Joseph Bergman

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.

Curcumin as an Add-On to Antidepressive Treatment: A Randomized, Double-Blind, Placebo-Controlled, Pilot Clinical Study

ObjectivesDepression is a widespread mental disorder in which nearly half of the affected people have recurrent symptoms. Drug combinations may produce cumulative adverse effects, especially in elderly and physically ill patients. It was demonstrated that curcumin possesses antidepressive activity in various animal models of depression, and a combination of curcumin with some antidepressants potentiates the antidepressive effect of these agents. We sought to evaluate the efficacy of curcumin as an antidepressive agent in a combination with other antidepressants in patients with major depression. MethodsForty patients with a first episode of depression participated in a 5-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 500-mg/d curcumin or placebo together with antidepressants (escitalopram or venlafaxine) during August 2010 until June 2011. The outcome measures were Clinical Global Impression—Severity Scale, Hamilton Depression Rating Scale, and Montgomery-Asberg Depression Rating Scale. ResultsAnalysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. These changes became significant from the first visit after 7 days of treatment. There was no difference between curcumin and placebo, which means negative results. However, the patients in the curcumin group demonstrated a trend to a more rapid relief of depressive symptoms in comparison to those in the placebo group. None of the patients complained of any adverse effect during the study. ConclusionsAlthough there is no definitive proof that curcumin can induce an earlier beneficial effect of antidepressive agents, it seems like an extended study is needed to prove it, using higher therapeutic doses of curcumin.

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.

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.

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.

Amisulpride versus moclobemide in treatment of clozapine-induced hypersalivation

Abstract 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.

Efficacy of bupropion XR in treatment-resistant elderly patients: a case series study.

Objectives:Many of the patients with depression fail to achieve an adequate response to a given antidepressant. Depression is often overlooked in elderly persons, which may produce a greater risk of suicide in this age group. The antidepressive characteristic of bupropion has been already validated in several studies. However, to the best of our knowledge, there is no research concerning treatment-resistant depressive elderly patients with bupropion. Methods:We present a consecutive series of elderly patients (13 subjects: 6 men and 7 women) with major depression. All patients were older than 60 years, with diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and were treatment resistant. Patients were treated openly for 6 weeks with bupropion XR (300 mg/d). Efficacy was assessed at baseline and every 3 weeks using the Hamilton Depression Rating Scale, the Montgomery-Asberg Depressive Rating Scale, and the Clinical Global Impression-Severity of Illness Scale. Results:The treatment was generally well tolerated without serious events. In all patients, the average Hamilton Depression Rating Scale scores diminished from 41.1 to 17.2 at the sixth week (P < 0.0001), the Montgomery-Asberg Depressive Rating Scale scores diminished from 44.0 to 19.9 (P < 0.0001), and Clinical Global Impression-Severity of Illness scores diminished from 5.7 to 3.2 (P < 0.0001). Of the 13 patients, 9 patients had marked and very marked improvement, and 4 patients did not demonstrate any mental state change. Conclusions:Treatment-resistant depressive elderly patients positively responded to and tolerated bupropion XR well. This case series demonstrates that bupropion could be a promising alternative therapy for elderly patients with treatment-resistant major depressive disorder. Further randomized controlled studies are necessary.

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

&NA;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. MethodsWe 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. ResultsThe 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. ConclusionsTreatment-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.

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

Abstract 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.