This study aims to investigate synaptic degeneration as a possible underlying mechanism for depression and whether antidepressants could alleviate the stated pathology.

Primary rodent hippocampal neurons treated with corticosterone were used as an in vitro model of depression. Toxicity of corticosterone was determined through the lactate dehydrogenase and caspase-3 activity assays. Immunocytochemical analysis of synaptic proteins was employed to investigate effects of corticosterone on synapses.

Neurotoxicity was observed in hippocampal neurons after treatment with corticosterone (10μM) for 24 hours. Aggregations of synaptotagmin and synaptophysin were observed 24 hours after treatment with corticosterone (10μM). Similar effects were observed after sub-lethal treatments with corticosterone (0.5μM and 1μM) for 48 and 72 hours. Pre-treatment for 1 hour with imipramine and escitalopram (20μM and 40μM for both agents) were able to alleviate these toxic effects.

These results suggest the involvement of synaptic degeneration in corticosterone-induced toxicity and that commonly used antidepressants are able to alleviate synaptic derangements. Taken together, synaptic degeneration could be a common pathway for neuronal demise occurring in AD and depression, which can be attenuated by antidepressant administration. Future research to elucidate the precise mechanism for the synaptic protective effect of antidepressants is warranted.

Generalized anxiety disorders (GAD) are characterized by persistent excessive worrying about minor hassles. GAD patients are high utilizers of medical services and medication.

According to an analysis of 21 double-blind placebo-controlled trials by of Hidalgo et al. (2007) highest effect sizes are reproted for pregabalin (0.50), hydroxyzine (0.45), venlafaxine XR (0.42), benzodiazepines (0.38), SSRIs (0.36), buspirone (0.17) and herbal medicines (-0.31). The question is how GAD is treated under conditions of routine treatment. This was studied in patients were admitted to inpatient treatment.

Psychotropic premedication and changes in medication during the inpatient treatment were analyzed in 107 patients.

Before admission, 27,1% of GAD patients got tricyclic antidepressants, 25,2% SSRI, 8,4% benzodiazepines, 7,4% atypical antidepressants, 1,9% anticonvulsants/pregabaline, 1,9% herbal drugs. Furthermore, 20,6% got betablocker, preferably because of hypertension.

During the inpatient stay changes in medication were made according to the clinical discretion of the therapist. At discharge 41,1% of GAD patients received SSRI, 23,4% tricyclic antidepressants, 22,4% pregabaline, 9,4% atypical antidepressants.

SSRI and tricyclic antidepressants play the major role in the drug treatment of GAD. Under clinical conditions there has been an optimization of treatment by increasing preferably the rate of SSRI treatments and of pregabaline treatment, while reducing benzodiazepine treatment and to some degree tricyclic antidepressants.

Hidalgo RB, Tupler LA, Davidson JRT (2007): An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol 21(8):864-872.

In Spain, consumption of psychotropic drugs is high and benzodiazepines represent 74% of the total. His prescription in primary care is very common and their use continues to grow. They are safe and effective drugs, but patients with prolonged use are elaborating the most adverse effects, particularly the dependency.

Descriptive ans cross-sectional.

Primary Health Care.

We seleted 202 patients treated with benzodiazepines, consecutive sample, belonging to the health center Los Barrio who were seen in consultation during 2009.

We conducted through a questionnaire that cointained the treatment and demographic characteristics.

We detect a frequency of use of benzodiazepines 9% (95% CI 4,7-12,1%). The profile of the consumer responds to middle-aged woman, with primary and housewives. Somatic diseases were associated in 72.6% (CI 67,2-77,5%) and had mental pathology at 59.7% (CI 53,9-65,3%). 35% (95% 29,6-40,6%) of prescribed benzodiazepines were clorazape dipotassium. Consumption was constant for over a year. The prescription from primary care represents 81% (95% 76,3-85,4%) and in 65% (CI 59,3-70,3%) is associated with other psychoactive drug.

In our area, highlights the prescription of benzodiazepines from primary care on demand and consumption during prolonged time. Interventions should be conducted on the prescription of benzodiazepines in medical and other interventions for patient support.

