Clinical studies on cognitive effects of second generation antipsychotics produced disappointing findings probably due to the heterogeneity of the clinical populations under investigation, as well as to poor sensitivity of neurocognitive indices. Event-Related Potentials (ERPs) provide a functional measure of electrical brain activity time-locked to discrete stages of information processing. They have been widely used as putative biological markers of cognitive abnormalities in schizophrenia and represent useful indices in the investigation of the cognitive effects of psychotropic drugs.

The present study investigated the effect of risperidone, haloperidol and placebo on N1 and P3 in male healthy subjects.

ERPs were recorded during a three-tone oddball task in which target, standard and rare-nontarget tones were randomly presented. Subjects had to press a button when hearing a target tone. Amplitude and topography of the ERP component maps at peak latencies were compared across conditions. If a significant drug effect was obtained, changes in the cortical sources of the corresponding ERP component were analyzed using Low-Resolution Electromagnetic Tomography (LORETA).

The amplitude of N1 for attended stimuli and of P3 for rare-nontargets (P3a) was significantly increased only by risperidone. No significant change was observed in overall topographic features and in LORETA cortical sources of the same components. No significant drug effect was demonstrated for the latency of all the investigated components and for P3b amplitude.

Our findings suggest that risperidone has a favorable effect on early attention processes and automatic attention allocation.

Tricyclic antidepressants (TCAs) are more likely to cause cardiovascular and neurological toxicity than compared to Selective Serotonin Reuptake Inhibitors (SSRIs).

In a prospective hospital-based cohort study, we addressed the question of severity and outcome of antidepressant self-poisonings in patients who attended the Loghman-Hakim Hospital Poison Center. The severity was judged by impairment of consciousness, the outcome criteria were the requirement of inpatient treatment and endotracheal intubation as well as mortality. The aim of the study was to find out if TCA intoxications require more therapeutic efforts than SSRI intoxications.

From 28 March to 20 May 20 2006, all patients presented to the Poison Center were documented using preformatted forms by three trained nurses blinded to any study hypotheses. From 3.578 intoxications, a number of 334 patients with antidepressant or lithium self-poisoning was identified (9.3% of all poisoning cases; 233 females, 101 males; median age 24 years, min 13, max 70).

As compared to SSRI single-substance intoxications (n = 17), TCA single-substance intoxications (n = 73) were associated with (1) a significantly lower level of consciousness (p = 0.005); (2) a significantly higher admission frequency (80.8% vs. 35.3%; p < 0.001) and (3) a higher intubation frequency (13.7% vs. 0%; p = ns). SSRI multiple-substance intoxications were associated with a significantly lower level of consciousness than SSRI single-substance intoxications (p = 0.042), while there was no significant difference between TCA multiple- and single-substance intoxications.

This study suggests that an overdose with SSRIs results in a more favorable clinical outcome than an overdose with TCAs.

Clinicians often prescribe depot medication assuming that it will improve medication adherence. Few studies have systematically explored patterns of non-adherence with depots or whether the beliefs and attitudes that influence adherence are similar to those that affect acceptability and adherence of oral medication.

To investigate adherence with and attitudes towards depot medication.

1. (1) To explore non-adherence with depot medication.

2. (2) To examine key determinants of acceptability of depot versus oral treatment.

Patients with a severe mental disorder receiving depot medication completed a face to face interview incorporating several ratings, including the Beliefs about Medication Questionnaire (BMQ). Frequency of depot injections and adherence rates were recorded over two years. Data were compared with that from similar patients receiving oral medication.

Full adherence with depots was only slightly higher than with oral medication (77% v 71%). Although side effect ratings were correlated with the BMQ-Concerns sub-scale (r.29) the most robust single predictor of adherence was a high score on the BMQ Necessity scale (r .46). In both oral and depot medication groups the combination of Low Necessity and High Concerns predicted poor adherence (Odds Ratio 4.21).

Depot medication is a necessary but not sufficient treatment for many non-adherent patients. Our findings suggest that barriers to acceptance of depots vary little from those that impair adherence with oral antipsychotics and that interventions to modify these beliefs are as important as the mode of delivery of treatment.

Clozapine treatment has been recognized as a superior treatment in schizophrenia. Clozapine treatment has also be accompanied with several rare but severe adverse events, like neutropenia, agranulocytosis, myocarditis, pericarditis and polyperositis. We report a patient that suffers from hyperleucocytemia, eosinophilia and pleuritis, due to clozapine treatment, the adverse events disappeared after a switch to aripiprazole.

