Risperidone Oral Solution Research Articles

Multiple therapies relieve long-term tardive dyskinesia in a patient with chronic schizophrenia: A case report

BACKGROUND Tardive dyskinesia (TD) is a serious and disabling movement disorder; it impairs social function and quality of life and increases the mortality rate. TD is usually induced by the use of antipsychotic drugs; however, the underlying mechanism remains unclear. Pharmacotherapy of TD includes cholinergic drugs, benzodiazepines, ginkgo biloba extract (GBE), antioxidants, amantadine, propanolol, botulinum toxin, valbenazine, and deutetrabenazine, whereas the non-pharmacotherapy approach includes modified electroconvulsive therapy (MECT) and deep brain stimulation. We successfully treated a chronic schizophrenia patient with comorbid long-term severe TD using deutetrabenazine, clozapine, and MECT. CASE SUMMARY A 69-year-old woman who was diagnosed as having schizophrenia 16 years ago developed severe TD after 6-mo prescription of risperidone oral solution. Her TD symptoms did not resolve despite various treatments, such as GBE, vitamin E, trihexyphenidyl, promethazine, benzodiazepines, and switching to quetiapine and olanzapine. After admission, she was given deutetrabenazine 6 mg bid. Her buccal tremor was slightly resolved 3 d later; however, her tongue remained protruded and could not be retracted. Quetiapine was switched to clozapine on day 4, and the buccal tremor remarkably resolved, and the tongue could be retracted into the mouth from day 6 onward. After three sessions of MECT, the buccal tremor resolved further. Since then, she has been able to take a semifluid diet, and her quality of life improved remarkably during 6 mo of follow-up. CONCLUSION TD is a serious condition which could be caused by antipsychotic medications; however, the best strategy against TD is prevention and monitoring during using antipsychotics. For patients with TD caused by antipsychotic medication use, multiple measures should be considered like switching to clozapine, adjunction with deutetrabenazine, or even MECT.

Comparison of risperidone oral solution and intramuscular haloperidol with the latter shifting to oral therapy for the treatment of acute agitation in patients with schizophrenia

This randomized, parallel-group, open study investigated the efficacy and safety of risperidone oral solution (RIS-OS) in combination with clonazepam and intramuscular haloperidol for the treatment of acute agitation in patients with schizophrenia, and the study explored the possibility of decreasing the efficacy of an acute 6-week treatment by switching intramuscular haloperidol injection to RIS-OS. Two hundred and five agitation-exhibiting schizophrenic inpatients at six hospitals were originally included in the study. The 47-day trial consisted of 5 days (session I) of receiving either oral treatment (RIS-OS plus clonazepam) or intramuscular treatment (intramuscular haloperidol) and a 42-day (session II) period of either withdrawing from clonazepam or shifting from intramuscular haloperidol to a RIS-OS period. The primary efficacy outcome was measured as the change in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) in session I and the change in the PANSS in session II. Safety was assessed by the frequency of the adverse events. Mean PANSS-EC improvement was significant after 5 days of treatment in both groups (P>0.05) and was similar between the two treatment groups (P<0.01). Most patients' PANSS-EC scores improved or remained stable during the drawback/shift treatment period. Efficacy was not significantly different between the two treatment groups after the 6-week treatment (P>0.05). However, combination treatment exhibited greater efficacy, and adverse events, especially extrapyramidal symptoms, were lower with the oral treatment than with the intramuscular treatment in session I. These results show that RIS-OS in combination with clonazepam is an effective treatment, comparable with intramuscular haloperidol, and is well-tolerated for acute agitation in patients with schizophrenia.

Peripheral Edema Associated With Risperidone Oral Solution

Department of Psychiatry Beitou Armed Forces Hospital Taipei, Taiwan Department of Psychiatry Beitou Armed Forces Hospital Taipei, Taiwan [email protected]

Risperidone oral solution versus standard tablets for the acute treatment of patients with schizophrenia

