High-dose Antipsychotics Research Articles

Nurses' attitudes towards the use of PRN psychotropic medications in acute and forensic mental health settings.

Many countries now have national mental health policies and guidelines to decrease or eliminate the use of seclusion and restraint yet the use of Pro Re Nata (PRN) medications has received less practice evaluation. This research aimed to identify mental health nurses' attitudes towards the use of PRN medications with mental health consumers. Participants were working in forensic mental health and non-forensic acute mental health settings. The "Attitudes towards PRN medication use survey" was used and data were collected online. Data were analysed using the Statistical Package Social Sciences, Version 22.0. Practice differences between forensic and other acute mental health settings were identified related to the use of PRN medications to manage symptoms from nicotine, alcohol and other drug withdrawal. Differences related to the useage of comfort rooms and conducting comprehensive assessments of consumers' psychiatric symptoms were also detected. Qualitative findings highlighted the need for increased accountability for the prescribing and administration of PRN medications along with more nursing education/training to use alternative first line interventions. Nurses administering PRN medications should be vigilant regarding the indications for this practice to ensure they are facilitating the consumer's recovery by reducing the use of all forms of potentially restrictive practices in the hospital setting. The reasons for using PRN medications and PRN administration rates must be continually monitored to avoid practices such as high dose antipsychotics use and antipsychotic polypharmacy to ensure the efficacy of the consumers' management plans on their health care outcomes.

Structural brain changes in schizophrenia at different stages of the illness: A selective review of longitudinal magnetic resonance imaging studies.

Schizophrenia is a devastating mental disorder accompanied by aberrant structural brain connectivity. The question whether schizophrenia is a progressive brain disorder is yet to be resolved. Thus, it is not clear when these structural alterations occur and how they develop over time. In our selective review, we summarized recent findings from longitudinal magnetic resonance imaging studies investigating structural brain alterations and its impact on clinical outcome at different stages of the illness: (1) subjects at ultra-high risk of developing psychosis, (2) patients with a first episode psychosis, and (3) chronically ill patients. Moreover, we reviewed studies examining the longitudinal effects of medication on brain structure in patients with schizophrenia. (1) Studies from pre-clinical stages to conversion showed a more pronounced cortical gray matter loss (i.e. superior temporal and inferior frontal regions) in those individuals who later made transition to psychosis. (2) Studies investigating patients with a first episode psychosis revealed a decline in multiple gray matter regions (i.e. frontal regions and thalamus) over time as well as progressive cortical thinning in the superior and inferior frontal cortex. (3) Studies focusing on patients with chronic schizophrenia showed that gray matter decreased to a greater extent (i.e. frontal and temporal areas, thalamus, and cingulate cortices)-especially in poor-outcome patients. Very few studies reported effects on white matter microstructure in the longitudinal course of the illness. There is adequate evidence to suggest that schizophrenia is associated with progressive gray matter abnormalities particularly during the initial stages of illness. However, causal relationships between structural changes and illness course-especially in chronically ill patients-should be interpreted with caution. Findings might be confounded by longer periods of treatment and higher doses of antipsychotics or epiphenomena related to the illness.

High doses of antipsychotic polypharmacy are related to an increase in serum levels of pentosidine in patients with schizophrenia

BackgroundCarbonyl stress in patients with schizophrenia has been reported to be reflected by an increase in peripheral pentosidine levels. This cohort study tested whether the accumulation of pentosidine was related to the disease severity or the treatment (routine administration of high antipsychotic doses). MethodsWe followed up our original investigation using a new group of 137 patients with acute schizophrenia and 45 healthy subjects, and then pooled the two cohorts to conduct the following analysis on a total of 274 patients. The associations of serum pentosidine and pyridoxal levels with duration of education, estimated duration of medication, the severity of symptoms, and daily doses of antipsychotics, antiparkinsonian drugs, and anxiolytics were evaluated by multiple linear regression analysis. ResultsThe combined cohort of 274 patients exhibited abnormally high serum levels of pentosidine, were associated with a higher daily dose of antipsychotic drugs and a longer estimated duration of medication without statistical significance of diagnosis. This was also observed in the patients treated with antipsychotic polypharmacy, but the serum pentosidine levels of patients treated with first- or second-generation antipsychotic monotherapy showed no relationship with these two variables. ConclusionHigh levels of serum pentosidine were associated with high daily doses of antipsychotic drugs and a longer estimated duration of medication in patients treated with antipsychotic polypharmacy.