To review the literature on reports on pleuritis and polyserositis in order searching for guidance in these clinical situation, like the need tot interrupt the medication, the prognosis and if rechallenges are reported. Another objective was to discover if something is known about the underlying mechanism.

To review the literature, we used the following terms: clozapine, treatment, immunological reaction, neutropenia, leucopenia, epicarditis, polyserositis, pleuritis, pleural effusion, underlying mechanisms, risk factors.

A literature search was performed in Pubmed® and Embase Psychiatry® in the period longing from 1972 till October 2010

Risk factors as well as the underlying mechanisms offer no guidance for dealing with the clinical critical situations.

There are only a few reports on pleural effusion, there are some reports on pleural effusion in combination with epicarditis, there are some reports on polyserositis including pleural effusion.

No rechallenges are reported of clozapine on pleural effusion.

There is no information in the literature on the risk that a pleuritis will extend to other organs, like the heart and the liver, when continuing the clozapine treatment.

Hypotheses about the underlying mechanism will be presented. A program of additional diagnostics will be described

Patients with severe mental illness are at increased risk of cardiovascular disease because of lifestyle, co-morbidity and medication effects.

The aim of this audit is to ascertain the regularity of blood tests (u&e's, fasting blood glucose, lipid profile)among patients on Antipsychotic medication under North Durham Psychosis team.

According to audit standards (based on NICE guidelines-Schizophrenia and Maudsley guidelines), All patients on antipsychotic medication should have Urea & Electorates, Fasting blood glucose and Fasting Lipid profile done at least once a year. All 67 patients in North Durham Psychosis Team were included. We searched for these readings between 1st September 2008 to 30th August 2009 in patient records. Of the 67 patients, notes were retrieved for 50. Of the 50, 46 were on antipsychotic medications.

Of 46 patients, 58% had urea & electorates, 58% had Fasting blood glucose and 46%had fasting lipid profile recorded.

Because of lifestyle, co-morbidity and medication effects, patients with severe mental illness are at increased risk of cardiovascular disease. Our audit identified a need for systemic assessment of physical health with appropriate blood investigations and follow up with appropriate management plan (lifestyle education, lipid modification therapy) which are critical to minimising risks and preventing long term adverse health consequences. This results may also reflect a lack of communication between primary care and secondary care as the physical health for these clients are primarily managed by General Practitioners. It may be that these investigations are conducted but not communicated to secondary care.

A single or more than two Antipsychotics above the recommended dose is known as High Dose prescription. Regular review of these patients is necessary due to the potential side effects.

Reviewing of the HDAT prescription and monitoring process between June and July 2010.

Standard - TEWV NHS Trust guidelines suggest that patients on High Dose Antipsychotics should have

1. 1) Documentation of Medical history and Physical examination at the Well Being Clinic

2. 2) Medication Alert on PARIS (Trust intranet)

3. 3) Documentation on Visual display Board

4. 4) Regular Blood tests and ECG

Referring Case notes, PARIS entries and Visual Display board.

Of the 8 patients at Well Being Clinic, Male −4, Female −4.

Details of medical history & physical examination were recorded for all patients.

Medication alerts were documented on PARIS.

Visual display board was up to date with dates for bloods & ECG. Bloods tests - FBC,U&E, LFT, Lipids, Blood glucose & Prolactin. The tests were done at baseline, repeated on 1,2,3,6,9,12 months & at dose increment. All the blood tests & ECGs were up to date. 2 male patients were discharged following dose review. Once the patients were discharged, the alert on PARIS was removed.

1 male patient was referred to GP for physical examination as the patient was quite obese. Prolactin levels of 2 patients were high. They were followed up with further blood investigations.

• • Side effect monitoring scales like “LUNSERS” to be used

• • Arrange educational meetings to the Support workers.

It is not uncommon that patients suffering from psychosis reveal a comorbidity of attention-deficit/hyperactivity disorder (ADHD). There is lack of evidence how to treat these patients as amphetamines are considered contraindicated for patients with psychosis.

To provide the case history of such a comorbid patient.

