Risperidone Maintenance Treatment Research Articles

Menstrual Dysfunction in Women With Schizophrenia During Risperidone Maintenance Treatment.

A percentage of women patients with schizophrenia may suffer from menstrual dysfunction associated with antipsychotic medication. This study evaluated menstrual dysfunction in women with schizophrenia given maintenance risperidone, and investigated the association between menstrual dysfunction and the duration and dose of risperidone and clinical symptoms. The data of 161 women were obtained from the Risperidone Maintenance Treatment in Schizophrenia study, including patients' characteristics, menstrual conditions, and duration and dosage of risperidone. Qualitative data regarding menstrual health were evaluated at baseline (clinical stabilization after 4-8 weeks maintenance treatment with a standard risperidone dose 4-8 mg/d) and follow-up interviews up to 52 weeks. At baseline, 73.2% (119/161) of the patients were eumenorrheic; specific rates of menstrual dysfunction were 14.3% (23/161) irregular menstruation, 6.8% (11/161) oligomenorrhea, and 5.0% (8/161) amenorrhea. At the end of follow-up, 16.0% (19/119) of those with eumenorrhea at baseline reported menstrual dysfunction. During the entire risperidone maintenance treatment, 37.9% (61/161) experienced menstrual dysfunction. The range of onset time from the beginning of risperidone treatment to menstrual dysfunction was 64 to 243 days. Risperidone dose was positively associated with menstrual dysfunction (r = 0.187, P = 0.046). The total Positive and Negative Syndrome Scale score was significantly associated with menstrual dysfunction (r = 0.274, P = 0.001). Attention should be given to menstrual dysfunction of women with schizophrenia that is an adverse effect of risperidone maintenance treatment. Menstrual dysfunction may occur early or late during maintenance treatment, partly depending on the dose.ClinicalTrials.govidentifier: NCT00848432.

Symptomatic remission in schizophrenia: Results from a risperidone maintenance treatment study

This study aimed to investigate remission following the treatment of schizophrenia patients with risperidone. Clinically stabilized patients with schizophrenia (n = 374) were randomly assigned to 4-week, 26-week, or no-dose-reduction groups, in which the baseline risperidone dose was continued for 4, 26, or all weeks during 1-year period. The ‘Positive and Negative Syndrome Scale’ (PANNS) was assessed at baseline and monthly for six months, followed by every two months until the last recruited patient completed 1-year follow-up. Symptomatic remission was defined according to criteria established by the Schizophrenia Working Group. A Generalized Linear Mixed Model indicated significant variation in remission over time, which increased after baseline in the entire group (F = 49.32, df = 1, 3114, P < 0.001). The overall length of risperidone treatment (F = 4.34, df = 1, 416, P = 0.038) and the duration of illness (F = 8.51, df = 1, 359, P = 0.004) had significantly negative effects upon remission. Baseline remission patients were associated with a significantly increased time to relapse compared with the baseline of non-remission patients over a one year follow up period (F = 5.74, df = 1, 367, P = 0.017). One-year risperidone maintenance treatment increased remission rates in schizophrenia. A shorter illness duration, risperidone treatment length, and a lower total PANSS score were clinically useful predictors of remission. Achieving remission may postpone relapse.

Prolactin related symptoms during risperidone maintenance treatment: results from a prospective, multicenter study of schizophrenia.

BackgroundThis study aimed to investigate prolactin related symptoms (PRS) in individuals with schizophrenia during risperidone maintenance treatment for one year, as well as to identify the risk factors for PRS.MethodsIn a multicenter, randomized, controlled, longitudinal study, clinically stabilized schizophrenia patients (N = 374) were randomized to a no-dose-reduction group (N = 129) and 4-week (N = 125) and 26-week (N = 120) reduction groups, in which the original dose was followed by a 50 % reduction over 8 weeks and subsequently maintained. PRS were assessed via a scale of prolactin related adverse events, which included 16 items: menstrual cycle, menstrual period, menstrual volume, menstrual irregularities, amenorrhea, dysmenorrhea, postpartum lactation, gynecomastia, breast tenderness, sexual dysfunction, decreased sexual desire, erectile dysfunction, ejaculatory dysfunction, impotence, increased body hair, and acne. The occurrence of PRS was assessed at baseline and monthly for six months, followed by every two months. A mixed model was used.ResultsPRS at baseline were reported in 18.4, 15.0, and 14.0 % of the 4-week, 26-week, and no-dose-reduction groups, respectively. Female gender, younger age at onset, and the Positive and Negative Syndrome Scale (PANSS) total scores at entry predicted the development of PRS. The mixed model indicated that PRS were more severe in females and at a high dose. In the 237 patients who remained in the study after one year, the incidence of PRS decreased to 9.6, 11.1, and 7.6 % in the 4-week, 26-week, and no-dose-reduction groups, respectively.ConclusionThese findings indicate that the PRS severity was alleviated during the one year treatment period because of the dose reduction. Attention should focus on the side effects of hyperprolactinemia during long-term treatment, especially with a high dose, females, younger age at onset, and more severe patients.Trial registrationClinicalTrials.gov identifier: NCT00848432. Registered February 19, 2009.

