Carin Binder

Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials.

OBJECTIVE The authors explored the effect of galantamine on behavioral symptoms in Alzheimer disease (AD). METHODS Data were pooled from 2,033 subjects with mild-to-moderate AD who had participated in one of three randomized, double-blind, placebo-controlled trials of 3-, 5-, and 6-month durations. Subjects included in this post hoc analysis had received treatment with either placebo (N=686) or galantamine (N=1347) in total daily doses of 16 mg, 24 mg, or 32 mg. Behavioral symptoms were measured on the 10-item Neuropsychiatric Inventory (NPI). Four symptom clusters were defined a priori: 1) delusions, hallucinations; 2) agitation, depression, anxiety, apathy, irritability; 3) disinhibition, elation, aberrant motor behavior; 4) hallucinations, anxiety, apathy, aberrant motor behavior. RESULTS At endpoint, mean changes from baseline in NPI scores were significantly different between galantamine-treated subjects and placebo-treated subjects, favoring galantamine for several measures: total NPI, individual domains of agitation/aggression, anxiety, disinhibition, and aberrant motor behavior, and Clusters 1, 3, and 4. The magnitude of the effect sizes was small. CONCLUSIONS In this pooled sample of more than 2,000 subjects with mild-to-moderate AD, those who received galantamine therapy experienced modestly better, but statistically significant, outcomes in their behavioral symptoms than placebo-treated subjects. The cluster of hallucinations, anxiety, apathy and aberrant motor behaviors may represent a specific group of cholinergic-responsive behavioral symptoms.

Adult ADHD and comorbid depression: A consensus-derived diagnostic algorithm for ADHD

Objective: Many patients present to their physician with depression as their primary symptom. However, depression may mask other comorbid disorders. This article presents diagnostic criteria and treatment recommendations (and monitoring) pertaining to the diagnosis of adult attention deficit hyperactivity disorder (ADHD), which may be missed in patients who present with depressive symptoms, or major depressive disorder (MDD). Other co-occurring conditions such as anxiety, substance use, and bipolar disorder are briefly discussed. Methods: A panel of psychiatrist-clinicians with expertise in the area of child and adolescent ADHD and mood disorders, adult mood disorders, and adult ADHD was convened. A literature search for recommendations on the diagnosis and treatment of co-occurring conditions (MDD, anxiety symptoms, and substance use) with adult ADHD was performed. Based on this, and the panel’s clinical expertise, the authors developed a diagnostic algorithm and recommendations for the treatment of adult ADHD with co-occurring MDD. Results: Little information exists to assist clinicians in diagnosing ADHD co-occurring with other disorders such as MDD. A three-step process was developed by the panel to aid in the screening and diagnosis of adult ADHD. In addition, comorbid MDD, bipolar disorder, anxiety symptoms, substance use and cardiovascular concerns regarding stimulant use are discussed. Conclusion: This article provides clinicians with a clinically relevant overview of the literature on comorbid ADHD and depression and offers a clinically useful diagnostic algorithm and treatment suggestions.

Acceptability and disintegration rates of orally disintegrating risperidone tablets in patients with schizophrenia or schizoaffective disorder.

Objective: To investigate the disintegration profile, acceptability, and tolerability of orally disintegrating risperidone tablets in patients with schizophrenia or schizoaffective disorder. Method: Ten patients stable for at least 10 days on monotherapy with oral risperidone 2 mg to 4 mg taken once daily were switched for 7 days to an equivalent dosage of orally disintegrating risperidone. Visual assessments for time to initial and complete disintegration were collected at each visit. Clinical Global Impression of Severity scores were collected at baseline and at the last visit. Patient acceptance of the new formulation, rated according to a visual analog scale, was obtained at the last visit. Results: All patients maintained stable clinical status. Mean time to initial disintegration was 5.1 seconds, SD 0.8, and mean time to complete disintegration was 29.4 seconds, SD 18.4. The formulation was rated as very acceptable. Adverse events were reported by 5 patients; all were mild. Conclusion: The orally disintegrating risperidone tablets were well tolerated and rated as very acceptable by all patients.

