in adolescent and adult patients with anorexia nervosa (AN) is presented. Open-label studies and case reports suggested beneficial effects of variable doses of olanzapine, quetiapine, risperidone and aripiprazole in AN subjects. Randomized, double-blind, controlled studies conducted mainly with olanzapine demonstrated its efficacy on specific psychopathological aspects of AN. Moreover, although not consistently, increases in Body Mass Index (BMI) or appetite with no significant side effects were also reported. Taken together, the data of olanzapine studies, even if with a number of different limitations, show that this pharmacological treatment can be effective in improving specific aspects of AN in adult but not in adolescent patients. Further studies are warranted to consolidate these findings. Quetiapine and aripiprazole seem to be potentially promising options in the treatment of severe adult and adolescent AN patients because of their lower propensity to induce weight gain, revealing positive psychopathological effects and good tolerability. Given the inherent cardiac risks associated with the treatment of low weight AN patients, care should be taken when SGA use is being considered. Moreover, although SGA use might be associated to several other side effects (increasing weight, developing glucose intolerance and/or diabetes, metabolic disturbances) little has been published on this topic in AN patients and only few of the analyzed studies have reported adverse reactions. The different mechanisms underlying these effects are therefore discussed. Future directions for pharmacologic treatment research in AN should include randomized controlled trials with different antipsychotic medications, inpatient versus outpatient trials and the assessment of medication effect for relapse prevention in weight-restored patients. Keywords: Anorexia nervosa, antipsychotics, cardiac side effects, eating disorders, olanzapine, quetiapine