Acute Phase Of Schizophrenia Research Articles

P-1223 - Schizophrenia: switching from any oral antypsychotics to RLAI, a good solution to avoid relapses

Introduction The long term treatment of schizophrenia must fulfill some medical and functional needs, like: good tolerability for a long time administration, maintaining and improving the patient's psychiatric condition obtained previously and keeping at good levels overall patient's functionality. Objectives Most atypical antipsychotics are effective in the acute phase of schizophrenia, but on long term, the compliance of the patient could get worse due to big amount of tablets, side effects, stigma, diminished ability to think or concentrate, sedation, increase of BMI or prolactin. Aims To improve patients' compliance by switching from oral treatment to RLAI (Risperidone Long Acting Injection) and keep them away from relapses. Methods We evaluated 2 patients: first, 26 years, stabilized with risperidone tablets, 8 mg/day; second, 29 years, treated with amisulpride 800 mg/day, both having previously relapses after refusing to take their tablets. We switched them on a treatment with RLAI 50 mg/i.m., twice a month. Evaluations were made weekly during the 6 weeks of stabilization period and a follow-up for a period of 6 months. The well-being of the patient was evaluated by using the following scales: PANSS, CGI-S, CGI-I, the patients' satisfaction with PSMQ questionnaire and activity with WPAI-GH. Results 1) There was none relapse for both patients. 2) We did not use any corrective co-medication. 3) The patients' satisfaction was greater and the functionality was better, due to a good compliance and fewer side-effects. Conclusions Switching from another antipsychotic to RLAI is a good solution to improve the patients compliance, functionality and quality of life overall.

368 Physical Problems on Schizophrenia in Acute Phase

This study examined the relationship between resting regional cerebral blood flow (rCBF) patterns in patients with major depressive disorder (MDD) and specific symptom clusters derived from ratings on the Hamilton Rating Scale for Depression (HRSD) and the Mini Mental State Examination. We hypothesized that the functional activity in frontal, parietal, anterior cingulate, basal ganglia and limbic regions would be related to specific symptom domains. Fifteen patients fulfilling DSM-IV criteria for MDD who were off all psychotropic medications for >4 weeks and 15 normal volunteers were recruited. Single photon emission computed tomography (SPECT) images were obtained after 99mTc-ECD injection, and correlations between rCBF patterns and symptom severity ratings were calculated on a voxel-by-voxel basis, using statistical parametric mapping (SPM). Severity of depressive mood was inversely correlated with rCBF in the left amygdala, lentiform nucleus, and parahippocampal gyrus, and directly correlated with rCBF in the right postero-lateral parietal cortex (p < 0.001, uncorrected for multiple comparisons). Insomnia severity was inversely correlated with rCBF in the right rostral and subgenual anterior cingulate cortices, insula and claustrum. Anxiety severity was directly correlated with rCBF in the right antero-lateral orbitofrontal cortex, while cognitive performance was directly correlated with rCBF in the right postero-medial orbitofrontal cortex and in the left lentiform nucleus. Our findings confirmed the prediction that separate symptom domains of the MDD syndrome are related to specific rCBF patterns, and extend results from prior studies that suggested the involvement of anterior cingulate, frontal, limbic and basal ganglia regions in the pathophysiology of MDD.

Difference in early prediction of antipsychotic non-response between risperidone and olanzapine in the treatment of acute-phase schizophrenia

