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.

To assess how effective paliperidone is for psychotic symptoms of patients with HIV/AIDS and to assess neuropsychiatric, liver and metabolic side effects associated with paliperidone.

The participants were 9 patients with HIV/AIDS who had psychotic symptoms. These patients were assessed with the brief psychiatric rating scale (BPRS), and the cut-off point was 21. Neurocognitive impairment was assessed with the mini-mental state examination (MMSE), using a cut-off point of 28. Hemathological tests serum transaminases were performed to determine liver function and metabolic syndrome study was implemented as defined by the National Cholesterol Education Program. All patients started taking medication with paliperidone up to 3-9 mg/kg. After a one, three and six-month period of treatment, the patients were reassessed using UKU side-effect rating scale, BPRS, hemathological tests and a full metabolic symdrome study.

Paliperidone is an effective antipsychotic drug: only one patient had psychotic symptoms. Paliperidone didn’t cause any side-effect in none of the nine patients, had a good profile of tolerance regarding liver function, any patient suffered changes in hemathological tests serum transaminases and there wasn’t any significant change in metabolic parameters of the nine patients. Any patient suffered cognitive impairment using MMSE.

Paliperidone can be considered a highly effective treatment for patients with psychotic symptoms and HIV/AIDS. This drug has a good antipsychotic profile, doesn’t affect liver function, doesn’t cause neuropsychiatric side-effects and doesn’t cause metabolic syndrome after a six-month treatment. These findings support this drug as first choice treatment of this kind of patients.

To value medication adherence and discontinuation of treatment among first episode psychosis patients (FEP) treated with quetiapine or extended release of quetiapine (XR).

Patients with a first episode of psychosis, age 26+/- 2(N=24) were randomly assigned to treatment with quetiapine 300 mg for twice daily(n=12), or quetiapine rp 300mg/day in one administration daily(n=12),for a 6 months period

The drop-out of patients for any cause thought the 6-months study was:2 for quetiapine and 6 for quetiapine XR. However, symptom reduction were the same in both groups.

To conclude: According to a interview conducted with patients, there is more compliance to therapy for patients treated with quetiapine XR, they prefer to be given a day instead of twice daily administration. Fewest drop-out with quetiapine XR is probably also due to steady-state quetiapiana rp is reached more quickly and better maintained, resulting in greater clinical control.

Transcranial magnetic stimulation (TMS) is a novel treatment for patients with depressive disorder. TMS is a noninvasive method to excite neurons in the brain: weak electric currents are induced in the tissue by rapidly changing magnetic fields. We report two cases suffering from pharmacoresistant depression and the efficacy of TMS in their treatment.

The first case was a 45-year-old male Caucasian patient suffering from unipolar depression and the second case was a 53-year-old female Caucasian patient suffering from bipolar depression.

The patients were under treatment with SSRI, SNRI, NASSA (one medicine or combination of them) without any or minor improvement.

So TMS sessions were performed daily in both patients for a period of one month.

A marked reduction of depressive symptoms was demonstrated in both patients. Thus, TMS sessions may help the pharmacoresistant depression by minimizing physical and subjective discomfort. Furthermore TMS appears to be safer and better tolerated than many others medicines or electroconvulsive therapy. Further studies are needed in order to investigate the effect of TMS in resistant depression

To describe the socio-demographic and clinical characteristics, complications and therapeutic response of patients treated with ECT in the Psychiatric Unit of the General Hospital from University of Campinas-Brazil (1993-2007).

All medical records of the patients who underwent ECT were reviewed and compiled for subsequent statistical analysis by SPSS program.

156 patients were studied. Ages ranged from 13 to 78 years-old, with a mean of 39.9±17.8 years-old [95% CI: 37.2-42.8 years]. There were 64 (41%) men and 92 (59%) women. The main diagnostic categories of the patients submitted to ECT were: schizophrenia (33.9%), depression without psychotic symptoms (30.8%), depression with psychotic symptoms (39.1%), bipolar disorder (18.6%) and schizoaffective disorder (3.2%). Complications occurred during the procedure in 98 cases (62.8%), immediately after the application in 85 cases (54.5%) and three days after the last session in 33 cases (21.2%).

The response to ECT was: good response in 132 (84.6%) patients, unchanged psychiatric symptoms in 14 (9%) patients and worsening in 3 (1.9%). The mean time of permanence inside the Psychiatric Unit was 57.5±38.2 days [95% CI: 51.4-63.2 days].

