There are no large scale studies on Epilepsy in populations with Learning disability in Ireland. As many as one fifth of these clients have epilepsy. Aggressive treatment may lead to diminishing returns in terms of symptomatic control, while causing unwanted effects.

1. 1. We aimed to quantify rates of epilepsy, aetiology and anti- epileptic drug (AED) use in our population.

2. 2. To look at degree of disability and correlation with AED use.

3. 3. To look at management/ quality of life issues using a validated instrument.

:

1. 1. Medline review using search terms Intellectual OR Learning difficult* OR Mental Retard* AND Epilepsy.

2. 2. Simple questionnaire used to identify all clients with Epilepsy. Database analysed using SPSS analysis.

3. 3. 11 cases selected for review looking at qualitative aspects, using Semi structured interview and GEOS scale.

1. · 210 patients found to have a history of epilepsy (42% of clients).

2. · Multiple Aetiologies identified. Commonest known Aetiology: Trisomy 21.

3. · Polypharmacy is common. Most commonly used AED: Sodium Valproate. Mean AED use: 1.595 (SD+- 1.077).

4. · Clients with Trisomy 21 aged less than 40 tended to be on more medication (2.05, SD= +-1.38) than those over 40 years (1.43, SD= +- 0.89)

5. · Greater concerns on qualitative measures regarding clients with refractory epilepsy or where epilepsy changed over time.

Our study highlights previously recognised changing patterns in aetiology of Learning Disability and also the changes over time in these clients. More study is required.

We examined the course of patients admitted for the first time in the Acute mental health ward of a Psychiatric Clinic in a Psychiatric Hospital within a ten-year hiatus. During this time the sociodemographic characteristics of the population were altered due to migration from former Eastern Europe countries, the transition from typical to atypical antipsychotic medication was completed and attempts were made to promote community psychiatry.

We compared two groups of 77 and 87 patients admitted for the first time during 1997 and 2007 respectively. Prescribed medication when given an exit diagnosis was calculated to haloperidol equivalency, following guidelines described in Kane et al.

Results indicate that the groups were comparable as to size, sex, age, entry diagnosis and length of stay. The groups differed significantly as to origin, with the 2007 group having significantly more migrants but also patients originating from more distant provinces within Greece. There was a significant increase in involuntary admissions. While there was an increase in the use of atypical antipsychotics there was no significant difference in treatment potency.

Introduction of atypical antipsychotics enabled the clinician to provide treatment of similar antipsychotic potency with better tolerance profile, but failed to reduce length of stay. The increase in involuntary admissions and number of admissions from more remote regions raises doubts on the efficiency of the psychiatric reforms attempted during that time in order to promote community psychiatry.

Serotonin Syndrome (SS) is an adverse drug reaction that drives mental-status changes, autonomic hyperactivity and neuromuscular abnormalities.

Neuroleptic Malignant Syndrome (NMS) is an idiopathic reaction to dopamine-antagonist that consists of extra-pyramidal symptoms, autonomic dysfunction, hyperthermia, diaphoresis and fluctuating consciousness.

Differential diagnosis is sometimes difficult for their overlapping clinical features. Potentially lethal, both require heightened clinical awareness for prevention, recognition and prompt treatment.

Caucasian 59 years-old woman with Catatonic profile (Scored: severity-17points/ 5 screening in Bush-Francis Catatonia-Rating-Scale).

1. - Hypothyroidism

2. - Bipolar Disorder type-2 (25 years of evolution)

15 days before hospitalization, anafranil and fluoxetine treatment was replaced by Trazodone 200 mg/day and venlafaxine 150mg/day. She was also on valpromida and lorazepam 15 mg/day.

Mutism, negativism. No reaction to painful stimuli, stuporous. Diaphoresis, pallor, tremor, axial rigidity without pyramidalism (>lower limbs), high fever (40°C), tachycardia (>100lpm), rhabdomyolysis (CPK reached 17.000, 48 hours after the admission), leukocytosis, upper transaminasas, hiponatremia with hiperpotasemia.