The prodromal syndrome in schizophrenia can be correlated with a series of neurobiological risk factors, the obstetrical traumas having an important role. The antipsychotic therapy at the male patients with obstetrical traumas in personal medical history can amplify the risk of cerebral structural changes.

We have studied 12 male patients (age 18-20 years), with prodromal schizophrenia syndrome or ARMS, negative symptoms, cognitive disabilities and poor social cognition. All the studied patients present obstetrical traumas in medical personal history, soft extrapyramidal symptoms, facial immobility and facial incapacity to express emotions (behavioral marker for poor social cognition and frontal-amygdala disconectivity). We administered aripiprazole (5mg/day) for 12 months associated with psychokinetotherapy technics, a series of facial mobility standard exercises.

These patients were evaluated at 6 and 12 months with PANSS, GAF, BARNES scales. The final results are: on the PANSS scale the evolution of negative and cognitive symptoms was ameliorated. The facial mobility and the capacity of emotional expression are also significantly ameliorated. The cognitive abilities and the level of social cognition are evaluated as very good. The extrapyramidal symptoms evaluated on the BARNES scale are not amplifying during the treatment.

The facial imobility and the facial incapacity to expressed emotions may be a clinical marker for neurodevelopmental abnormalities in the schizophrenia prodrome. Aripiprazole associated with the psychokinetotherapy technics improve in a significantly way the prodromal symptoms of schizophrenia at the male with obstetrical traumas in medical personal history.

The hypofrontaliety syndrome and the hippocampal alterations are correlated with the dopamine deficit secondary to D2 receptors blockade by the antipsychotic substances. The dopamine deficit amplifies the cognitive deficit, which is an important predictor for poor outcome in schizophrenia. The psychopharmacological action of aripiprazole is a dopamine modulator compared to haloperidole which is a highly potent D2 receptors blocker.

We have studied 3 groups, each consisted of 5 male adults Winstar rats each (200-250g), held through the study in temperature, humidity, food and ambient stressless conditions: N1 - control group; N2 - intraperitoneal administration of haloperidol (equivalent of 3mg); N3 - administration of aripiprazole (equivalent of 10mg). After 14 days, the rats were sacrificed and sections of their frontal cortex and hippocampus. The sample brain was histopathologically processed.

Compared with control group N1, the rats of group N2 (haloperidol) have shown significant alterations in frontal cortex (neuronal loss, pinocytosis and neuronal depopulation in III, IV and VI layers) and hippocampal areas (neuronal loss). The rats of group N3 (aripiprazole) have shown minimal, non-significant changes in frontal cortex and minimal loss in hippocampal areas.

The decrease of neuroprotection realised by haloperidole in frontal cortex and hippocampal areas suggest the aggravation of the structural cerebral abnormalities comparative to the aripiprazole action which presented a high level of neuroprotection.

After initial psychological treatment patients with Obsessive Compulsive Disorder are treated with selective serotonin re-uptake inhibitors (SSRIs). Treatment may later be augmented with clomipramine and/or an antipsychotic. This study focuses on the biological treatment received after, or in parallel to, the psychological.

To collate and evaluate the levels of biological treatment currently received by OCD outpatients in the Bedford east catchment of Bedfordshire and Luton mental health and social care partnership NHS trust.

In particular we wished to establish how many of the patients were receiving an atypical antipsychotic as well as maximal SSRIs.

An anonymised database of 45 outpatients with symptoms of OCD was prepared. Treatment groups were identified and the percentage of the cohort occupied by these groups was calculated. The possibilities for increased medication were noted.

Only 7% of patients had one SSRI, at maximum dose, plus clomipramine, plus an antipsychotic, even here the dosing was not maximal. Another 7% had a second SSRI instead of the tricyclic and may benefit from a trial of clomipramine. In the remaining 86% there was further scope for increasing biological therapy.

Relatively few of our patients were having maximal SSRI treatment and an antipsychotic, despite guideline recommendations.

