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.

The beneficial effect of escitalopram on obsessive-compulsive-related musical hallucinations in elderly patients with hearing impairment: a case series.

Musical hallucinations (MHs), characterized by the hearing of tunes, melodies, or songs, is a relatively under-recognized phenomenon among elderly individuals with hearing impairment. In some patients, MHs represent a complex psychopathological phenomenon, hallucinatory in content and obsessive-compulsive (OC) in form, justifying trial with an antiobsessive agent. In the present case series, we describe our clinical experience with escitalopram in six (two men, four women; age 74-85 years) elderly individuals with OC-related MH and hearing impairment who did not respond to previous antipsychotic treatment. Switch to escitalopram (mean 12.5 mg) led to a substantial improvement in the MH symptom severity, as reflected in a decrease in the global score of the Yale-Brown Obsessive-Compulsive Scale adapted to OC-related MH (scores before escitalopram, 13.2±0.9; after 12 weeks of treatment, 7.8±2.8; P<0.01). Escitalopram was well tolerated, and the only detected side effects, nausea and headache, were mild and transient. If confirmed in controlled trials, escitalopram and probably other selective serotonin reuptake inhibitors may be a therapeutic option in elderly individuals with OC-related MH.

Beneficial effect of low-dose mirtazapine in acute aripiprazole-induced akathisia.

Low-dose mirtazapine was found to be efficacious for neuroleptic-induced akathisia. We evaluated whether mirtazapine is also effective for akathisia induced by the partial dopamine D2 receptor agonist aripiprazole. Medical charts were retrospectively analyzed for eight patients who developed akathisia while being treated with aripiprazole. All scored at least 2 (mild akathisia) on the Barnes Akathisia Rating Scale (BARS) and were treated with mirtazapine (15 mg/day) for a mean of 8.5 days. There was a statistically significant reduction in the BARS subjective, distress, and global (P<0.01 to P<0.001), but not objective (P=0.21) subscales. Five (62.5%) patients fulfilled the criteria of response, a decrease of at least two points on the BARS global subscale. Low-dose mirtazapine was well tolerated, and mild sedation, the only side effect (three patients), was transient. A large-scale controlled investigation is warranted to substantiate clinical utility of mirtazapine for akathisia induced by aripiprazole and other second-generation antipsychotics.

The effect of reboxetine co-administration with olanzapine on metabolic and endocrine profile in schizophrenia patients.

RATIONALE: We previously demonstrated that the addition of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain. Using the same study sample, we also sought to determine whether reboxetine's weight-attenuating effect was accompanied by a beneficial effect on metabolic and endocrine parameters relevant to antipsychotic-induced weight gain and obesity. METHOD: Blood samples at baseline and at the end of the 6-week trial were available for 54 participants who participated in previous double-blind, placebo-controlled studies of reboxetine (4 mg BID) addition to olanzapine-treated schizophrenia patients. Fasting glucose, lipid profile, insulin, leptin, cortisol, dehydroepiandrosterone (DHEA), prolactin, and thyroid-stimulating hormone (TSH) were analyzed. RESULTS: In contrast to the olanzapine/placebo group, the olanzapine/reboxetine group exhibited a reduction in blood triglyceride (p < 0.05) and leptin (p < 0.05) levels, and elevation in cortisol (p < 0.05) and DHEA (p < 0.008) levels. No significant between-group differences were detected in the changes in cholesterol, glucose, insulin, TSH, and prolactin. CONCLUSIONS: Reboxetine addition resulted in meaningful improvement of some metabolic and endocrine measures associated with olanzapine-induced weight gain. The potential role of reboxetine in the prevention of olanzapine-induced weight gain and cardio-metabolic morbidity merits further large-scale, long-term investigation.

Reducing antipsychotic-induced weight gain in schizophrenia: a double-blind placebo-controlled study of reboxetine-betahistine combination.

