Relative Bioavailability of Methylphenidate Extended-release Chewable Tablets Chewed Versus Swallowed Whole.

PURPOSE: Methylphenidate hydrochloride extended-release chewable tablet (MPH ERCT) is approved for treatment of attention deficit hyperactivity disorder in patients aged 6 years and older. This article evaluates the pharmacokinetic parameters and relative bioavailability of MPH ERCT when chewed versus swallowed whole. METHODS: In this open-label, single-dose, 3-period, 3-treatment crossover study, 12 healthy adult volunteers were randomly assigned to treatment sequence. In each period, subjects received a single 40-mg dose of the assigned treatment (MPH ERCT chewed, MPH ERCT swallowed whole, or methylphenidate extended-release oral suspension [MEROS]). Blood samples for pharmacokinetic analysis were collected for 24 hours postdose. Key pharmacokinetic parameters included Cmax, AUC0-t, and AUC0-∞. FINDINGS: The geometric mean values for AUC0-t, AUC0-∞, and Cmax were similar for MPH ERCT chewed, MPH ERCT swallowed whole, and MEROS. In all pairwise between-treatment comparisons, the 90% CIs of the geometric mean ratios for AUC0-t, AUC0-∞, and Cmax were fully contained within the bioequivalence range of 80% to 125%. Early exposure over the first 4 hours after dosing (AUC0-4) was similar for MPH ERCT chewed versus swallowed whole; AUC0-4 was approximately 15% lower for MPH ERCT, either chewed or swallowed, compared with MEROS. Each treatment was generally well tolerated. IMPLICATIONS: There was no difference in overall rate or extent of exposure of methylphenidate when MPH ERCT was chewed versus swallowed whole by healthy volunteers.

Optimization of Methylphenidate Extended-Release Chewable Tablet Dose in Children with ADHD: Open-Label Dose Optimization in a Laboratory Classroom Study.

OBJECTIVE: To examine methylphenidate extended-release chewable tablets (MPH ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom scores, and safety during the 6-week, open-label (OL) dose-optimization period of a phase 3, laboratory classroom study. METHODS: Boys and girls (6-12 years) diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20 mg/day; participants were titrated in 10-20 mg/day increments weekly based on efficacy and tolerability (maximum dose, 60 mg/day). Dose-optimization period efficacy assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a post hoc analysis using a mixed-effects model for repeated measures with final optimized dose (20, 30/40, or 50/60 mg), visit, final optimized dose and visit interaction, and baseline score as terms. Adverse events (AEs) and concomitant medications were collected throughout the study. RESULTS: Mean MPH ERCT daily dose increased weekly from 29.4 mg/day after the first dose adjustment at week 1 (n = 90) to 42.8 mg/day after the final adjustment at week 5 (n = 86). Final optimized MPH ERCT dose ranged from 20 to 60 mg/day. Mean final optimized MPH ERCT dose ranged from 40.0 mg/day in 6-8 year-old participants to 44.8 mg/day for 11-12 year-old participants. There was a progressive decrease in mean (standard deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at OL week 5, with similar improvement patterns for hyperactivity/impulsivity and inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60 mg/day had a significantly higher mean (standard error) ADHD-RS-IV score at baseline compared with participants optimized to MPH ERCT 20 mg/day (42.4 [1.34] vs. 35.1 [2.55]; p = 0.013). Treatment-emergent AEs were reported by 65/90 (72.2%) participants in the dose-optimization period. CONCLUSIONS: Dose-optimization period results describing relationships between change in ADHD symptom scores and final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT dose.

Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study. METHODS: Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10-20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs. RESULTS: The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache. CONCLUSION: AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

Effect of Food Intake on the Pharmacokinetics of a Novel Methylphenidate Extended-Release Oral Suspension for Attention Deficit Hyperactivity Disorder.

