Clinical efficacy of lamotrigine and changes in the dosages of concomitantly used psychotropic drugs in Alzheimer's disease with behavioural and psychological symptoms of dementia: a preliminary open-label trial.

AIM: We investigated the clinical efficacy and changes in the dosages of concomitantly used psychotropic drugs in lamotrigine therapy in Alzheimer's disease with behavioural and psychological symptoms of dementia (BPSD). METHODS: This study was a 16-week, preliminary open-label trial. The subjects were 40 inpatients. The outcome measures assessed were BPSD and cognitive function. BPSD was assessed with the Neuropsychiatric Inventory (NPI) and cognitive function was assessed with the Mini-Mental State Examination. The changes in the dosages of concomitant psychotropic drugs were also assessed. RESULTS: Although the mean changes from baseline NPI scores and the two NPI subscales (anxiety and irritability) were significantly lower within the lamotrigine therapy group, no significant differences were found when we compared the lamotrigine therapy group to the control group. The mean decrease from baseline on the NPI agitation subscale, however, was significantly greater in the lamotrigine therapy group than in the control group (P < 0.05). Furthermore, the mean decrease from baseline in the diazepam-equivalent dose was significantly greater in the lamotrigine therapy group than in the control group (P < 0.05). CONCLUSIONS: The results of this study suggest that the administration of lamotrigine to patients with severe Alzheimer's disease with BPSD may be effective and may make it possible to avoid increasing the dosage of antipsychotic medications prescribed to elderly patients.

Relationship between the plasma concentration of paliperidone and the clinical and drug-induced extrapyramidal symptoms in elderly patients with schizophrenia.

OBJECTIVE: We investigated the relationship between the plasma concentration of paliperidone (PAL) and clinical and drug-induced extrapyramidal symptoms (EPS) in elderly patients with schizophrenia. METHODS: In this study, 15 patients with schizophrenia receiving risperidone were switched to PAL and treated for 12 weeks. Their clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impression-Severity of Illness Scale. Their EPS were assessed using the Drug-induced EPS Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Scale at baseline and 12 weeks. Plasma concentrations were measured by the liquid chromatography-mass spectrometry/mass spectrometry method. RESULTS: The results revealed that there were significant correlations between the plasma concentration of PAL and improved Positive and Negative Syndrome Scale total, negative, and general psychopathology scores (p<0.05). However, the efficacy did not improve linearly with plasma level. No significant correlations were found between the PAL plasma concentration and the mean change from baseline in the Drug-induced EPS Scale total score, Barnes Akathisia Scale, or Abnormal Involuntary Movement Scale. CONCLUSIONS: The results of this research suggested that, in elderly patients, although none of an increased plasma concentration of PAL, a worsening of EPS, or an increase in prolactin level occurs, linear clinical efficacy may not be obtained.

The influence and changes in the dosages of concomitantly used psychotropic drugs associated with the discontinuation of donepezil in severe Alzheimer's disease with behavioral and psychological symptoms on dementia: a preliminary open-label trial.

OBJECTIVE: We investigated the influence on behavioral and psychological symptoms on dementia (BPSD) and the changes in the dosages of concomitant psychotropic drugs associated with the discontinuation of donepezil in patients with severe Alzheimer's disease (AD) who developed BPSD during donepezil therapy. METHODS: The subjects were 44 inpatients who had been diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). The outcome measures assessed were BPSD and cognitive function. BPSD was assessed using the Neuropsychiatric Inventory (NPI) and cognitive function was assessed using the Mini Mental Examination (MMSE). The changes in the dosages of concomitant psychotropic drugs were also assessed. RESULTS: Significant decreases were found in the donepezil treatment discontinuation group in the following NPI total score and two NPI subscales (agitation and irritability), but no significant differences were seen between the donepezil treatment discontinuation group and the control group. Furthermore, the mean changes from baseline in the risperidone equivalent dose and the diazepam equivalent dose were hardly changed in the donepezil treatment discontinuation group. CONCLUSION: The results of this study suggest that the discontinuation of donepezil treatment in patients with AD with BPSD may afford superior efficacy and may make it possible to not increase the dosage of other psychotropic drugs.

A naturalistic comparison study of the efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular levomepromazine in acute agitated patients with schizophrenia.