Purpose We examined whether early response/non-response to risperidone according to the Clinical Global Impressions-improvement scale (CGI-I) at 2 weeks could predict subsequent response. This prediction was also applied to olanzapine. We then investigated whether early non-responders (ENRs) to risperidone or olanzapine who switched to the other showed significantly greater improvement, compared with those staying on the initial antipsychotic. We performed a rater-blinded, randomized controlled trial in 18 psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as CGI-I ≤ 3 following 2 weeks of treatment. The primary outcome measure was achievement of remission and ≥ 50% improvement in the Positive and Negative Syndrome Scale at 4 weeks. Results At 4 weeks, 53% of risperidone early responders (ERs) went into remission, whereas only 9% of ENRs staying on risperidone ( n = 11) did ( P = 0.016). Similarly, at 4 weeks, 81% of risperidone ERs achieved ≥ 50% response, whereas only 9% of ENRs staying on risperidone achieved ≥ 50% response ( P < 0.0001). In contrast, 58% of olanzapine ERs ( n = 33) went into remission, whereas 38% of ENRs staying on olanzapine ( n = 8) did at 4 weeks ( P = 0.44). Similarly, 61% of olanzapine ERs achieved ≥ 50% response, whereas 25% of ENRs staying on olanzapine achieved ≥ 50% response ( P = 0.12). The negative likelihood ratio for the prediction of ≥ 50% response at 4 weeks by early response status to risperidone at 2 weeks was 0.057. Conclusion In newly admitted patients with acute schizophrenia, non-response to risperidone using CGI-I at 2 weeks can predict subsequent response. It looks like there is significant response to olanzapine that doesn't occur until 4 weeks. Thus, clinicians may want to switch to another drug earlier when risperidone is the first drug, and later when olanzapine is the first drug.

Neuroleptic Malignant Syndrome Induced by Blonanserin

Back to table of contents Previous article Next article LettersFull AccessNeuroleptic Malignant Syndrome Induced by BlonanserinKeiko Ohoyama, M.D., Hisashi Tanii, M.D., Ph.D., Eishi Motomura, M.D., Ph.D., Yoshiaki Konishi, M.S., Masanori Nakagawa, M.D., Takuya Matsumoto, M.D., Ph.D., Takashi Shiroyama, M.D., Ph.D., and Motohiro Okada, M.D., Ph.D.Keiko OhoyamaDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, JapanSuisawa Psychiatric Hospital Yokkaichi, Mie, JapanSearch for more papers by this author, M.D., Hisashi TaniiDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu Mie, Japan; Brain Science and Animal Model Research Center (BSAM), Mie University, Tsu, Mie, JapanSearch for more papers by this author, M.D., Ph.D., Eishi MotomuraDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, JapanSearch for more papers by this author, M.D., Ph.D., Yoshiaki KonishiDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, JapanSearch for more papers by this author, M.S., Masanori NakagawaDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, JapanSearch for more papers by this author, M.D., Takuya MatsumotoDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, JapanSearch for more papers by this author, M.D., Ph.D., Takashi ShiroyamaDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, JapanSearch for more papers by this author, M.D., Ph.D., and Motohiro OkadaDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, JapanSearch for more papers by this author, M.D., Ph.D.Published Online:1 Jan 2011AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We report herein, what is, to our knowledge, the first case of neuroleptic malignant syndrome (NMS) related to blonanserin.Case ReportA 30-year-old woman with a diagnosis of mental retardation and with profound intellectual impairment (IQ<45) was admitted to a psychiatric hospital for the first time because of insomnia, psychomotor agitation, monologue, and persecutory delusions. After a 7-day period of medication withdrawal, blonanserin, 8 mg/day, was introduced for psychiatric symptoms such as emotional agitation, auditory hallucinations, and delusions. Her disturbed behavior with high agitation was slightly improved by the medication. After treatment with blonanserin for 7 days, the patient had a high fever (100.4°F) and was obtunded with muscle rigidity. She had a high pulse rate (104 bpm), and an elevated leukocyte level (8.5×109/liter), with extrapyramidal symptoms and perspiration. The patient was suspected to be developing NMS. Blonanserin was discontinued, and the patient received diazepam treatment. The next day, the fever disappeared and the serum leukocyte level was normalized (5.7∼5.9×109/liter). The possibility of infectious disease was excluded since the level of C-reactive protein was within the normal range and all the symptoms disappeared rapidly after treatment for neuroleptic malignant syndrome.DiscussionThis case report shows that neuroleptic malignant syndrome can occur after the introduction of blonanserin treatment. Blonanserin is a novel dopamine-serotonin antagonist with potent dopamine D2 and serotonin 5HT2 antagonist properties.1 Because of the receptor binding profile and pharmacological property of blonanserin, side effects such as extrapyramidal symptoms tend to occur less often with blonanserin than haloperidol.2 This patient had not been medicated with antipsychotic drugs before. Another important issue to be mentioned in this case is mental retardation, which is one of the risk factors for neuroleptic malignant syndrome.3 Several other risk factors should be taken into account in cases involving mentally retarded patients, whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Special caution with regard to patients who have risk factors for neuroleptic malignant syndrome is therefore necessary when starting to administer antipsychotic drugs.Department of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, JapanSuisawa Psychiatric Hospital Yokkaichi, Mie, JapanDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu Mie, Japan; Brain Science and Animal Model Research Center (BSAM), Mie University, Tsu, Mie, JapanDepartment of Psychiatry, Mie University Graduate School of Medicine, Tsu, Mie, Japan1. Oka M , Noda Y , Ochi Y, et al.: Pharmacological profile of AD-5423, a novel antipsychotic with both potent dopamine-D2 and serotonin-S2 antagonist properties. J Pharmacol Exp Ther 1993; 264:158–165Medline, Google Scholar2. Garcia E , Robert M , Peris F, et al.: The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study. CNS Drugs 2009; 23:615–625Crossref, Medline, Google Scholar3. Viejo LF , Morales V , Punal P, et al.: Risk factors in neuroleptic malignant syndrome: a case-control study. Acta Psychiatr Scand 2003; 107:45–49Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 23Issue 1 Winter 2011Pages E13-E13 Metrics PDF download History Published online 1 January 2011 Published in print 1 January 2011

