Treatment of Clozapine-Associated Sialorrhea: The Role of Benzamide Derivatives.

PURPOSE: Hypersalivation is one of the most prevalent and distressing adverse effects associated with clozapine treatment. Currently, there is no standard therapeutic approach toward how to overcome it. Clinicians use various medications for managing this adverse effect. However, some of the agents are not effective enough, whereas others can induce other adverse effects. Recently, several reviews have been published on the treatment of clozapine-associated hypersalivation, in which the focus was on drugs from various pharmacological groups, and little attention was paid to drugs from the group of substituted benzamides. The intention of this brief narrative review is to draw the attention of clinicians to the use of the benzamide group for the treatment of this unpleasant adverse effect. METHODS: A MEDLINE search was conducted to identify published treatment studies and case reports in the literature from 2000 to September 2021, concerning a treatment of clozapine-associated hypersalivation, mainly substituted benzamides. RESULTS: Accumulating evidence during the last 2 decades indicates that agents derived from the benzamide group may be effective and safe agents for treatment of clozapine-associated hypersalivation. Whether with a psychotropic effect or without, medications from this group may produce a beneficial response. CONCLUSIONS: Substitute benzamide derivatives have emerged as effective and well-tolerated agents for treatment clozapine-associated hypersalivation.

Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine.

Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC.

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.

Risk factors for coercion length at psychiatric hospitals in Israel: Relationship with staff.

Background: Coercive interventions continue to be applied frequently in psychiatric care when patients are at imminent risk of harming themselves and/or others. Aim: The purpose of this study was to demonstrate the relationship between the length of coercion and a variety of factors, including the sociodemographic background of patients, their diagnoses and the characteristics of hospital staff. Methods: This is a one-year cross-sectional retrospective study, including records of 298 patients who underwent restraint and/or seclusion interventions in male acute, closed wards in two psychiatric hospitals in Israel. Results: A higher proportion of academic nurses to nonacademic nurses on duty leads to a shorter coercion time (P < 0.000). The number of male staff on duty, without any relation to their level of education, also leads to the shortening of the coercion time. Conclusion: The presence of registered, academic female nurses, male staff on duty and the administration of medication before coercive measures can reduce the length of restriction.

Motor symptoms of schizophrenia: is tardive dyskinesia a symptom or side effect? A modern treatment.

Abnormal involuntary dyskinetic movements in schizophrenia patients have been documented for more than 140 years. Clinicians should distinguish between two kinds of disturbances-spontaneous dyskinetic movements and movements induced by psychotropic medications-which may look familiar clinically. As a modern term, tardive dyskinesia (TD) is a potentially permanent neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. Several distinct forms of TD exist, specifically tardive akathisia, tardive blepharospasm, tardive dystonia, tardive gait, tardive myoclonus, tardive tremor, and tardive tics, and they have different pathophysiologies and treatment. The pathogenesis of TD remains unclear, and the pathophysiology is complex and multifactorial. Moreover, there is solid evidence of a genetic predisposition to TD. This article summarizes recent relevant publications concerning TD and the most recent studies regarding treatment of this disorder with antioxidative agents.

Clinical and demographic characteristics of secluded and mechanically restrained mentally ill patients: a retrospective study.

BACKGROUND: Restraint or seclusion measures in acute psychiatric care are used as a last resort when all other methods for removal of physical threat have failed. The purpose of this study is to find a correlation between coercive measures, demographic characteristics within this patient group, and factors associated with shortened periods of restriction. METHODS: This is a one-year retrospective study conducted in a male acute closed ward of a psychiatric hospital in Israel. The data from January 1, 2014 to December 31, 2014 were retrieved from the records of patients who underwent restraint and/or seclusion interventions during this period. The analyzed data included age, psychiatric diagnosis, marital status, education, race, ethnicity, length of hospital stay, legal status during admission, type of coercive measure (mechanical restraint, seclusion), number and duration of coercive episodes, reasons for coercion, time of event, number of previous hospitalizations, aggression in past and present treatment, and treatment during events. RESULTS: During this time period, there were 563 admissions in the study ward. Over this period, 176 subjects (31.3%) underwent 488 restraints and/or seclusions. 98% were aggressive in the past. (Although some results reached statistical significance, we prefer to emphasize here only the most important results, while the others will be presented in the text.) Patients with personality disorders were physically limited for the longest time, while schizophrenia patients were restricted for the shortest time compared with other diagnoses (p = 0.007). A negative correlation was found between the length of coercion and the number of academic female nurses on duty (p = 0.005), as well as the administration of sedative medications during the restricting procedure. CONCLUSIONS: We believe that the presence of registered, academic female nurses on duty and medication administration during coercive measures can reduce the length of restriction.