OBJECTIVE: This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine, IM haloperidol, and IM levomepromazine in acute agitated patients with schizophrenia. METHODS: The subjects were 122 inpatients. Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS, and Agitation-Calmness Evaluation Scale, and their safety were assessed using the Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale (BARS), and Drug-induced Extrapyramidal Symptoms Scale (DIEPSS). RESULTS: The mean changes from baseline on the PANSS-EC, Agitation-Calmness Evaluation Scale, Abnormal Involuntary Movement Scale, BARS, and DIEPSS scores were significantly better in both IM olanzapine and IM levomepromazine than in IM haloperidol. Of these, the mean changes from baseline on the BARS and DIEPSS scores were significantly better in IM olanzapine than in IM levomepromazine. The mean change from baseline on the PANSS positive score was significantly better in both IM olanzapine and IM haloperidol than in IM levomepromazine. CONCLUSIONS: The results of this study suggest the possibility that the anti-agitation effects of IM olanzapine and IM levomepromazine are more rapid than those of IM haloperidol. No worsening of EPS was observed. Our results also suggest that compared with IM levomepromazine, IM olanzapine is safer and affords greater improvement in symptoms.

The influence of switching from risperidone to paliperidone on the extrapyramidal symptoms and cognitive function in elderly patients with schizophrenia: a preliminary open-label trial.

OBJECTIVE: This study was to evaluate the effects on clinical symptoms and cognitive function of switching the treatment of elderly patients with schizophrenia from risperidone to paliperidone (PAL). METHODS: This study was a 12-weeks, preliminary open-label trial. The subjects were 17 inpatients. Their extrapyramidal symptoms (EPS) were assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Scale (BAS), and their cognitive function was assessed using the Brief Assessment Cognition in Schizophrenia: Japanese language version (BACS-J), and their clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity of illness scale (CGI-S) at the 0 and 12 weeks. RESULTS: The DIEPSS and BAS significantly improved after switching from risperidone to PAL. Furthermore, improvement was found on AIMS. The mean change from baseline in z-score of the digit sequencing task was significantly increased. All items on the PANSS and CGI-S were not significant; however, changes in some cognitive function were correlated with changes in EPS. CONCLUSIONS: The results of this study suggest the possibility that switching elderly patients from risperidone to PAL may have improved pre-existing EPS, and may also have helped improve working memory.

A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular haloperidol in agitated elderly patients with schizophrenia.

OBJECTIVE: This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine and IM haloperidol in agitated elderly patients with schizophrenia at 2 hours postdose. METHODS: The subjects were 23 inpatients who had been diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS and Agitation Calmness Evaluation Scale (ACES), and their safety were assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and laboratory tests. RESULTS: The mean reduction from baseline on the PANSS-EC total score, the PANSS total score and the ACES score were significantly greater in the IM olanzapine injection group than in the IM haloperidol injection group. The mean changes from baseline on the AIMS score, the BARS score and the DIEPSS total score were significantly better in the IM olanzapine injection group than in the IM haloperidol injection group. No serious adverse events such as paralytic ileus, diabetic ketoacidosis, neuroleptic malignant syndrome or tardive dyskinesia occurred between the two groups. CONCLUSION: The results of this study suggest the possibility that agitated elderly patients may result in superior efficacy and safety after IM olanzapine without serious adverse events in comparison with IM haloperidol.

Clinical efficacy and changes in the dosages of concomitantly used psychotropic drugs in memantine therapy in Alzheimer's disease with behavioral and psychological symptoms on dementia.

OBJECTIVE: We investigated the clinical efficacy and changes in the dosages of concomitantly used psychotropic drugs in memantine therapy in Alzheimer's disease (AD) with behavioral and psychological symptoms on dementia (BPSD). METHODS: The subjects were 38 inpatients who had been diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). The outcome measures assessed were BPSD and cognitive function. BPSD was assessed using the neuropsychiatric inventory (NPI) and cognitive function was assessed using the mini-mental examination (MMSE). The changes in the dosages of concomitant psychotropic drugs were also assessed. RESULTS: SIGNIFICANT DECREASES WERE FOUND IN THE MEMANTINE THERAPY GROUP IN THE FOLLOWING NPI TOTAL SCORE AND FIVE NPI SUBSCALES: delusions, hallucinations, agitation, irritability, and aberrant motor behavior, but no significant differences were seen between the memantine therapy group and the control group. Furthermore, the memantine therapy group allowed the dosage of the psychotropic drugs to be significantly reduced compared with the control group. CONCLUSION: The results of this study suggest that the administration of memantine to patients with AD with BPSD may afford superior efficacy and may also make it possible to reduce the risperidone equivalent dose, the diazepam equivalent dose and the dosage of the psychotropic drugs.

