David Hough

Only anti-inflammatory medications increased mortality risk with risperidone. The reduced risks of CVAE in patients with comorbid depression and delusions, and of mortality with depression, may have clinical implications when weighing the benefits and risks of treatment with risperidone in patients with dementia.

Patients received once-monthly doses of the 1-month formulation of paliperidone palmitate (50, 75, 100, or 150 mg eq) during the transition phase, followed by a single dose of the 3-month formulation (3.5 times the stabilized dose of once-monthly paliperidone palmitate) during the maintenance phase. Stabilized patients were randomized to receive either a fixed dose of 3-month paliperidone palmitate (175, 263, 350, or 525 mg eq) or placebo once every 3 months during the DB phase.

Results… Show more

Patients received once-monthly doses of the 1-month formulation of paliperidone palmitate (50, 75, 100, or 150 mg eq) during the transition phase, followed by a single dose of the 3-month formulation (3.5 times the stabilized dose of once-monthly paliperidone palmitate) during the maintenance phase. Stabilized patients were randomized to receive either a fixed dose of 3-month paliperidone palmitate (175, 263, 350, or 525 mg eq) or placebo once every 3 months during the DB phase.

Results In the interim analysis, time to first relapse was significantly different in favor of the paliperidone palmitate group vs the placebo group (hazard ratio = 3.45; 95% CI, 1.73-6.88; P < .001); median time to relapse was 274 days for placebo but not estimable for 3-month paliperidone palmitate. An independent data monitoring committee recommended early study termination due to efficacy. In the DB phase, 183 of 305 patients (62% with 3-month paliperidone palmitate; 58% with placebo) had at least 1 treatment-emergent adverse event; those noted more frequently in the group receiving paliperidone palmitate than in the placebo group were headache (9% vs 4%), weight increased (9% vs 3%), nasopharyngitis (6% vs 1%), and akathisia (4% vs 1%).

Conclusions: Compared with placebo, the 3-month formulation of paliperidone palmitate administered 4 times yearly significantly delayed time to relapse in patients with schizophrenia. The 3-month formulation was generally tolerable and has a safety profile consistent with other marketed paliperidone formulations. Show less

Paliperidone palmitate (PP) is a once-monthly long-acting injectable antipsychotic approved for the treatment of schizophrenia in many countries. To evaluate the different injection site options, we compared the pharmacokinetic profile of paliperidone after multiple injections of PP 100 mg eq. (156 mg of PP, equivalent to 100 mg of paliperidone) on days 1, 8, 36 and 64 into the deltoid (n = 24) or gluteal muscle (n = 25) in patients with schizophrenia. After four injections in the… Show more

Paliperidone palmitate (PP) is a once-monthly long-acting injectable antipsychotic approved for the treatment of schizophrenia in many countries. To evaluate the different injection site options, we compared the pharmacokinetic profile of paliperidone after multiple injections of PP 100 mg eq. (156 mg of PP, equivalent to 100 mg of paliperidone) on days 1, 8, 36 and 64 into the deltoid (n = 24) or gluteal muscle (n = 25) in patients with schizophrenia. After four injections in the deltoid-muscle, paliperidone exposure was higher for AUCτ and Cmax, compared with the gluteal-muscle (geometric mean AUCτ-based ratio: 120% [90% CI: 93.1-154.7%], and geometric mean Cmax-based ratio: 130% [90% CI: 100.6-168.9%]). The mean [SD] fluctuation index was higher, with a larger interpatient variability, after deltoid-injections (75.9% [30.9%]) than gluteal-injections (58.5% [14.3%]). The median tmax was similar for both sites. PP was generally tolerable in patients, with more favorable local-site tolerability for gluteal-injection. In conclusion, to achieve therapeutic-concentrations quickly, the first-two injections of PP are best administered into the deltoid-muscle, whereas thereafter maintenance-injections can be administered either in the deltoid or gluteal muscle. Show less

Background: Advanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied.
Methods: Association of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the… Show more

Background: Advanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied.
Methods: Association of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the primary results of which are published (NCT00518323).
Results: The mean (SD) paternal age was 29.2 (6.2) years, range (16–50) and maternal age was 26.8 (5.7) years range (17–42) at childbirth for the 201 adolescents (ages 12–17 years) included in the analysis. While parental ages were uncorrelated with age of onset or initial symptom severity, both maternal and paternal ages showed significant effects on treatment response (p b 0.03) of all paliperidone ER arms versus placebo. Paternal age was significantly correlated to improvement in positive symptoms and maternal age significantly related to negative symptoms, although only paternal age remained significantly associated with the treatment response in analyses that included both parents' ages.
Conclusions: APAwas associatedwith greater treatment response to both paliperidone ER and placebo, but not to age of onset or initial symptom severity in adolescents with schizophrenia. The results support the contention that APA-related schizophrenia has distinct underpinnings from other cases. Further studies are required to explore the role of genetic and environmental factors, and their interactions, in treatment response in this complex disorder. Show less

Poster submitted today

Nasrallah H, Turkoz I, Bossie CA, Fu DJ, Gopal S, Alphs L, Hough D. American College of Neuropsychopharmacology Dec 8-12, 2013, Hollywood FL.

Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5–17 years), received risperidone (low-dose: 0.125 mg/day [20 to\45 kg], 0.175 mg/day [[45 kg] or high-dose: 1.25 mg/day [20 to \45 kg], 1.75 mg/day [[45 kg]) or placebo. Mean baseline (range 27–29) to endpoint change in Aberrant Behavior Checklist-Irritability (primary endpoint) was significantly greater in the highdose—(-12.4 [6.5]; p\0.001), but not low-dose (-7.4
[8.1]; p… Show more

Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5–17 years), received risperidone (low-dose: 0.125 mg/day [20 to\45 kg], 0.175 mg/day [[45 kg] or high-dose: 1.25 mg/day [20 to \45 kg], 1.75 mg/day [[45 kg]) or placebo. Mean baseline (range 27–29) to endpoint change in Aberrant Behavior Checklist-Irritability (primary endpoint) was significantly greater in the highdose—(-12.4 [6.5]; p\0.001), but not low-dose (-7.4
[8.1]; p = 0.164) group, versus placebo (-3.5 [10.7]). Clinical Global Impressions-Severity and Children’s Yale- Brown Obsessive Compulsive Scale scores improved significantly only in the high-dose group, consistent withABC-I results. Somnolence, sedation and increased appetite occurred more frequently in high-versus low-dose groups. Show less

Coppola D, Liu Y, Gopal S, Remmerie B, Samtani M, Hough DW, Nuamah I, Sulaiman AH, Pandina G. A one-year prospective study of the safety, tolerability and pharmacokinetics of the highest available dose of paliperidone palmitate in patients with schizophrenia BMC Psychiatry 2012, 12:26

Fleischhacker, W.W., Gopal, S., Lane, R., Gassmann-Mayer, C., Lim, P., Hough, D., Remmerie, B., Eerdekens, M., A randomized trial of paliperidone palmitate and risperidone long-acting injectable in schizophrenia. Int J Neuropsychopharmacol. 2012; 15: 107-118.

Hough, D.W., Gopal, S., Coppola, D., Remmerie, B.M., Berwaerts, J., Nuamah, I.F., Sterkens, P.C., Xu, Y. Prolongation of cardiac ventricular repolarization under paliperidone: how and how much? J Cardiovasc Pharmacol. 2012. 59: 298-9

Emsley, R., Nuamah I, Hough D, Gopal S., Treatment response after relapse in a placebo-controlled maintenance trial in schizophrenia, Schizophr. Res. (2012), doi:10.1016/j.schres.2012.02.030.

Singh J, Robb A, Vijapurkar U, Nuamah I. Hough D. A randomized, double-blind study of paliperidone extended-release in treatment of acute schizophrenia in adolescents. Biological Psychiatry 2011 Dec 15;70(12):1179-87

Kozma CM, Slaton T, Dirani R, Gopal S, Hough D. Changes in Schizophrenia-related Health Care Resource Utilization Among Patients Receiving Paliperidone Palmitate: Results From a 52-week, Maintenance of Effect Clinical Trial. Current Medical Research and Opinion. 2011 Jun 27(8):1603-1611.

Gopal S, Vijapurkar U, Lim P, Morozova M, Eerdekens M, Hough D. A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia. J Psychopharmacol 2011 May 25(5):685-697.

Gopal S, Pandina G, Lane R, Nuamah I, Remmerie B, Coppola D, Hough D. A Post-hoc Comparison of Paliperidone Palmitate to Oral Risperidone During Initiation of Long-acting Risperidone Injection in Patients with Acute Schizophrenia. Innovations in Clinical Neuroscience 2011;8(8):26-33

Coppola D, Melkote R, Lannie C, Singh J, Nuamah I, Gopal S, Hough D, Palumbo J. Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia. Psychopharmacology Bulletin 2011;44(2):1-20.

Gopal S, Berwaerts J, Nuamah I, Akhras, K, Coppola D, Daly E, Hough D, Palumbo J. Number needed to treat and number needed to harm with paliperidone palmitate relative to long-acting haloperidol, bromperidol, and fluphenazine decanoate for treatment of patients with schizophrenia. Neuropsychiatr Dis Treat 2011;7:93-101. Epub 2011 Mar 8.