1. - NMS: Intensity, duration and high CPK are suggestive (Sternbach). This syndrome has been described due to Venlafaxine.

2. - SS: Combination of Venlafaxine and Trazodone favors but she doesn't have acatisia, hiperreflexia, diarrhea and it wasn't resolved after 96 hours.

Drugs were removed and Lorazepam on high doses (5mg/day) was prescribed. One month later the patient was totally recovered of the episode.

If unsure diagnoses it's priority to remove the causing drugs and supportive care. Afterwards, it can be used benzodiacepines, also dantroleno in SNM.

Neuroleptic Malignant Syndrome (NMS) is a rare and potentially lethal adverse reaction generally associated with typical antipsychotics. Cardinal features include muscle rigidity, hyperthermia, mental status changes, elevated CPK levels.

We report on a patient receiving olanzapine, an atypical antipsychotic, who developed NMS.

A 31 year-old male with a 5 year history of paranoid psychosis, was successfully treated with olanzapine 15 mg per day. He was also receiving oxcarbazepine for epilepsy (1200 mg/ day) and also suffered from spastic congenital paraparesis. He was almost asymptomatic for 4 years. At some point there was a recurrence of his illness with restlessness and aggressive behaviour. The patient decided to receive additionally 5 mg of olanzapine,without consulting psychiatrist. Soon he developed hyperthermia, hypertonia and confusion. He was initially admitted in a general hospital with leukocytosis and elevated CPK levels (1999 U/L). Other laboratory examinations were within normal limits. He was treated with ceftriaxone and parenteric fluids. After 48 hours he was improved and olanzapine was reinitiated (10 mg/day), and a few hours later he developed fever (40' C), hypertonia, dysphagia, confusion, CGS: 7/15 and elevated CPK levels (4900 U/LT). He was then transferred to the Intensive Care Unit and received treatment for NMS with bromocryptine and dantrolene sodium. His temperature returned to normal in two days and in 6 days he was physically stable. Twenty days later he received treatment for psychosis with low dose quetiapine.

NMS characterized by muscular rigidity and fever may rarely occur with atypical neuroleptics, such as olanzapine.

To assess the impact of lisdexamfetamine dimesylate (LDX; Vyvanse®, Shire US Inc.), which is the first long-acting prodrug stimulant indicated for treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults in the United States, on performance and quality of life (QOL) in adults with ADHD.

Subjects (n=142; aged 18 to 55 years) with ADHD entered a 4-week open-label dose-optimisation phase, then a 2-week, double-blind crossover phase. The primary efficacy measure was the average postdose total score on the Permanent Product Measure of Performance (PERMP) math test given predose and 2, 4, 8, 10, 12, and 14 hours postdose. The Adult ADHD Impact Module (AIM-A) was self-administered during the dose-optimisation phase. Safety was assessed by monitoring adverse events (AEs).

In the intention-to-treat population (n=105), postdose average PERMP least squares mean (SE) scores were higher (P< .0001) for LDX (312.9 [8.59]) vs placebo (289.5 [8.59]) and at every postdose time point ≥14 hours (P≤.0017 for each). Mean change from baseline scores on AIM-A subscales (n=127) showed improvement (P< .001) with LDX in 6 measured QOL domains (living with ADHD; general wellbeing; work, home, and school performance and daily functioning; relationships and communication; interference with life; and concern caused by symptoms). Treatment-emergent AEs (≥10%) in the dose-optimisation phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), and insomnia (18.3%).

LDX improved QOL and performance (up to 14 hours) and demonstrated a safety profile consistent with long-acting stimulant use.

Supported by funding from Shire Development Inc., Wayne, PA, US.

Cardiovascular side effects of antipsychotics are been studied both in typical and atypical antipsychotics but, in particular, with clozapine few systematic studies of these effects have been performed. In this study, we reviewed electrocardiographic (ECG) data from patients treated with clozapine.