Quality of life, self-stigma, and hope in schizophrenia spectrum disorders: a cross-sectional study.

GoalsThe aim of this study was to explore the quality of life, self-stigma, personality traits, and hope in patients with schizophrenia spectrum disorders.Patients and methodsA total of 52 outpatients participated in this cross-sectional study. The attending psychiatrist assessed each patient with Mini International Neuropsychiatric Interview (MINI). The patients then completed Quality of Life Satisfaction and Enjoyment Questionnaire (Q-LES-Q), Internalized Stigma of Mental Illness (ISMI) Scale, Temperament and Character Inventory – Revised (TCI-R), Adult Dispositional Hope Scale (ADHS), Drug Attitude Inventory 10 (DAI-10), and Liebowitz Social Anxiety Scale (LSAS)-Self-report. The psychiatrist evaluated Clinical Global Impression Severity – the objective version (objCGI-S), and the patients completed the Clinical Global Impression Severity – the subjective version (subjCGI-S). Each participant also completed Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI).ResultsThe quality of life was significantly higher in employed patients and individuals with higher hope, self-directedness (SD), and persistence (PS). The quality of life was lower among patients with higher number of psychiatric hospitalizations, those with higher severity of the disorder, and individuals who were taking higher doses of antipsychotics. Patients with more pronounced symptoms of depression, anxiety, and social anxiety had a lower quality of life. Finally, the quality of life was lower among individuals with higher harm avoidance (HA) and self-stigmatization (ISMI). Backward stepwise regression was applied to identify the most significant factors connected to self-stigma. The regression analysis showed that occupation, level of depression (BDI-II), attitude to using medication (DAI-10), social anxiety (LSAS), and antipsychotic index were the most relevant factors associated with lower quality of life.ConclusionDetection of the quality of life in the context of personality traits, hope, self-stigma, and demographic and clinical factors may be an important part of the assessment of the patient with schizophrenia.

Clinical Practice Guidelines for Management of Schizophrenia.

Clinical Practice Guidelines for Management of Schizophrenia.

Association of the Cholinergic Muscarinic M2 Receptor with Autonomic Nervous System Activity in Patients with Schizophrenia on High-Dose Antipsychotics

Background: Patients with schizophrenia have abnormal autonomic nervous system (ANS) activity compared with the general population. One reason for this difference is the muscarinic affinity for antipsychotic drugs; therefore, single nucleotide polymorphisms (SNPs) of the muscarinic receptor gene influence this ANS dysfunction. This study sought to determine the effect of SNPs of the cholinergic muscarinic receptor (CHRM) gene on ANS activity in patients with schizophrenia receiving antipsychotic drugs. Methods: A total of 173 Japanese patients with schizophrenia were included in this study. Heart rate variability (HRV) was measured as an index of ANS activity. SNPs in CHRM1 (rs542269 and rs2075748), CHRM2 (rs324640, rs8191992, rs1824024, and rs7810473), and CHRM3 (rs3738435, rs4620530, and rs6429157) were genotyped using the TaqMan® method. Patients were grouped according to standard equivalent conversions of chlorpromazine (CP) into a high-CP group (HG; ≥1,000 mg) and a low-CP group (LG; <1,000 mg). ANS activity was compared between the groups. In addition, we compared the total, low-frequency (LF), high-frequency (HF), and LF/HF components of the patients' HRV, and the genotype of the SNPs in both the HG and LG groups. Bonferroni correction was applied for multiple comparisons, and the Bonferroni-corrected critical p value was <0.005. Results: The A allele of the CHRM2 rs8191992 polymorphism in HG was associated with decreased ANS activity. Conclusion: Our results show reduced ANS activity in association with the CHRM2 rs8191992 polymorphism in patients with schizophrenia on high-dose antipsychotics. CHRM2 polymorphisms may play an important role in ANS activity in patients with schizophrenia.

Cardiometabolic health, prescribed antipsychotics and health-related quality of life in people with schizophrenia-spectrum disorders: a cross-sectional study.

