Effect of antipsychotic replacement with quetiapine on the symptoms and quality of life of schizophrenic patients with extrapyramidal symptoms
Takahide TaniguchiSatsuki SumitaniMichitaka AonoJun‐ichi IgaSawako KinouchiHirosi AkiMami MatsushitaKyoko TaniguchiMami TsunoKazunari YamanishiMasahito TomotakeY KanedaTetsuro Ohmori
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Abstract Replacement of antipsychotic drugs with quetiapine (QTP) was tried in a naturalistic setting in chronic schizophrenic patients who still showed moderate psychiatric symptoms and either showed extrapyramidal symptoms (EPS) or took anti‐parkinson drugs for the EPS. QTP was added on and gradually increased while the previous drugs were tapered and discontinued whenever possible. Clinical symptoms, objective and subjective QOL, and EPS were measured before and 6 months after QTP addition, using Brief Psychiatric Rating Scale (BPRS), Quality of Life Scale (QLS), Schizophrenia Quality of Life Scale (SQLS) and Drug‐Induced Extrapyramidal Symptom Scale (DIEPSS), respectively. Twenty‐one patients completed the trial and received the assessment. It was found that replacement with QTP‐improved clinical symptoms, objective and subjective QOL and EPS. This improvement was equally observed in not only patients who switched to QTP monotherapy ( n = 11) but also patients who took QTP together with reduced small doses (4.4 ± 4.3 mg/day) of previous drugs ( n = 11). The results suggest that replacement with QTP improves symptoms as well as objective and subjective QOL in a subgroup of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd.Keywords:
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Quetiapine ('Seroquel') is a well-tolerated, novel, atypical antipsychotic with consistent efficacy in the treatment of schizophrenia. To date, no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics, yet this type of patient is most frequently seen by psychiatrists. Therefore, this international, multicentre, double-blind study was conducted to compare the efficacy and tolerability of 8 weeks' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine (20 mg/day) treatment. Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure, mean Positive and Negative Symptom Scale (PANSS) score, after 4 weeks' treatment (-9.05, -5.82, respectively,P= 0.061) and at study end (-11.50, -8.87, respectively,P= 0.234). Similarly, there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures (Clinical Global Impression, PANSS subscale and Brief Psychiatric Rating Scale scores) [week 4 (baseline) to week 12 (end)], but the difference between treatments did not reach significance. Significantly more patients on quetiapine than on haloperidol showed a clinical response — patient response rates, defined as ≥ 20% reduction in PANSS total score between weeks 4 and 12, were 52.2% for quetiapine and 38.0% for haloperidol (P= 0.043). Patients receiving quetiapine required less anticholinergic medication (P≤ 0.011), had greater reduction in extrapyramidal symptoms (EPS) (P= 0.005) and fewer treatment-emergent EPS-related adverse events compared to those on haloperidol (P< 0.001). Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73% of patients. Between weeks 4 and 12, elevated serum prolactin concentrations significantly decreased in quetiapine-treated patients compared to those receiving haloperidol (P< 0.001). At the end of quetiapine treatment, 83% of patients had normal prolactin levels while only 21% of patients receiving haloperidol were within the normal range. These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics.
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Abstract Aim This analysis evaluated the tolerability profile of quetiapine using data from all comparative controlled studies in patients with schizophrenia or related disorders in the AstraZeneca clinical trials database, focusing on extrapyramidal symptoms (EPS). Methods Adverse event (AE) data from randomised, double‐blind, controlled studies in the AstraZeneca clinical trials database were pooled, allowing comparison of quetiapine (mean daily doses 357–496 mg/day) with placebo, haloperidol (10.4 mg/day), risperidone (5.5 mg/day) or chlorpromazine (552 mg/day). Incidence of EPS‐related AEs in relation to quetiapine dose was also analysed using a subset of data from fixed‐dose studies. Results Data from 4956 patients were analysed. Quetiapine was well tolerated, and did not increase EPS‐related AEs when compared with placebo (9.6 vs. 10.6%, respectively). The incidence of EPS‐related AEs with quetiapine was consistent across the dose range (4.2–13.2% vs. 11.1% with placebo). Patients receiving haloperidol, risperidone and chlorpromazine experienced significantly higher levels of EPS‐related AEs than those on quetiapine. The most common quetiapine‐ associated AEs, with significantly higher incidence than placebo, were sedation, somnolence and orthostatic hypotension. Conclusion Quetiapine is generally well tolerated in patients with schizophrenia or related disorders, with placebo‐level EPS‐related AEs. Quetiapine has a more favourable EPS profile than haloperidol, chlorpromazine or risperidone. Copyright © 2007 John Wiley & Sons, Ltd.
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Antipsychotic drugs are the mainstay of treatment of patients with schizophrenia. These drugs cause many side-effects, of which the most problematic are extrapyramidal symptoms. This paper reviews published preclinical and clinical studies on quetiapine, a new atypical antipsychotic. The preclinical studies predict a low risk of extrapyramidal symptoms, and this is borne out in clinical trials in patients with relapses of moderate or severe schizophrenia. Indeed, the occurrence of extrapyramidal symptoms with quetiapine is indistinguishable from that with placebo across the dose range. In general, quetiapine is well tolerated, producing side-effects no worse than those encountered with standard antipsychotics. With regard to efficacy, quetiapine appears as effective as the older antipsychotics haloperidol and chlorpromazine in treating schizophrenia. Quetiapine thus offers the clinician a significant advance over standard antipsychotic drugs.