Abnormal laboratory values during the acute and recovery phases in schizophrenic patients: a retrospective study

During treatment of acute-phase schizophrenia, attention needs to be given to physical as well as psychological symptoms. It is often difficult, however, to obtain information on physical symptoms from patients with psychomotor excitation, and only laboratory examinations can provide objective data. The results of laboratory parameters measured in 68 patients with schizophrenia during psychomotor excitation and approximately 1 month later during the medicated recovery phase have been analyzed retrospectively. Abnormal laboratory values during psychomotor excitation were frequent. The most frequent (>/=35% of patients) were increased white blood cell count, low serum potassium levels, high levels of fasting blood sugar, lactate dehydrogenase and uric acid. There were fewer abnormal values during the medicated recovery phase. The most frequent (>/=25% of patients) were high serum levels of triglycerides, amylase, creatinine kinase, and low-density lipoprotein cholesterol. Abnormal triglyceride levels were found significantly more frequently in patients receiving olanzapine than those receiving risperidone. Abnormal values during the acute phase may be the result of excitation such as increased sympathetic tone and dehydration. Abnormal values during the recovery phase appeared to be related to the adverse metabolic effects of antipsychotic drugs. The frequency of these abnormal values was particularly high in patients receiving olanzapine alone or in combination with other medications.

The risk of death among adult participants in trials of antipsychotic drugs in schizophrenia11The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the EMEA or one of its committees or working parties or the BfArM.

In this paper we investigate mortality in short-term placebo-controlled trials conducted to demonstrate efficacy and safety of atypical antipsychotic drugs for the treatment of schizophrenic patients in the acute phase of illness. Arguments are provided, why short-term placebo-controlled studies are required. This is an integrated analysis of results from randomized placebo-controlled trials conducted pre-licensing for risperidone, olanzapine, quetiapine IR, ziprasidone, risperidone consta, aripiprazole, paliperidone, and quetiapine XR. Information was retrieved from study publications, EPAR, and from the FDA SBA, all in the public domain. 7553 patients were randomized in the remaining 23 short-term acute phase clinical trials. 2/5738 patients died after having been randomized to an active treatment. 5/1815 died in the placebo group. The crude odds-ratio for an increased death risk with placebo treatment is 7.92 (95% confidence interval (1.45 to 40.87), two sided P=0.0134). Death narratives show: (i) both deaths in active treatment groups occurred during randomized treatment period, (ii) two deaths in the placebo group of a trial in the elderly were observed in patients with severe co-morbidities not usually included in a randomized trial, and (iii) two further deaths in the placebo groups occurred 9 and 23 days after the end of the randomized treatment period. Under these circumstances the crude odds-ratio for an increased risk of death for patient with placebo as compared to active treatment is 1.58 (95% confidence interval (0.14-17.45), two sided P=0.71). Confidence intervals are generally wide indicating a still limited knowledge about a potential increase in mortality with placebo treatment. Unless, however, society is willing to take the risk that ineffective drugs are licensed and cause undetected harm thereafter, or is willing to restrict licensing to drugs that are superior to current treatments, short-term placebo-controlled trials in the acute phase of schizophrenia are necessary. Measures are proposed to minimize risks.

Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine

Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second-generation antipsychotics in dopamine D(2) receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D(2/3) receptor apparent binding potential (BP(app)) and occupancy in midbrain and temporal cortex among clozapine-, olanzapine- and haloperidol-treated schizophrenia patients. Dopamine D(2/3) binding was studied on single-photon emission computed tomography ligand [(123)I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug-naïve patients and seven healthy controls. Statistically significant differences in midbrain dopamine D(2/3) receptor BP(app) (P = 0.015) and occupancy (P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine-treated patients (5%), followed by olanzapine-treated patients (28%), compared to haloperidol-treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug-naïve vs healthy controls) in the examined brain areas (P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used. Both typical and second-generation antipsychotics occupy cortical dopamine D(2/3) receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D(2/3) occupancy between classical antipsychotics and second-generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.

The Efficacy and Safety of Blonanserin Compared with Haloperidol in Acute-Phase Schizophrenia

Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p < 0.001); blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p < 0.001), but blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of blonanserin throughout the study period. There was a lower incidence of EPS with blonanserin 10 mg (26.6%) than with haloperidol 10 mg (53.3%). Blonanserin was effective in the treatment of acute schizophrenia and showed greater efficacy in negative symptoms compared with placebo and haloperidol. Blonanserin was well tolerated and its safety profile compared favourably with haloperidol, particularly with respect to prolactin elevation and EPS frequency.

Effectiveness of second-generation antipsychotics with acute-phase schizophrenia

Purpose Although olanzapine may have advantages over other second-generation antipsychotics (SGAs) regarding longer time to treatment discontinuation among chronically ill patients, little evidence has been provided for the comparative effectiveness of SGAs in the acute phase. We aimed to determine if any of four SGAs were more effective in treating newly admitted acute schizophrenic patients. We performed a rater-blinded, randomized controlled trial of four SGAs in 15 psychiatric emergency sites. Eligible patients were 18–64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A final total of 78 patients were randomly assigned by means of sealed envelopes to receive risperidone (3–12 mg/day; n = 20), olanzapine (10–20 mg/day; n = 17), quetiapine (300–750 mg/day; n = 20), or aripiprazole (12–30 mg/day; n = 21), with follow-up at 8 weeks. The primary outcome measure was all-cause treatment discontinuation. Results Overall, 37% (29/78) of patients discontinued the study medication before 8 weeks: 25% for risperidone; 12% for olanzapine; 55% for quetiapine; and 52% for aripiprazole. Time to treatment discontinuation for any cause was significantly longer in the olanzapine group than in the quetiapine ( p = 0.006) or aripiprazole ( p = 0.008) groups, but not compared to the risperidone group ( p = 0.32). Time to treatment discontinuation was significantly longer in the risperidone group than in the quetiapine group ( p = 0.048), but not compared to the aripiprazole group ( p = 0.062). However, the rate of p.r.n. intramuscular haloperidol use was significantly higher in the aripiprazole group than in other groups ( p = 0.029). Conclusion Olanzapine and risperidone are superior to quetiapine and aripiprazole for the acute treatment of psychosis in hospitalized patients.

Olanzapine orally disintegrating tablets (Zyprexa ZydisR) rapidly improve excitement components in the acute phase of first-episode schizophrenic patients: An open-label prospective study

An open-label study was performed to investigate the clinical efficacy and tolerability of olanzapine orally disintegrating tablets (Zyprexa ZydisR) in ameliorating excitement symptoms in the acute phase of schizophrenia. Fifty-three patients meeting DSM-IV criteria for first-episode schizophrenia and treated with olanzapine monotherapy were evaluated with regard to their clinical improvement, behavioural response to medication, and extrapyramidal side effects using the Positive and Negative Syndrome Scale Excited Component (PANSS-EC), Nursing Assessment of Medication Acceptance (NAMA), and Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), respectively. Scores of PANSS-EC were significantly reduced after 3 days of olanzapine administration. A reduction in NAMA scores was also observed 7 days after administration of olanzapine. The DIEPSS score was unaffected by olanzapine administration. These results suggest that olanzapine orally disintegrating tablets are effective and well-tolerated for treatment excitement in the acute phase of schizophrenic patients. In addition, it is possible that adherence to medications is improved by using olanzapine orally disintegrating tablets.