Table1 1: Complications during the procedure

Table 2: Complications immediately after the proce

Table 3: Complications at least three days after t

The diagnostic categories for which ECT therapy corresponded to those described in the literature. Data suggest that the incidence of complications was moderate and the response to treatment was positive in most cases, reinforcing the importance of this therapeutic method for the treatment of patients with severe mental illness.

To determine the outcome of patients who underwent ECT in a Brazilian General Hospital between 1993 and 2007.

Telephone contact with all patients (or their relatives) who were submitted to ECT during psychiatric hospitalization in HC-Unicamp-Brazil. Data were compiled for statistical analysis at SPSS.

There were 53 successful telephone contacts (33.9% of 153 patients who underwent ECT). Losses were due to changes of telephones/addresses. No refuses occurred. The mean time between the procedure and the contact was 55.4 months (3-170). Twenty patients (37.3%) and 37 relatives (69.8%) were interviewed. Most were women (60.4% n=32), 4 were inpatients by the occasion of the call and 4 died. The mean age was 42.9±19.4. The assessments of current mental state by patients were: excellent in 5-9.4% cases, good in 12-22.6%, poor in 2-3.8%. The evaluation by family members was: excellent in 11-20.8% cases, good in 11-20.8%, poor in 7-13.2% and very poor in 5-9.4%. In 42 cases (79.2%) the patient was still under psychiatric treatment (taking psychotropic medication in 39-73.6%). In 28 cases (54%) there was need for new admission in a psychiatric inpatient ward. In 38 cases (74%) the patient reported knowing that he/she had undergone ECT, and only in 5 cases (9.4%) there was a lasting side effect of treatment reported, which was change in memory.

Data of the evolution of patients corroborate the importance of treatment with ECT for severe mental disorders, and also shows the low rate of long-term complications related to the procedure.

To explore the relationship between symptomatic and functional outcomes in a five week, double blind, fixed dose, placebo controlled study in adults (age 18-65 years) with ADHD.

Post hoc-analysis of a five-week, double-blind (DB), parallel arm, placebo-controlled trial in adult subjects with ADHD (DSM-IV) and a Conners’ Adult ADHD Rating Scale (CAARS) score >= 24 at baseline. Subjects were randomized to OROS-MPH (18mg, 36mg, 72 mg/day) or placebo. Symptomatic outcomes were assessed by total CAARS score (TCS). Functional outcomes were assessed by Sheehan Disability Scale (SDS) total score and subscales (work, social life and family life), quality of life by Q-LES-Q total score. The relationship of CAARS with SDS and Q-LES-Q was assessed by Pearson's partial correlation analysis, with adjustment for baseline scores of CAARS, SDS, Q-LES-Q, CGI-S, age, sex, and randomization group.

401 subjects were enrolled (54.4% male, mean (SD) age 34 (10.24) yrs). There was a significant treatment effect as measured in TCS at DB endpoint for all OROS MPH treatment groups compared to placebo (P< 0.05). The absolute value of partial correlations of symptomatic outcome with functional outcomes and quality of life varied between 0.54 and 0.36; all correlations were significant (p< 0.0001). These correlations were compared between the functional and quality of life measures, but none differed significantly.

Subjects’ symptomatic improvements during treatment with PR OROS MPH are reflected in improvements in their vocational and social function as measured by the SDS, and quality of life.

For the investigation well be study binding of 3H-PK11195 with mitochondrial membranes prepared from different brain regions and the binding of 3H-PK 11195 with peripheral blood trombocytes were separated from fresh blood.

A comparative studies of 3H-PK11195 binding to PBR from brain cortex, caudatus and cerebellum in alcoholics (A) and non-alcoholics (NA) post-mortem showed that properties of PBR are not identical in different brain regions. The largest density of binding sites was found in brain cortex, the less one - in cerebellum and in nucleus caudatus (in A and in NA). The highest binding affinity for the PBR was found in nucleus caudatus than for PBR in brain cortex and in cerebellum (in A and in NA). Study of the properties of PBR in NA (non-alcoholic) and A (alcoholic) in different brain structures showed the reduction of the affinity and increasing of PBR binding sites in A. We found similar alterations of PBR in peripheral blood trombocytes that suggests close connection between central and peripheral benzodiazepine receptor systems

Complex central actions of ethanol could include effects on neurosteroid production mediated through peripheral types of benzodiazepine receptors located in mitochondrial membranes in nervous tissue and plasmatic membrane of trombocytes.