Observational, retrospective study in our Clozapine Day Clinic from 2000 to 2008. We recluted 197 patients (70% men) with mean age 31,75 ± 9,0 years who began treatment with clozapine. All of them had an electrocardiogram taken before starting treatment and after 18 weeks of follow-up. None suffered from heart diseases. QTc was evaluated by Bazett formula (QT/ (R-R’)1/2). Treatment prescribed was taken down and drug serum levels were detected. Statistical analysis was executed by SPSS 17.0.

There was significant correlation between doses prescribed and levels of clozapine and norclozapine (r=.304, p=.023; r=.354 p=.007), between levels of clozapine, norclozapine and QTc enlargement (r=.348, p=.008; r=.268 p=.046) and between levels of clozapine, norclozapine and heart rate (r=.390, p=.003; r=.326 p=.014). There were no differences between QTc and treatment with clozapine or other antipsychotic (p=0.902), between sex or if polypharmacy existed. ECG alterations were a case of supraventricular extrasystoles, another of Wolf-Parkinson -White Syndrome and other inespecific alterations like repolarizations or left hypertrophy.

We did not find either major incidence on cardiological effects or significative QTc enlargement during treatment with clozapine in contrast to other antipsychotic previously prescribed. Therefore clozapine may be in the same cardiologic safety rank than other antipsychotics.

To develop consensus-based clinical diagnostic criteria for neuroleptic malignant syndrome (NMS).

A 17-member international expert panel of psychiatrists, neurologists, anesthesiologists and emergency medicine specialists was asked to identify clinical features that are most important or valuable in diagnosing NMS; when the feature was quantitative in nature, they were also asked to provide the corresponding critical value. The Delphi technique is a formal consensus procedure that employs a postal survey method to solicit opinions from each panel member, and to feed this information back to the entire panel in the form of anonymous, statistically aggregated data. This iterative process of information exchanges (opinions collected, group responses analyzed, feedback given to panel), or “rounds”, continues until consensus has been reached. In the present study, the predetermined consensus criterion was a round-round mean change of 10% or less for any survey item, and 5% or less across all items.

The expert panel reached consensus on the following diagnostic criteria in five iterations:

1. (1) exposure to a dopamine antagonist, or dopamine agonist withdrawal, within past 72 hours;

2. (2) hyperthermia;

3. (3) rigidity;

4. (4) mental status alteration;

5. (5) creatine phosphokinase elevation;

6. (6) sympathetic nervous system lability (2 or more of blood pressure elevation, blood pressure fluctuation, diaphoresis, urinary incontinence);

7. (7) tachycardia and tachypnea; and

8. (8) negative work-up for infectious, toxic, metabolic and neurological causes.

These are the first consensus-based diagnostic criteria for NMS, and may be preferred to previous ad hoc approaches to diagnosing this disorder.

The aim of this study was to compare the clinical efficacy and the safety of venlafaxine and fluoxetine in the treatment of obsessive-compulsive disorder (OCD).

One hundred and Eight inpatients who met the Diagnostic and Statistical Manual of Mental Disorders, the Forth Edition(DSM-IV) for OCD were involved in this study. The subjects were randomly divided into venlafaxine group or fluoxetine group. Efficacy of venlafaxine and fluoxetine in treatment of OCD were assessed with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression-Severity(CGI-S), the side effects were evaluated with Treatment Emergent Symptom Scale (TESS).

The therapeutic efficacy in venlafaxine group was similar to that in fluoxetine (70.36%vs68.29%, P>0.05) after eight weeks’ therapy. The improve-rates of Y-BOCS after 2 weeks’ therapy of venlafaxine were significant higher than those of baseline, while the improve-rates of Y-BOCS after 4 weeks’ therapy of fluoxetine were significant higher than those of baseline(P< 0.05). The side effects of venlafaxine group were similar to fluoxetine group (P>0.05).

The results indicate that both venlafaxine and fluoxetine is effective in the treatment of OCD, but venlafaxine work faster than fluoxutine.

To describe and compare the demographic and clinical characteristics of adult patients with depression in the UK treated with duloxetine and venlafaxine XR.