Risperidone in acute and continuation treatment of mania

&NA; In a prospective study, we examined the efficacy of risperidone added‐on to mood stabilizers in the acute and continuation treatment of mania over a 12‐week period. Patients (n=108) with a DSM‐IV diagnosis of bipolar disorder, manic or mixed episode requiring treatment with an antipsychotic were recruited. All subjects were on one or two mood stabilizers at the time of initiation of risperidone (range 0.5–4 mg). No other antipsychotic medication or ongoing benzodiazepine therapy was allowed. There was a significant decrease in mean Young Mania Rating Scale (YMRS) scores from baseline (27.5±7.5) to week 1 (‐10.8, P < 0.0001), week 3 (‐17.7, P<0.0001) and to week 12(‐22.6, P < 0.0001). When response was defined as >= 50% reduction in YMRS scores from baseline, 32%, 68% and 90% of patients met criteria at week 1, week 3 and week 12, respectively. Significant decreases in mean 21‐item Hamilton Depression Rating Scale scores from baseline (12.2±7.7) to week 3 (‐5.7, P < 0.0001) and week 12 (‐5.7, P <0.0001) were also observed. No significant changes in extrapyramidal symptoms were noted between baseline and endpoint. The mean daily dose of risperidone was 2 mg with a median of 1.8 mg. These findings support the results of the two previous double‐blind, randomized trials and indicate that the addition of risperidone to mood stabilizers is a safe and effective treatment for acute and continuation treatment of mania. Risperidone add‐on does not induce depressive symptoms and, furthermore, risperi‐done may have efficacy in treating comorbid depressive symptoms in bipolar patients.

Does OROS-methylphenidate improve core symptoms and deficits in executive function? Results of an open-label trial in adults with attention deficit hyperactivity disorder

ABSTRACT Objective: This pilot, uncontrolled, open-label study evaluated the safety/tolerability and potential effectiveness of OROS-methylphenidate (OROS-MPH) in adult attention deficit hyperactivity disorder (ADHD). Methods: Adults with DSM-IV-defined ADHD were enrolled in this 38-day study. Retrospective childhood diagnosis was made using the Wender Utah Rating Scale. Eligible patients required a baseline Conners Adult ADHD Rating Scale (CAARS) score ≥24, Clinical Global Impression of Severity (CGI-S) score ≥4 (at least moderate illness), and Montgomery–Asberg Depression Rating Scale (MADRS) score ≤ 16. Safety/tolerability measurements included adverse event reporting, vital signs, electrocardiograms (ECGs), weight, physical examination. Primary effectiveness evaluated changes in CAARS scores. Secondary effectiveness parameters included executive function. Results: Thirty-two patients formed the safety analysis; however, 30 comprised the effectiveness analysis since two patients did not meet diagnostic inclusion criteria. No serious adverse events were reported and there were no early withdrawals due to adverse events. There were no clinically significant changes in endpoint ECGs, physical examination, or blood pressure. Mean pulse rate increased by 5.9 beats/min (p = 0.003) and mean body weight decreased by 2.2 kg at endpoint (p < 0.0001). Total CAARS scores decreased significantly at endpoint as well as the inattention (p < 0.0001) and hyperactivity/ impulsivity symptom subscales (p < 0.0001) separately. Statistically significant improvements were observed in executive function and all other secondary measures, including the CAARS self report, CGI-S/CGI-I, Subject Satisfaction with treatment and the Sheehan Disability Scale (SDS). Mean dose of OROS-MPH = 52.3 ± 14.0 mg. Modal dose = 54 mg. Study limitations include: the lack of placebo control in the study design leading to potential observer bias, the exclusion of adults with unstable psychiatric and other medical conditions which is less reflective of clinical practice, and the short study duration. Conclusions: This uncontrolled, open-label trial suggests that OROS-MPH is well tolerated, providing core symptom control with the added benefit of improving executive function. However, future larger, randomized, controlled trials are required.

Persistence with cholinesterase inhibitor therapy for dementia: an observational administrative health database study.