BackgroundPeople with schizophrenia–spectrum disorders (SSD) often have high levels of obesity and poor cardiometabolic health. Certain types of antipsychotics have been shown to contribute towards weight gain and there is some equivocal evidence that obesity is related to poor health-related quality of life (HRQoL) in people with SSD. It is also still uncertain if antipsychotic polypharmacy/higher doses of antipsychotics are linked with HRQoL and/or increased risk of obesity/Cardiovascular Disease (CVD). Therefore, this study aimed to examine potential relationships between prescribed antipsychotic medication regimens, cardiometabolic health risks and HRQoL in community-based Chinese people with SSD.MethodThis cross-sectional study reports the results of baseline measurements of a random sample of patients in an ongoing controlled trial of physical health intervention for people with severe mental illness. Data from these randomly-selected participants (n = 82) were analysed to calculate 10-year CVD relative-risk (using QRISK®2 score), estimate the prevalence of metabolic syndrome and contextualize patients’ prescribed antipsychotics (types, combinations and Daily Defined Dose equivalent). Patients self-reported their HRQoL (SF12v2) and their obesity condition was assessed by waist-circumference and Body Mass Index (BMI).ResultsTwo-thirds of patients had a BMI ≥23 kg/m2, almost half were centrally obese and 29% met the criteria for metabolic syndrome. The individual relative-risk of CVD ranged from 0.62 to 15, and 13% had a moderate-to-high 10-year CVD risk score. Regression models showed that lower physical HRQoL was predicted by higher BMI and lower mental HRQoL. Higher Defined Daily Dose, clozapine, younger age and male gender were found to explain 40% of the variance in CVD relative risk.ConclusionThe findings indicate that cardiometabolic health risks in people with SSD may be more common than those reported in the general Hong Kong population. The results also provide further support for the need to consider antipsychotic polypharmacy and higher doses of antipsychotics as factors that may contribute towards cardiometabolic risk in Chinese patients with SSD. Clinicians in Hong Kong should consider using routine CVD risk screening, and be aware that younger male patients who are taking clozapine and prescribed higher Defined Daily Dose seem to have the highest relative-risk of CVD.Trial registrationClinicaltrials.gov NCT02453217. Prospectively registered on 19th May 2015.

Effect of antipsychotic pharmacotherapy on clinical outcomes of intermittent theta-burst stimulation for refractory depression.

Theta-burst stimulation is an emerging protocol for repetitive transcranial magnetic stimulation that takes 1-3 min to administer, yet offers equal/superior potency to conventional protocols lasting 30-60 min. However, preclinical evidence suggests that D2 receptor blockade may abolish the acute effects of theta-burst stimulation on synaptic facilitation or inhibition. As many patients presenting for repetitive transcranial magnetic stimulation are taking antipsychotic medications as augmentation for treatment-resistant depression, this finding is potentially concerning for the implementation of theta-burst stimulation in clinical settings. Here, we examined whether treatment-resistant depression patients taking antipsychotics have worse outcomes after a course of intermittent theta-burst stimulation. A chart review identified 105 treatment-resistant depression patients who underwent dorsomedial prefrontal-intermittent theta-burst stimulation; clinical outcomes on Hamilton Depression Rating Scale and Beck Depression Inventory were compared for those taking and not taking antipsychotics. The 29 of 105 patients who were taking antipsychotics showed non-significantly better response and remission rates, and non-significantly larger percentage improvements on both scales, with a positive but non-significant correlation between higher antipsychotic dose and larger percentage improvement. Contrary to expectations, outcomes were not significantly worse, and in some analyses trended towards being better, in patients taking antipsychotics. Future randomized controlled studies of repetitive transcranial magnetic stimulation combined with standardized dopaminergic manipulations may be justified and warranted.

Metacognition deficits as a risk factor for prospective motivation deficits in schizophrenia spectrum disorders.

Although motivation deficits are key determinants of functional outcomes, little is known about factors that contribute to prospective motivation in people with schizophrenia. One candidate factor is metacognition, or the ability to form complex representations about oneself, others, and the world. This study aimed to assess whether metacognition deficits were a significant predictor of reduced prospective motivation, after controlling for the effects of baseline motivation, anticipatory pleasure, and antipsychotic medication dose. Fifty-one participants with a schizophrenia spectrum disorder completed measures of metacognition and anticipatory pleasure at baseline; participants also completed a measure of motivation at baseline and six months after the initial assessment. Baseline antipsychotic dose was obtained from medical charts. Hierarchical regression analysis revealed that lower levels of baseline metacognition significantly predicted reduced levels of motivation assessed six months later, after controlling for baseline levels of motivation, anticipatory pleasure, and antipsychotic dose. Higher baseline antipsychotic dose was also a significant predictor of reduced six month motivation. Results suggest that metacognition deficits and higher antipsychotic dose may be risk factors for the development of motivation deficits in schizophrenia. Implications include utilizing interventions to improve metacognition in conjunction with evaluating and possibly lowering antipsychotic dose for people struggling with motivation deficits.