RATIONALE: Combination treatment with reboxetine, a selective norepinephrine reuptake inhibitor, and betahistine, a histamine H1 receptor agonist/H3 antagonist, was developed to produce complementary action in CNS pathways regulating appetite and body weight. In the present placebo-controlled study, we evaluated whether a reboxetine-betahistine combination attenuates olanzapine-induced weight gain in schizophrenia patients. METHOD: Forty-three inpatients with DSM-IV schizophrenic disorder participated in a randomized double-blind study. Reboxetine (4 mg/day) with betahistine (48 mg/day) (N = 29) or placebo (N = 14) was co-administered with olanzapine (10 mg/day) for 6 weeks. Mental status was assessed at baseline and endpoint with relevant rating scales. Intention-to-treat method was used for statistical analysis. RESULTS: Seven patients in the study group and four in the placebo group discontinued the trial. At the end of the trial, patients in the olanzapine/reboxetine + betahistine group gained significantly less weight than those in the olanzapine/placebo group [2.02 ± 2.37 and 4.77 ± 3.16 kg, respectively; t = 2. 89, degrees of freedom (df) = 41, p = 0.006]. The weight-attenuating effect of this combination was twofold larger than the weight-attenuating effect previously demonstrated with reboxetine alone. Significantly fewer patients in the study group than in the comparison group increased their initial weight by >7 %, the cutoff for clinically significant weight gain [3/29 (10.3 %) and 6/14 (42.9 %), respectively; χ (2) = 6.03, df = 1, p = 0.014]. The reboxetine-betahistine combination was safe and well tolerated. CONCLUSIONS: Reboxetine-betahistine combination produces a clinically meaningful attenuation of olanzapine-induced weight gain. These results justify direct comparison between the reboxetine-betahistine combination and reboxetine alone.

Effect of the selective norepinephrine reuptake inhibitor reboxetine on cognitive dysfunction in schizophrenia patients: an add-on, double-blind placebo-controlled study.

The noradrenergic (NE) system mediates cognitive dysfunction in schizophrenia patients, and the NE transporter represents a putative target for cognitive enhancing therapy. In a double-blind placebo-controlled study we evaluated the effect of add-on reboxetine (4 mg/day), a selective norepinephrine reuptake inhibitor (NRI), co-administered with atypical antipsychotic olanzapine (10 mg/day) on cognitive functioning in DSM-IV schizophrenia patients. The Automated Neuropsychological Assessment Metrics battery and Wisconsin Card Sorting Test were used to assess selective cognitive functions at baseline and endpoint (6 weeks). Clinical assessment was also performed. No between-group differences were found in neurocognitive tests, suggesting that reboxetine did not significantly change patients' cognitive performance compared to placebo. Reboxetine was well-tolerated and did not interfere with the therapeutic effect of olanzapine. Long-term studies using higher reboxetine dosages and alternative NRIs (e.g., atomoxetine) are needed to determine the role of NRIs as cognitive enhancers in patients with schizophrenia and other disorders associated with cognitive impairments.

Clinical characteristics of schizotypal-related obsessive-compulsive disorder.

In this study we compared 15 patients with DSM-IV obsessive-compulsive disorder (OCD) and schizotypal personality disorder (SPD) and 31 non-SPD OCD patients. OCD-SPD patients had poorer insight, more negative symptoms, lower functioning, more antipsychotic augmentation and more first-degree relatives with schizophrenia-spectrum disorders. A distinct clinical phenotype of OCD associated with SPD should be considered when investigating etiopathogenetic mechanisms.

Awareness of illness and insight into obsessive-compulsive symptoms in schizophrenia patients with obsessive-compulsive disorder.

Obsessive-compulsive symptoms (OCS) have been revealed in a substantial proportion of schizophrenia patients. We sought to evaluate insight into OCS in schizo-obsessive patients. We evaluated insight into OCS and awareness of schizophrenia, using the Brown Assessment of Beliefs Scale (BABS) and the Scale to Assess Unawareness of Mental Disorder (SUMD), respectively. Fifty-seven inpatients that met DSM-IV criteria for both schizophrenia and OCD were recruited. To determine a possible modifying effect of OCS on the awareness of schizophrenia, we included a comparison group of non-OCD schizophrenia patients (N = 80). Nine (15.8%) schizo-obsessive patients revealed lack of insight into OCS, whereas a majority (48 patients, 84.2%) exhibited good or fair insight. In the schizo-obsessive group, insight into OCS positively correlated with awareness of schizophrenia but not with awareness of delusions. Roughly 40% of the schizo-obsessive and non-OCD schizophrenia patients revealed unawareness of schizophrenia. Our findings indicate that OCS in schizophrenia represent an identifiable dimension of psychopathology independent of core schizophrenia symptoms.

Attenuating effect of reboxetine on appetite and weight gain in olanzapine-treated schizophrenia patients: a double-blind placebo-controlled study.

