Assessment of adverse drug events of atypical antipsychotics in cases with schizophrenia

Background: Atypical antipsychotics are the drug of choice to manage schizophrenia in general clinical practice. Antipsychotics cause various side effects, including metabolic syndrome, extrapyramidal symptoms, hyperlipidemia, weight gain, and hypotension in patients treated for schizophrenia. Aims and Objectives: The aim of the study was to assess the side effects due to antipsychotic drugs and their effect on the outcome in schizophrenia cases. Materials and Methods: A total of 200 cases with the diagnosis of schizophrenia were recruited. Cases were divided into five groups based on administered drugs (Asenapine, Iloperidone, Olanzapine, Aripiprazole, and Ziprasidone). Treatment procedure and side effect profile were documented. Drug side effects were assessed by a standard antipsychotic side-effects evaluation questionnaire. Cases were followed up for the status of side effects at the end of 1st month, 3rd month, 6th month, 9th month, and 12th month. Results: The rates of weight gain were 20%, 30%, 50%, 25%, and 15% and menstrual complications were seen at 2.5%, 7.5%, 7.5%, 7.5%, and 1% in all five groups, respectively. Lactation disturbance was observed in 5%, 5%, 12.5%, and 5% iloperidone, olanzapine, aripiprazole, and ziprasidone, respectively. The extrapyramidal symptoms were higher in the iloperidone group compared to the asenapine, olanzapine, aripiprazole, and ziprasidone drug groups. Conclusion: Atypical antipsychotic drug consumption leads to considerable weight gain and few metabolic abnormalities. Clinicians should estimate the adverse events associated with atypical antipsychotics and compare the benefits of antipsychotics versus the quality of life of cases.

A prospective study of adverse drug reactions of antipsychotic drugs in a tertiary care public psychiatry hospital

Background: Antipsychotic drugs are commonly used pharmacological agents, which have varied adverse reactions. There is a need to investigate the prevalence of these adverse reactions due to the implications for clinical practice and research. Studies on the prevalence of these adverse reactions are few, especially from Indian subcontinent. Aim and Objectives: The objectives of this study were as follows: (i) To investigate the drug emergent adverse drug reactions (ADRs) in patients who are on antipsychotic drugs and (ii) to study the severity of ADRs due to antipsychotic agents and association between the adverse reaction and the suspected drug. Materials and Methods: This is a prospective observational study, in which 99 patients out of 120 patients suffering with mental illness were enrolled. Base-line investigations such as CBP, ESR, serum creatinine, serum electrolytes, serum cholesterol, serum prolactin, and FBS (fasting blood sugar) were performed and the same were repeated at 1st month and 3rd month and checked for any abnormality. Any suspected ADRs were noted after 1 month and 3 months in patients after starting the treatment with antipsychotic drugs. The patients were assessed with semi-structured interview, the patient rated side effects scale (LUNSERS), and an adverse drug probability scale (Naranjo probability scale). The results were analyzed with SPSS software. The ADRs in patients were also compared between in-patients and out-patients. Results: The atypical drugs particularly risperidone and olanzapine were commonly prescribed for the patients, than typical antipsychotic drugs such as haloperidol. Out of the 99 patients, risperidone was prescribed for 56.6% of patients, olanzapine was prescribed for 40.4% patients, amisulpride was prescribed for 1% of patient, and haloperidol for 2% of patients. About 79% of the patients under study developed ADRs within a month and 21% developed after a month. These drugs were given twice-daily dosage regimen for 89.9% of the patients than once daily dosage regimen, which is 10.1%. Forty-one were in-patients and 58 patients were out-patients. Among the in-patients, risperidone drug was given for 28 (68.3%) patients, olanzapine was given for 11 (26.8%) patients, amisulpride for 1 (2.4%) patient, and haloperidol for 1 (2.4%) patients. The most common ADRs in in-patients was EPS (90.24%) with a statistically significant P < 0.0001. In out-patients, risperidone was prescribed for 28 (48.3%) patients, olanzapine was given for 29 (50%) patients, and haloperidol for 1 (1.7%) patient. The most common ADR among out-patients was sedation (82.75%) with P = 0.0001, which is statistically significant. The ADRs were “significant” according to LUNSERS overall score and are “probable” according to Naranjo’s probability assessment scale. Conclusion: The most common antipsychotic drugs used were risperidone and olanzapine. The common drug emergent adverse reactions were EPS and sedation when the drugs were prescribed twice-daily dosage regimen. The time taken for these ADRs to emerge is ?1 month. The ADRs are significant according to LUNSERS and probable due to suspected drug according to Naranjo’s probability assessment scale. In comparison between in-patients and out-patients, EPS was found more among in-patients and sedation in out-patients. Depending on the intensity of the ADRs, the antipsychotics drug dosage was reduced or drug changed or another was added to combat the ADRs.