Curcumin as Add-On to Antipsychotic Treatment in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Introduction of old and new generations of antipsychotics leads to significant improvements in the positive symptoms of schizophrenia. However, negative symptoms remain refractory to conventional trials of antipsychotic therapy. Recently, there were several open clinical human trials with curcumin. Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including antioxidative and neuroprotective effects. The studies showed that curcumin improved the negative symptoms of schizophrenia. The purpose of our study was to examine the efficacy of curcumin as an add-on agent to regular antipsychotic medications in patients with chronic schizophrenia. METHODS: Thirty-eight patients with chronic schizophrenia were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 3000 mg/d curcumin or placebo combined with antipsychotics from January 2015 to February 2017. The outcome measures were the Positive and Negative Symptoms Scale (PANSS) and the Calgary Depression Scale for Schizophrenia. RESULTS: Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. There was a significant response to curcumin within 6 months in total PANSS (P = 0.02) and in the negative symptoms subscale (P = 0.04). There were no differences in the positive and general PANSS subscales, and the Calgary Depression Scale for Schizophrenia scores between the treatment and placebo groups. No patient complained of any adverse effect. CONCLUSIONS: The promising results of curcumin as an add-on to antipsychotics in the treatment of negative symptoms may open a new and safe therapeutic option for the management of schizophrenia. However, these results should be replicated in further studies.ClinicalTrials.gov Identifier: NCT02298985.

Association between mental disorders, cognitive disturbances and vitamin D serum level: Current state.

BACKGROUND & AIMS: Vitamin D deficiency has been identified as a global problem. Approximately 14% of the world population has inadequate vitamin D levels. This vitamin has been usually associated with bone disorders such as rickets, osteomalacia, and osteoporosis. However, these disorders present only a small part of all the disturbances which can be induced by its deficiency. Low serum vitamin D is associated with development of cardiovascular diseases, hypertension, neurodegenerative diseases, diabetes mellitus, metabolic syndrome and even cancer. This vitamin may be an important factor in the development of psychiatric illnesses, therefore clinicians should not leave this serious issue unresolved. The aim of this review is to describe the current data concerning the association between vitamin D serum levels, cognition and mental disorders. METHODS: We conducted a systematic bibliographical research, of PubMed, MedLine literature and Cochrane database without language restriction to identify all publications concerning this issue from 1995 to the first quarter of 2017. RESULTS: We found 48,937 articles concerning vitamin D, published during the last 22 years and 3 months (1995-2017). We selected only those publications focused on the association between vitamin D serum deficiency and mental disturbances (depression, schizophrenia, cognitive disturbances, attention deficit disorder, and autism). One hundred and sixty-seven papers were found suitable to our selection criteria. Careful evaluation of the relevant literature demonstrates that addition of vitamin D to conventional antidepressive agents can improve antidepressive effect in contrast to placebo. Regarding other mental conditions there are no clear-cut conclusions. CONCLUSIONS: An association between low vitamin D serum levels and different mental disorders was found. Yet, nonetheless there is no clear consensus that addition of vitamin D improves or is related to a beneficial effect on mental health. More randomized clinical control trials should be performed in order to reach evidence based conclusions.

High-dose vitamin B6 decreases homocysteine serum levels in patients with schizophrenia and schizoaffective disorders: a preliminary study.