The time required to attain the maximum plasma level of risperidone (RIS) is shorter for RIS oral solution (OS) than for RIS standard tablets (ST), although both forms have equal bioavailability. The objective of this study was to clarify whether RIS-OS shows a faster onset of efficacy and lower adverse events than RIS-ST. The two forms of risperidone were compared with respect to effectiveness including a speed of response, efficacy and tolerability. An open-label, 24-week, multicentre, randomized, flexible-dose study comparing the RIS-OS (mean dose, 3.7 mg; N=44) to the RIS-ST (mean dose, 3.7 mg; N=37) in acutely ill patients with schizophrenia showed no differences. Outcome measures included psychopathology, tolerability (extrapyramidal symptoms and serum prolactin), and Drug Attitude Inventory. This study was conducted between October 2006 and October 2008. Both RIS-OS- and RIS-ST-treated patients showed statistically significant reductions from the baseline in the mean scores of the Positive and Negative Syndrome Scale (PANSS)-total and PANSS-excite component, with no statistically significant differences between the treatment groups. The accumulated treatment response ratio was similar between the two groups. There was no significant difference in the Drug-Induced Extrapyramidal Symptom Scale score or serum prolactin increase between the treatment groups, but RIS-OS appeared to induce less serum prolactin increase than RIS-ST in drug-naïve female patients. Because there is no theoretical reason why this should be so, these results will require confirmation from a double-blind study in a larger sample. No significant difference was observed in the subjective drug attitude between the two groups. The original hypothesis that RIS-OS shows an earlier onset of efficacy or less adverse events than RIS-ST was not supported in this study. Subsequent studies should carefully establish the differences among various forms of antipsychotic drugs.

Comparison of plasma levels between oral solution and fine granule dosage forms of risperidone

Objective. In Japan, there are several clinical reports that risperidone (RIS) oral solution (OS) requires shorter time for tranquilization and induces fewer extrapyramidal symptoms (EPS) than other dosage forms; i.e. fine granules (FG). Our aim is to compare plasma levels of RIS, its active metabolite (9-OH-RIS), and their sum (active moiety; AM) between RIS-OS and RIS-FG in a multiple-dose regimen. Method. A 12-week cross-over study was conducted in nine patients with schizophrenia treated with 3 mg of RIS twice daily. The study period was divided into four terms, each term being 3 weeks. RIS-FG and RIS-OS were given in two alternate terms each. Blood samples were collected on the last day of each term just before and at 1 h after RIS treatment to measure plasma levels of RIS, 9-OH-RIS, and prolactin. Result. Plasma levels of RIS, 9-OH-RIS, AM, and prolactin before treatment were significantly lower for RIS-OS than for RIS-FG, while no significant difference was observed between the two forms at 1 h after administration. Conclusion. In a multiple-dose regimen, RIS-OS treatment caused a larger diurnal fluctuation in plasma level of AM than RIS-FG. These variations may explain the differences in severity of EPS between the 2 forms.

Rash and Desquamation Associated With Risperidone Oral Solution

Sir: Antipsychotic agents are known to cause adverse cutaneous reactions in approximately 5% of the individuals for whom they are prescribed,1 and there have been some reports of dermatologic disorders associated with conventional antipsychotics.2–5 Although atypical antipsychotics cause fewer dermatologic symptoms than typical antipsychotics,6 some recent reports have associated olanzapine7–9 and clozapine10–13 with skin lesions. To our knowledge, there have not been any reports of adverse cutaneous reactions associated with risperidone or risperidone oral solution. We present a case in which adverse cutaneous reactions were developed after the initiation of risperidone oral solution treatment and soon disappeared after discontinuation of this antipsychotic agent. Case report. Mr. A, a 37-year-old man with DSM-IV bipolar I disorder, was referred to our inpatient clinic in July 2007. His first manic episode had developed at the age of 23 and he had experienced several manic episodes since then. Mr. A was euphoric and irritable. His speech was rapid. He continuously complained about politicians, and said that God had given him an enormous power to punish them. His sleep and appetite were severely disturbed. We started treatment with risperidone oral solution 2 mg at bedtime, lithium 900 mg/day, diazepam 15 mg/day, zolpidem 10 mg at bedtime, and procyclidine hydrochloride 5 mg at bedtime. On the third day of treatment, Mr. A complained of the facial flushing, and we could find rashes under both eyes. On the fourth day of treatment, risperidone oral solution was titrated to 4 mg/day, and lithium was titrated to 1200 mg/day due to his persisting manic symptoms. Other medications were maintained at previous doses. On the fifth day of treatment, the rashes had spread over Mr. A's whole face and neck, and areas of desquamation had developed over his face. On the sixth day of treatment, risperidone oral solution treatment was stopped, and quetiapine 150 mg/day was started and titrated up to 600 mg/day to manage his manic symptoms. On the second day after risperidone oral solution treatment was stopped, Mr. A's skin lesions had completely disappeared. Lithium 1200 mg/day was maintained and serum lithium level was 0.73 mmol/L. Some studies have indicated that several cutaneous adverse effects, which may be dose dependent, are associated with lithium treatment.14,15 In our case, although lithium was coadministered with risperidone oral solution, the immediate improvement of the skin lesions after stopping risperidone oral solution suggests that the adverse skin reactions were because of risperidone oral solution rather than lithium. The combined effect of risperidone oral solution and lithium on the skin cannot be completely excluded, however, and further studies are needed. After the replacement of risperidone oral solution with quetiapine, the skin lesions did not recur. We think that quetiapine is relatively safer than risperidone oral solution in view of the dermatologic adverse effect. The majority of adverse cutaneous events are benign and easily treated.1 However, these adverse events may impact compliance. Our case suggests that risperidone oral solution may cause adverse skin reactions like rashes and desquamation and that quetiapine can be an alternative choice in such cases. Beang-Jin Chae, M.D. Department of Psychiatry, Daedong Hospital, Daegu, Republic of Korea Byung-Jo Kang, M.D. Department of Psychiatry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