Descriptive epidemiological study on patients with movement disorders, with emphasis on Parkinson's disease

ABSTRACT BACKGROUND: Knowing the epidemiological profile is relevant for improving healthcare practices. Movement disorders are neurological disorders characterized by the presence of involuntary movements. They have a negative impact on patients' quality of life. OBJECTIVES: To outline the frequencies of the different diagnoses seen among patients, along with their demographic characteristics, at a hospital in São Paulo (SP), Brazil, and to highlight the clinical aspects of those with Parkinson's disease. DESIGN AND SETTING: Retrospective descriptive epidemiological analysis at a specialized outpatient clinic in a state public hospital in São Paulo. METHODS: Patients treated at this clinic over a four-year period were analyzed. Diagnoses, demographic variables and associations with clinical aspects of Parkinson's disease were evaluated. RESULTS: Out of the 680 medical records analyzed, 58.4% related to females. Most patients were over 60 years of age, white, married and teachers. The most frequent diagnosis was Parkinson's disease, followed by essential tremor and dystonia. Parkinson's disease presented in the mixed clinical form; the most common initial symptom was tremor. The akinetic-rigid clinical form occurred in younger individuals and mostly presented with postural instability and freezing of gait in the early years of disease. CONCLUSIONS: Parkinson's disease, essential tremor and dystonia were the most frequent diagnoses. Characteristics like sex, frequency of other pathological conditions and the clinical and demographic aspects of Parkinson's disease were consistent with the data in the relevant literature.

In vitro characterization and in vivo performance of mefenamic acid-sodium diethyldithiocarbamate based liposomes

Mefenamic acid (MFA) is a hydrophobic drug with low dissolution rate. This study aimed to develop stable and reproducible aqueous formulations of MFA using liposomes as drug carriers. The drug entrapment, particles size and drug release profiles, and stability and reproducibility of the liposomes were determined. In addition, the maximum tolerated dose (MTD) was determined in rats via the oral and intraperitoneal routes of administration. Also, the anti-inflammatory efficacy of these liposomes was evaluated using carrageenan-induced paw edema model in rats. MFA-DDC based liposomes demonstrated a drug entrapment efficacy of 93.6%, particles size of 170.9 nm, and polydispersity index of 0.24 which were not statistically affected when stored in room and refrigerated temperatures for at least 4 weeks. The MTD of the intraperitoneally administrated MFA-loaded liposomes was 20 mg MFA/kg, whereas for those of oral administrations, it was up to 80 mg MFA/kg. Intraperitoneal dose (80 mg MFA/kg) of MFA-DDC liposomes induced extrapyramidal symptoms associated with significant elevation in serum potassium and muscle enzymes. Moreover, significant inhibition of paw edema was demonstrated by the oral and intraperitoneal routes. These findings suggest that MFA-DDC based liposomes are an effective formulation of MFA and recommend the use of bioequivalence assessments with commercial formulations.

Characterization of neurological soft signs in a Brazilian sample of stable patients with schizophrenia / Caracterização de sinais neurológicos sutis em uma amostra brasileira de pacientes estáveis com esquizofrenia

Abstract Introduction: Neurological soft signs (NSS) have been considered one of the target features and a potential endophenotype for schizophrenia. The present study aimed to characterize NSS in a sample of patients with chronic schizophrenia and to compare them with healthy control individuals. Methods: In this study, we evaluated the presence of NSS in a sample of stable patients (n = 24) diagnosed with schizophrenia according to DSM-IV criteria, recruited at the Schizophrenia Outpatient Clinic of Instituto Raul Soares, Belo Horizonte, state of Minas Gerais, southeastern Brazil. Assessment was made with the Brief Motor Scale (BMS), and extrapyramidal symptoms (EPS) were evaluated with the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). A control group (n = 21) was also submitted to the same battery of tests. Results: We observed a significant difference in relation to BMS and SAS scores (p < 0.0001), revealing that individuals with schizophrenia present more NSS and EPS than healthy ones. BMS total scores correlated positively with SAS scores (r = 0.495, p = 0.014), but not with AIMS scores, indicating that NSS could be influenced by the intensity of EPS. Nevertheless, we observed that this relationship remained only for motor coordination tasks (r = 0.550, p = 0.005), while motor sequencing tasks were not influenced by EPS (r = 0.313, p = 0.136). Conclusion: The results suggest that NSS are more frequent in patients with schizophrenia and that motor sequencing tasks could be more specific to the syndrome.