UNLABELLED: Vitamin B6 plays an essential role in the normal functioning of the central nervous system. Normal homocysteine (Hcy) serum level is maintained by remethylation of Hcy to methionine by enzymes that require folic acid and vitamin B12 and by catabolism to cysteine by a vitamin B6-dependent enzyme. These findings may be consistent with the hypothesis that the vitamin B6 status may influence plasma Hcy levels. The aims of this preliminary study were (1) to determine whether a correlation exists between Hcy and vitamin B6 levels in patients with schizophrenia and schizoaffective disorders and (2) to investigate whether treatment with high-dose vitamin B6 may reduce Hcy levels in these patients. METHODS: In this preliminary study, we enrolled 11 patients with schizophrenia or schizoaffective disorders (7 men and 4 women; mean age +/- SD, 50 +/- 12 years) receiving high doses of vitamin B6 treatment (1200 mg/d) for 12 weeks. Blood samples for the assessment of pyridoxal-5-phosphate and Hcy serum levels were obtained at baseline and after 12 weeks of treatment. RESULTS: Age was significantly positively correlated with Hcy levels at baseline (r = 0.392, P = 0.004). All other parameters, including diagnosis, disease duration, and pyridoxal-5-phosphate serum level, were not correlated with Hcy serum levels at baseline. After vitamin B6 treatment, Hcy serum levels significantly decreased (14.2 +/- 3.4 vs. 11.8 +/- 2.0 micromol/L, respectively, t = 2.679, P = 0.023); this decrease being statistically significant in men but not in women. CONCLUSIONS: High doses of vitamin B6 lead to a decrease in Hcy serum level in male patients with schizophrenia or schizoaffective disorder.

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.

Successful Use of Escitalopram for the Treatment of Visual Hallucinations in Patients With Parkinson Disease.

INTRODUCTION: Patients with Parkinson disease (PD) frequently experience visual hallucinations (VH). Visual hallucinations are most often viewed as an adverse effect of antiparkinsonian treatment. Possible treatments for this disturbance include a reduction of antiparkinsonian medications, adding atypical antipsychotics, or cholinesterase inhibitors. Some studies demonstrated that selective serotonin reuptake inhibitors may be an optional treatment for patients experiencing psychosis or agitation in dementia. Currently, there is no standard recommended treatment for VH in patients with PD. We present here our clinical experience with escitalopram (selective serotonin reuptake inhibitor) for treating this disturbance. METHODS: Thirteen patients with PD (8 men and 5 women; age range 67-83 years) experiencing VH were openly treated with escitalopram 10 or 15 mg/d as add-on. Efficacy was assessed at baseline, then after 4 and 8 weeks of treatment using Clinical Global Impression-Severity and Clinical Global Impression-Improvement. RESULTS: At the end of the 4th week of treatment, of 13 patients, 11 subjects demonstrated improvement, and in only 2 patients were there no changes in their condition. After an additional 4 weeks, 2 of the responders showed very significant improvement, 6 demonstrated much improvement, and 3 patients demonstrated minimal improvement. Only 1 patient showed no change in his condition. One additional patient stopped taking escitalopram after 5 weeks because of an absence of improvement in his state. CONCLUSIONS: Escitalopram was well tolerated as treatment of VH in PD patients. This medication could be a promising optional therapy for this disturbance; however, further randomized controlled and bigger studies are necessary.

The effect of sudden clozapine discontinuation on management of schizophrenic patients: A retrospective controlled study.

BACKGROUND: The aims of our study were (1) to compare the dose of clozapine needed to achieve remission in patients who stopped their treatment (study group) versus patients who continued taking this medication (control group) and (2) to compare the clinical characteristics of remission between these 2 groups. METHOD: We retrospectively reviewed the medical records of all treatment-resistant schizophrenic and schizoaffective patients (according to DSM-IV criteria) who were treated with clozapine over a period of 9 years, from January 1995 through December 2003. The study group consisted of 43 patients and the control group of 12 patients. All patients' files from both groups were examined, and each patient's remission was scored twice--initially on discharge from the hospital and subsequently after final discharge for the study group, or at the end of the study for the control group. RESULTS: The change of clozapine dose from the first to the last remission expressed by percentage shows a significant difference between the 43% increase in clozapine dose in the study group and the 12.5% decrease in clozapine dose in the control group (p < .001). Quality of remission assessment showed deterioration in the global remission score in the study group, while the quality of remission assessment in the control group did not show any change. CONCLUSIONS: Our findings suggest that the discontinuation of clozapine treatment leads to a deterioration in the quality of remission, with a need for an increased dose of clozapine. Further prospective studies on larger samples are needed to confirm these findings.

Vitamin B12 and folate serum levels in newly admitted psychiatric patients.