Depressed adults treated with duloxetine or venlafaxine XR between 1/1/2006 and 9/30/2007 were identified using the General Practice Research Database (GPRD), which represents all primary care practices in the UK. Demographic (age and sex) and clinical characteristics (psychiatric and physical comorbid conditions and concomitant medication use) were examined and the characteristics of the two treatment groups were compared using chi-square or t tests, as appropriate.

Of 2,195 patients identified (mean age 47.2 years; 65.8% female), 41% were prescribed duloxetine and 59% were prescribed venlafaxine XR. On average, patients treated with duloxetine were older than patients treated with venlafaxine XR (49.6 years versus 45.5 years; p< 0.001). Compared to patients treated with venlafaxine XR, patients treated with duloxetine had higher prevalence of a variety of comorbid physical health conditions, including diseases of the circulatory, digestive, respiratory systems, as well as a higher prevalence of diabetes (p< 0.01 for all). Additionally, patients treated with duloxetine had higher prevalence of unexplained pain (p< 0.001). Greater proportions of patients treated with duloxetine had prescription utilization of medications in a variety of classes, including anticonvulsants, analgesics, migraine medications, as well as medications used to treat cardiovascular and gastrointestinal disorders (p< 0.01 for all).

Depressed patients treated with duloxetine in the UK are slightly older and appear to be in poorer health overall than patients treated with venlafaxine XR.

Poststroke depression (PD) occurs in approximately one third of the patients within first two years of a cerebrovascular event. However, no definite consensus has been reached on the best treatment option. The aim was to determine the efficacy and safety escitalopram, a selective serotonin reuptake inhibitor, in PSD treatment.

Patients with symptoms of depression within 6 months of a cerebrovascular event were included. Patients with Hamilton depression (HAM-D) score of < 13, mini mental standardized test score of < 23, schizophrenia, behavioral disorders, substance abuse, history of alcoholism, current use of antidepressants, and history of stroke or major depression within the last one year were excluded. Patients were administered escitalopram 10 mg/day for 3 months. HAM-D scores, stroke severity and extent of functional impairment were assessed and side effects were recorded; the relationship between HAM-D scores and sociodemographic variables and stroke localization was investigated.

Totaly,35 patients (60% female; mean age, 67± 6) were included. Depression was diagnosed 3±1.2 months after the stroke. HAM-D scores decreased significantly in all visits (days 15, 30, 45 and 90). The mean HAM-D score decreased from 27.5±4.7 to 4.65±2.47 at day 90 (p< 0.0001). No significant correlation was found between HAM-D scores and cerebrovascular event localization, sociodemographic variables and medical history (p>0.05). Escitalopram was well tolerated. A total of 9 patients reported nausea, anxiety, drowsiness and dyspepsia.

In this open-label study escitalopram was found to be safe and effective for use in poststroke depression patients.

Previous research has indicated that rats selectively bred for high and low saccharin preference exhibit differential drug-taking behavior within multiple phases of the animal model of human drug abuse. Namely, rats bred for high saccharin preference (HiS) show heightened vulnerability to addiction compared to rats bred for low saccharin preference (LoS). Prior research has also shown phenotypes that confer vulnerability to be more responsive to pharmacological interventions. For example, the GABA(B) agonist baclofen is more effective at blocking cocaine acquisition in female rats, who are typically more vulnerable to addiction, compared to males.

To examine the differential effects of baclofen on the escalation of cocaine-seeking behavior in female rats bred for high and low saccharin preference.

HiS and LoS female rats were trained to administer cocaine (0.4 mg/kg/infusion, i.v.) within daily 2-hr sessions under a fixed ratio (FR1) schedule until criteria for stability were met. Next, the escalation phase began in which daily session length was extended to 6-hrs for 21 days. Thirty minutes prior to session during this phase, one HiS and one LoS group of rats received baclofen injections (1.25 mg/kg) while one HiS and one LoS group received saline injections.

Baclofen potentiated escalation of cocaine infusions in HiS rats compared to HiS rats treated with saline. Conversely, baclofen attenuated escalation in LoS rats.