Resumo Introdução: Sinais neurológicos sutis (SNS) têm sido considerados características básicas e potenciais endofenótipos na esquizofrenia. O presente estudo procurou caracterizar os SNS em uma amostra de pacientes com esquizofrenia crônica e compará-los com indivíduos controles saudáveis. Métodos: Neste estudo, avaliamos a presença de SNS em uma amostra de pacientes estáveis (n = 24) com o diagnóstico de esquizofrenia de acordo com os critérios do DSM-IV, recrutados no Ambulatório de Esquizofrenia do Instituto Raul Soares, Belo Horizonte, MG, Brasil. A avaliação foi realizada com a Escala Motora Breve (BMS) e sinais extrapiramidais (SEP) foram observados com a Escala de Simpson-Angus (SAS) e a Escala de Movimentos Involuntários Anormais (AIMS). Um grupo controle (n = 21) também foi submetido à mesma bateria de testes. Resultados: Observamos uma diferença significativa em relação aos escores da BMS e da SAS (p < 0,0001), revelando que indivíduos com esquizofrenia apresentam mais SNS e SEP que indivíduos saudáveis. Os escores da BMS se correlacionaram positivamente com os da SAS (r = 0,495, p = 0,014), mas não com os da AIMS, indicando que os SNS podem ser influenciados pela intensidade de SEP. No entanto, observamos que essa relação permaneceu somente para as tarefas de coordenação motora (r = 0,550, p = 0,005), enquanto as tarefas de sequenciamento motor não foram influenciadas pelos SEP (r = 0,313, p = 0,136). Conclusão: Os resultados sugerem que os SNS são mais frequentes em pacientes com esquizofrenia e que tarefas de sequenciamento motor podem ser mais específicas na síndrome.

Physical Activity of Patients with Chronic Schizophrenia and Related Clinical Factors

OBJECTIVE: This study aimed to investigate clinical factors contributing to the low physical activity (PA) of patients with chronic schizophrenia. METHODS: PA was measured in 50 outpatients with chronic schizophrenia using the International Physical Activity Questionnaire Short Form (IPAQ-SF). Psychopathology, psychosocial functioning, and extrapyramidal symptoms were assessed using the 18 item-Brief Psychiatric Rating Scale (BPRS-18), Global Assessment of Functioning (GAF), and Drug-Induced Extrapyramidal Symptom Scale (DIEPSS), respectively. We examined differences in these clinical variables between “inactive,”“minimally active,” and “health enhancing physical activity” groups. Linear regression analysis was used to examine the clinical factors explaining low PA levels in patients with schizophrenia. RESULTS: Subjects spent an average of 130.18±238.89 min/wk on moderate/vigorous-intensity PA and only 26% of them met the recommended PA guideline of 150 minutes of at least moderate PA per week. The inactive group showed significantly higher BPRS-18 and DIEPSS scores, and a lower GAF score than the other groups. Linear regression analysis showed that DIEPSS scores independently explained the amount of total PA (p=0.001) and time spent being sedentary (p=0.028). CONCLUSION: This study provides preliminary evidence that extrapyramidal symptoms could be a major impediment to the PA of patients with schizophrenia.

Five Month-Persistent Extrapyramidal Symptoms following a Single Injection of Paliperidone Palmitate: A Case Report

Long-acting injectable (LAI) antipsychotics are useful in the treatments for schizophrenic patients with poor adherence due to their maintaining feature of therapeutic plasma level without daily administrations. However, their long-lasting property can cause complicated problems such as a long-lasting side effect. We report a patient who experienced LAI-induced extrapyramidal symptoms (EPSs) for 5 months after a single injection. During that period, every trial to ameliorate this condition turned out to be a failure. The 3-month formulation of paliperidone palmitate is now close at hand. We have to be aware of possible long-lasting adverse events and confirm the tolerability to LAI before use.

Association between Antipsychotic Use and Extrapyramidal Symptoms: / 医薬品情報学

<b>Objective: </b>To examine the association between atypical and typical antipsychotics and extrapyramidal symptoms (EPS), we analyzed the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) from the Pharmaceuticals and Medical Devices Agency (PMDA).<br><b>Methods: </b>A reporting odds ratio was calculated and used to detect spontaneous report signals, with detection defined as a lower limit >1 in a 95% confidence interval.  In addition, time to onset and age at onset of EPS were investigated.<br><b>Results: </b>Drug-reaction pairs were identified in both FAERS (<i>n</i>=29,017,485) and JADER (<i>n</i>=2,079,653).  In analyses of both databases, significant associations were found between atypical and typical antipsychotics and EPS.  Atypical antipsychotics cause EPS with a longer duration of therapy compared to typical ones.  EPS in patients treated with atypical antipsychotics was observed at a broad range of ages compared to the patients treated with typical ones.<br><b>Conclusion: </b>Atypical antipsychotics, like typical ones, may increase the risk of EPS.  Because of the longer latency of onset, it may be difficult to find EPS associated with atypical antipsychotics.  Therefore, the severe symptom may be developed in patients treated with atypical antipsychotics.  The attention should be paid to the EPS in patients of all ages treated with atypical antipsychotics.

