Abnormalities in Glucose Blood Level during Antipsychotic Treatment in Schizophrenia Patients

Background: Schizophrenia is one of the mental disorder with many problematic issues, in both psychologically and socially. This disease requires provision of long-term antipsychotic therapy, hence could rise other potential health problems. Antipsychotic treatment can cause serious glucometabolic side-effects, including type 2 diabetes and hyperglycemic emergency. Recent attention has also been focused on antipsychotic-induced hyperglycemic emergencies experienced by new users of typical and atypical antipsychotic. Patients treated with atypical APDs have ~10 times higher risk in developing hyperglycaemic emergencies. In our pre-eliminary study, hyperglycemia condition in new patients occurs in four in seven patients who received typical and atypical antipsychotics. This condition is often overlooked and is not routinely evaluated. Moreover, it can develop into diabetes and increase the risk of morbidity and mortality in schizophrenia patients. In this study, we would like to determine the acute effects of metabolic (hyperglycemia) in patients treated with antipsychotic (Risperidone and Haloperidol) Measurement of blood sugar levels was performed in groups treated with haloperidol (N = 15) and treated with risperidone (N = 15). Plasma samples were taken at the beginning of treatment, in week IV, and in week VIII. The measurement of glucose levels was performed after meal and in early morning before breakfast (fasting blood glucose level 8 hours). Results: The blood sugar level after meals was significantly higher in the Risperidone group compared to the Haloperidol group (p <0.001) after IV and VIII weeks. Meanwhile, the fasting blood sugar level was significantly higher in the Risperidone group compared to the Haloperidol group after VIII weeks of treatment ( p <0.001). Conclusions: Both antipsychotics can cause an increase in blood sugar levels. Treatment with Risperidone significantly increased the blood sugar levels compared to treatment with haloperidol. Measurement of blood sugar level is needed to monitor the metabolic effect of antipsychotic, especially in patients treated with Risperidone. It is necessary to have dietary regulation and physical activities to prevent undesired metabolic side effects.

Differentiation in Neurological Soft Sign Scores on Schizophrenic Patients with Antipsychotic Treatment

Background: Schizophrenia is a chronic mental illness that affects cognitive aspect of a patient which need long term care with antipsychotics. Long term use of antipsychotic itself causes neurobiological change in the brain which results in alteration of cognitive function. The latest research had demonstrated that NSS (Neurological Soft Sign) reflect a rather wide range of cognitive impairments in schizophrenia which was not accounted for by age, education or severity of global cognitive deficits. Therefore, we examined the effects and impact of antipsychotic Haloperidol and Risperidone treatment in schizophrenic patient using NSS scores. The Study showed that chronic schizophrenia patients had a higher NSS scores than acute patients. NSS also significantly associated with all neuropsychological domains of MMSE in both groups and were confirmed when age, education and severity of global cognitive deficits were not accounted for. This study also obtained a lower NSS score in patients who received Risperidone therapy compared to Haloperidol with p = 0.003. Out of 5 NSS domain in the Heidelberg scale, there was a significant improvement in motor coordination and motor sequencing (p = 0.004) and (p = 0.048) in patients who received Risperidone therapy compared to Haloperidol. There was an association between the chronicity of the disease and NSS, NSS also shows that it’s not influenced by age, education and severity of global cognitive deficits as a screening instrument. Finally the improvement of NSS scores in the Risperidone group was far superior compared to the Haloperidol group particularly in motor coordination and motor sequencing.

The Augmentation Effect of N-Acetyl Cysteine Antioxidant on Superoxide Dismutase Levels in Schizophrenic Patients Treated with Risperidone

