Current Psychopharmacology - Volume 5, Issue 1, 2016

Background: Vitamin D deficiency has been identified as a global problem and about 14% of the world population has inadequate vitamin D levels. It is a neuroactive com- pound, a prohormone, and highly active in a variety of body tissues including the brain. The role of vitamin D in normal bone physiology, the pathogenicity of rickets, osteomalacia, and osteo- porosis has been long recognized. However, in recent years a body of evidence has accumulated associating low serum vitamin D deficiency with a myriad of pathologies including cardiovas- cular disease, hypertension, neurodegenerative disorders, diabetes mellitus, metabolic syndrome and even cancer. Objective: Many researches demonstrate that the brain contains huge amount of vitamin D and investigators began to be interested in its part in mental disorders. Vitamin D may be an important contributor to psychiat- ric illnesses so clinicians should not leave this serious issue unresolved. The aim of this review is to describe our current understanding of the association between vitamin D and depression. Method: It was conducted a systematic bibliographical research, of PubMed, MedLine literature and Cochrane database without language restriction to identify all studies concerning the association between vit- amin D deficiency and mental disorders from 1995 to October 2015. Results: Our searches yielded 198 appropriate citations, from which we included 61 relevant studies. Conclusion: The repeated findings have delineated a positive correlation between vitamin D deficiency and de- pression. However, there is no clear consensus regarding the use of vitamin D for the treatment of depression.

Objective: Schizophrenia is usually characterized by abnormal social behavior, lack of insight, and positive and negative symptoms. While there is increasing evidence that atypical antipsychotics have advantages over conventional ones, few long-term studies have directly compared the atypical antipsychotics with each other. Therefore, in the present as- sessment, the efficacy and safety of aripiprazole had been compared with quetiapine. Method: 50 schizophrenic patients entered into two comparable groups for participation in a twelve-week, double-blind study, for random assignment to quetiapine or aripiprazole. The main outcome scales included the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS). Also, the Clinical Global Impressions-Severity Scale (CGI-S), the Simpson An- gus Scale (SAS), and finally the schedule for Assessment of Insight (SAI) had been used as the auxiliary ones. Results: While both of aripiprazole and quetiapine demonstrated important efficacy in alleviation of positive symptoms (p<0. 04 & p<0. 01, respectively), their efficacy was not so with respect to negative cluster of symptoms (p<0. 07 & p<0.06, respectively). CGI-S and SAI, as well, revealed significant improvement with aripiprazole (p<0.05 & p<0.05, respectively) and quetiapine (p<0.05 & p<0. 04, respectively) at the end of the assessment. In contrast, in neither of groups any significant increase in SAS was detectible. Conclusion: Based on the outcomes of the current study, no significant difference was evident between ari- piprazole and quetiapine regarding improvement of positive and negative symptoms of schizophrenia.

Objectives: Since according to some studies, atypical antipsychotics were con- nected with better results and lesser adverse effects in comparison with conventional ones, at the present time the later kind of medications are the preferred category of antipsychotics in clinical management of schizophrenia. But such a maneuver has not decreased hitherto the dilemma of treatment -resistance. The objective of the present assessment included evalua- tion of the effectiveness of adjunctive flupentixol decanoate in schizophrenic patient, who had responded inadequately to aripiprazole. Method: 24 male inpatients with diagnosis of schizophrenia, who had displayed poor response to aripiprazole, were entered into an eight-week, single-blind evaluation for random assignment to current antipsychotic treatment (aripiprazole) or aripiprazole plus adjunctive flupentixol decanoate. While the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS) were used as the primary outcome measures, the Clinical Global Impressions-Severity Scale (CGI-S), the Schedule for As- sessment of Insight (SAI), and finally the Simpson-Angus Scale (SAS) were used as ancillary measures. Results: According to the results, while the mean total scores of CGI-S, SAI and SAPS in the augmented group dropped significantly in comparison with the aripiprazole group (p<0.007, p<0.03, p<0.001, respective- ly), with around 19.55% decrement of SAPS in the augmented group, the reduction in the mean total score of SANS was not significant in between -group analysis (P<0. 07). In addition, the mean total score of SAS was meaningfully improved in the target group (P< 0. 0000). The effect size (ES) analysis also revealed a great improvement with flupentixol augmentation regarding SAPS, SAI and CGI-S. Conclusion: While occurrence of extra-pyramidal adverse effects should not be overlooked by clinicians, addition of flupentixol decanoate to aripiprazole can be helpful for a number of poorly responsive schizophrenic patients.