Association of Physical and Social Anhedonia with Depression in the Acute Phase of Schizophrenia

Background/Aims: Researchers have shown interest in the association between anhedonia and depression in schizophrenia. The aim of the current study was to investigate the relationship between physical and social anhedonia with depression in a sample of inpatients with schizophrenia in the acute phase of their illness. Methods: Sixty-two patients with acute schizophrenia consecutively admitted at the Eginition Hospital, Department of Psychiatry, University of Athens were assessed using the revised Physical Anhedonia Scale, the revised Social Anhedonia Scale and the Calgary Depression Scale for Schizophrenia. Results: The Calgary Depression Scale for Schizophrenia score correlated with both physical anhedonia and social anhedonia ratings. The revised Social Anhedonia Scale score significantly correlated to self-depreciation, guilty ideas of reference, pathological guilt, early wakening, suicidality and observed depression. The revised Physical Anhedonia Scale score significantly correlated with depressive mood, self-depreciation, pathological guilt and observed depression. Self-depreciation, pathological guilt and observed depression were correlated with both social and physical anhedonia. Conclusion: Depression in schizophrenia and anhedonia may overlap, and it could therefore be difficult to clinically differentiate them, especially in acute schizophrenia patients.

Validity of the Executive Function Performance Test in Individuals with Schizophrenia

The purpose of this study was to examine the reliability and validity of the Executive Function Performance Test (EFPT) in a schizophrenic population. Participants were 30 individuals with the acute phase of schizophrenia and 31 with the chronic stage. Internal consistency using Cronbach's alpha was high (α = .88). Two-way multiple analysis of covariance revealed that the acute group scored significantly higher than the chronic group on almost all tasks and components of the EFPT ( p = .045 to .000), supporting construct validity. Moderate to high Spearman correlation coefficients were found between the total EFPT score and the total Behavioral Assessment of the Dysexecutive Syndrome profile and standardized scores within each of the groups ( r =.433 to .764; p &lt; .017 to .000), supporting criterion validity. The findings support the use of the EFPT for identifying executive functions in the context of everyday life and instrumental activities of daily living tasks. However, further studies are needed in different populations and cultures.

Effect of initial dosage of olanzapine in acute phase of schizophrenia

Shigemoto Hospital 15th Annual Meeting of the Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan, 11–13 October 2005

Efficacy of risperidone and social skills training in treatment of acute-phase schizophrenia

Efficacy of risperidone and social skills training in treatment of acute-phase schizophrenia

Adding sarcosine, but not D-serine, to risperidone improves symptoms in people with acute phase schizophrenia

Adding sarcosine, but not D-serine, to risperidone improves symptoms in people with acute phase schizophrenia

Physical anhedonia in the acute phase of schizophrenia

BackgroundThe aim of the current study is to investigate the relationship between physical anhedonia and psychopathological parameters, pharmacological parameters or motor side-effects in a sample of inpatients with schizophrenia in an acute episode of their illness.MethodEighty one patients with schizophrenia, consecutively admitted, with an acute episode of their illness, at the Eginition Hospital, Department of Psychiatry, University of Athens, during a one-year period were investigated regarding possible relationships between physical anhedonia, social-demographic data and clinical parameters as well as motor side-effects, induced by antipsychotic agents. All patients were assessed using the Chapman Revised Physical Anhedonia Scale (RPAS), the Positive and Negative Syndrome Scale (PANSS), the Rating Scale for Extrapyramidal Side-Effects (EPSE), the Barnes Akathisia Rating Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). Simple cross tabulations were initially employed. Subsequently, multiple regression analysis was performed.ResultsBoth positive and negative symptoms were associated with physical anhedonia. A positive association between physical anhedonia and the non-paranoid sub-category of schizophrenia was also proved.ConclusionAccording to these results, it seems that in the acute phase of schizophrenia, physical anhedonia may be a contributing factor to patient's psychopathology.

