Vladimir Lerner

Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson's disease.

The risk of psychosis among patients with Parkinsons disease (PD) is high, and the management of these patients remains a substantial problem for physicians. Atypical antipsychotics, despite their advantages over conventional antipsychotics, can cause different side effects and deterioration of PD. Several reports have suggested that donepezil can be helpful in the treatment of psychotic conditions in patients with dementia with Lewy bodies and Alzheimers disease. This report presents the results of preliminary study of six patients (four women, two men; age range, 60–75 years) with PD (range of duration, 3–7 years) and dementia complicated by psychosis. All patients were treated with antiparkinsonian therapy, and donepezil was added to their regular treatment. The severity of the psychotic symptoms was assessed using the Scale for the Assessment of Positive Symptoms, and extrapyramidal symptoms were assessed using the Simpson–Angus Scale. With the addition of donepezil (as much as 10 mg/day) to their constant antiparkinsonian treatment, five patients had clinically significant (more than 53%) improvement on the assessment scale, and one patient had minimal (24%) improvement after 6 weeks of the treatment. None of the patients had side effects or deterioration of parkinsonian symptoms. The results suggest that donepezil may ameliorate psychotic symptoms in patients with PD, but this will need to be tested further in controlled, double-blind trials.

Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial.

OBJECTIVE Pregnenolone (PREG) and dehydroepiandrosterone (DHEA) are reported to have a modulatory effect on neuronal excitability, synaptic plasticity, and response to stress; they are associated with mood regulation and cognitive performance. We investigated the influence of PREG and DHEA on psychotic symptoms and cognitive functioning as an add-on to ongoing antipsychotic treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD This 8-week, double-blind, randomized, placebo-controlled, 2-center study compared 30 mg/d of PREG (PREG-30), 200 mg/d of PREG (PREG-200), 400 mg/d of DHEA, and placebo as an adjunctive treatment of 58 chronic schizophrenia or schizoaffective disorder patients (DSM-IV). The data were collected from February 2005 until June 2007. The outcome measures were symptomatic and neurocognitive changes, functioning, and tolerability as assessed primarily by the Clinical Global Impressions-Severity of Illness scale and the Positive and Negative Syndrome Scale. Analyses are presented for 44 patients who completed 8 weeks of treatment and for 14 noncompleters. RESULTS Compared with subjects who received placebo, those administered PREG-30 had significant reductions in positive symptom scores and extrapyramidal side effects (EPS) and improvement in attention and working memory performance, whereas subjects treated with PREG-200 did not differ on outcome variable scores for the study period. The general psychopathology severity and general functioning of patients receiving placebo and PREG-30 improved more than that of those subjects treated with DHEA, while EPS improved more in subjects treated with DHEA than in patients receiving placebo. Negative symptoms and akathisia were not significantly benefited by any treatment. The administration of PREG and DHEA was well tolerated. CONCLUSIONS Low-dose PREG augmentation demonstrated significant amelioration of positive symptoms and EPS and improvement in attention and working memory performance of schizophrenia and schizoaffective disorder patients. Further double-blind controlled studies are needed to investigate the clinical benefit of pregnenolone augmentation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00174889.

Combined use of risperidone and olanzapine in the treatment of patients with resistant schizophrenia: a preliminary case series report.

Polypharmacy, or the use of multiple drugs in the therapy of psychiatric disorders, is not recommended. However, appropriate combinations of pharmacologic mechanisms may enhance the efficacy of antipsychotic drugs and alter the course of schizophrenia. In recent years, some articles have been published about the successful use of clozapine and risperidone in combination for the treatment of patients with resistant schizophrenic and schizoaffective disorders. However, safety of this drug combination is open to discussion. This report presents the results of a preliminary study of five patients with resistant schizophrenia successfully treated with risperidone-olanzapine combination. The results suggest that this combination may be useful. In the future, the efficacy of risperidone-olanzapine combination should be confirmed in larger study populations before its clinical application is considered.

L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study.

OBJECTIVE L-theanine is a unique amino acid present almost exclusively in the tea plant. It possesses neuroprotective, mood-enhancing, and relaxation properties. This is a first study designed to evaluate the efficacy and tolerability of L-theanine augmentation of antipsychotic treatment of patients with chronic schizophrenia and schizoaffective disorder. METHOD 60 patients with DSM-IV schizophrenia or schizoaffective disorder participated in an 8-week, double-blind, randomized, placebo-controlled study. 400 mg/d of L-theanine was added to ongoing antipsychotic treatment from February 2006 until October 2008. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), the Hamilton Anxiety Rating Scale (HARS), the Cambridge Neuropsychological Test Automated Battery (CANTAB) for neurocognitive functioning, and additional measures of general functioning, side effects, and quality of life. RESULTS 40 patients completed the study protocol. Compared with placebo, L-theanine augmentation was associated with reduction of anxiety (P = .015; measured by the HARS scale) and positive (P = .009) and general psychopathology (P < .001) scores (measured by the PANSS 3-dimensional model). According to the 5-dimension model of psychopathology, L-theanine produced significant reductions on PANSS positive (P = .004) and activation factor (P = .006) scores compared to placebo. The effect sizes (Cohen d) for these differences ranged from modest to moderate (0.09-0.39). PANSS negative and CANTAB task scores, general functioning, side effect, and quality of life measures were not affected by L-theanine augmentation. L-theanine was found to be a safe and well-tolerated medication. CONCLUSIONS L-theanine augmentation of antipsychotic therapy can ameliorate positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients. Further long-term studies of L-theanine are needed to substantiate the clinically significant benefits of L-theanine augmentation.