BACKGROUND & AIMS: Deficiencies of cobalamin and folate may play a causal role in the development or exacerbation of psychiatric illnesses. We compared cobalamin and folate levels in newly admitted psychiatric patients to mentally healthy controls and assessed their correlation with various psychiatric conditions. METHODS: All patients consecutively admitted to a psychiatric hospital were examined for serum cobalamin and folate levels. Controls were obtained from a population with no known mental illness. Values were considered to be below normal if cobalamin was <223 pg/ml and folate <3.1 ng/ml. RESULTS: The 224 newly admitted patients did not differ significantly from controls, both with regard to the mean cobalamin level and to the prevalence of lower than normal levels. About 30% of patients had low folate values compared to 2.5% in the control group (P<0.0001). Mean folate level in controls was significantly higher than in patients (P<0.0001), where a positive correlation was found between low folate levels and depression. CONCLUSIONS: The results of our study suggest that folate levels be assessed in patients admitted to psychiatric wards, especially in those with depression. Further study is needed to evaluate the role of folate and cobalamin in psychiatric illness.

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

Treatment strategies against acute neuroleptic-induced akathisia (NIA) include anticholinergic (antimuscarinic) agents, dopamine agonists, GABAergic agents, beta-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 B(6), mianserin and placebo in the treatment of acute NIA. Sixty schizophrenia and schizoaffective inpatients who have NIA were randomly divided to receive vitamin B(6) 1,200 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 B(6)-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 B(6) 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 B(6) and a low dose of mianserin may be a useful addition to current treatments of NIA. The efficacy of vitamin B(6) 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.

Donepezil as Add-on Treatment for Resistant Obsessive-Compulsive Disorder: Retrospective Case Series.

UNLABELLED: Obsessive-compulsive disorder (OCD) is one of the most common and disabling psychiatric disorders. Treatment with serotonin selective reuptake inhibitors (SSRIs) shows significant improvement; however, residual symptoms remain in most patients despite continued adequate OCD treatment. For patients exhibiting partial or no response to multiple SSRIs, augmentation strategies are usually recommended. Here, we introduce a retrospective consecutive sample of aged patients with resistant OCD treated with donepezil augmentation to regular pharmacotherapy. METHODS: Ten patients (5 males, 5 females; mean [SD] age, 63.8 [7.5] years), suffering from resistant OCD, were openly treated with donepezil 10 mg/d as add-on. Efficacy was assessed at baseline and after 8 weeks of treatment using the Yale-Brown Obsessive Compulsive Scale, Clinical Global Impression-Severity, and Clinical Global Impression-Improvement. RESULTS: The treatment was generally well tolerated without adverse events. In all patients, mean (SD) Yale-Brown Obsessive Compulsive Scale scores diminished from 27.3 (4.3) points at baseline to 16.9 (4.5) points at week 8 (P < 0.0001). Mean (SD) Clinical Global Impression-Severity scores diminished from 5.5 (0.7) points to 3.1 (1.0) points, (P < 0.001). According to Clinical Global Impression-Improvement, 7 patients demonstrated "very much" or "much" improvement and 3 patients did not demonstrate any improvement. CONCLUSIONS: Donepezil was a well-tolerated add-on to regular pharmacotherapy in treatment-resistant OCD patients in this small cases series. Donepezil could be a promising optional therapy for patients suffering from resistant OCD, but further randomized controlled studies are necessary.

High serum homocysteine levels in young male schizophrenic and schizoaffective patients with tardive parkinsonism and/or tardive dyskinesia.

BACKGROUND: The pathogenesis of neuroleptic-induced tardive movement disorders (TMD), including tardive parkinsonism and tardive dyskinesia (TD), has not yet been established. An elevated serum level of total homocysteine has been implicated as a risk factor for various neuropathologic states and some movement disorders. The aim of our study was to determine whether there is an association between serum total homocysteine level and the presence of TMD among schizophrenic and schizoaffective patients. METHOD: This study was conducted in Be'er Sheva Mental Health Center from August 2002 to May 2004. Fifty-eight patients with schizophrenia or schizoaffective disorder (DSM-IV) and TMD for at least 1 year (38 men, 20 women; age range, 28-73 years) were compared to a control group of 188 patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder without TMD (123 men, 65 women; age range, 19-66 years) regarding serum total homocysteine levels. RESULTS: Men with TMD (demonstrating tardive parkinsonism and/or TD) had significantly higher mean serum total homocysteine levels compared to sex- and age group-matched controls. The difference between groups was almost entirely attributable to the homocysteine levels of young male patients (age group, 19-40 years old) with TMD. CONCLUSION: High serum total homocysteine level may constitute a risk factor for certain variants of TMD, especially in young schizophrenic or schizo-affective male patients. Further prospective studies are needed to clarify these findings.