There is plenty of leeway for the escalation of patients’ biological therapy. Given the number of patients currently receiving secondary care, an escalation of their treatment should result in better patient health and a subsequent increase in discharges.

Numerous reports have pointed out the risks adverse hematological effects associated with psychotropic drugs. We report a severe case of thrombocytopenia in a healthy 79 year-old patient happened after mirtazapine administration. Suggesting an immune mechanism.

Report a case of mirtazapina-induced inmuno tromnbocitopenia, review of bibliography and to propose monitoring and management strategies.

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Care report: PPD (n°HC 16996) treatment with mirtazapina 15 mg/d.Clinical: equimosis cutaneous multiple. Without focalidad. From the point of view etiológico discards organicity (aplasia megacariocítica, processes linfoproliferativos and infectious). An analytical previous examination supports normal platelets until April, 2009, in February the dose doubles from 15 to 30 mg (of mirtazapina). Fatal conclusion: exitus for hemorrhage intracraneal in September, 2009. Clinical judgment: Several Trombopenia, uncertain origin.

Literature review: The first well-documented case of mirtazapine-induced immune thrombocytopenia is “Glycoprotein IIb/IIIa complex is the target in mirtazapine-induced immune thrombocytopenia” (Blood Cells, Molecules, and Diseases, 2003).The analysis “Proportion of drug-related serious rare blood dyscrasias” (American Journal of Hematology, 2004) suggests that a substantial fraction of blood dyscrasias may be attributable to drug therapy.

Hematologic side effects from psychotropics may present as serious or even fatal consequences of treatment. Incidences of hematological changes for antidepressants were much lower (about 0.01%).

Before initiating therapy with antidepressants, a carefully case history, with special attention to heart disease, family record and medical treatments, should be obtained. Clinical best practice regarding the safe and effective use of psychotropic medications is based on appropriate monitoring of drug-related problems.

HepatitisC, a viral infection,is one the most important causes of the chronic liver disease.As a consequence of interferon alpha 2a treatment of chronic hepatitis C, there is a number of side effects:headache, muscle aches, exhaustion, weight loss, hair loss, irritability, insomnia and other.

The aim of this study was to establish the frequency and the level of insomnia in patients with chronic hepatitis Cthat were treated with Interferon and Ribavirin for 24 weeks. We also evaluated the efficacy of Mirtazapin in the treatment of insomnia,in these patients.

30 patients in all, with serologically and patohistologically established diagnosis of hepatitis C, were included in this study. These patients were treated with 180mg of Pegasus interferon injected subcutaneously, once a week. They also received 800mg of Ribavirin perorally a day. This treatment lasted 24weeks.

PITTSBURGH SLEEP QUALITY INDEX-PSQI was used as a measuring instrument for the evaluation of the level of insomnia.All the patients tested were at the beginning of the Interferon treatment,and after 3,5,and 7 months of treatment.Patients with diagnosed severe sleeping disorders were given small doses of Mirtazapin-15 mg every evening for 6 weeks.

On the initial rounds,two patients had a PSQI score higher than 5.After a three month long Interferon treatment,five patients had a PSQI score higher than 5. After 7 months from the beginning of interferon treatment, ten patients had a PSQI score higher than 5, which indicates a significant sleeping disorder.

The administration of small doses of Mirtazapin/15 mg every evening shows useful effects in reduction of sleeping disorders caused by the Pegasus interferon treatment in patients suffering from chronic hepatitis C.

To highlight significant increase in serum creatine kinase(CK) without occurrence of Neuroleptic Malignant Syndrome (NMS), during treatment with atypical antipsychotics (Olanzapine and/or Quetiapine) in a patient with paranoid schizophrenia and the absence of recurrence on treatment with Clozapine.

Clinical biochemistry data was collected at regular intervals to monitor the relevant changes in serum CK levels,of a patient with paranoid schizophrenia who was an inpatient in our low secure forensic psychiatric ward in 2008-09. We also did a literature search in Pubmed and Google with the key words ‘Increase in serum Creatine Kinase’ and ‘antipsychotics’.