Augmentation with amisulpride for schizophrenic patients nonresponsive to antipsychotic monotherapy.

Despite the effectiveness of antipsychotic medications in treatment of schizophrenia, about 30% of patients who receive an adequate treatment have significant persisting symptoms. The problem of treatment-resistant psychosis is an important and difficult one. The aim of this study was to retrospectively evaluate the efficacy and safety of amisulpride augmentation in treatment-resistant schizophrenic patients. To the best of our knowledge, this is the first report about resistant schizophrenic and schizoaffective patients treated with the combinations of risperidone and amisulpride and ziprasidone and amisulpride. Data were collected from patient records. A total of 15 resistant schizophrenic patients (7 men, 8 women, 54.0 ± 16.9 years old) were included in the study. Before addition of amisulpride, the patients were treated with monotherapy by atypical neuroleptics (clozapine, olanzapine, risperidone, or ziprasidone). The mean amisulpride dose was 693.3 ± 279.6 mg/d. The mental state of 12 (80%) patients treated with combination was improved. Three (20%) patients showed no change in their mental state. Only 2 patients treated with a combination of risperidone and amisulpride had mild side effects. The results are preliminary and require confirmation in a randomized controlled trial. The authors suggest that amisulpride may be a promising option as an augmentation strategy in treatment-resistant schizophrenic patients.

Characteristics of suicidal attempts in major depression versus adjustment reactions

BACKGROUND The aim of this present study was to compare the characteristics of suicidal attempts of patients with major depression (MD) and adjustment reaction (AR). METHOD Sixty-nine patients with MD and 86 with AR admitted to the Moscow Institute of Emergency Help after the first suicide attempts were studied. All the attempters were interviewed by at least by two psychiatrists and the diagnosis was made according to agreement and to ICD-9CM criteria. RESULTS Differences between the two groups were found with regard to social-demographic, clinical-psychological and suicidal characteristics: the AR patients were less educated, had lower social status and in most cases were unmarried, compared with the MD patients. A large number (51.2% of the attempters in the AR group and 34.8% in the MD group) had an unstable parental family, early orphanhood or an emotionally deprived childhood. No differences were found in the methods of the suicidal attempts between the groups. Suicidal attempts under alcohol abuse occurred more often among the AR group (34.9 vs. 10.1%). The interval from the beginning of the disorder until the suicidal attempt was significantly shorter within the AR group. In this group the suicidal attempts were not planned, in comparison with the MD group. LIMITATION The sample is a selected study, because the research included only inpatients with AR and MD after their first suicidal attempt. CONCLUSION We believe that our data may be important for improving the assessment of suicidal risk and in planning treatment strategies for prevention of repeated suicidal attempts.

Vitamin B6 versus mianserin and placebo in acute neuroleptic-induced akathisia: a randomized, double-blind, controlled study.

Abstract: Treatment strategies against acute neuroleptic-induced akathisia (NIA) include anticholinergic (antimuscarinic) agents, dopamine agonists, GABAergic agents, &bgr;-blockers, benzodiazepines, and serotonin antagonists. However, many patients who have acute akathisia fail to respond. In previous studies, mianserin and vitamin B6 were found to be effective in the treatment of acute akathisia. The purpose of this study was to compare the efficacy of B6, mianserin and placebo in the treatment of acute NIA. Sixty schizophrenia and schizoaffective inpatients who have NIA were randomly divided to receive vitamin B6 1200 mg/d, mianserin 15 mg/d, or placebo for 5 days, in a double-blind design. The Barnes Akathisia Rating Scale, Brief Psychiatric Rating Scale, and Clinical Global Impression were used to assess the severity of NIA and psychotic symptoms. The assessment was made at baseline and daily for the duration of the study. Compared with the placebo group, the vitamin B6-treated and mianserin-treated patients showed a significant improvement in the subjective (P < 0.0001), subjective distress (P < 0.0001), and global (P < 0.0001) subscales. The objective subscale did not show significant positive results (P = 0.056), but there was a trend toward symptom amelioration in both groups. A reduction of at least 2 points on the Barnes Akathisia Rating Scale global subscale was noted in the vitamin B6 group (13/23, 56%) as well as in the mianserin groups (13/20, 65%), and in only one patient in the placebo group (1/17, 6%; P < 0.0005). Our results indicate that high doses of B6 and a low dose of mianserin may be a useful addition to current treatments of NIA. The efficacy of vitamin B6 and mianserin suggests that the pathophysiology of acute NIA is heterogeneous with the various subtypes of acute NIA responding differently to the various pharmacological approaches.