A 21 year old male patient is committed to the psychiatric clinic displaying massive assaultive behavior. He has been consuming cannabis heavily over the last few years; for a couple of days now he has been displaying psychotic features. Occasional aggressive outbursts have been known to occur since childhood. The patient’s own accounts and those of his relatives also make an ADHD highly probable. During inpatient stay there are massive, dangerous aggressive assaults without detectable reasons along with complete disorganized behavior and massive thought disorders on three different occasions. Medication with very high doses of antipsychotics, benzodiazepines as well as mood stabilizers could not prevent the patient from his aggressive outbursts. The lack of efficacy of conventional treatment led us to propose to the patient a trial dose of methylphenidate, which calmed the patient instantly. Psychotic symptom, aggression and symptoms of ADHD improved during further treatment with methylphenidate, which was replaced by atomoxetine later. The patient was dismissed on a regimen of atomoxetine, Risperidone and Valproate and was well at a follow-up investigation 2 months later.

The use of methylphenidate in patients with adult ADHD comorbid with psychosis seems to be possible and helpful on some occasions.

Depression is associated with high rates of comorbidity with other psychiatric disorders. Adherence to antidepressant medication regimens has been associated to different factors. Few studies have analyzed the influence of comorbid psychiatric disorders and adjunctive pharmacological treatments on antidepressant adherence.

The study evaluates the association of comorbid psychiatric disorder and pharmacological treatments with adherence rates to antidepressants in a large sample of depressive outpatients.

3606 depressive patients were included in a cross-sectional epidemiological study, involving a stratified sample of 750 psychiatrists selected to participate. Patients were included if they met DSM-IV criteria for current single or recurrent non-psychotic major depressive disorder. Simplified Medication Adherence Questionnaire (SMAQ) and Hamilton Depression Rating Scale (HDRS) were used to assess adherence and depression severity.

Adherence rates are lower in depressive patients with psychiatric comorbidity (62.8%) than in patients without comorbidity (69.1%) (Chi-square = 15.9, p < 0.001, OR = 1.6, 1.2–1.8). There are no significant differences in adherence rates between those patients taking or not benzodiacepines.

Psychiatric comorbidity plays a negative role in adherence to antidepressant treatment. Benzodiazepine use has no influence on adherence rates. Special attention should be paid to the symptom overlapping between anxiety and depression and to the benzodiazepine prescription in comorbid depressive patients.

Pharmacological and non-pharmacological antidepressant therapies increase the firing rate of lateral septal nucleus neurons (a brain structure involved in mood state regulation) and reduce immobility in the forced swim test (FST), whereas the neurosteroid allopregnanolone appears to produce antidepressant-like effects through actions at GABAA receptors.

To explore the participation of the lateral septal nucleus and GABAA receptors in the antidepressant-like effects of allopregnanolone in Wistar rats.

First, the minimally effective dose of allopregnanolone that produces antidepressant-like effects in the FST was determined. Second, the effect of this minimally effective dose in the FST was evaluated on the firing rate of lateral septal neurons. Third, the antidepressant-like effects of microinjection of allopregnanolone (1.0 μg/rat) into the lateral septal nucleus was evaluated in the FST. Fourth, we explored whether the effects of allopregnanolone on the lateral septal neuron firing rate and FST are blocked by picrotoxin or bicuculline, two GABAA receptor antagonists.

The minimally effective dose of allopregnanolone with antidepressant-like effects in the FST was 1.0 mg/kg (i.p.) and significantly increased the firing rate of lateral septal neurons. Microinjection of allopregnanolone into the lateral septal nucleus produced antidepressant-like effects in the FST. Pretreatment with picrotoxin and bicuculline blocked the increase in lateral septal neuron firing rate and the antidepressant-like effects of allopregnanolone in the FST.

The lateral septal nucleus participates in the antidepressant-like effects of allopregnanolone through actions on GABAA receptors in Wistar rats.

Current data reveal that aripiprazole is associated with minimal weight gain. Patients who were stable and had gained excessive weight during olanzapine treatment were switched to aripiprazole. The objective was to evaluate the effect of this switch on body weight.

The effective dosage of aripiprazole 15 mg/day was started while olanzapine 10 mg/day was gradually tapered and stopped.

Case 1. M.A, a 49 -year old woman, had a history of bipolar disorder. She was treated with olanzapine and had gained 14 Kgr while taking aripiprazole, she had lost 9 kgr.

Case 2. Ms B, a 34-year-old woman had a history of schizophrenia. She had been treated with olanzapine and gained 10 kgr. She took aripiprazole and lost 4 Kgr.