Our patient developed a significant increase in serum CK levels with Olanzapine and also Quetiapine without the occurence of NMS. The CK levels came back to normal on stopping these medications.Following this he was initiated on Clozapine and has remained stable for almost a year without a significant increase in serum CKlevels. There have been previous case reports on the use of Clozapine in patients with significant increase in CK secondary to other antipsychotics, without recurrence in elevation of creatine kinase.

Clinicians should be aware that Clozapine can be considered as a treatment option in patients presenting with (non NMS) significant increase in CK due to other antipsychotics. Clozapine has been known to cause Neuroleptic Malignant Syndrome and previous literature suggests Clozapine-induced NMS may present with fewer extrapyramidal side effects and a lower rise in Creatine Kinase levels.

To evaluate risperidone long-acting injectable (RLAI) versus placebo in prevention of mood episodes in adults with bipolar I disorder.

A 12-week open-label period with RLAI (N=585) was followed by an 18-month randomized, double-blind period with RLAI (25, 37.5 or 50 mg/2 weeks; N=137) or placebo (N=140); a third group (N=138) was randomized to olanzapine for reference and exploratory comparisons. Primary efficacy endpoint: time to relapse of any mood episode for risperidone LAI vs. placebo in the double-blind period (Kaplan-Meier analysis). Relapse was defined by criteria including DSM diagnosis, further treatment, hospitalisation, or Clinical Global Impression score ≥4 combined with YMRS or MADRS >12.

Dosing was fixed during the double-blind period at patients’ final open-label dose (25 mg, 66%; 37.5 mg, 31%; 50 mg, 4%). Time to recurrence (any mood episode) was longer with RLAI versus placebo (log-rank test stratified by region and patient type, p=0.062; stratified by region only, p=0.032); the difference was significant for time to recurrence of elevated mood episodes (p=0.005) but not depressive episodes (p=0.587). Discontinuations due to adverse events (AEs) occurred in 2% of patients in the open-label period, and 4% and 1% in the RLAI and placebo groups, respectively, in the double-blind period. The most frequently reported AE in the open-label period was insomnia (15%). During double-blind treatment, the most frequently reported AEs with RLAI were weight increased (24%; placebo, 9%) and insomnia (16%; placebo, 17%).

Table 1.Type of recurrence

RLAI significantly delayed time to relapse of elevated mood episodes and was well tolerated.

The current paper reports on a double-blind, randomized study of the role of lamotrigine as an augmentation agent to haloperidol deaconate in the treatment of out patient's schizophrenia with verbal resistant hallucinosis.

Three hundred fifty patients were studied. The patients were then randomly divided into two groups on 175 subjects in each group. First group patients received either haloperidol deaconate 100 mg in month intramuscular and lamotrigine 150-200 mg in day per so for 12 weeks. Second group patients were given haloperidol deaconate 100 mg in month intramuscular and placebo per os for 12 weeks. The expressiveness of psychopathology was estimated on PANSS.

75 (44%) of the 168 first group participants responded by 12 weeks, versus one (0.6%) of the 167 second group treated participants.

Our data suggest that haloperidol with the combination of lamotrigine was more effective than placebo.

To describe the prevalence of the different phenotypes for genes CYP2C19 and CYP2D6 in a population of first episode psychotic patients and its relation to clinical outcome, dose and race during a 2 years follow-up period.

Patients with a first psychotic episode were recruited form January 2006 to January 2009. Clinical and treatment related variables were registered at baseline and during a 2 years follow up period. CYP2D6 and CYP2C19 genotype were determined.

From the 48 initially recruited patients, 21 (44%) were genetically determined. Amongst them, 13 subjects (62%) presented an efficient phenotype for the CYP2D6, 3(14%) presented an increased phenotype (ultra rapid metabolizers), 3 (14%) were intermediate metabolizers and 2 (9%) were poor metabolizers. All the patients presented an efficient phenotype for CYP2C19. The patients were Caucasian (71%) and other ethnic groups (29%). Patients were treated with risperidone (42,85%), olanzapine (47,61%), clozapine (4,76%) and aripiprazol (4,76%).