We conducted an open-label, single-dose, randomized, crossover study in healthy adults to assess the impact of food on the bioavailability of 60 mg methylphenidate extended-release oral suspension (MEROS; Quillivant XR™)-a long-acting stimulant for the treatment of attention deficit hyperactivity disorder-by comparing the pharmacokinetic parameters under fed and fasting conditions. When MEROS 60 mg was administered under fed conditions compared with fasting conditions, the exposure of methylphenidate (d enantiomer) was higher, with a mean area under the plasma concentration-vs-time curve (AUC)0-t of 160.2 ng·h/mL vs 140.4 ng·h/mL, and a mean AUC0-inf of 163.2 ng·h/mL vs 143.7 ng·h/mL, respectively. The ratios of the ln-transformed geometric means for methylphenidate for AUC0-t and AUC0-inf were 119.5% (90%CI, 115.7% to 123.5%) and 119.0% (90%CI, 115.2% to 122.8%), respectively, within the standard 80% to 125% bioequivalence acceptance range indicating no food effect on the overall exposure (rate and extent). There was a small increase in the peak plasma concentration (127.6% [90%CI, 119.9% to 135.8%]). However, this effect was small and not likely to be clinically significant. Overall, MEROS 60 mg was safe in both the fed and fasting condition when administered to healthy volunteers in this study.

Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: This phase 3, laboratory classroom study assessed the efficacy and safety of methylphenidate hydrochloride extended-release chewable tablets (MPH ERCT) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Following a 6-week, open-label, dose-optimization period, children 6-12 years of age (n = 90) with ADHD were randomly assigned to double-blind MPH ERCT at the final optimized dose (20-60 mg/day) or placebo. After 1 week of double-blind treatment, efficacy was assessed predose and 0.75, 2, 4, 8, 10, 12, and 13 hours postdose in a laboratory classroom setting. The primary efficacy measure was the average of postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores, analyzed using a mixed-model, repeated-measures analysis. Secondary efficacy measures included Permanent Product Measure of Performance (PERMP) total number of problems attempted and total number of problems correct. Safety assessments included adverse event (AE) monitoring and the Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: MPH ERCT treatment statistically significantly reduced the average of all postdose SKAMP-Combined scores versus placebo (least-squares mean difference [95% confidence interval], -7.0 [-10.9, -3.1]; p < 0.001). Statistically significant treatment differences in SKAMP-Combined scores were observed at 2 hours postdose through 8 hours postdose (p-values <0.001). Statistically significant differences between MPH ERCT and placebo in PERMP total number of problems attempted and total number of problems correct were observed at 0.75 hours postdose through 8 hours postdose (p-values ≤0.049). Common AEs in the open-label period (≥5%) were decreased appetite, upper abdominal pain, mood swings, irritability, insomnia, upper respiratory tract infection (URTI), dysgeusia, and headache; URTI was the only AE reported by >1 subject receiving MPH ERCT in the double-blind period (placebo: URTI, contusion, wound, and initial insomnia). No suicidal ideation or behavior was reported on the C-SSRS at baseline or at any postbaseline assessment. CONCLUSIONS: MPH ERCT 20-60 mg significantly improved ADHD symptoms compared with placebo at 2 hours postdose through at least 8 hours postdose. MPH ERCT was generally safe and well tolerated, with a safety profile consistent with other MPH ER formulations. ClinicalTrials.gov Identifier: NCT01654250. www.clinicaltrials.gov/ct2/show/NCT01654250 .

Efficacy, Safety, and Tolerability of a Novel Methylphenidate Extended-Release Oral Suspension (MEROS) in ADHD.

OBJECTIVE: To test whether an optimal dose of Quillivant XR (methylphenidate extended-release oral suspension [MEROS]) would significantly reduce symptoms of ADHD in children. METHOD: A randomized, double-blind, placebo-controlled, cross-over, efficacy, safety, and tolerability study of MEROS in 45 children aged 6 to 12 years (open-label dose-optimization phase, followed by double-blind cross-over period). RESULTS: MEROS was significantly more efficacious than placebo during double-blind cross-over laboratory classroom days (Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale and Permanent Product Measure of Performance). During the open-label phase, improvements were observed in scores of ADHD Rating Scale-IV, and Clinical Global Impression-Severity and -Improvement Scales. No occurrences of suicidal ideation or behavior were recorded; the most common open-label treatment-emergent adverse events were typical of stimulant use: decreased appetite, insomnia, and abdominal pain. CONCLUSION: MEROS was efficacious in the treatment of children aged 6 to 12 years with ADHD, with a safety profile similar to that of other extended-release methylphenidate pharmacotherapies.

Single-dose Pharmacokinetic Properties and Relative Bioavailability of a Novel Methylphenidate Extended-release Chewable Tablet Compared With Immediate-release Methylphenidate Chewable Tablet.