Case 3. Mr C, a 45-year-old man, had a history of delusional disorder. He was treated with olanzapine and gained 12 kgr. He took aripiprazole and lost 5 Kgr

Case 4. Mr D, a 25-year-old man, had a diagnosis of schizotypal personality disorder. He was treated with olanzapine and gained 9 kgr, while taking aripiprazole, he had lost 8 Kgr

Case 5. Mr E, a 40-year-old woman, had a diagnosis of schizophrenia. She was treated with olanzapine and had gained 14 kgr, while taking aripiprazole, she had lost 6 Kgr

This study suggests that switching treatment to aripiprazole may be a useful strategy for patients who have gained excessive weight with olanzapine.

White matter (WM) abnormalities are considered integral to the pathophysiology of Schizophrenia (SZ) and Bipolar Disorder (BD), but there is ongoing uncertainty about the contribution of medication to these findings.

Diffusion Tensor Imaging (DTI) is a neuroimaging technique that provides quantitative indices of the structural and orientational characteristics of WM. These indices include mean diffusivity (MD), which is a directionally averaged measure of the apparent diffusion coefficient, and fractional anisotropy (FA), which summarizes the orientational dependence of diffusivity. We wanted to determine if these indices are affected by antipsychotic medication.

Our aim was to examine the available literature in order to differentiate antipsychotic effects from disorder-specific WM abnormalities on DTI measures.

We conducted a systematic qualitative review of the DTI literature in Bipolar Disorder (BD) and Schizophrenia (SZ), between 1998 and 2010 and included only studies where the relationship between DTI measures and antipsychotic medication was explicitly examined and reported.

We identified 40 studies in SZ and 8 in BD. All studies were cross-sectional and involved relatively small patient samples. 32 studies (80%) did not find any relationship between antipsychotic medication (dose, cumulative exposure) and FA or MD.

Current evidence does not indicate a major impact of antipsychotic treatment on DTI indices of WM integrity. However, the lack of longitudinal, within-subject designs is a major gap in the current literature.

One of the problems of many studies and clinical trials is that don’t reflect the patient's opinion about the medication that they receive and their satisfaction.

The aim of this study was to assess the degree of outpatients satisfaction with antipsychotic treatment in four outpatients clinics in Mallorca. The adherence rates was estimated from information provided by the patients and their psychiatrists.

A cross.-sectional and descriptive study was conducted during one month, from May to June 2010, by administering several questionnaires to outpatients with psychotic disorders. It was designed a case report data which recorded the following variables: age, gender, diagnosis (schizophreniform, schizophrenia, schizoaffective disorder, delusional, psychotic disorder not otherwise specified), time since diagnosis, substance use, number of antipsychotic drugs, type of antipsychotic (oral and / or im), number of doses per day and number of tablets, via of administration (buttocks or deltoid). The psychometric instruments used were: the Morisky-Green test, Haynes-Sacket test, the MSQ (Medication Satisfaction Questionnaire) and CGI (Clinical Global Impression).

The sample was of 92 patients with a mean age of 42.1 years (SD 12.2): 57.6% male and the most frequent diagnosis was schizophrenia in 65.2%. The duration of treatment from diagnosis was more than 5 years in 66.3%.

The patients on maintenance monotherapy with RLAI showed better adherence rates and more insight, evaluated by their psychiatrits.

78% of patients receiving antipsychotic medication injections were satisfied with the treatment.

Patients with RLAI administrating in deltoid were satisfied in 65.7%.

We investigated effect of long-term dosing of original anticonvulsant Galodif® (derivative of meta-chlor-benzhydrilourea). On activity of liver cytochrome P-450 system of alcoholics.

68 patients with alcoholism were examined. Pharmacokinetic parameters were calculated with method of statistical moments of K. Yamaoka.

In chronic alcoholism elimination of antipirine becomes slower. Examined by us patients had enough long term of alcoholization and we may suppose that acceleration of elimination of antipirine, occurring at the onset of disease was replaced by some suppression of activity of microsomal monooxigenases; accordingly, elimination of model connection has become slower. This supposition corresponds to data about decrease of consumption of oxygen and suppression of oxidative processes in chronic alcoholization both in experimental animals and people. Hypermetabolic state is observed at the onset of disease conditioning probably increase of tolerance toward alcohol, xenobiotics resistance and high resistance of organism. Subsequently exhaustion of adaptive mechanisms occurs and possibly hypermetabolic state disappears. This is confirmed by decrease of tolerance toward alcohol during long course of illness. In addition, it should be taken into account that liver hypermetabolism is mostly expressed in alcohol withdrawal syndrome.

