Resting cerebral blood flow (rCBF) in striatum and thalamus is increased in medicated patients with psychosis, but whether this is caused by treatment or illness pathology is unclear. Specifically, effects of partial dopamine agonism, sex, and clinical correlates on rCBF are sparsely investigated. We therefore assessed rCBF in antipsychotic-naïve psychosis patients before and after aripiprazole monotherapy and related findings to sex and symptom improvement.

We assessed rCBF with the pseudo-Continuous Arterial Spin Labeling (PCASL) sequence in 49 first-episode patients (22.6 ± 5.2 years, 58% females) and 50 healthy controls (HCs) (22.3 ± 4.4 years, 63% females) at baseline and in 29 patients and 49 HCs after six weeks. RCBF in striatum and thalamus was estimated with a region-of-interest (ROI) approach. Psychopathology was assessed with the positive and negative syndrome scale.

Baseline rCBF in striatum and thalamus was not altered in the combined patient group compared with HCs, but female patients had lower striatal rCBF compared with male patients (p = 0.009). Treatment with a partial dopamine agonist increased rCBF significantly in striatum (p = 0.006) in the whole patient group, but not significantly in thalamus. Baseline rCBF in nucleus accumbens was negatively associated with improvement in positive symptoms (p = 0.046), but baseline perfusion in whole striatum and thalamus was not related to treatment outcome.

The findings suggest that striatal perfusion is increased by partial dopamine agonism and decreased in female patients prior to first treatment. This underlines the importance of treatment effects and sex differences when investigating the neurobiology of psychosis.

In spite of the long history of antipsychotic treatment there are still no clear criteria, which can be robust support for drug decision-making.

To determine the important hallmarks of patient’s current state, life span and history of illness defining the doctor’s decision about the type of antipsychotic to be chosen.

The data from the case charts of 275 patients with episodic schizophrenia and rather benign course of the disease were analyzed.

The group included: male 62%, mean age 33 (SD 11), education 10 years 23%, 13 years 27%, 16 years 29%, disability - 51%, number of hospitalizations due to psychotic episodes in the past 7 (SD 6). The symptoms of the current episode varied from patient to patient: delusions and hallucinations, symptoms of disorganization, negative symptoms of different severity were registered Atypical antipsychotics were more often than typical prescribed to the patients with developmental problems: traumatic obstetric complications (p=0,009), poor somatic health in the childhood (p= 0,02), cognitive dysfunction during school years (p=0,04), and quality of first remission – presence of residual symptoms in the first remission (p=0.005). Good compliance in the past was one more important factor for choosing a atypical antipsychotic for a patient (p=0.05). It appeared that the most important for the decision-making was the specific features of the patient’s development and early period of the disease, but not the specific signs of current psychotic state.

Doctor’s decision upon the type of antipsychotics in this category of patients is most probably based on other than current clinical symptoms signs.

To assess the coronary heart disease (CHD) risk and prevalence of the metabolic syndrome (MS) in patients with schizoaffective disorder (SD) receiving antipsychotics.

Patients meeting DSM-IV criteria for SD and receiving antipsychotic treatment were recruited in a retrospective, cross-sectional, multicenter study (the CLAMORS study). MS was defined as at least three of the following components: waist circumference greater than 102cm (men)/greater than 88cm (women); serum triglycerides greater or equal to 150mg/dl; HDL cholesterol less than 40mg/dl (men)/less than 50mg/dl (women); blood pressure greater or equal to 130/85mmHg; fasting blood glucose greater or equal to 110mg/dl. The 10-year CHD risk was assessed by the Systematic coronary risk evaluation (SCORE) (cardiovascular mortality) and Framingham (any cardiovascular event) functions. Clinical severity was assessed using the PANSS and CGI-S scales.

A total of 268 valuable patients with SD (127 men, 48.1%), 41.9±12.3years (mean±S.D.), were analyzed. The 10-year overall cardiovascular mortality and CV-event risk were 0.8±1.6 (SCORE) and 6.5±6.8 (Framingham), respectively. A high/very high risk of any CV event (Framingham≥10%) was associated with severity [CGI-S=3–4; OR: 4.32 (1.15–16.26), P = 0.03)]. MS was present in 26.5% (95%CI: 21.2–31.8) of subjects, without gender differences, but significantly associated with patient's impression of severity: CGI=3–4; OR=1.90 (0.83–4.36), and CGI=5–7; OR=3.13 (1.06–9.24), P = 0<0.001, and age [OR=1.91 (1.09–3.34), P<0.024)].

CHD risk and MS prevalence were high among patients with SD, being MS prevalence associated with age and severity of disease.

Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints.

Patients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression–Improvement (CGI-I) scale score, was also analyzed.

Of 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92–94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo.

AL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.

Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis.

A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1–3, posterior CA1–3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability.

Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans.

This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.

Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments.

Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures.

Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P= .043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons.

Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

The purpose of this study was to examine the efficacy and safety of aripiprazole in the treatment of delirium in hospitalized cancer patients, and to examine differential responses based on delirium subtypes.

We conducted an analysis of 21 hospitalized cancer patients at Memorial Sloan-Kettering Cancer Center (MSKCC) who had been evaluated and treated for delirium with aripiprazole, using an MSKCC Institutional Review Board (IRB) approved Clinical Delirium Database. Measures used were the Memorial Delirium Assessment Scale (MDAS), the Karnofsky Scale of Performance Status (KPS), and side effect rating at baseline (T1), 2–3 days (T2), and 4–7 days (T3). All measurements were integrated into the routine clinical care of patients. Doses of aripiprazole were adjusted based on clinical response.

Patients treated for delirium with aripiprazole experienced significant improvement and resolution of delirium, with MDAS scores declining from a mean of 18.0 at baseline (T1) to mean of 10.8 at T2 and a mean of 8.3 at T3. KPS scores improved from 28.1 at baseline (T1) to 35.2 at T2 and 41 at T3. Delirium resolved (based on MDAS < 10) in 52.4% of cases at T2 and in 76.2% at T3. The mean dosage of aripiprazole required was 18.3 mg (range of 5–30) daily at T3. In our cohort of patients with hypoactive delirium, we observed a delirium resolution rate of 100% compared to the cohort of patients with hyperactive delirium (58.3% rate of delirium resolution). MDAS scores improved from 15.6 at T1 to 5.7 at T3 in hypoactive delirium and from 19.9 at T1 to 10.2 at T3 in hyperactive delirium. In patients with pre-morbid cognitive deficits and the hyperactive subtype of delirium, we observed a more limited treatment response to aripiprazole treatment for delirium. There were no clinically significant side effects noted.

Aripiprazole is effective and safe in the treatment of delirium in hospitalized cancer patients. These preliminary finding suggest that aripiprazole may be most effective in resolving delirium of the hypoactive subtype.