Most of the patients presented an efficient phenotype. However a considerable proportion were ultrarapid or poor metabolizers. Due to the small sample size, differences between ethnic groups, relapse or drug intolerance could not be found, however first glance differences were not apparent. Further studies using larger samples and considering other confounding factors would be needed.

On average dose of Risperidone 5.1 mg pro die there was found 18.2% reduction on the Positive syndrome scale after two months. Negative syndrome scale showed improvement of 20.5%; General psychopathology scale was reduced for 15.7%. Finally, total PANSS score was reduced 17.2%. Results were also discussed according to sex, age, illness duration and schizophrenia type.

Therapeutically efficacy of Risperidone has been shown on the positive, as so as the negative schizophrenia symptoms. Better results were in disorganized form of schizophrenia then the paranoid form.

Psychiatry makes use of a wide range of medications, such as anti-epileptic drugs in the treatment of affective disorders, impulsive behavior or epilepsy. The authors aim to present a particular clinical presentation in order to reinforce the awareness of the side effects of our prescriptions.

54 year-old man, epileptic, medicated with Sodium Valproate (VPA) and Phenobarbital, admitted to our hospital due to insomnia, irritability and aggressiveness with two weeks of duration. Early evaluations showed disorientation, slow and poor speech, and prejudice ideas towards his family. Disequilibrium, asterixis and slurred speech imposed evaluation by Neurology. Analytic evaluations demonstrated high phenobarbital and ammonia levels. Both anti-epileptics were slowly withdrawn, with clinical resolution.

VPA may be associated with elevation of ammonia levels, and eventually with encephalopathy without evidence of liver failure. There is a wide range of clinical presentations of hyperammonemic encephalopathy ranging from decreased level of consciousness, irritability, agitation, focal neurological deficits, cognitive slowing, vomiting, drowsiness, and lethargy. On the other hand, high doses of phenobarbital may have similar presentations which could be potentiated by VPA.

There was a good correlation between the fall in serum ammonia levels, clinical improvement, and anti-epileptics withdrawal, suggesting the implication of medication in this clinical picture. The case illustrates the need to check ammonia and anti-epileptic levels, and to consider this diagnosis in patients taking VPA and Phenobarbital who present with new neuropsychiatric manifestations.

To compare the efficacy and safety of the intramuscular formulations of ziprasidone and haloperidol in treating agitation in schizophrenic patients attended in an emergency room.

Consecutive patients were alternatively assigned to receive 20 mg of IM ziprasidone or 10 mg of IM haloperidol. Efficacy measures were improvement in Behavioral Activity Rating Scale (BARS), in the sum of five items of the Positive and Negative Syndrome Scale that focused on agitation (PANSS-A) and scores on the Clinical Global Impression improvement scale (CGI-I), obtained 45 minutes and 2 hours after the IM medication. Tolerability assessments included changes in ECG, monitoring of vital signs and register of adverse events.

Finally 18 patients (13 men, mean age 40.8 ±10.2) were included in the analysis of data. At arrival in the emergency room, there were no differences between ziprasidone (Z) and haloperidol (H) groups in age, mean QTc length, mean BARS and mean PANSS-A scores. Analyzing the global sample there was an improvement in agitation scores. No significant differences were found between the groups in change of BARS and PANSS-A scores, in CGI-I scores or in the variation of the length of QTc interval at two hours. No serious adverse events were reported.

In spite of the small sample size, both treatments ziprasidone IM and haloperidol IM seems to be similarly effective for the management of psychotic agitation in the emergency room. Both were well tolerated. Lengthening of QTc interval due to ziprasidone IM had not been found in our sample.