The higher background of activity of monooxigenases system of liver is at baseline, the major degree of manifestation of inducer is and vice versa. It is possible that reinforcement of reactivity of microsomal monooxigenases of liver of alcoholics toward Galodif is associated with synergetic action of preparation-inducer and ethanol.

Multiple-complex Developmental Disorder (McDD) is a developmental disorder characterized by peculiar clinical features: affective dysregulation (anxiety, panic and aggressivity), impairment of social behaviour and hypersensitivity, impaired cognitive processing. McDD is usually included within the Pervasive Developmental Disorders not otherwise specified (PDD NOS) (Cohen et al. 1986; Towbin et al. 1993). Aripiprazole is a new atypical antipsychotic drug. Efficacy of aripiprazole in children and adolescents is supported by some studies (Findling et al. 2007, Wink at al 2010; Kim et al 2010).

The aim of our study is to describe the efficacy and safety of aripiprazole in 4 children with Multiple-complex Developmental Disorder.

Mean dosage of aripiprazole was 5 mg/day. Response was evaluated by clinical assessment and by Clinical Global Impressions Scale-Severity, Clinical Global Impressions Scale- Improvement, Children's Global Assessment Scale (CGAS) and by Brief Psychiatric Rating Scale. This assessment was administered at baseline, and at weeks 4, 12 and 24.

A significant reduction of social impairments, thought disorders and affective dysregulation was observed. Drug therapy was well tolerated, even though children complained of mild and transient nausea and somnolence.

To date there are only a few reports on the use of aripiprazole in McDD patients. The present case series suggest that aripiprazole may be effective and well tolerated in McDD patients.

To explore functioning in adult patients with recently diagnosed (< 5 years) and more chronic (> 5 years) schizophrenia treated with flexible doses of paliperidone ER.

International prospective open-label 6-month study. Endpoints were the Positive and Negative Syndrome Scale (PANSS), patient functioning (Personal and Social Performance Scale; PSP) and treatment-emergent adverse events (TEAEs).

Of 713 recently diagnosed patients, most were male (60.9%), mean age was 33.6 ± 11.2 years and mean time since diagnosis was 2.3 ± 1.7 years. Chronic patients (n = 1003) were predominantly male (59.2%) with a mean age of 43.8 ± 11.4 and mean time since diagnosis of 15.6 ± 9.2 years. Mean mode doses of paliperidone ER were similar between recently diagnosed and chronic patients (7.0 ± 2.9 mg/day and 7.2 ± 2.9 mg/day). At endpoint PANSS total scores were improved by 13.7 and 12.9 points, respectively, in recently diagnosed and chronic patients. The rate of patients with mild or less functional impairment increased from 17.7% to 39.8% in recently diagnosed and from 14.4% to 32.9% in chronic patients. Major functional improvements were observed for socially useful activities and personal and social relationships. TEAEs reported in >5% of recently diagnosed or chronic patients were insomnia (10.7% and 8.1%), anxiety (8.6% and 6.0%) and somnolence (5.8% and 3.4%), respectively.

These data suggest that both recently diagnosed and chronic patients previously unsuccessfully treated with other oral antipsychotics may benefit from paliperidone ER, with a tendency for recently diagnosed patients showing some higher treatment response in psychotic symptoms and patient functioning, particularly in socially useful activities and personal and social relationships.

Quinine, is an anti-malarial drug that specifically blocks connexin 36 at gap junction channels.

Quinine has suppressed ictal epileptiform activity in vitro without decreasing neuronal excitability.

We considered the possible anticonvulsant effects of quinine in the pentylenetetrazole (PTZ) model of seizure.

In five groups, the mice were given quinine at the doses of 20, 30, 40, 50, or 60 mg/kg 30 min before the administration of PTZ (90 mg/kg). Two groups were injected with diazepam, the positive control (0.5, 1 mg/kg) and one group, the control group, was injected with saline + Tween 80 before the administration of PTZ. The onset of a general clonus was used as the endpoint. The general clonus was characterized by forelimb clonus followed by full clonus of the body.

In the PTZ model, quinine at the dose of 60 mg/kg increased the latency of seizure. However, quinine at 40-60 mg/kg decreased the duration of seizure, dose dependently.

The present study provides evidence for anticonvulsant activity of quinine in the generalized clonic seizure of PTZ model. As a result of these finding, we suggest that gap junctions represent an appropriate target for the development of drugs aimed at decreasing epileptiform synchronization and preventing epileptogenesis.