Objective: A number of studies have shown that olanzapine and risperidone are more clinically effective than other antipsychotics. Consequently, if a treatment-resistant schizophrenic patient has not received them so far in their treatment history, it would be a sensible choice to use these drugs in treatment before beginning a clozapine regimen. In the present investigation the efficacy and safety of these two atypical antipsychotics were compared with each other. Method: Sixty schizophrenic patients, allocated randomly into 2 matching groups to participate in a twelve-week, double-blind evaluation for random assignment to risperidone or olanzapine. The chief procedures used for assessment were Scale for Assessment of Negative Symptoms (SANS)' and 'Scale for Assessment of Positive Symptoms (SAPS)'. The Scale for Assessment of Negative Symptoms (SANS)' and 'Scale for Assessment of Positive Symptoms (SAPS)' were used as supplementary measures. Treatment efficacy was evaluated statistically by the use of the t statistic and repeated -measures analysis of variance (ANOVA). Clinical response was defined as a decrease of at least twenty percent in total scores of SANS and/or SAPS. Results: Both risperidone and olanzapine were significantly beneficial for alleviation of positive symptoms (p<0.001 & p<0.0001, respectively), but only olanzapine improved significantly the negative symptoms (p<0.001). In addition, SAI was boosted significantly by olanzapine (p<0.02). CGI-S had shown significant alterations by both of risperidone and olanzapine (p<0.05 and p<0.04, separately). Finally, risperidone triggered significant escalation of SAS in the related group (p<0.0001). Conclusion: In this evaluation, risperidone and olanzapine were equally useful in control of clinical symptoms of schizophrenia, but olanzapine demonstrated higher efficiency in comparison with risperidone.

Background: Clozapine induced granulocytopenia has gained wide attention and effec- tive monitoring has been able to prevent a number of untoward deaths. However, other myelodys- plasias induced by Clozapine are still unrecognized and unreported. Another clinical complication of Clozapine is eosinophilia. However, this entity is unrecognized as the focus is mostly on granulocytopenia and neutropenia. Objective: To describe a case of Clozapine induced eosinophilia without any other clinical or biochemical abnormali- ties induced by Clozapine. Methodology: The file records of a patient with Schizoaffective disorder who developed eosinophilia while receiving Clozapine were studied and analyzed. Results: The patient with Schizoaffective disorder who was on Clozapine with stringent monitoring developed eo- sinophilia with eosinophil counts rising up to 2850, with a fall in neutrophil counts up to 2320, all of which was re- versed after stopping Clozapine. Conclusion: Clozapine induced eosinophilia should also be considered as one of the important side effects along with neutropenia and leukopenia. Along with neutropenia and leukopenia it might be a manifestation of undergoing immunological abnormality associated with Clozapine.