PURPOSE: A novel methylphenidate hydrochloride extended-release chewable tablet (MPH ERCT) was developed to potentially address an unmet need for patients with attention-deficit/hyperactivity disorder, especially children, who cannot or will not swallow tablets or would prefer the convenience of a chewable tablet. This randomized, open-label, crossover trial compared the pharmacokinetic properties and relative bioavailability of MPH ERCT with an MPH chewable immediate-release tablet (IR MPH) formulation in healthy adults. METHODS: Healthy men and women 18 to 55 years of age were randomly assigned to MPH ERCT 40 mg or 40 mg IR MPH administered in 2 equal doses of 20 mg 6 hours apart with a 7-day washout period. Plasma concentrations of MPH at selected time points up to 24 hours were measured, and pharmacokinetic parameters were determined using a noncompartmental approach in the SAS (Version 9.2) PROC general linear model procedure. FINDINGS: A total of 33 participants were enrolled in the study; 31 participants were included in the pharmacokinetic analysis. The exposure ratios for MPH ERCT and IR MPH (MPH ERCT/IR MPH) for area under the analyte concentration versus time curves (AUC) from time zero to the last measurable analyte concentration (AUC0-last) (87.64%; 95% CI, 84.96-90.41) and AUC0-∞ (89.11%; 95% CI, 86.57-91.73) were within the standard 80% to 125% bioequivalence acceptance criteria. Mean Cmax for MPH ERCT and IR MPH was 12.51 ng/mL and 15.57 ng/mL, respectively; mean time to Cmax was 4.16 hours and 6.43 hours, respectively. The mean Cmax of MPH ERCT was 80% of the Cmax of IR MPH due to a higher peak concentration that occurs after the second dose of IR MPH. All adverse events were mild in severity. IMPLICATIONS: The relative bioavailability of MPH ERCT 40 mg, based on the exposure (AUC), was comparable to that of IR MPH 40 mg administered in 2 equal doses of 20 mg 6 hours apart. Both formulations were generally well tolerated.

NWP06, an extended-release oral suspension of methylphenidate, improved attention-deficit/hyperactivity disorder symptoms compared with placebo in a laboratory classroom study.

OBJECTIVE: The purpose of this study was to determine the efficacy of NWP06, a novel extended-release (ER) liquid formulation of methylphenidate (MPH), compared with placebo in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a laboratory school. METHODS: A total of 45 subjects ages 6-12 years were enrolled in this dose-optimized, randomized, double-blind, placebo-controlled, crossover laboratory school study. Following open-label dose optimization, subjects received 2 weeks of double-blind treatment (1 week of NWP06 and 1 week of placebo). The treatment sequence (NWP06/placebo or placebo/NWP06) was randomly assigned with the last day of each week-long treatment occurring on the laboratory school test day. Efficacy measures included Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) Rating Scale-Combined and Permanent Product Measure of Performance (PERMP) mathematics tests measured at pre-dose and at 0.75, 2, 4, 8, 10, and 12 hours post-dose on each laboratory classroom day. Safety assessments included physical examination, screening electrocardiogram (ECG), vital signs, clinical laboratory tests, adverse event measures, and assessment of suicidality with the Columbia Suicide Severity Rating Scale. RESULTS: NWP06 resulted in significant (p<0.0001) improvements in the SKAMP-Combined score at 4 hours post-dose (mean=7.12) as compared with placebo (mean=19.58) in the completers (n=39). Significant separation from placebo occurred at each time point tested (0.75, 2, 4, 8, 10, 12 hours), with onset of action of NWP06 at 45 minutes post-dose and duration of efficacy extending to 12 hours post-dose. Adverse events (AEs) and changes in vital signs following NWP06 treatment were generally mild and consistent with the known safety profile of MPH. The most common AEs in the open-label phase were decreased appetite (55.6%), upper abdominal pain (42.2%), affect lability (26.7%), initial insomnia (22.2%), insomnia (17.8%), and headache (17.8%). CONCLUSIONS: NWP06 treatment effectively reduced symptoms of ADHD in children beginning at 45 minutes and continuing for 12 hours post-dose. NWP06 was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00904670. http://www.clinicaltrials.gov/ct2/show/NCT00904670 .

Pharmacotherapy of attention-deficit hyperactivity disorder in adolescents.

Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder in children and adolescents, consisting of developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity. The majority of children with ADHD will continue to experience significant ADHD symptoms as teens. ADHD in adolescents can result in significant functional impairment and poorer quality of life. Children and adolescents with ADHD are at higher risk of developing other psychiatric illnesses such as mood, conduct and substance abuse disorders. Stimulants (amphetamines and methylphenidates) and nonstimulants (atomoxetine, guanfacine extended-release (XR) and clonidine XR) have been found to be effective and are approved by the US FDA for the treatment of ADHD in adolescents in the US. Of the agents approved in the US, only guanfacine XR and clonidine XR are not approved in any other countries. There is growing evidence that treatment of ADHD with stimulants reduces the risk of development of other psychiatric co-morbidities, including substance abuse disorders. To date, all FDA-approved stimulants and nonstimulants that have been adequately studied have been demonstrated to be safe and effective in treating ADHD in both children and adolescents. Therefore, clinical decisions used in selecting pharmacotherapy to treat ADHD in children aged 6-12 years can be applied in the adolescent population.

Single-dose pharmacokinetics of NWP06, an extended-release methylphenidate suspension, in children and adolescents with ADHD.

BACKGROUND: Extended-release formulations of stimulants provide once-daily treatment options for patients with attention-deficit/hyperactivity disorder (ADHD). Such preparations are more convenient and may improve compliance, and thus, improve outcomes. Currently, there is no extended-release liquid oral preparation of any stimulant. As such, there is a medical need for a liquid extended-release preparation of methylphenidate for the management of ADHD in children who are unable or unwilling to swallow solid formulations. OBJECTIVE: To evaluate the single-dose pharmacokinetics of an extended-release oral liquid formulation of methylphenidate (NWP06) in pediatric subjects with ADHD. METHODS: Subjects with ADHD received a single oral dose of NWP06 20 or 60 mg. Serial blood samples were obtained before and after drug administration for determination of plasma methylphenidate concentrations and standard pharmacokinetic parameters. Dose- and weight-corrected pharmacokinetic parameters were presented by age group (9-12 years and 13-15 years). RESULTS: A total of 14 youths (7 children aged 9-12 years and 7 adolescents aged 13-15 years) were enrolled and completed the study. Body mass index ranged from 12.08 to 34.08 kg/m(2). Mean values of dose and body weight-adjusted maximum plasma concentration (Cmax) (23.8, 22.3, 22.1, 25.7 [ng/mL]/mg) and area under the concentration-time curve (AUC) (208, 199, 239, 210 [hr·ng/mL]/[mg/kg]) were similar among all age/dose groups, suggesting dose proportionality and a similar rate and extent of absorption in children and adolescents. Values for Cmax were observed between 2 and 4 hours after the dose. The elimination half-life and body weight-adjusted clearance also appeared to be independent of dose and age. NWP06 was well tolerated with no serious adverse events and no adverse event-related treatment discontinuations. CONCLUSION: There were no age-related pharmacokinetic differences after oral administration of NWP06 to children or adolescents in this small sample. Over the dose range of methylphenidate used in this study (0.45-3.3 mg/kg), the pharmacokinetics of NWP06 were linear and dose proportional.

The single-dose pharmacokinetics of NWP06, a novel extended-release methylphenidate oral suspension.

OBJECTIVE: To determine the single-dose pharmacokinetics of 60 mg NWP06, a novel extended-release (ER) liquid formulation of methylphenidate (MPH) compared with 30 mg immediate-release (IR) liquid MPH, dosed at Hours 0 and 6, in adults. METHODS: After institutional review board approval, 30 healthy subjects aged 18 to 68 years were enrolled in this open-label, crossover study and randomly assigned to receive NWP06/IR MPH after an overnight fast. Blood samples were collected prior to dose at Hour 0 and at post-dose hours 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 5, 6, 6.5, 7, 7.33, 7.67, 8, 8.5, 9, 10, 12, 14, 16, 24, and 36. Plasma concentrations of d- and l-MPH were determined and pharmacokinetic parameters were calculated. Safety assessments included vital signs, electrocardiogram, laboratory evaluations, adverse event (AE) collection, and suicidality assessment. RESULTS: Twenty-eight subjects completed the study. The AUC0-∞ of d-MPH for NWP06 and IR MPH were 143.65 and 153.31 ng-hr/mL, respectively. The peak plasma concentration, Cmax (ng/mL), was 13.61 for NWP06 and 20.94 for IR MPH. The half-life of NWP06 was 5.65 hours and Tmax was 5 hours. For IR MPH, the half-life was 3.74 hours and Tmax was 7.33 hours. Vital sign changes were in the expected range for MPH and there were no clinically significant laboratory or ECG changes. The most common AEs reported were headache, dizziness, palpitations, nausea, and nervousness. CONCLUSIONS: A single dose of 60 mg NWP06 is equally bioavailable to two 30-mg doses of IR MPH. NWP06 has a lower peak concentration than IR MPH. Both study treatments were well tolerated, as all AEs were rated as mild in this healthy adult population.