RATIONALE: Search for safe and effective strategies to diminish weight gain associated with second generation antipsychotics (SGAs) is imperative. In the present study, we sought to replicate our preliminary findings, which indicated that coadministration of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain. MATERIALS AND METHOD: Fifty-nine patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in this randomized double-blind study. Reboxetine (4 mg/day; 31 patients) or placebo (29 patients) was coadministered with olanzapine (10 mg/day) for 6 weeks. Analysis was by intention-to-treat. RESULTS: Nine patients in each group prematurely discontinued the trial. Olanzapine/reboxetine-treated patients showed a significantly lower increase in body weight (mean = 3.31 kg, SD = 2.73) than their olanzapine/placebo-treated counterparts (mean = 4.91 kg, SD = 2.45). Significantly fewer olanzapine/reboxetine-treated patients gained at least 7% of their initial weight, the cutoff for clinically significant weight gain (6 [19.4%] of 31 patients vs 13 [46.4%] of 28 patients). Seven (22.6%) olanzapine/reboxetine-treated patients compared to only one patient (3.6%) in the olanzapine/placebo group revealed no weight change or even modest weight loss. Appetite increase was significantly lower in the olanzapine/reboxetine than olanzapine/placebo group and was correlated with attenuation of weight gain. Reboxetine addition was safe and well tolerated. CONCLUSIONS: The results confirm that coadministration of reboxetine promotes a clinically meaningful attenuation of olanzapine-induced weight gain in schizophrenia patients. If substantiated in long-term studies, along with behavioral management and diet counseling, reboxetine may have a clinical utility in controlling SGA-induced weight gain.

Preferential aggregation of obsessive-compulsive spectrum disorders in schizophrenia patients with obsessive-compulsive disorder.

OBJECTIVE: To validate a complex association between schizophrenia and obsessive-compulsive disorder (OCD). METHOD: We used the Structured Clinical Interview for DSM-IV Axis I disorders to compare the rate of OCD spectrum and additional Axis I disorders in 100 patients who met criteria for both schizophrenia and OCD, non-OCD schizophrenia (n = 100), and OCD (n = 35). RESULTS: There was a robust between-group difference in the number of patients with one or more OCD spectrum disorders (schizo-obsessive n = 30, compared with schizophrenia n = 8; P = 0.001), that is, higher rates of body dysmorphic (8% compared with 0%) and tic (16% compared with 4%) disorders. No difference was revealed in affective, anxiety, and substance use disorders. We found comparable rates of OCD spectrum disorders in the schizo-obsessive and OCD groups (30% and 42.8%, respectively; P = 0.32). CONCLUSION: Preferential aggregation of OCD spectrum disorders in the schizo-obsessive group supports this unique clinical association. Whether a schizo-obsessive interface represents comorbidity or a specific subtype of schizophrenia warrants further investigation.

Obsessive-compulsive disorder in bipolar disorder patients with first manic episode.

BACKGROUND: Evidence indicates that obsessive--compulsive disorder (OCD) co-occurs with schizophrenia and bipolar disorder (BD) at a higher rate than in the general population. The inflated rate of comorbidity may result from chronic illness, antipsychotic therapy or treatment-seeking behavior. To control for these factors we evaluated the prevalence of OCD in patients with first-episode acute mania who met DSM-IV criteria for BD-I, and compared them with our previously reported group of first-episode schizophrenia patients. METHOD: Fifty-six BD-I patients with a first-episode of acute mania were screened for OCD and additional comorbid disorders using the Structured Clinical Interview for DSM-IV Axis-I disorders and appropriate rating scales. RESULTS: Only one patient (1.8%) met DSM-IV criteria for OCD, and two (3.6%) met criteria for sub-threshold OCD. In contrast, there was a substantial aggregation of substance use disorders 32.1% (N=8), anxiety disorders, other than OCD 26.8% (N=15) and eating disorders 14.3% (N=8). LIMITATIONS: Small sample size, cross-sectional nature of the assessments and the inclusion of only BD-I patients. CONCLUSION: The rate of OCD in first-episode BD-I patients did not differ significantly from that found in the general population and was substantially lower than in previously reported first-episode schizophrenia patients (1.8% vs. 14%). We suggest that a preferential association of OCD with schizophrenia early in the course of illness represents a pathophysiological linkage between the two disorders, and putatively a specific schizo-obsessive subtype. In contrast, OCD in BD-I may stand for "true" comorbidity. Large-scale parallel comparative evaluations of comorbidity in BD-I and schizophrenia may contribute to the search for specific pathophysiological mechanisms of distinct comorbid-related subsets in either disorder.