Bexarotene as Add-on to Antipsychotic Treatment in Schizophrenia Patients: A Pilot Open-label Trial

Objectives: Bexarotene is a synthetic retinoid used for treatment of neoplastic or dermatologic disorders. Based on the retinoid dysregulation hypothesis, it was hypothesized that bexarotene augmentation would have a beneficial effect in the antipsychotic treatment of schizophrenia patients. This study is the first to investigate the safety and efficacy of add-on oral bexarotene to ongoing antipsychotic treatment in chronic schizophrenia patients who were stabilized on regular antipsychotic treatment. Methods: A 6-week open label trial was conducted in 2 mental health centers from October 2005 to October 2006. Twenty-five patients with chronic schizophrenia received a low dose of bexarotene (75 mg/d) augmentation. Mental condition and laboratory tests were assessed at baseline and after weeks 2, 4, and 6 of the study. The primary outcome measure was change from baseline in 4 symptom scales: the Positive and Negative Symptom Scale, Extrapyramidal Symptom Rating Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Scale. Blood cell count, liver and thyroid functions, cholesterol, and triglyceride rates were followed. Results: Significant improvement from baseline to endpoint was observed on total Positive and Negative Symptom Scale score (P = 0.022), general psychopathology (P = 0.024), positive (P = 0.012), and the dysphoric mood (P = 0.028) factor scores. Furthermore, a trend to a diminishing Extrapyramidal Symptom Rating Scale score (P = 0.053) was found. Bexarotene was found to be a safe medication as measured by all laboratory parameters with the exception of increased total cholesterol serum level. Conclusions: This short-term pilot study supports bexarotene as a potential valuable adjunct in management of schizophrenia. Low doses of bexarotene were well tolerated. A double-blind controlled study should be performed to replicate these preliminary positive results.

Tardive dyskinesia (syndrome): Current concept and modern approaches to its management

Tardive dyskinesia is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. The pathophysiology of tardive dyskinesia is complex, multifactorial and still not fully understood. A number of drugs were tried for the management of this motor disturbance, yet until now no effective and standard treatment has been found. It is very disappointing to realize that the introduction of antipsychotics from the second generation has not significantly decreased the prevalence and incidence of tardive dyskinesia. Therefore, the management of this motor disturbance remains an actual topic as well as a challenge for clinicians. This review summarizes recent relevant publications concerning the treatment of tardive dyskinesia.

Donepezil as add-on treatment of psychotic symptoms in patients with dementia of the Alzheimer's type.

Traditionally, the neuropsychiatric symptoms of Alzheimers disease (AD) have been managed with neuroleptics or benzodiazepines, which have serious side effects. Preliminary observations suggest the possible value of cholinesterase inhibitors in the amelioration of psychotic symptoms in patients with dementia of the Alzheimers type, dementia with Lewy bodies, and in patients with Parkinsons disease. Twelve inpatients with AD with psychotic symptoms and lack of improvement of their delusions/hallucinations during perphenazine treatment (8 mg/day) for 3 weeks received random open-label donepezil 5 mg daily in addition to an ongoing treatment of 8 mg/day perphenazine or 16 mg/day perphenazine. Assessments conducted at baseline and after weeks 2 and 4 included the Mini-Mental State Examination, the Global Deterioration Scale, the Positive and Negative Symptoms Scale, and the Clinical Global Impressions scale. Frequency of extrapyramidal symptoms was measured according to the Abnormal Involuntary Movement Scale. The donepezil–perphenazine group exhibited substantially greater and clinical improvements in mental state. At the end of the trial (4 weeks), Positive and Negative Symptoms Scale scores revealed significant differences between both groups (p = 0.006). The Clinical Global Impressions scale and the Mini-Mental State Examination scores also showed significant differences between the donepezil–perphenazine group and the perphenazine group (p = 0.028 and p = 0.027 respectively). No significant differences were found in the Global Deterioration Scale scores. Abnormal Involuntary Movement Scale scores showed a significant deterioration in extrapyramidal symptoms in the perphenazine group compared with the donepezil–perphenazine group (p = 0.016). Donepezil augmentation of neuroleptics may be appropriate for those patients for whom neuroleptic monotherapy either does not lead to symptom remission or is associated with intolerable adverse effects. This was an open-label study and there is need for larger studies with double-blind control and a long-term study design to define the efficacy of donepezil for patients with AD and psychotic symptoms.