ObjectiveTo determine if choice of drug and ease of administration affect persistence of therapy with Cholinesterase inhibitors (ChEIs) for treatment of dementia.MethodsAn observational administrative health database study was conducted in 5622 patients aged ≥65 years who received a new prescription for donepezil (DON), rivastigmine (RIV) or galantamine (GAL) from February to May 2006. Patients were followed for 1 year from initiation of therapy to determine percentage persistence and days of therapy. Once-daily galantamine extended release (GAL-ER) was compared with twice-daily galantamine immediate release (GAL-IR) to determine if ease of administration affected persistence. Previous treatment with ChEIs was also documented.ResultsOne-year persistence rates were significantly different among the ChEIs: GAL-ER 54% (95% CI 51, 57), DON 46% (95% CI 43, 49) and RIV 40% (95% CI 37, 43). Average days of therapy were greater for GAL-ER (293) than for RIV (272), but there were no differences between DON (287) and GAL-ER or DON and RIV. One-year persistence was significantly greater for GAL-ER 54% (95% CI 48, 59) than for GAL-IR 44% (95% CI 39, 50), although there was no significant difference in days of therapy (293 vs 286, respectively). More patients currently treated with RIV (40.5%) or GAL-ER (32.3%) had received previous treatment with a different ChEI than with DON (21.9%).ConclusionAmong possible factors affecting persistence of ChEI therapy for dementia, choice of drug, ease of administration and previous treatment appear to be important.

A 6-month randomized open-label comparison of continuation of oral atypical antipsychotic therapy or switch to long acting injectable risperidone in patients with bipolar disorder

Objective:  To determine the safety and effectiveness of long‐acting injectable risperidone (LAI‐ris) add‐on in bipolar patients.

Risperidone plus lithium versus risperidone plus valproate in acute and continuation treatment of mania.

This exploratory analysis was performed to compare the efficacy and tolerability of risperidone when added to two different mood stabilizers (lithium or valproate) for mania in bipolar disorder. Patients receiving lithium or valproate at baseline were drawn from the database of a 12-week, open-label risperidone study. The primary efficacy measure was the Young Mania Rating Scale (YMRS). Other assessments included the Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression (CGI) of improvement, and safety measures. The analysis included 33 patients on lithium plus risperidone and 46 patients on valproate plus risperidone. Both subgroups had comparable baseline YMRS scores (lithium 28.2, valproate 28.7) and both had significant reductions in score by week 1 (P<0.0001). Comparable reductions in score continued for both subgroups until the end of the study (YMRS scores at week 12: lithium 4.6 and valproate 6.7). There were no significant differences in response rates (≥50% improvement on YMRS) or remission rates (YMRS score ≤8) between the two subgroups. At week 12, 88% of the lithium plus risperidone patients and 80% of the valproate plus risperidone patients were in remission. Similarly, HAM-D scores were significantly and comparably reduced in both subgroups, and improvement in CGI was the same. There was no difference between subgroups in the incidence of adverse events or weight gain. These data suggest that risperidone can be safely combined with either lithium or valproate, and that the efficacy is similar regardless of the mood stabilizer used.

Open-label adjunctive topiramate in the treatment of unstable bipolar disorder

Objective: To assess open-label adjunctive topiramate in the treatment of outpatients with unstable bipolar disorder (BD). Method: Outpatients with DSM-IV–defined BD (I or II) exhibiting mood instability were enrolled in this 16-week, open-label, multicentre study. Topiramate was added to existing mood stabilizers and other psychotropic treatments. The primary effectiveness measure was the Clinical Global Impression of Severity (CGI-S) scale; other scales included the Young Mania Rating Scale (YMRS) and the Montgomery–Asberg Depression Rating Scale (MADRS). Safety assessments included monitoring adverse events, measuring tremor, monitoring vital signs and weight, and laboratory indices. We also evaluated patient satisfaction with treatment. Results: A total of 109 patients were enrolled. Intent-to-treat analysis showed significant improvement from baseline in the CGI-S, YMRS, and MADRS, starting at Week 2 (P < 0.001), with further accrual of benefit between Week 2 and Week 16 (P < 0.001). The mean modal dosage of topiramate during the stable dosing period was 180 mg daily. There was a mean 1.8 kg decrease in patient weight from topiramate initiation to Week 16 (P < 0.001). Topiramate was well tolerated by most patients; 11% withdrew from the study owing to adverse events. We noted a significant reduction in the mean severity score for preexisting tremor by Week 8 of treatment (P < 0.005); no notable changes in vital signs were observed. At Week 16, 50% of the patients were “completely satisfied” with topiramate treatment. Conclusions: Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms, as well as reducing tremor and weight in outpatients with BD I or II.