Assessment of strategies for switching patients from olanzapine to risperidone: a randomized, open-label, rater-blinded study.

BACKGROUND: In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone. METHODS: In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation): (i) abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii) gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii) gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued. RESULTS: The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (+/- standard deviation (SD)) baseline Positive and Negative Syndrome Scale (PANSS) total score of 75.6 +/- 11.5. All-cause treatment discontinuation was lowest (12%) in the group with the slowest olanzapine dose reduction (gradual 2) and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1). The relative risk of early discontinuation was 0.77 (confidence interval 0.61-0.99) for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at endpoint were seen in PANSS total score (-7.3; p < 0.0001) and in PANSS positive (-3.0; p < 0.0001), negative (-0.9; p = 0.171) and anxiety/depression (-1.4; p = 0.0005) subscale scores. Severity of movement disorders and weight changes were minimal. CONCLUSION: When switching patients from olanzapine to risperidone, a gradual reduction in the dose of olanzapine over 2 weeks was associated with higher rates of retention compared with abrupt or less gradual discontinuation. Switching via any strategy was associated with significant improvements in positive and anxiety symptoms and was generally well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov NCT00378183.

Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia.

OBJECTIVE: Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown. METHODS: We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function ("disposition index", DI) by intravenous glucose tolerance test. RESULTS: At baseline, groups (risperidone: n=28; olanzapine: n=31) were overweight or obese by body mass index (risperidone: 28.4+/-5.4, olanzapine: 30.6+/-7.0kg/m2). Both drugs induced weight gain (p<0.004). Total adiposity was increased by olanzapine at 6 weeks (p=0.0006) and by both treatments at 24 weeks (p<0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p<0.003). S(I) did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and S(I), we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p<0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p=0.033), indicating inadequate pancreatic compensation for insulin resistance. CONCLUSIONS: This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.

Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics.

BACKGROUND: The safety and efficacy of the first long-acting injectable atypical antipsychotic, risperidone, were assessed in stable patients with schizophrenia switched from oral antipsychotic medications. METHOD: Data were collected between July 1, 2001, and October 25, 2002. The study population included patients from clinics, hospitals, and physicians' offices. After a 4-week run-in period, symptomatically stable patients with schizophrenia (DSM-IV) who had been taking haloperidol (N = 46), quetiapine (N = 45), or olanzapine (N = 50) received 25 mg of long-acting risperidone. The oral antipsychotics were continued for 3 weeks after the first injection of long-acting risperidone. Injections were administered every 2 weeks at 25 mg up to a maximum dose of 50 mg for 12 weeks in this multicenter, open-label study. RESULTS: Long-acting risperidone was well tolerated. Of the 141 patients who participated in the study, the most frequently reported adverse events were insomnia (16%), headache (15%), psychosis (11%), and agitation (11%). The mean increase in body weight was 0.4 kg. No other clinically relevant laboratory abnormalities or significant electrocardiogram changes were observed during the 12-week treatment. Extrapyramidal Symptom Rating Scale total scores were reduced during treatment with long-acting risperidone. Improvements in symptoms of schizophrenia were observed with long-acting risperidone at week 4 and continued through the 12-week treatment with significant reductions in total Positive and Negative Syndrome Scale (PANSS) scores at week 8 (-2.5, p <.01) and week 12 (-3.9, p <.001). At endpoint, 37% (50/135) of these stable patients were rated as clinically improved (> or = 20% decrease in PANSS total scores). CONCLUSIONS: Switching treatment from oral antipsychotics to long-acting risperidone without an intervening period of oral risperidone was safe and well tolerated. Long-acting risperidone also significantly reduced the severity of symptoms in these stable patients with schizophrenia.