Amisulpride versus moclobemide in treatment of clozapine-induced hypersalivation.

OBJECTIVES: Previous publications demonstrated substitute benzamides as effective agents in treatment of clozapine-induced sialorrhea (CIS). The aim of this study was to compare efficacy of amisulpride and moclobemide (both from the substitute benzamide group) in controlling, or at least minimizing, CIS. METHODS: The study was designed as a 6-week, two-center, fixed-dose, comparison study of 400 mg/day of amisulpride versus 300 mg/day of moclobemide as an adjunctive treatment in 53 schizophrenia and schizoaffective disorder patients (diagnosed according to DSM-IV) suffering from CIS. The patients were treated with each medication during 2 weeks, followed by a washout period of 2 weeks. Primary outcome measures included the reduction in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Secondary outcomes included the Positive and Negative Syndrome Scale (PANSS), Manic State Assessment Scale, and Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: Both amisulpride and moclobemide were very effective in reducing CIS. Almost 74% of patients treated with amisulpride and 83% of patients treated with moclobemide showed some level of improvement on NHRS. Only in one patient treated with amisulpride, CIS worsened. CONCLUSIONS: Both medications were safe and effective as treatment of CIS. Although moclobemide exceeded amisulpride in antisalivation activity, treatment of CIS with amisulpride leads to improvement in psychotic symptoms.

Moclobemide treatment of clozapine-induced hypersalivation: pilot open study.

OBJECTIVES: Clozapine-induced hypersalivation (CIHS) affects a mean of approximately 30% patients and is a troublesome adverse effect that leads to massive compliance problems in patients with schizophrenia. For the management of this distressing adverse effect, different pharmacological agents have been recommended, yet none of them have been proven to be effective. The aim of our study was to investigate moclobemide, a reversible monoamine oxidase inhibitor-A, as an additional possibility for controlling or at least minimizing CIHS. METHODS: We enrolled 14 patients with schizophrenia who experienced CIHS. Moclobemide (150-300 mg/d) was added to their conventional regular treatment during 14 days. Hypersalivation was assessed at the start of the treatment and at its end point by the 5-point Nocturnal Hypersalivation Rating Scale. RESULTS: Two thirds of the subjects who experienced CIHS have demonstrated a beneficial effect after the addition of moclobemide, whereas one third of them have been nonresponders. None of the patients had any adverse effects. CONCLUSIONS: We assume that moclobemide can be another additional and safe medication for the treatment of CIHS; however, more data, based on controlled studies, are needed.

Pyridoxal plasma level in schizophrenic and schizoaffective patients with and without tardive dyskinesia.

BACKGROUND: Motor disturbances in vitamin B6-deficient animals were described. Some clinical experiments showed that vitamin B6 may ameliorate different drug-induced movement disorders, including tardive dyskinesia (TD). The aim of this study was to compare plasma pyridoxal-5-phosphate (PLP) levels in schizophrenic patients with and without TD. METHOD: This study was conducted in the Be'er Sheva Mental Health Center from February 2006 to August 2006. Eighty-nine schizophrenic inpatients (40 have TD, 22 men and 18 women, 20-66 yrs old [mean, 48 yrs] and 49 schizophrenic inpatients, 30 men and 19 women, 21-66 yrs old (mean, 49 yrs), without any symptoms of motor disturbances [the control group]) were enrolled in the study. Measurement of PLP is performed by high-performance liquid chromatography separation in all patients. RESULTS: There was a significant difference in plasma PLP levels between patients with TD and those without TD. The discrepancy between the groups was almost entirely attributable to the PLP levels of male patients: 12.4 +/- 11.4 vs 29.0 +/- 12.9 nM in men (P < 0.001), and 19.7 +/- 14.8 vs 22.0 +/- 13.6 nM in women (P > 0.5). CONCLUSIONS: Our results suggest that schizophrenic and schizoaffective male patients with TD have lower PLP plasma levels than non-TD patients.

Vitamin B6 treatment for tardive dyskinesia: a randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Tardive dyskinesia (TD) is a significant clinical problem. Vitamin B(6) is a potent antioxidant and takes part in almost all of the possible mechanisms that are suggested as being associated with appearance of TD. The aims of this study were (1) to reexamine the efficacy and safety of higher doses of vitamin B(6) versus placebo in a greater sample of patients for a longer time and (2) to evaluate the carryover effect of vitamin B(6). METHOD: A 26-week, double-blind, placebo-controlled trial was conducted in a university-based research clinic from August 2002 to January 2005 on 50 inpatients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder and TD. In a double-blind crossover paradigm, all study subjects were randomly assigned to start treatment with either vitamin B(6) (daily dose of 1200 mg) or placebo. After 12 weeks of treatment and then a 2-week washout, subjects were crossed over to receive the other treatment for 12 weeks. The primary outcome measure was the change from baseline in Extra-pyramidal Symptom Rating Scale (ESRS) scores. RESULTS: The mean decrease in ESRS clinical global impression scores from baseline to endpoint was 2.4 points in patients treated with vitamin B(6) and 0.2 points in patients treated with placebo (p < .0001). The mean decrease in the parkinsonism subscale score was 18.5 points and 1.4 points, respectively (p < .00001), and the mean decrease in the dyskinesia subscale score was 5.2 points and -0.8 points, respectively (p < .0001). CONCLUSION: Vitamin B(6) appears to be effective in reducing symptoms of TD. The specific mechanisms by which vitamin B(6) attenuates symptoms of TD are not clear.