Background: Although methamphetamine (MA) use during adolescence has be- come associated with increased aggressive, violent, and criminal behavior in humans, there is a relative lack of empirical research substantiating any direct link between acute and re- peated exposure to the drug, and heightened aggression. There is also little known about ex- posure during adolescence and subsequent effects on aggression in adulthood. Objective: The study aimed to determine effects of a single dose and repeated administration of MA on aggression-related behavior in adolescent rats, and subsequent effects in early adulthood. Method: Male and female adolescent rats were administered saline (via intraperitoneal injection) or a single dose of MA (2mg/kg) on postnatal day (PND) 35 followed by the same dose twice a day from PND36 to PND45. By means of the resident/intruder test, aggression-related behavior was assessed in all rats following their single exposure, after completion of the final repeated exposure, and again in early adulthood (PND90) after 45 drug-free days. Results: Both a single and repeated exposures to MA generally decreased aggression-related behavior in the adolescent animals. However, when tested again in early adulthood, increased aggression followed their ado- lescent experiences. Conclusion: While the effects of MA during adolescence could have arisen from decreased aggression, in- creased anxiety or decreased play fighting, its subsequent effects during early adulthood suggested changes in the developing adolescent brain that resulted in higher aggression.

Background: Previous cross-sectional studies have concluded that the positive relationship between vitamin D status and cognition may reflect reverse causality, that is, low vitamin D status results from cognitive decline, associated behaviours and comorbidities, and not the reverse. The present study therefore investigated relationships between total 25-0H-D (25-0H-D3 plus 25-0H-D2) and 15 integrated scores of cognition and mood cognitively-normal, healthy elderly subjects. Methods: The study was cross-sectional and based in Adelaide, South Australia (lat: 34.93°S) during summer months of 2008. Participants, from the 0lder People, 0mega-3 and Cognitive health (EP0CH) Study (ACTRN12607000278437), were community-dwelling (N=387), 65 to 90 years (mean 73.1), 54% female and cognitively normal at baseline (MMSE>24). Blood sampling, cognition and mood testing at a single timepoint occurred from January to April. Participants were characterised by multiple biometric and clinical measures and bloods were analysed for 25-0H-D3 and 25-0H-D2, homocysteine, C-reactive protein and malondialdehyde. Results: Based on a cut-off of 75 nM 25-0H-D, 44% of participants were considered deficient. Fully adjusted models controlling for all parameters significantly associated with vitamin D status or cognition/mood measure demonstrated that 25-0H-D was significantly related to one cognition (Reasoning Speed, p=0.03) and two mood measures (General Positive Affect, p=0.02; Attentiveness, p=0.02). Additional relationships were present for sub-populations based on gender, vitamin D sufficiency and AP0E genotype. Conclusion: The positive relationships between vitamin D status and selected brain functions observed within this cognitively healthy cohort support a causal, protective role of vitamin D in brain function however, clini- cal substantiation is required.

Background: Quetiapine - an antipsychotic multidrug resistance protein 1 (MDR-1) substrate - has a large interindividual variability in its pharmacokinetics. Objective: In order to unravel the true effect of MDR-1 activity in the plasma levels of quetiapine, we studied the bioavailability of quetiapine in healthy subjects with different transporter activity. Method: Fifty-four Mexican mestizo healthy subjects, both male and female, with a median age of 32, were enrolled in a bioavailability study. Before starting the clinical trial, a flow cytometric daunorubicin-efflux assay was carried out in peripheral blood leukocytes to determine their MDR-1 phenotype. Plasma concentrations of quetiapine were monitored by an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC/MS/MS). The trial was approved by the Ethics Committee of our institution and by the Federal Commission for the Protection against Sanitary Risks (COFEPRIS) of Mexico. All subjects provided written informed consent before screening. Results: Subjects were classified as having high or low MDR-1 activity, according to the relative fluores- cence intensity of efflux of daunorubicin from their leukocytes. Although the maximum concentration (Cmax) of quetiapine in plasma was reached earlier in the high MDR-1 subjects, the overall pharmacokinetic profile was not different between both groups. Conclusion: MDR-1 activity in leukocytes does not affect significantly the bioavailability of a single dose of queti- apine in healthy individuals. Thus, interindividual differences in pharmacokinetics and subsequently clinical response to quetiapine cannot be predicted only by flow cytometric measurement of MDR-1 activity in leukocytes.