Background: Schizophrenia affects approximately 1% of the population and in Indonesia the prevalence is about 400.000 people or as many as 1.7 per 10000 individuals of the population. Schizophrenia is characterized by positive symptoms, negative symptoms and also cognitive, aggressive, and affective symptoms, where negative symptoms reflect loss of function. One important factor that plays a role in the pathophysiology of schizophrenia is the excessive production of free radical substances and the failure of the anti-oxidant defense process. The aim of this study is to see how levels of superoxide dismutase change after N-acetylcystein augmentation in schizophrenic patients treated with risperidone. This study is a pre-post experimental test design, where schizophrenic patients meet inclusion and exclusion criteria. At baseline, and after 8 weeks of N-acetyl cysteine administration, patients were assessed at each of the time points using PANSS, and SOD was measured in blood at both time points. The average negative PANSS score in the Risperidone + NAC baseline group was 29.93 (±1.83); in the Risperidone group was 29.83 (±1.19) (p = 0.87). The average negative PANSS score at the end of week 8 was statistically significantly different (p = 0.001) in the Risperidone + NAC group (17.40 ±1.84) and in the Riseridone group (21.00±0.74). The average baseline SOD levels in the Risperidone + NAC group were 63.57 (±22.44), and in the Risperidone group was 85.79 (±101.05). SOD levels at week 8 in the Risperidone + NAC group were 71.72 (±31.20) and in the Risperidone group 128.27 (±117.67). ∆ SOD in the Risperidone + NAC group was 8.15 (19.54) and ∆ SOD in the Risperidone group was 42.48± (54.30). p value of 0.028Research data shows that NAC augmentation can improve the negative symptoms of schizophrenia through reducing SOD levels in the blood.

Total Cholesterol Levels in Men with Schizophrenia Receiving Risperidone and Haloperidol Treatment

AIM: The objectives of the study were to compare total cholesterol levels in men with schizophrenia receiving risperidone and haloperidol treatment. METHODS: We conducted on treatment analysis experiment study involving 30 subjects who received risperidone and 30 subjects who received haloperidol. Total cholesterol levels were examined at week 0 and week 8. RESULTS: There were no statistically significant differences in baseline characteristics. At week 8, mean of total cholesterol level in the risperidone group was 207.23 ± 21.49 compared to 188.17 ± 17.00 in the haloperidol group. A difference of 19.06 ± 5.00 (95% CI 9.05–29.08) was observed, which is statistically significant (p < 0.001). CONCLUSIONS: There was a statistically significant increase in total cholesterol levels in men with schizophrenia receiving risperidone compared to haloperidol.

Proteome Analysis of PC12 Cells Reveals Alterations in Translation Regulation and Actin Signaling Induced by Clozapine

Although antipsychotics are routinely used in the treatment of schizophrenia for the last decades, their precise mechanism of action is still unclear. In this study, we investigated changes in the PC12 cells’ proteome under the influence of clozapine, risperidone, and haloperidol to identify protein pathways regulated by antipsychotics. Analysis of the protein profiles in two time points: after 12 and 24 h of incubation with drugs revealed significant alterations in 510 proteins. Further canonical pathway analysis revealed an inhibition of ciliary trophic factor signaling after treatment with haloperidol and showed a decrease in acute phase response signaling in the risperidone group. Interestingly, all tested drugs have caused changes in PC12 proteome which correspond to inhibition of cytokines: tumor necrosis factor (TNF) and transforming growth factor beta 1 (TGF-β1). We also found that the 12-h incubation with clozapine caused up-regulation of protein kinase A signaling and translation machinery. After 24 h of treatment with clozapine, the inhibition of the actin cytoskeleton signaling and Rho proteins signaling was revealed. The obtained results suggest that the mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) play a central role in the signal transduction of clozapine.

A comparative study of effectiveness, safety and cost effectiveness of olanzapine, risperidone and aripiprazole therapy in schizophrenia

Background: Schizophrenia is the most common psychotic disorder and responsible for approximately half of long-term psychiatric hospitalizations. Antipsychotic medications reduce the psychotic symptoms and prevent relapses. The choice of drug for treatment of schizophrenia depends on many issues, including effectiveness, cost, side-effect burden, availability, and tolerability. Many studies have compared antipsychotic drugs with one another, but no broad consensus has been reached. Our study compares the clinical effectiveness, safety and cost effectiveness of atypical antipsychotics in our setting.Methods: This was an observational, prospective study in which schizophrenia patients receiving either olanzapine, risperidone or aripiprazole were enrolled. Patients were followed up for 3 months. Evaluation of effectiveness was done by analysing mean reduction in PANSS score. Analysis of ADRs was done using WHO causality scale and Hartwig and Siegel severity scale. Cost analysis was done by comparing all three groups in term of cost range of antipsychotic drugs per improvement in PANSS score during the study period.Results: In the present study, the average dose of antipsychotic drugs received by a patient per day was 8.83±2.98 mg in olanzapine group, 4.76±1.12 mg in risperidone group and 20.43±8.5 mg in aripiprazole group. Mean reduction in PANSS score from baseline to 12 weeks was 23.79% in olanzapine group, 25.41% in risperidone group and 24.65% in aripiprazole group. Conclusions: All the groups were equally effective in reduction in PANSS score while risperidone was the most cost effective.