While these results do not support the original hypothesis of the present study, they underscore the importance of considering vulnerability factors while treating human drug addiction.

It is generally acknowledged that individuals with intellectual disabilities (ID) benefits from psychotropic treatment for mental disorders (MD) in the same way as people in the general population. It has also been shown that problem behavior (PB) does not respond to psychotropic treatment. Thus, we hypothesized that the presence of MD was assocated with psychotropic treatment, whereas PB (not MD) was not.

In a community sample of adults with ID (N=593), the presence of dementia, psychoses, depression, mania, obsessive-compulsive disorders, five anxiety disorders and eight problem behaviors were screened using the Psychopathology Checklists for Adults with Intellectual Disability (P-AID). Information regarding the use of psychotropic medicine (ACT-N) was collected. Staff members in group homes served as informants both for the screening and the use of drug.

Psychotropic medication was reported in 40% of the sample. Of the 23% that presented with MD only, 44% received psychotropic medication (p=.310). Of the 12% that presented with both MD and PB, 51% received such medication (p=.032). The strongest association was found between psychotropic treatment and having PB only. Among the 8% that showed PB only, 52% received psychotropic medication (p=.022).

Contrary to our expectations, the presence of PB rather than MD were associated with the use of psychotropic treatment. The present findings suggest that people with ID often receives no psychotropic treatment for MD, or they receives such treatment for the wrong reason, leaving the accuracy of psychotropic treatment to a minimum.

Present study focuses on metabolic and neuroendocrinologic effects of long-acting injectable risperidone (LAIR) treatment in a naturalistic sample of patients with schizophrenia spectrum disorders.

Twenty three outpatients with schizophrenia or schizoaffective disorder (ICD X) (age 32.3±6.5years, illness duration 8.7±5.1 years, PANSS 78.1±14.7) were included. At the time of evaluation the patients were treated with LAIR for 1.4±0.7 years, average dose 38.6±9.9mg. Total duration of antipsychotic therapy was 8.0±4.8 years. Control group (n=23) were healthy volunteers matched by age, sex and education.In the morning serum we measured leptin, prolactin, cortizol, IGF1, T4, FSH, LH, HbA1c, total cholesterol, HDL, LDL and triglicerides. Both groups were tested by oral glucose load (OGTT), with measuring insulin levels and anthropometric parameters.

In comparison to control group, the patients had higher BMI (p< .001), waist circumference (WC, p=.004), increased leptin (p=.013), prolactin (p< .001), triglycerides (p=.029) and fasting glucose (p=.004). After controlling for BMI, WC and sex, only prolactin (p< .001, ηp2= .50) and leptin (p=.040, ηp2=.13) were significantly increased in the patient group.

This is the first study of LRAI effects on metabolic and neuroendocrine parameters. Our cross-sectional study has shown that the most consistent side effects of LAIR were increased prolactin and leptin, while other deviations might be attributed to confounding covariates. Whether pharmacokinetic and pharmacodynamic advantages of LAIR over oral drug formulation are accompanied with favorable metabolic and neuroendocrine profile remains to be assessed by head to head studies.

This study was supported by a grant from the Ministry of Science, Republic of Serbia (Project 145019).

The European Federation of Psychiatric Trainees (EFPT), a trainee-led organisation, encompassing official representatives from 24 countries, set up a research group to foster trainee-led collaborative research, emphasising training and clinical practice.

The first survey of the group assessed trainees’ treatment choices for patients and themselves, across psychiatric disorders, in addition to factors influencing decision-making and guideline use.

A web-based survey was piloted, and distributed to 16 European countries. For validity, a 50% response rate from a homogenous sample, with sample size 50 or more was required,

12 countries met inclusion criteria.

1. (a) Antipsychotic choice and factors influencing decision-making

93% (n=600) of respondents chose to prescribe 2nd Generation atypical antipsychotics for patients, and 89% (n=530) chose this treatment for themselves. 79% (n=458) of respondents felt efficacy was the most important factor influencing decision-making.