A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular levomepromazine in agitated elderly patients with schizophrenia.

BACKGROUND: There have not been any reports in Japan clarifying the efficacy and safety of intramuscular (IM) olanzapine and IM levomepromazine in agitated elderly patients with schizophrenia. This study was a comparative investigation of the clinical efficacy and safety of IM olanzapine and IM levomepromazine in agitated elderly patients with schizophrenia at 2 hours post-dose. METHODS: The subjects were 52 inpatients who were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV. Their clinical symptoms were assessed using the Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS, and Agitation Calmness Evaluation Scale (ACES), and their safety was assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), and glucose test. RESULTS: The PANSS-EC total score, the ACES score, and the glucose level significantly decreased from baseline in both the IM olanzapine group and the levomepromazine injection group; however, no between-group differences were observed. Mean change from baseline in the PANSS total score, positive score, the BARS score, and the DIEPSS total score was significantly greater in the IM olanzapine injection group compared with the levomepromazine injection group. CONCLUSION: The results of this study suggest that agitated elderly patients rapidly respond to IM olanzapine and IM levomepromazine treatment. Furthermore, these results suggest that IM olanzapine is safer than IM levomepromazine and causes greater improvement in positive symptoms.

Comparison of the anti-dopamine D2 and anti-serotonin 5-HT(2A) activities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof.

Second-generation antipsychotics, which have become the standard drug therapies for schizophrenia, are known to have a serotonin 5-HT(2A) receptor blocking effect in addition to a dopamine D2 receptor blocking effect. However, although chlorpromazine (CPZ) has a 5-HT(2A) receptor blocking effect and has the profile of a second-generation antipsychotic in vitro, it loses this pharmacological profile in vivo. In order to elucidate the differences between the in vivo and in vitro pharmacological characteristics of CPZ, we used a radioreceptor assay to measure the anti-D2 activity and the anti-5-HT(2A) activity of CPZ and five major metabolites of CPZ, and compared the results to the anti-D2 activity and anti-5-HT(2A) activity of risperidone, zotepine, perospirone, the major metabolites of each of these drugs, and olanzapine, bromperidol, and haloperidol. The subjects were 182 patients who had received diagnoses of schizophrenia based on the DSM-IV criteria. The results revealed that CPZ exhibited little anti-5-HT(2A) activity, regardless of the anti-D2 activity level, and that none of the metabolites possessed anti-5-HT(2A) activity. However, both the parent compounds and the metabolites of each of the second-generation antipsychotics possessed both anti-D2 activity and anti-5-HT(2A) activity. This clarified that, unlike second-generation antipsychotics, the reason CPZ loses its second-generation antipsychotic profiles in vivo is because it does not have any metabolites that possess anti-5-HT(2A) activity.

Study of the efficacy and safety of switching from risperidone to paliperidone in elderly patients with schizophrenia.

AIM: We investigated the clinical efficacy and safety of switching to paliperidone (PAL) in elderly schizophrenia patients receiving risperidone. METHODS: The subjects were 27 inpatients who had been diagnosed with schizophrenia according to the DSM-IV. The patient's clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impression-Severity of Illness Scale, and their safety was assessed using the Drug-induced Extrapyramidal Symptoms Scale, bodyweight, body mass index, and laboratory tests. We also investigated patient satisfaction using the Drug Attitude Inventory, a subjective outcome measure. RESULTS: No significant differences in clinical symptom improvement efficacy were seen between the PAL-switching group and the control group. The mean changes from baseline on the Drug-induced Extrapyramidal Symptoms Scale total score, Drug Attitude Inventory score, and prolactin level were significantly greater in the PAL-switching group than in the control group. Furthermore, patients with PAL needed less biperiden, even though they had similar risperidone-equivalent daily dosages to the control group. CONCLUSIONS: The results of this study suggest that switching elderly patients from risperidone to PAL may result in superior safety and patient satisfaction, and may also make it possible to reduce the dosage of biperiden.