Olanzapine orally disintegrating tablet vs. risperidone oral solution in the treatment of acutely agitated psychotic patients

Objective Efficacy and tolerability of risperidone oral solution (RIS-OS) and olanzapine orally disintegrating tablet (OLZ-ODT) were compared for the treatment of acute psychotic agitation. Method During a 2-month period, patients scoring ≥15 on the Excited Component for Positive and Negative Syndrome Scale (PANSS-EC) were assigned to treatment with OLZ-ODT ( n=34) or RIS-OS ( n=53) on psychiatric emergency situations, and assessed every 15 min. Results Two (OLZ-ODT and RIS-OS) by five (0-, 15-, 30-, 45- and 60-min time points) repeated-measures analysis of variance revealed only a significant main effect of time course on PANSS-EC ( F=82.2, P<.0001). No differences in the number of patients receiving additional injection due to worsening were found (OLZ-ODT, 11.8%; RIS-OS, 9.4%). No differences in rate of extrapyramidal symptoms and patient satisfaction with assigned treatment were found. However, patients in the OLZ-ODT group recovered significantly more from tachycardia than those in the RIS-OS group ( t=2.17, P=.03). Conclusion OLZ-ODT and RIS-OS treatments yielded similar improvements in acutely agitated patients who accepted oral medication. However, on one physiological parameter (i.e., tachycardia) OLZ-ODT might be superior to RIS-OS. Physiological indicators may also be useful for measuring levels of agitation.

Low-dose oral risperidone lengthened sleep duration in healthy participants

We examined the effects of low-dose oral risperidone (RIS) on nocturnal sleep in healthy participants. This study was performed in a placebo-controlled manner in 10 healthy male volunteers (mean age, 23.6 years), with administration of 0.5 mg of RIS oral solution or a placebo in the morning or evening for 2 consecutive days. Each night, polysomnography (PSG) was performed, and PSG data during non-rapid-eye movement (REM) sleep were processed by power spectral analysis. An evening administration of 0.5 mg RIS significantly increased total sleep time, sleep efficiency and sleep stage 3, and significantly decreased total waking time and waking after sleep onset (P < 0.05). A morning administration of 0.5 mg RIS significantly increased sleep stage 3 (P < 0.05). According to power spectral analysis, the evening administration of RIS significantly increased the theta power (P < 0.05) and decreased the beta power (P < 0.05) during non-REM sleep. The administration of 0.5 mg oral RIS increases sleep stage 3 and increases total sleep time following evening administration.

Lack of bioequivalence between generic risperidone oral solution and originator risperidone tablets

Risperidone is an atypical anti-psychotic, available in various formulations. The objective of the study was to compare the bioavailability of a generic oral solution of risperidone (Test formulation) and Risperdal tablets (Reference formulation). Both formulations contained 1 mg risperidone per dosing unit. The study was carried out in 32 healthy volunteers under fasting conditions. Risperidone and 9-hydroxyrisperidone concentrations in plasma were determined using HPLC/MS/MS. The results show that the 90% confidence intervals for the geometric mean ratios of the solution and the tablet formulations were not within the acceptance range of 80 125% for risperidone, whereas the confidence intervals for 9-hydroxyrisperidone were within the acceptance range of 80 - 125%. Bioequivalence between the generic 1 mg/ml risperidone solution and the originator tablet formulation was not proven in this study.