Acamprosate-induced Extrapyramidal Symptoms in an Elderly Patient with Alcohol Dependence

Acamprosate reduces the craving for alcohol by decreasing glutamate activity and increasing gamma-aminobutyric acid (GABA) action in patients with alcohol dependence. Acamprosate has tolerable side effects that include diarrhea, headache, dizziness and pruritus. In this study, we report acamprosate-induced extrapyramidal symptoms in an elderly patient with no history of neurologic disease. Severe extrapyramidal symptoms developed two days after the administration of acamprosate and improved over one week after the acamprosate was stopped. Extrapyramidal symptoms are commonly associated with dopamine receptor antagonists. However, there have been several reports of extrapyramidal symptoms occurring with drugs targeting other systems, including GABA, glutamate and serotonin. Acamprosate may decrease dopamine levels in the ventral tegmental area mediated by glutamatergic action and thus cause extrapyramidal symptoms. We suggest that acamprosate carries the risk of causing extrapyramidal symptoms.

A meta-analysis on the efficacy and safety of risperidone in patients with Behavioral and Psychological Symptoms of Dementia (BPSD)

OBJECTIVE: To determine the efficacy and safety of risperidone compared to placebo and haloperidol in the treatment of behavioral and psychological symptoms of dementia. METHODOLOGY: In a systematic review of literature, all articles published from January 1990 - September 2005 that conducted double-blind, randomized controlled clinical trials evaluating the efficacy and safety of risperidone and haloperidol for the treatment of BPSD were selected. The search was performed by means of MEDLINE, PUBMED, Cochrane Library database limited to studies written in English from 1990 to 2005. Key journals and textbooks were also searched in addition to the electronic database search. References mentioned in these studies were likewise reviewed. Two reviewers independently did validity assessment. Analysis of data was done by statistical packs Revman 4.2.7 from Cochrane Collaboration and SPSS (statistical package for the social sciences) v 9.0. RESULTS: Five trials were included in this study. A total of 964 patients were evaluated. Risperidone was superior to placebo as evidenced by significant reduction in the scores of total BEHAVE-AD score (WMD = 2.97, 95% CI = 1.65 - 4.29), BEHAVE-AD aggression subscale (WMD = 1.40, 95% CI = 1.34 - 1.46), and CMAI total aggression subscale (WMD = 3.82, 95% CI = 3.04 - 4.60). Comparison of risperidone and haloperidol showed significant reduction in the total BEHAVE- AD score in patients receiving risperidone (WMD = 1.80, 95% CI = 0.43 - 3.18). Comparing the odds ratio of having an adverse effect, analysis revealed greater chance of developing somnolence (OR = 1.88, 95% CI = 1.27 - 2.77), peripheral edema (OR = 2.43, 95% CI = 1.29 - 4.59) and extrapyramidal symptoms (OR = 1.93, 95% CI = 1.04 - 3.61) with risperidone. CONCLUSION: Risperidone is effective and relatively safe in the treatment of behavioral and psychological symptoms of dementia. Higher incidence of somnolence, peripheral edema and extrapyramidal symptoms was noted with risperidone compared to placebo. Compared with haloperidol, risperidone was superior in the total BEHAVE- AD scale and showed more favorable results in the total CMAI scale, BEHAVE-AD aggression and CMAI total aggression subscales.

Prolonged Drug-Drug Interaction between Terbinafine and Perphenazine

I report here an elderly woman receiving perphenazine together with terbinafine. After 1 week of terbinafine treatment she experienced extrapyramidal symptoms and, in particular, akathisia. Her symptoms did not disappear for 6 weeks, and so at 2 weeks prior to this most recent admission she had stopped taking terbinafine. However, these symptoms persisted for 3 weeks after discontinuing terbinafine. It is well known that terbinafine inhibits CYP2D6 and that perphenazine is metabolized mainly by CYP2D6. Thus, when terbinafine and perphenazine are coadministrated, the subsequent increase in the concentration of perphenazine may induce extrapyramidal symptoms. Thus, terbinafine therapy may be associated with the induction and persistence of extrapyramidal symptoms, including akathisia. This case report emphasizes the importance of monitoring drug-drug interactions in patients undergoing terbinafine and perphenazine therapy.