The influence of switching from haloperidol decanoate depot to risperidone long-acting injection on the clinical symptoms and cognitive function in schizophrenia.

OBJECTIVE: This study was a comparative investigation of the effects on clinical symptoms and cognitive function of switching the treatment of schizophrenia patients from haloperidol decanoate depot to risperidone long-acting injection (RLAI) compared with a control group that continued receiving haloperidol decanoate depot. METHODS: This study was a 24-week, non-randomized, non-double blind, open-label trial. The subjects' clinical symptoms were assessed using the Positive and Negative Syndrome Scale, and their cognitive function was assessed using the Wisconsin Card Sorting Test: Keio Version to assess executive function and the St. Marianna University School of Medicine's Computerized Memory Test to assess memory and concentration at 0 and 24 weeks. RESULTS: The mean change from baseline in the number of categories achieved at the second stage of the Wisconsin Card Sorting Test: Keio Version was significantly greater in the RLAI group than in the control group. The mean changes from baseline in the individual St. Marianna University School of Medicine's Computerized Memory Tests were significantly greater in the RLAI group than in the control group. The RLAI group needed a lower dosage of biperiden compared with the control group, even though they had similar risperidone-equivalent daily dosages. CONCLUSION: The results of this study suggest the possibility that switching from haloperidol decanoate depot to RLAI may improve cognitive function including memory, executive function, motor processing function, and attention.

The relationship between the plasma concentration of blonanserin, and its plasma anti-serotonin 5-HT(2A) activity/anti-dopamine D2 activity ratio and drug-induced extrapyramidal symptoms.

AIMS: Blonanserin is a second-generation antipsychotic that was developed in Japan. We investigated the relationships between plasma concentration, the plasma anti-5-HT(2A) activity/anti-D2 activity (S/D) ratio and extrapyramidal symptoms (EPS) in blonanserin dosing. METHODS: The subjects were 29 outpatients with schizophrenia. We assessed EPS using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The plasma concentrations were measured by high performance liquid chromatography, and the plasma anti-D2 and anti-5-HT(2A) activities were measured by [³H]-spiperone and [³H]-ketanserin radioreceptor assays. RESULTS: The results revealed that there were significant correlations between both the plasma concentration and the DIEPSS total score (P<0.05). A negative correlative tendency was found between the S/D ratio and the DIEPSS total score. Furthermore, the plasma concentrations were divided into a low plasma concentration group and a high plasma concentration group, and the S/D ratios were divided into a low S/D ratio group and a high S/D ratio group. We then compared each group based on the DIEPSS total scores. The score in the high plasma concentration-low S/D ratio group was significantly higher than in the high plasma concentration-high S/D ratio, low plasma concentration-high S/D ratio and low plasma concentration-low S/D ratio groups (P<0.05 for all). CONCLUSIONS: These findings indicate that the incidence of EPS during treatment with blonanserin is mainly determined by plasma concentration, but the incidence of EPS may be inhibited when anti-5HT(2A) activity is predominant over anti-D2 activity.

The influence of switching from oral risperidone to risperidone long-acting injection on the clinical symptoms and cognitive function in schizophrenia.

OBJECTIVE: This study was a comparative investigation of the effects on clinical symptoms and cognitive function of switching schizophrenia patients from oral risperidone to risperidone long-acting injection (RLAI) compared with a control group that continued receiving oral risperidone. METHODS: The subjects were 21 patients who had been diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Their clinical symptoms were assessed using the positive and negative syndrome scale (PANSS), and their cognitive function was assessed using the Wisconsin Card Sorting Test: Keio Version (KWCST) to assess executive function, and the St Marianna University School of Medicine's Computerized Memory Test (STM-COMET) to assess memory and concentration. RESULTS: No significant differences in clinical symptom improvement efficacy were seen between the group that was switched to RLAI and the control group. No significant differences were seen between the two groups in the mean change from baseline in any of the KWCST tests. The mean changes from baseline on the STM-COMET memory scanning test and memory filtering test were significantly greater in the group that switched to RLAI than in the control group. Furthermore, patients with RLAI needed less biperiden, even though they had similar risperidone-equivalent daily dosages as the group with oral risperidone. CONCLUSION: The results of this study suggested that switching from oral risperidone to RLAI may affect motor processing function and attention improvement efficacy by allowing the dosage of anti-Parkinson's medication to be reduced.