Relation between hyponatremia and alteration in gross metabolic parameters after atypical antipsychotic therapy

Background: Weight gain and hyponatremia which is dilutional in nature, has been well known adverse effects associated with use of atypical antipsychotic medication but the plausible impact of dilutional hyponatremia on weight gain has not been explored.Methods: One hundred and three patients more than 18 years of age of either gender who were prescribed, olanzapine or risperidone, were tested for serum electrolytes (Na+ and K+) and gross metabolic parameters (weight and waist circumference) were measured for baseline and post drug testing.Results: Most common age group was 30-39 years of age in the patient study sample (n=103) with 38 (36.90%) patients were females while rest 63 (63.10%) were males. There was no significant association between serum sodium levels and weight gain was observed (p >0.05). It was observed that in olanzapine group 64% of the studied cases had weight gain whereas in risperidone group only 20.8% reported weight gain (p <0.001). There was significant association between olanzapine and increase in waist circumference over risperidone, irrespective to serum sodium status (x2=0.0148, p >0.05).Conclusions: Olanzapine was primarily responsible for weight gain and increase in waist circumference over risperidone. These gross metabolic parameters were not influenced by hyponatremia.

Treatment with Risperidone vs. Olanzapine in Naturalistic Study of Bipolar Manic Inpatients

IntroductionThere are very few comparative controlled trials of risperidone versus olanzapine in manic patients. No previous naturalistic study has compared the efficacy of these two antipsychotics in the natural environment of manic inpatients.ObjectiveThe aim of this retrospective and naturalistic study was to evaluate the efficacy of acute treatment with risperidone vs. olanzapine in Bipolar I manic inpatients.Methods(1) Patients: the study includes all the inpatients diagnosed with bipolar I manic episode (DSM-IV) who were admitted during the years 2009 to 2014. Patients treated with risperidone and olanzapine concomitantly (n = 6) and patients not treated with risperidone or olanzapine (n = 129) were excluded.The patients finally included (n = 183) were separated in two groups:– treated with risperidone (n = 89);– treated with olanzapine (n = 94).(2) The Student-T test was used to compare, between the groups, the mean of scores in YMRS and CGI-S scales and the mean of length of stay.ResultsBaseline characteristics were similar between the groups. The majority of patients were also treated with mood stabilizers (46% with lithium and 45% with valproate).The mean decrease in CGI-S scores from baseline to the day of discharge was significantly (P < 0.003) higher in the risperidone group (−2.81 vs. −2.36). The length of stay was significantly (P < 0.004) lower in the olanzapine group (mean of 23.03 days vs. mean of 30.3).Conclusions(1) The CGI-S scores in manic patients treated with risperidone decreased more than in patients treated with olanzapine during admission. (2) The length of stay was significantly lower in patients treated with olanzapine.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The effect of Qing Huan Ling on the hypoglutamatergic schizophrenia model in mice

ObjectiveTo investigate the effect of Qing Huan Ling and (or) risperidone on activity and preferences behavior of the hypoglutamatergic schizophrenia model in mice.MethodsSeventy kunming mice were randomly divided into 5 groups, one group as placebo group. The rest groups intraperitoneal injection MK-801 continuously 14 day, then randomly numbered: model group, Qing Huan Ling group, risperidone groupand Qing Huan Ling combined risperidone group. Intragastric administration give corresponding drugs for each group one month, at the same time observe high activities and changes in the preferences of five groups.ResultsCompared with the blank group, activity of the rest model groups induced by MK-801 was increased (P < 0.05). After intragastric administration one month, model groups of high activity was decreased, especially risperidone combined Qing Huan Ling group. There was no statistical meaning in inquiry activity of five groups (P > 0.05). Compared with model group, latent period of step-through test was prolonged 35.5 s (P < 0.05), of step-down test was prolonged 11.4 s in risperidone combined Qing Huan Ling group.ConclusionThe combination of Qing Huan Ling and risperidone can suppress the high activity; also can protect harmed memory of the preference behavior in the hypoglutamatergic schizophrenia model in mice.Disclosure of interestThe authors have not supplied their declaration of competing interest.