Extrapyramidal Symptoms During Risperidone Maintenance Treatment in Schizophrenia: A Prospective, Multicenter Study.

The risperidone maintenance treatment in schizophrenia study was designed to identify the duration of maintenance treatment required with an initial therapeutic dose in contrast to reducing the dose over time. This study investigated extrapyramidal symptoms (EPSs) in different risperidone maintenance treatment paradigms over 1 year. Clinically stabilized patients with schizophrenia (n = 374) were randomized to a no-dose-reduction group and 4-week and 26-week reduction groups, in which the dose was gradually reduced by 50% over 8 weeks and maintained. Extrapyramidal symptoms were assessed at baseline and monthly for 6 months, followed by every 2 months. The Simpson-Angus Scale of Extrapyramidal Symptoms-Chinese version assessed EPS severity. Data were analyzed by a generalized linear mixed model (GLMM). The frequency of EPS at baseline was 23.2%, 20.0%, and 21.3% in the 4-week, 26-week, and no-dose-reduction groups, respectively. Risperidone dosage, positive symptoms, and disorganized thoughts at baseline predicted development of EPS. The GLMM indicated that a significant decrease in EPS was maintained, and different trajectories occurred over time across groups. In the 235 patients who continued treatment after 1 year, the incidence of EPS decreased to 4.1%, 2.8%, and 10.0% in the 4-week, 26-week, and no-dose-reduction groups, respectively, whereas the numbers of dropouts because of intolerable EPS were not significantly different (4.8%, 6.7%, and 6.2%, respectively). These novel findings indicate EPSs were tolerable and differentially decreased depending on the dose paradigm during the 1-year treatment period. Future studies should implement a GLMM to investigate antipsychotic adverse effects during long-term treatment.

Optimal treatment allocation for placebo-treatment comparisons in trials with discrete-time survival endpoints.

In many randomized controlled trials, treatment groups are of equal size, but this is not necessarily the best choice. This paper provides a methodology to calculate optimal treatment allocations for longitudinal trials when we wish to compare multiple treatment groups with a placebo group, and the comparisons may have unequal importance. The focus is on trials with a survival endpoint measured in discrete time. We assume the underlying survival process is Weibull and show that values for the parameters in the Weibull distribution have an impact on the optimal treatment allocation scheme in an interesting way. Additionally, we incorporate different cost considerations at the subject and measurement levels and determine the optimal number of time periods. We also show that when many events occur at the beginning of the trial, fewer time periods are more efficient. As an application, we revisit a risperidone maintenance treatment trial in schizophrenia and use our proposed methodology to redesign it and compare merits of our optimal design.

Weight Changes and their Associations with Demographic and Clinical Characteristics in Risperidone Maintenance Treatment for Schizophrenia

This study aimed to characterize weight changes in schizophrenia patients taking risperidone as part of a randomized, controlled, open-label clinical trial. A total of 374 patients with schizophrenia who had been clinically stabilized following an acute episode were randomly assigned to a 'no-dose-reduction' group (initial optimal therapeutic doses continued throughout the study), a '4-week group' (initial optimal therapeutic doses continued for 4 weeks followed by a half dose reduction that was maintained until the end of the study) or a '26-week group' (initial optimal therapeutic doses continued for 26 weeks followed by a half dose reduction until the end of the study). Participants were assessed monthly using standardized assessment instruments during the first 6 months, and then every 2 months until the last recruited patient completed the 1-year follow-up. Weight gain was defined as gaining at least 7% of initial body weight, weight loss as losing at least 7% of initial body weight. A BMI <18.5 kg m⁻² was defined as underweight, 18.5-24.9 kg m⁻² as normal range, and ≥ 25 kg m⁻² as overweight or obese. At the end of follow-up, of the patients who started within the underweight range (n=22), 77.3% gained weight, whereas 4.5% lost weight. The corresponding figures were 39.6% and 4.8% in patients who started at normal weight (n=273), respectively, and 17.7% and 17.7% in patients who started at overweight (n=79), respectively. At the same time, 59.1% of the patients who started at underweight range went into the normal weight and 13.6% into the overweight/obese range, respectively, while 24.5% of those who started at normal weight went into the overweight/obese range, and 1.1% into underweight range, respectively; 20.3% of those who started at overweight range went into normal weight at the end of the follow-up. Multiple logistic regression analyses revealed that being underweight or normal weight at study entry predicted weight gain compared to being overweight, whereas being overweight at entry was associated with a higher likelihood of weight loss compared to being normal weight. No correlation was found between weight change and dose reduction. Weight change is a common, long-term, but heterogeneous side effect in risperidone maintenance treatment for stable schizophrenia patients. Special attention should be paid to fluctuations in weight that may occur throughout the course of treatment with risperidone.