A study of the efficacy and safety of switching from oral risperidone to risperidone long-acting injection in older patients with schizophrenia.

OBJECTIVE: We investigated the clinical efficacy and safety of switching to risperidone long-acting injection (RLAI) in older patients with schizophrenia receiving oral risperidone. METHODS: The subjects were 48 inpatients who had been diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Their clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impression - Severity of Illness scale, and their safety was assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), body weight, body mass index, and blood biochemistry tests. RESULTS: No significant differences in clinical symptom improvement efficacy were seen between the group switched to RLAI and the control group. The mean changes from baseline on the DIEPSS total score and prolactin level were significantly greater in the older group switched to RLAI than in the control group. Furthermore, in older patients, RLAI allowed the dosage of the concomitant medication to be significantly reduced compared with the control group. CONCLUSION: The results of this study suggest that switching older patients from oral risperidone to RLAI may result in superior efficacy and safety, and may also make it possible to reduce the dosage of the concomitant medication.

An unblinded comparison of the clinical and cognitive effects of switching from first-generation antipsychotics to aripiprazole, perospirone or olanzapine in patients with chronic schizophrenia.

The objective of this study, the effect of aripiprazole on clinical symptoms and cognitive function in patients with chronic schizophrenia was compared to that of perospirone and olanzapine. The subjects were 31 patients, they were diagnosed with schizophrenia on the basis of the criteria of the DSM-IV. Clinical symptoms were assessed using Brief Psychiatric Rating Scale (BPRS), and cognitive function was assessed using the Wisconsin Card Sorting Test (Keio Version: KWCST) and the St. Marianna University School of Medicine's Computerized Memory Test (STM-COMET) as executive function and memory/attention function tests at baseline and 8 weeks after switching. As a result, comparison of the BPRS mean total score revealed no significant difference between aripiprazole and the other medications. Aripiprazole resulted in significant changes in the number of categories achieved (CA) and difficulty maintaining set (DMS) compared to olanzapine at the second level of the KWCST. Comparison thus revealed no difference in clinical effect between aripiprazole and the other medications, but might suggest possible differences between aripiprazole and olanzapine in the profiles of the improvement effects on executive function, memory, and attention function.

The relationship between the daily dose, the plasma concentration of blonanserin, and its plasma anti-dopamine D2 and anti-serotonin 5-HT2A activity.

OBJECTIVE: Blonanserin (BNS) possesses anti-serotonin 5-HT(2A) activity in addition to anti-dopamine D(2) activity, which is characteristic of second-generation antipsychotics, little information is available on its pharmacologic profile in vivo. We investigated the BNS daily dose, plasma concentration, plasma anti-D(2) activity, and plasma anti-5-HT(2A) activity in schizophrenia in a total of 14 subjects. METHODS: Blood samples were taken 14 days after the BNS dose was fixed, and the plasma concentration was measured by means of high-performance liquid chromatographic (HPLC) method. In addition, the plasma anti-D(2) activity and anti-5-HT(2A) activity were measured by means of radioreceptor assays in which [(3)H]-spiperone and [(3)H]-ketanserin were used. RESULTS: The results revealed a statistically significant correlation between the daily dose and the plasma concentration (p = 0.04). Statistically significant correlations were also observed between the plasma concentration and the anti-D(2) activity and between the plasma concentration and the anti-5-HT(2A) activity (p = 0.003 and 0.04). CONCLUSIONS: It is therefore believed that both the anti-D(2) activity in plasma and the anti-5-HT(2A) activity in plasma are regulated almost solely by the unchanged principal. Moreover, the mean plasma serotonin/dopamine (S/D) ratio was 0.9 and BNS exhibited both anti-D(2) activity and also anti-5-HT(2A) activity in vivo, as well, so it was clear that the in vitro pharmacological profile was retained in vivo.