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Antipsychotic agents are the most effective treatment for psychosis, but the typical neuroleptics are associated with dose-related emergence of extrapyramidal side-effects (EPS) (Gerlach, 1999). Older patients are particularly sensitive to EPS and, therefore, typical neuroleptics are not ideal for the treatment of psychosis in the elderly. Atypical antipsychotics with their lower propensity to cause adverse effects such as extrapyramidal symptoms offer benefit to the older psychotic patient (Kasper et al., 2002; Tariot, 1999). Quetiapine is a dibenzothiazepine with the properties of an atypical antipsychotic agent. Early placebo-controlled clinical trials showed quetiapine to have no greater propensity to cause EPS than placebo (Arvanitis and Miller, 1997). In addition, quetiapine has shown to be an efficient antipsychotic drug for the treatment of psychosis in Parkinson's disease (Brandstädter and Oertel, 2002), although there is still controversy in the literature whether it equals clozapine's ability to safely treat drug-induced psychosis without the risk of parkinsonism (Molho and Factor, 2001).
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Antipsychotic medications have a modest effect on the neuropsychiatric symptoms of dementia, but product labels warn of the excess risk of death and morbidity associated with their use in older patients. As such, these agents should not be the first choice for the treatment of behavioral and psychotic symptoms of dementia. Nevertheless, a trial of these agents may be indicated in instances in which the severity of symptoms is extreme, or symptoms do not respond to nonpharmacologic methods or other medications. Most clinical trials in which the efficacy of these agents was studied for the treatment of neuropsychiatric symptoms were of short duration, and thus may not be representative of true efficacy over the long term. There is no evidence to suggest differences in effectiveness between atypical and conventional antipsychotics; therefore, the choice of an antipsychotic for neuropsychiatric symptoms often relies on side effect profile and individual patient circumstances. Extrapyramidal symptoms and QTc prolongation are concerns with conventional antipsychotic agents. The incidence of cerebrovascular events with either atypical or conventional antipsychotics appears increased compared with placebo. A discussion of the risk-benefit ratio of antipsychotics with the patient's family and/or caregivers should precede the decision to use these agents.
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About 5% of visits to emergency departments are made up of conversion disorder cases. This study was designed with the aim of comparing the effectiveness of quetiapine and haloperidol in controlling conversion disorder symptoms.The present single-blind clinical trial has been performed on patients with conversion disorder (based on the DSM-IV definition) presenting to emergency department of 9-Day Hospital, Torbat Heydariyeh, Iran, from January 2017 until May 2018.73 patients were allocated to haloperidol and 71 to quetiapine group. Mean age of these patients was 32.03 ± 12.80 years (62.50% female). Two groups were similar regarding the baseline characteristics. Within 30 minutes, 90.41% of haloperidol cases and 91.55% of quetiapine cases were relieved (p=0.812). The most common side effects after 30 minutes were extrapyramidal symptoms (9.59%) in the haloperidol group and fatigue and sleepiness (7.04%) in the quetiapine group. Extrapyramidal symptoms was significantly higher than the quetiapine group (p=0.013).The results of the present study showed that although quetiapine and haloperidol have a similar effect in relieving the patients from conversion disorder symptoms, the prevalence of extrapyramidal symptoms is significantly lower in the group under treatment with quetiapine. Therefore, it seems that quetiapine is a safer drug compared to haloperidol.
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Antipsychotic medication, stress, gender, and age are factors that influence prolactin levels in patients with psychosis. The aim of the study was to investigate the level of prolactin response to antipsychotic treatment in acute patients, taking into account the total duration of psychosis.The study was conducted on 170 acute patients with schizophrenia spectrum disorders and bipolar disorder. Subjects were divided into three subgroups according to the duration of the psychosis (less than 5 years, between 5 and 10 years and more than 10 years of disorder duration). The initial prolactin response under antipsychotic treatment was measured, while the severity of the psychiatric symptoms was assessed with the BPRS (Brief Psychiatric Rating Scale). Hyperprolactinemia was found in 120 (70.6%) patients, amongst which 80 (66.7%) were females and 40 (33.3%) were males. The average increase in prolactinemia was 2.46 times the maximum value in women, and 1.59 times in men. Gender (β = 0.27, p<0.0001), type of antipsychotic medication according to potency of inducing hyperprolactinemia (β = -0.23, p<0.003), and the duration of psychosis over 10 years (β = -0.15, p = 0.04) significantly predicted prolactin levels, when age, diagnosis, antipsychotic category (conventional/atypical/combinations of antipsychotics), and BPRS total scores were controlled for.Prolactin levels in patients treated with antipsychotic medication appeared to depend on patients' gender, on the type of antipsychotic medication according to potency of inducing hyperprolactinemia, and on the duration of the psychosis. An increase in prolactin levels was associated with female gender, while the use of prolactin sparing antipsychotics and a duration of psychosis over 10 years were associated with lower prolactin levels.
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A 6‐week, double‐blind, randomized, multicentre, parallel‐group study was conducted to compare the efficacy of quetiapine (“Seroquel”) ( n =101) with that of chlorpromazine (n=100) in hospitalized patients with acute exacerbation of subchronic or chronic schizophrenia, or schizophreniform disorder. The tolerabilities of the two treatments were also compared. The mean daily doses of quetiapine and chlorpromazine at the end of the study were 407 mg and 384 mg, respectively. Both treatments were effective in the treatment of positive and negative symptoms, with a trend towards superior efficacy for quetiapine. The quetiapine group had a lower incidence of adverse events than the chlorpromazine group, and a low incidence of treatment‐emergent extrapyramidal symptoms. Quetiapine was not associated with a sustained increase in serum prolactin. These clinical data support the preclinical profile of quetiapine as an atypical antipsychotic agent.
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