Open Clinical Trial to Assess the Efficacy and Safety of Quetiapine in Patients of Schizophrenia / 대한정신약물학회지

OBJECTIVE: The efficacy, tolerability and safety of quetiapine in schizophrenia patients diagnosed by the diagnostic criteria of schizophrenia of the Diagnostic Statistical Manual 4th edition was studied in psychiatric department of 4 hospital in Korea. METHODS: Sixty-four patients (male 31, female 33;age 34.2+/-10.4 years; illness duration 8.1+/-8.3 years) who showed acute exacerbation, partial response, or intolerable adverse event to previous antipsychotic drugs were recruited. Doses of quetiapine were adjusted to maximize efficacy and minimize adverse events. Efficacy was assessed by the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scale. Tolerability and safety were assessed by reports of adverse events, clinically significant abnormal laboratory values and changes from the baseline to week 8 in the Abnormal Involuntary Movement Scale (AIMS) and Simpson-Angus total score as index of extrapyramidal symptoms (EPS). RESULTS: Fiftythree patients completed the 8 weeks trial. The clinical symptoms indexed by BPRS were significantly improved (baseline score=37.9+/-13.0, score at the end=24.3+/-13.6;F=41.5, d.f.=2.4, p=0.000). The CGI score of severity of illness was also significantly reduced (baseline score=4.7+/-1.1, score at the end= 3.6+/-1.2;F=27.6, d.f.=2.2, p=0.000). The frequencies of the worsening of AIMS and Simpson-Angus scores at the end of study were 7.5% and 4.2%, respectively. The most common adverse events of at least moderate intensity were EPS (9.3%), constipation (6.3%), and sedation (4.7%). CONCLUSION: The results of this study suggest that quetiapine is effective, may have a favorable EPS, and has overall safe tolerability in the patients with schizophrenia, and schizophreniform disorder.

Open Clinical Trial to Assess the Efficacy and Safety of Quetiapine in Patients of Schizophrenia / 대한정신약물학회지

OBJECTIVE: The efficacy, tolerability and safety of quetiapine in schizophrenia patients diagnosed by the diagnostic criteria of schizophrenia of the Diagnostic Statistical Manual 4th edition was studied in psychiatric department of 4 hospital in Korea. METHODS: Sixty-four patients (male 31, female 33;age 34.2+/-10.4 years; illness duration 8.1+/-8.3 years) who showed acute exacerbation, partial response, or intolerable adverse event to previous antipsychotic drugs were recruited. Doses of quetiapine were adjusted to maximize efficacy and minimize adverse events. Efficacy was assessed by the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scale. Tolerability and safety were assessed by reports of adverse events, clinically significant abnormal laboratory values and changes from the baseline to week 8 in the Abnormal Involuntary Movement Scale (AIMS) and Simpson-Angus total score as index of extrapyramidal symptoms (EPS). RESULTS: Fiftythree patients completed the 8 weeks trial. The clinical symptoms indexed by BPRS were significantly improved (baseline score=37.9+/-13.0, score at the end=24.3+/-13.6;F=41.5, d.f.=2.4, p=0.000). The CGI score of severity of illness was also significantly reduced (baseline score=4.7+/-1.1, score at the end= 3.6+/-1.2;F=27.6, d.f.=2.2, p=0.000). The frequencies of the worsening of AIMS and Simpson-Angus scores at the end of study were 7.5% and 4.2%, respectively. The most common adverse events of at least moderate intensity were EPS (9.3%), constipation (6.3%), and sedation (4.7%). CONCLUSION: The results of this study suggest that quetiapine is effective, may have a favorable EPS, and has overall safe tolerability in the patients with schizophrenia, and schizophreniform disorder.

Clinical Characteristics of Dementia with Lewy Bodies

The dementia with Lewy bodies which was common next to the Alzheimer's dementia had been oftenly misdiagnozed as vascular dementia. The pathologic diagnosis of dementia with Lewy bodies was increasing with the development of immunocytochemical techniques, and it also drew much interest recently. The clinical criteria included core symptoms such as fluctuation of cognitive function, well-formed visual hallucination and extrapyramidal symptoms. For the pathologic criteria, presence of brainstem or cortical Lewy bodies were essential, besides of other pathology. However, it was difficult to obtain satisfactory consensus between investigators about the clinical and pathologic criteria of the dementia with Lewy bodies. There were several reports which suggested good response to the cholinesterase inhibitors.