The prevalence of neuroleptic drug-induced tardive movement subsyndromes among schizophrenic and schizoaffective patients residing in the southern region of Israel.

The aim of the current study was to assess the prevalence of tardive movement disorders (TMD) among a group of institutionalized schizophrenic and schizoaffective patients in southern region of Israel. Chronic schizophrenic and schizoaffective inpatients of a psychiatric hospital and its affiliated hostels were screened for the presence of TMD subsyndromes. Twenty percent (107 patients) of 523 patients with schizophrenia and schizoaffective disorder exhibited TMD. Of those with TMD, 36% had only one subsyndrome, whereas 64% had a combination of several TMD subsyndromes. With regard to patients with TMD, the most frequent TMD subsyndrome was tardive tremor (TT). TT appeared more often in males compared to females and at a younger age (44.3+/-8 vs. 54.3+/-11 years, P<0.04). TD appearing in combination with other TMD subsyndromes was significantly more prevalent among females than in males (57% vs. 35%; P<0.02). TMD generally appears in a combined fashion. Further prospective studies from different geographical areas are recommended.

Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.

BACKGROUND: Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation. METHOD: The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure. RESULTS: The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003). CONCLUSION: Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00190008.

"Internet delusions": the impact of technological developments on the content of psychiatric symptoms.

The inclusion of computers and the Internet in our daily lives has become an increasingly pervasive phenomenon. Naturally, this phenomenon found its reflection in the quick inclusion of these technologies in the content of delusions. There have already been a few reports describing patients with Internet delusions. In this report, we describe two patients and their social background who were without previous psychiatric history and whose first psychosis involved delusions surrounding the Internet. Our opinion is that Internet delusions do not represent a new diagnostic entity, but rather modified delusions of persecution, broadcasting and control.

Combination of "atypical" antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder.

BACKGROUND: This article reviews the published clinical data on treatment-resistant schizophrenic and schizoaffective patients managed with combinations of "atypical" antipsychotic medication. METHOD: A computerized MEDLINE literature search covering an 18-year period (1985-2003) was conducted. All pertinent papers on the subject of the use of combination "atypical" antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder were obtained with subsequent analysis and discussion of the retrieved data. RESULTS: The search identified 29 case reports and case series reports (172 patients) and one double-blind placebo-controlled trial (28 patients) describing the use of combination "atypical" antipsychotic medication (clozapine-risperidone; clozapine-sulpiride; clozapine-olanzapine; clozapine-quetiapine; olanzapine-sulpiride; olanzapine-quetiapine; risperidone-olanzapine; risperidone-quetiapine) in the treatment of resistant schizophrenic and schizoaffective patients. An overview of results suggests that the combinations were beneficial in the described patients with reduction of positive symptoms and occasionally negative symptoms. Significant adverse effects, while rare, were reported in a few cases and did not appear to different in nature from those managed on monotherapeutic regimens. CONCLUSION: Combinations of "atypical" antipsychotic medications are well tolerated and may be effective in the management of treatment refractory schizophrenia and schizoaffective disorder. However, further double-blind placebo-controlled trials are required in order to test and confirm these observations.

High-dose olanzapine-induced improvement of preexisting type 2 diabetes mellitus in schizophrenic patients.

OBJECTIVE: During the last few years there have been numerous publications concerning glucose dysregulation and antipsychotic treatment with new-onset diabetes and exacerbation of existing disease being reported. At the same time three anecdotal reports describing decrease of blood glucose level during clozapine and olanzapine treatment were published. Here we report two cases of clinically significant dose-related reductions in glucose levels in schizophrenic and schizoaffective patients suffering from pre-existing type 2 diabetes during high dose (40 mg/day) olanzapine treatment. To the best of our knowledge, this is a first report of decreasing glucose blood levels in association with olanzapine therapy in pre-existing type 2 diabetes. Antipsychotic treatment with high doses of olanzapine showed that the relationship between olanzapine and glucose regulation is more unambiguous than usually assumed. CONCLUSIONS: There is a need for further studies in order to define the influence of high dose olanzapine for schizophrenic and schizoaffective patients suffering from type 2 diabetes.