Lithium intoxication associated with intramuscular ziprasidone in schizoaffective patients.

Antipsychotic agents have been used for the treatment of mood disorders in schizophrenic and schizoaffective patients. It has also been suggested that combinations of lithium and antipsychotics may be more effective than either class alone in treatment of schizoaffective patients. Lithium is known to interact with a variety of medications, including conventional and atypical antipsychotics. Although these combinations are generally well tolerated, they may sometimes lead to various adverse side effects. The authors report two schizoaffective patients with manic psychotic state and psychomotor agitation treated with lithium. Both patients developed symptoms of lithium intoxication after intramuscular ziprasidone treatment. To the best of their knowledge, this is the first description of such an adverse effect of this new atypical neuroleptic drug. They assume that lithium intoxication in the two presented cases was associated with the fast increase of ziprasidone serum level after its parenteral application, possibly affecting lithium excretion and thereby leading to lithium intoxication.

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.

Amisulpride as add-on treatment for resistant obsessive-compulsive disorder: retrospective case series.

UNLABELLED: Obsessive-compulsive disorder (OCD) is one of the most common and disabling psychiatric disorders. Treatment with selective serotonin reuptake inhibitors (SSRIs) shows significant improvement; however, residual symptoms remain in most patients despite continued treatment. For partial or nonresponding patients to multiple SSRIs, augmentation strategies are usually recommended. Here we present a consecutive sample of patients with resistant OCD treated with amisulpride augmentation to SSRIs. METHODS: We present 10 patients (5 males, 5 females) experiencing resistant OCD. Subjects were treated openly for 6 weeks with amisulpride 200 mg/d as add-on, excluding 1 patient who was treated with only 100 mg/d due to acute extrapyramidal adverse effect on a larger dose. Efficacy was assessed at baseline and after 6 weeks of treatment using the Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impression-Severity, and Clinical Global Impression-Improvement. RESULTS: The treatment was generally well tolerated without serious events. In all patients, average Yale-Brown Obsessive-Compulsive Scale scores diminished from 25.3 ± 5.96 points at baseline to 12.2 ± 5.98 at the sixth week (P < 0.0005). Of 10 patients, 7 had significant and partial improvement, and 3 patients did not demonstrate any improvement. CONCLUSIONS: Treatment-resistant OCD patients positively responded and well tolerated amisulpride add-on to their ongoing regular pharmacotherapy. This case series demonstrates that amisulpride could be a promising optional therapy for patients who have resistant OCD. Further randomized controlled studies are necessary.

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

BACKGROUND: Treatment strategies for acute neuroleptic-induced akathisia (NIA) contain anticholinergic (antimuscarinic) agents, dopamine agonists, gamma-aminobutyric acid (GABA)-ergic agents, beta-blockers, benzodiazepines, and serotonin antagonists. Nevertheless, many patients who suffer from acute akathisia fail to respond to treatment. In earlier studies, vitamin B6 was found to be effective in the treatment of neuroleptic-induced movement disorders. The purpose of this study was to evaluate the efficacy of vitamin B6 in the treatment of acute NIA. This is the first report of B6 as a treatment for NIA. METHOD: This study was conducted in 2 mental health centers from February 2003 to November 2003. Twenty schizophrenia and schizoaffective inpatients with a DSM-IV diagnosis of NIA were randomly divided to receive vitamin B6 600 mg/day b.i.d. (N = 10) or placebo (N = 10) twice a day for 5 days in a double-blind design. The Barnes Akathisia Scale (BAS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions scale (CGI) were used to assess the severity of NIA and psychotic symptoms. The BAS assessment was made at baseline and every day during the study. The BPRS and CGI were completed at baseline and at the end of the study. RESULTS: The vitamin B6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004) subscales of the BAS. The objective subscale did not demonstrate significant positive results (p = .079), but there was a trend of symptom amelioration in the vitamin B6 group. A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B6 group (80%), and in only 3 patients in the placebo group (30%) (p = .037). CONCLUSION: Our preliminary results indicate that high doses of vitamin B6 may be useful additions to the available treatments for NIA, perhaps due to its combined effects on various neurotransmitter systems.