Venlafaxine (V) is a SNRI metabolized primarily by the highly polymorphic cytochrome P4502D6 enzyme (CYP2D6) in O-desmethylvenlafaxine (ODV), the main active metabolite. Four CYP2D6 metabolizer phenotypes have been identified: poor (PM), intermediate (IM), extensive (EM) and ultrarapid (UM). Approximately 5-10% Caucasians are PMs; in these individuals metabolism of substrate is decreased and adverse clinical effects may be expected. The effectiveness of pharmacogenetic tests is controversial because the association between plasma levels of V/ODV and side effects is not attested.

We discuss the association between CYP2D6-genotype and Venlafaxine clinical effects.

We will recruit Caucasian patients aged 18 to 65, eligible for Venlafaxine treatment, satisfying DSM-IV criteria for major depressive episode, dysthymia or depressive adjustment disorder. Exclusion criteria will be: pregnancy, acute suicidality, alcohol/substance abuse, concomitant/prior antidepressive treatment in the previous 3 months. We will assess patients’ age, gender, DSM-IV diagnosis, Venlafaxine dose, concomitant pharmacological treatment, BMI, BP, tobacco use, liver and kidney functionality. Clinical response and side effects will be monitored using CGI, HAM-D and SIDE at T0 (onset), T1 (1 week later) and T2 (6 weeks later).

The patients will be analyzed for the presence of 16 CYP2D6-genotype variants by INFINITITTM CYP2D6 assay which utilizes AutoGenomics proprietary film-based microarray technology.

We expect to find out a correlation between CYP2D6-genotype, Venlafaxine dose and clinical response to treatment.

We will investigate whether a pharmacogenetic test prior to treatment can be useful in clinical practice to detect a proper Venlafaxine dosage or to switch to a different drug.

The Clinic of Psychiatry and Psychotherapy of Nuremberg established rTMS as a standard tool in the treatment of patients with depressive disorder since 2001. The stimulation protocol was modified in October 2008 to match the current standard procedure reported in the literature. The pulse number was heightened form 800 to 2000 per proceeding. This study examines the effects of the modified stimulation protocol and contrasts the results with the former stimulation efficacy.

The authors compared patients suffering from depression, who were treated by rTMS with 800 pulses/day and with 2000 pulses/day. The results of psychological examinations (MADRS, HAMD, BDI, grading, cognitive screening) prior to and afterwards the three-weeks-rTMS-cycle were submitted. Variance analyses were used for statistical reason.

The subsamples were comparable by sex, age, premorbid intellectual level as well as by self- and other-rated depression severity at treatment beginning. Statistical analyses showed a significant reduction of the depression symptoms in both stimulation protocol groups. Solely the HAMD score reduction in the 2000 pulse sample exceeded the decrease in the 800 pulse sample. Analogically the grading of human functions partly differed depending on the sample affiliation. Concerning the screening of cognitive functioning neither group was impaired.

rTMS still seems to be a well-functioning tool in the treatment of depressive disorders in the bounds of daily psychiatric health care. Although the modified stimulation protocol didn’t show many advantages in respect to improving depression symptoms, the results indicate the continual adjustment of the stimulation parameter to meet the current standards.

Tardive dyskinesia (TD) is a difficult-to-treat condition. The presence of genetically abnormal D2 and D3 dopamine receptors is associated with increased like hood of TD in patients with schizophrenia. We present a case of a patient with TD and genetically abnormal dopamine D3 receptors with chronic schizophrenia, treated successfully by sertindole.

A 47-year old male with history of chronic chizophrenia was assessed clinically by means of SCID IV, PANSS and AIMS, and was genotyped for DRD3ser-gly and 5-HT2C receptor gene polymorphisms.

The patient suffered from an exacerbation of positive and negative psychotic symptoms and TD. He was also found to be DRD3ser-gly heterozygous. He had been suffering from TD for two years, developed by chronic administration of haloperidole and resperidone. A trial with quetiapine failed to ameliorate his TD and psychotic symptoms, whereas a successive trial with clozapine induced life-treating hematological side effects. After the administration of sertindole (16mh/day) his psychotic and TD symptoms remitted (PANSS:29, AIMS : 0). One year later his level of improvement was wholly preserved.

Sertindole might be beneficial for the treatment of TD in patients who have genetically abnormal D3 receptors.