Risperidone Maintenance Treatment in Schizophrenia: A Randomized, Controlled Trial

Prevention of relapse is the crucial task in the maintenance treatment of schizophrenia. The investigators in this study sought to determine the duration of maintenance treatment needed with the initial therapeutic dose, in contrast to a reduced dose. In a multicenter open-label, randomized, controlled study, patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to a no-dose-reduction group (initial optimal therapeutic dose continued throughout the study), a 4-week group (initial optimal therapeutic dose continued for 4 weeks, followed by a 50% dose reduction that was maintained until the end of the study), or a 26-week group (initial optimal therapeutic dose continued for 26 weeks, followed by a 50% dose reduction until the end of the study). All patients continued until the last recruited patient completed the 1-year follow-up. Of the 404 patients who met the entry criteria and were randomly assigned, 374 completed the study. The estimated mean time from entry to relapse was 571 days in the 4-week group, 615 days in the 26-week group, and 683 days in the no-dose-reduction group, with estimated relapse rates of 30.5%, 19.5%, and 9.4%, respectively. Patients in the no-dose-reduction group experienced greater reduction in the severity of psychotic symptoms. Patients who continued to receive the full risperidone dose used for their acute episode had fewer relapses than those who had dose reductions after 4 weeks or 26 weeks during the maintenance period. There was negligible difference in side effects among the three groups.

A Randomized, Crossover Comparison of Herbal Medicine and Bromocriptine Against Risperidone-Induced Hyperprolactinemia in Patients With Schizophrenia

Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD) with bromocriptine (BMT), a dopamine agonist widely used for PRL-secreting disorders, in the treatment of risperidone-induced hyperprolactinemia. Twenty schizophrenic women who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 mug/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment with PGD (45 g/d) followed by BMT (5 mg/d) or BMT followed by PGD at the same doses for 4 weeks each, with an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients during PGD treatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals with schizophrenia.

Risperidone maintenance treatment increases time to symptom recurrence in young people with disruptive behaviour disorders

Risperidone maintenance treatment increases time to symptom recurrence in young people with disruptive behaviour disorders

A Randomized, Double-Blind, Placebo-Controlled Study of Risperidone Maintenance Treatment in Children and Adolescents With Disruptive Behavior Disorders

The authors compared the effects of maintenance versus withdrawal of risperidone treatment in children and adolescents with symptoms of disruptive behavior disorder. Patients with disruptive behavior disorder (5-17 years of age and a range of intellect) who had responded to risperidone treatment over 12 weeks were randomly assigned to 6 months of double-blind treatment with either risperidone or placebo. The primary efficacy measure was time to symptom recurrence, defined as sustained deterioration on either the Clinical Global Impression severity rating (/2 points) or the conduct problem subscale of the Nisonger Child Behavior Rating Form (/7 points). Secondary efficacy measures included rates of discontinuation due to symptom recurrence, disruptive behavior disorder symptoms, and general function. Safety and tolerability were also assessed. Risperidone dosage was based on weight (patients <50 kg: 0.25-0.75 mg/day; patients /50 kg: 0.5-1.5 mg/day). Treatment was initiated in 527 patients, with 335 randomly assigned to a double-blind maintenance condition. Time to symptom recurrence was significantly longer in patients who continued risperidone treatment than in those switched to placebo. Symptom recurrence in 25% of patients occurred after 119 days with risperidone and 37 days with placebo. Secondary efficacy measures also favored risperidone over placebo. Weight increased over the initial 12 weeks of treatment (mean weight z score change=0.2, SD=2.7, N=511), after which it plateaued. This study is the first placebo-controlled maintenance versus withdrawal trial of its kind in disruptive behavior disorder and provides evidence that patients who respond to initial treatment with risperidone would benefit from continuous treatment over the longer term.

Quality of life in schizophrenia: Long-term follow-up in 362 chronic Spanish schizophrenic outpatients undergoing risperidone maintenance treatment

Our aim was to determine the effect of risperidone monotherapy treatment on disability and on the quality of life of 318 schizophrenic outpatients who had been previously treated with other neuroleptics. Patients were assessed at baseline 2, 4 and 8 months using the BPRS, CGI, WHO/DDS and SF-36. BPRS scores showed a significant decrease at month 2, both in the total score and in each of the three clusters, negative, positive and depression/anxiety. WHO/DDS scores significantly decreased both in the overall score (from 51.8 to 37.4, P < 0.0001) and in the four dimensions. SF-36 scale scores and summary measures showed a significant improvement after 8 months of risperidone treatment. Risperidone long-term treatment (8 months) has a positive effect on clinical and on psychosocial outcomes. Females, paranoids patients and patients without history of use-abuse of substances showed greater improvements in quality of life.