1. (b) Mood stabiliser choice and factors influencing decision-making 41% (n=263) of trainees chose to prescribe lithium to patients, with 35% (n=224) stating they would wish to receive this themselves. 66% (n=538) of respondents felt perceived efficacy was the most important factor influencing decision-making.

2. (c) Antidepressant choice and factors influencing decision-making 75% (n-461) of trainees would prescribe SSRIs to patients with a moderate depressive episode, 78% (n=438) wishing to receive SSRIs themselves. 67% (n=523) of respondents felt efficacy to be the most important determining facor.

Trainees are able to provide clinically-relevant research through trainee networks, and a number of decisions governing treatment do not appear to be based on current evidence.

Recent evidence has questioned modern psychiatric clinical practice, specifically the prescribing of “atypical” antipsychotics. Our Pan-European Research Group wished to ascertain clinical practice amongst European trainees, which treatments trainees would desire for themselves, and factors influencing this.

A semi-structured survey was constructed from prior literature, piloted, and a homogenous sample size of at least 50 was agreed upon from each country, with 50% minimum response rate. It was distributed via web-link, with questions on preference of antipsychotic for patients in given scenarios, and factors influencing choice. Physicians were asked for their preference should they develop psychosis.

1. i) Treatment choice of antipsychotic for patients

93% (n=600) of respondents chose to prescribe “atypical” antipsychotics (excluding Clozapine), 6% (n=42) choosing “typical” antipsychotics, 1% (n=6) choosing Clozapine as first-line therapy.

1. ii) Treatment choice if trainees developed psychosis

89% (n=530) of responders chose to prescribe “atypical” antipsychotics (excluding Clozapine), 7% (n=40) choosing “typical” antipsychotics, 4% (n=23) choosing Clozapine as first-line therapy.

1. iii) Factors influencing choice

These mapped onto three domains: cost, efficacy and side-effect profile (less than 5% other reasons). 79% (n=458) of those who responded felt efficacy most important, 46% (n=270) felt side-effect profile most important and 3% (n=16) considered cost of paramount importance.

38% (n=272) of those who responded to the survey stated that the CATIE trial had influenced their decision-making.

Psychiatry trainees’ choice of antipsychotic medication for both patients and themselves is based on perceived benefits, as opposed to evidence base and recent literature.

Twenty-five-year old man suffering from paranoid psychosis was given quetiapine for persisting symptoms. He also had myoclonic disorder which has become worse just after administering quetiapine. Physical, neurological and laboratory findings were normal. He once had a generalized seizure in our clinic. The electroencephalography (EEG) revealed an epileptic focus on frontal region. He has been diagnosed as frontal lobe epilepsy exacerbated by quetiapine. He has recovered and was doing well after withdrawn the drug.

Twenty-three-year old women who had bipolar disorder was hospitalized due to a manic episode. Physical examination and routine laboratory tests were normal. Lithium at 600mg/d and quetiapine at 300 mg/d were started. Quetiapine has been gradually increased up to 900 mg/d at which the myoclonic symptoms first noted. They were disappeared after quetiapin was tapered to 600 mg/d. To control manic symptoms, quetiapine dosage had to be increased up to 700 mg/d again, but myoclonus was reappeared. Quetiapin was replaced with risperidon and manic symptoms subsided. No myoclonic seizures were noted during follow-up.

EEG abnormalities particularly likely with clozapine and olanzapine, moderate with risperidone, and the lowest with quetiapine. The risk of quetiapine-induced epilepsy was estimated as 0.75%. Evaluating of patients for the epileptic background is important in selecting proper antipsychotic medication.

Recent studies suggest that such neuroactive steroids as dehydroepiandrosterone-sulfate (DHEAS) and cortisol play an important part in conditioning psychiatric disorders in combatants. Cortisol may have a neurotoxic effect whereas DHEAS can produce a neuroprotective impact.

We have investigated the morning plasma level of DHEAS and cortisol as well as DHEAS/cortisol ratio in the group of forty combat veterans in the remote period of combat stress and the same parameters - in the control group consisting of 30 healthy males (N=30).