Ｒｉｓｐｅｒｉｄｏｎｅ内用液の錐体外路症状発現に関する検討

Though it has been reported that the incidence of extrapyramidal symptoms with risperidone oral solution is lower than that for risperidone tablets,there has still been no detailed comparision of the 2 dosage forms in this respect.With this in mind,we investigated the usage of anti-parkinsonism drugs for a period of 1 month from starting to take risperidone oral solution or tablets,and compared the incidence of extrapyramidal symptoms between a risperidone oral solution group of subjects and a tablets group.The incidence of extrapyramidal symptoms for the oral solution group (4.8%) was significantly lower than that for the tablets group (23.2%)(p=0.022; χ2-test)(p=0.011; Log rank test) and the number needed to treat was 5.4.From this,we concluded that risperidone oral solution is safer to use than risperidone tablets in virew of the lower incidence of extrapyramidal symptoms.

Compatibility and stability tests of risperidone with soft-drinks by isothermal titration microcalorimetry

Isothermal titration microcalorimetry has been applied to investigate the compatibility testing of risperidone oral solution with soft-drinks and the interaction with tea tannin such as (–)-epigallocatechin, (–)-epicatechin, theaflavin and their gallates. In aqueous solution, risperidone was exothermically bound to tea tannin with binding affinity (103–104 M–1), small enthalpy and entropy changes reflecting van der Waal’s interaction to form an insoluble complex at 1:1 molar ratio. The heat effect of risperidone titrated into soft-drinks containing tannin was exothermic and proportional to the quantity of the complex. While, no significant heat effect was found for risperidone titrated into a pet-bottled water and an infusion of parched barley without tea tannin. These results were agreed with stability testing of risperidone in some soft-drinks by HPLC method.

Risperidone oral solution is suitable for a wide range of applications, and is not only an alternative to intramuscular haloperidol

Kikuyama, Hirokia b; Okamura, Takehikoa; Morimoto, Kazushigea b; Yoneda, Hiroshia b Author Information

Risperidone plasma concentrations after treatment with risperidone oral solution and fine granules

Risperidone plasma concentrations after treatment with risperidone oral solution and fine granules

Decreased adverse effects with risperidone oral solution: report of five cases

Decreased adverse effects with risperidone oral solution: report of five cases

Comparative study of the administration of risperidone oral solution with intramuscular injection of haloperidol to treat psychotic raptus

Hirabayashi, Eiichia b; Ikeda, Norihikoa; Toyama, Kaorua; Ishikawa, Juna; Osako, Masayukic; Mine, Yoshiakib; Fushimi, Motoyukia b; Iimori, Makioa Author Information

The effect of risperidone oral solution on patients refractory to risperidone tablets and fine granules

The effect of risperidone oral solution on patients refractory to risperidone tablets and fine granules

Changes produced by the introduction of risperidone oral solution to our psychiatric treatment and care

Hokyo, Akiraa; Takizawa, Yoshitadaa; Momoe, Murataa; Nishimoto, Yoshiyukia; Matsumura, Hitoshib Author Information

Effects of risperidone oral solution on the quality of sleep in patients with schizophrenia

Suga, Hidemichia; Okamura, Takehikob; Kikuyama, Hirokib; Ota, Munehirob; Morimoto, Kazunarib; Kobayashi, Shinichib Author Information

熱測定法を用いたリスペリドンと市販飲料との配合変化試験および茶葉タンニンとの相互作用

Compatibility between risperidone and soft drinks was examined by means of isothermal titration microcalorimetry, and the interaction of risperidone with tea tannin- (-)-epigallocatechin, (-)-epicatechin, theaflavin and their gallates-was investigated thermodynamically. Risperidone exothermically bound to tea tannin monomers with a binding affinity of 103-104 M-1 in aqueous solution to form an insoluble complex at a 1:1 molar ratio. The binding reaction was characterized by small enthalpy and entropy changes, reflecting hydrophobic and van der Waal's interactions.After mixing Risperdal® liquid (1 mg/mL risperidone oral solution) with soft drinks containing tannin-such as green tea, black tea and oolong tea, there was an immediate decrease in the risperidone content and the mixtures became cloudy. The heat effect of risperidone titrated into these soft drinks was exothermic and proportional to the quantity of the complex formed in the mixture. However, no significant heat effect was noted when risperidone was titrated into drinks in PET bottles that do not contain tea tannin, such as mineral water and an infusion of parched barley. Isothermal titration microcalorimetry is thus a rapid and effective method for evaluating the compatibility and physico-chemical interactions of drugs.

P.3.e.007 Risperidone oral solution, therapeutic possibility in treatment of acute and agitated psychotic patients

P.3.e.007 Risperidone oral solution, therapeutic possibility in treatment of acute and agitated psychotic patients