Serum lipid profiles and schizophrenia: Effects of conventional or atypical antipsychotic drugs in Taiwan

This study investigated the relationships between serum lipid profiles and schizophrenia and the effects of conventional or atypical antipsychotic drugs on serum lipid profiles. During a 1-year period, fasting blood samples for serum lipid profiles were collected from 126 schizophrenic patients and 59 healthy control subjects. The serum lipid profiles were detected by enzymatic determination. Patients were assessed for disease severity at baseline and endpoint at 3 weeks using the Positive and Negative Syndrome Scale. At baseline, patients with acute-phase schizophrenia had lower high-density lipoprotein (HDL) levels, higher low-density lipoprotein (LDL) levels, and higher ratios of total cholesterol / high-density lipoprotein (TC / HDL) and LDL / HDL than healthy control subjects. At endpoint, after a 3-week treatment with antipsychotics, the blood samples of the 97 schizophrenic patients were assessed again. Responders to antipsychotic treatment ( n = 68) but not nonresponders ( n = 29) had significantly increased TC, triglyceride (TG), and very low-density lipoprotein (VLDL) levels and decreased ratio of LDL / HDL. Experimental findings also showed significantly increased TC, TG, HDL, and VLDL levels and decreased ratio of LDL / HDL in responders taking atypical antipsychotic drugs ( n = 32), but not in patients treated with conventional antipsychotic drugs ( n = 36). In conclusion, this study identified strong associations between dyslipidemia and acute-phase schizophrenia and dyslipidemia and responders taking atypical antipsychotics; both associations would increase the risk of developing diabetes and coronary heart disease.

An open study of risperidone liquid in the acute phase of schizophrenia

An open-label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty-eight patients (M/F: 50/38; age: 18-74 years;, mean +/- SD =32 +/- 16 years) meeting DSM-IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC-ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders. An improvement in the PANSS scores related to excitement, hostility and poor impulse control was seen within 7 days after administration of risperidone liquid, and an improvement with regard to hallucinatory behaviour and uncooperativeness was seen within 14 days after its administration. Finally, 68% of patients were classified as responders 4 weeks after risperidone liquid administration. The scores of SAS were not changed after risperidone liquid administration. Pretreatment plasma homovanillic acid (HVA) levels in the responders (8.1 +/- 2.9 ng/ml) were higher than those in nonresponders (5.9 +/- 1.9 ng/ml). In addition, a negative correlation was seen between the changes in plasma HVA levels and the percentage of improvement in PANSS scores. On the other hand, there were no differences between pretreatment plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and those of nonresponders. These results suggest that risperidone liquid is effective and well tolerated for the treatment of acute phase schizophrenic patients, and that efficacy is related to its affects on dopaminergic activity, not noradrenergic activity.

Risperidone liquid is effective for patients with acute phase of schizophrenia

Yoshimura, Reiji; Kakihara, Shingo; Shinkai, Koji; Kaji, Kyoko; Yamada, Yasuhisa; Goto, Makiko; Ueda, Nobuhisa; Nakamura, Jun Author Information

Leukocyte Elastase and Autoantibodies to Nerve Growth Factor in the Acute Phase of Schizophrenia and their Relationship to Symptomatology

SummaryMany investigations suggest that abnormalities of the immune system are involved in the pathophysiology of schizophrenia. We recently found increased activity of leukocyte elastase (LE) and elevated levels of autoantibodies to neurospecific protein‐nerve growth factor (Aab to NGF)‐products of the innate and adaptive arms of the immune system in the serum of patients with acute stage schizophrenia. The aim of this study is to elucidate whether or not the changes of LE activity and Aab to NGF level are related to prominent features of schizophrenia. Patients (n=71) corresponding to ICD-10 criteria for relapseremitting schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS). Patients with predominantly positive symptoms showed significantly elevated serum levels of Aab to NGF compared to patients with predominantly negative symptoms, who were more likely to exhibit the high LE activity. Moreover, progression of positive symptoms was coupled with gradual increase of Aab to NGF level and reduction of LE activity. Based on these findings we conclude that the high levels of Aab to NGF relate to a clinical picture characterised mainly by positive symptoms of schizophrenia, whereas high LE-activities relate to a clinical picture with mainly negative symptoms of schizophrenia.