In comparison with the control group, the combatants reliably showed considerably higher level of cortisol (p< 0,05), lower level of DHEAS (p< 0,001) and lower DHEAS/cortisol ratio (p< 0,001). Then the veterans were divided into two groups with the help of the “Mississippi Scale for Combat-Related Posttraumatic Stress Disorder”: those having post-traumatic stress disorder (PTSD) and those without this diagnosis. As a result, no trustworthy difference between levels of DHEAS, cortisol and their proportion was found in PTSD-positive and PTSD-negative veterans. Each of these groups displayed the reliable reduction of DHEAS level as compared to the control group.

The results of our investigation demonstrate that the veterans differed significantly from the control group in the level of neurosteroids. This fact apparently cannot be linked to PTSD symptoms. Thus there is an urgent need for further examination of clinical and psychological components correlated with altered levels of DHEAS and cortisol in combat veterans.

To explore maintenance of effect with OROS MPH in adults with ADHD.

Multicenter study randomizing adult subjects with ADHD who completed open-label (OL) treatment with OROS MPH (18-90mg/day) for at least 52-week and consented to a 4-week, randomized, double-blind (DB), placebo-controlled (PLC) withdrawal period. Efficacy measures included total CAARS score, CAARS-S:S, GAE, CGI-S and CGI-C. Endpoint analyses were performed using LOCF.

99/155 patients completed the OL OROS MPH treatment phase, only 45/99 patients consented to double-blind randomization. At DB baseline, mean ± SD TCS was 12.1±5.34 (n=23) in the continued OROS MPH group and 16.5±7.49 (n=22) in the placebo group. CAARS changed from DB baseline to DB endpoint by 4.0±7.61 and 6.5±7.82, respectively (p = 0.2586 between groups). CGI-C scores indicated more worsening of symptoms in the placebo group compared to the continued PR OROS MPH (p = 0.0422). Median (range) GAE scores at endpoint were 2.0 (0-3) and 0.5 (0-3), respectively (p=0.0254). Other efficacy endpoints were numerically in favor of OROS MPH. The randomized withdrawal phase may have been underpowered to show statistical significance between treatment groups for the primary outcome. The incidence of treatment-emergent AEs during the DB phase was comparable between groups.

The results indicate that treatment discontinuation after long-term exposure of adults with ADHD to OROS MPH is associated with worsening of clinical symptoms. Statistical significance for several outcomes was not reached, possibly due to study limitations.

To explore functionality and quality of life outcomes in children and adolescents with ADHD transitioning from IR MPH, ER MPH or ATX onto OROS MPH.

Pooled analyses of two similar 12 week open label, flexibly dosed studies including children (6-18 yrs) diagnosed with ADHD (ICD-10) transitioning from shorter acting stimulants or Atomoxetine onto OROS MPH. Connor's parents rating scale, children's global assessment scale and quality of life (ILC, LQ-0-28) were applied.

822 patients (84.9% boys; median age 10 yrs) were analyzed. 81% of patients concluded the study. Starting and final dose was based on physician's judgment. Median dose at baseline and endpoint was 36mg/day. On average, C-GAS ratings improved by 12 points (p< 0.001). The percentage of children showing “variable functioning with sporadic difficulties” at baseline or worse decreased from 57,2% to 43,3% at endpoint. 61% of patients improved by at least 30% on CPRS. The percentage of children meeting educational demands at school at least “rather good” increased from 26,6% to 47,4% at endpoint. Results were similar for “social interaction with other children”, “emotional status”, “occupying with him or herself”. Burden of disease (patients or care givers) decreased (p< 0.001). Improved C-GAS and LQ 0-28 correlated with decreased CPRS. Treatment emergent AEs occurred in 35.6%. AEs ≥ 4%: insomnia (8%), muscle twitches (5%) and anorexia (4%).

Transitioning onto OROS MPH was associated with clinically relevant improvements in daily functioning, aspects of quality of life and decreased burden of disease in patients and their cares.