Factors Related to Early Clinical Effects of Quetiapine Extended-Release: A Multinational, Prospective, Observational Study.

The first weeks of treatment with antipsychotics are important for the development of their long-term efficacy. The objective of this study was to identify factors related to early clinical effects and quality of life (QoL) improvements with quetiapine extended-release (XR). Six hundred and sixty-five patients starting with quetiapine XR were followed up for 8weeks (schizophrenia=153, major depression=200, bipolar depression=252, other psychiatric conditions=60). Clinical effects were assessed by the Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse events were explored: movement disorders by the UKU and Simpson-Angus scales, weight gain by calibrated balances, and diurnal somnolence by the Epworth Somnolence Scale (ESS). The mean dose of quetiapine XR during follow-up was 195.6±154.8mg/day. CGI and QoL-VAS scores improved significantly at week 8 by 2.7±0.1 points and 25.1±0.9 points. Adverse events were observed in 34 and 26% of patients at weeks 4 and 8, respectively. A significant reduction in ESS score was also observed at week 8. Factors independently associated with change in QoL-VAS≥20 points (n=292, 43%) were female gender, more severe disease at baseline, higher antipsychotic dose during follow-up, and improvements in somnolence. Factors independently associated with clinically significant improvement (CGI-C≥5, n=610, 93%) were greater change in QoL-VAS, less frequent movement disorders at baseline, and lack of adverse events during follow-up, especially somnolence. Results from this real-setting, large observational study in Central America suggest that disease severity at baseline, gender, antipsychotic dose, and occurrence of adverse reactions has a significant impact on the early clinical effects of quetiapine XR. Clinicaltrials.gov registration number NCT02409823.

Does race affect prescribing for acute psychosis? Evaluation by a case vignette

Black people are over represented in mental health services and prescribing of antipsychotics differs by race in some countries. Our previous UK research into the prescribing of antipsychotics in large, multicentre studies found no important differences for black and white patients. However, we received several comments challenging our findings. We wanted to test the validity of these anecdotes by devising two case vignettes that differed only by race and asking prescribers to choose antipsychotic treatment. A case study was sent to all medical prescribers in the South London and Maudsley NHS Trust. Half of the prescribers for each grade of staff were sent the case study where the ethnicity of the patient was white and the other half where the ethnicity was black. Participants were asked to describe what they would prescribe for the patient. Outcomes were total percentage maximum dose, high dose, type of antipsychotic, route of administration and antipsychotic polypharmacy. We received 123 completed case studies and demographic data forms from prescribers. There were no differences in percentage maximum dose, high dose, type, route and number of antipsychotics prescribed by case study ethnicity. Prescribing for UK black and white patients is broadly similar when tested in clinical and theoretical studies.

Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder – Results from a prospective study

BackgroundPeripheral blood brain-derived neurotrophic factor (BDNF) and inflammatory markers may reflect key pathophysiological mechanisms in bipolar disorder in relation to disease activity and neuroprogression. AimsTo investigate whether neutrophins and inflammatory marker vary with mood states and are increased in patients with bipolar disorder type I during euthymia as well as in all affective states as a group, compared to levels in healthy control subjects. MethodsIn a prospective 6–12 months follow-up study, we investigated state specific, intra-individual alterations in levels of BDNF, hsCRP, IL-1β, IL-6, IL-8, IL-18 and TNF-α in 60 patients with bipolar I disorder with an acute severe manic index episode and in subsequent euthymic and depressive and manic states and compared with repeated measurements in healthy control subjects. Data were analysed with linear mixed effects model and with adjustment for gender, age, BMI, alcohol intake and smoking. ResultsFrom inclusion to end of the 6–12 months follow-up, samples of blood were drawn from the 60 patients during a total of 180 affective states, comprising 57 manic, 11 mixed, 23 depressive and 89 states of euthymia. Further, 69 blood samples were drawn from 35 healthy control subjects with three months apart. In unadjusted mixed-model analysis, levels of IL-6 and IL-8 were increased 64% (b=1.64, 95% CI: 1.31–2.05, p=<0.0001) and 24% (b=1.24, 95% CI: 1.05–1.47, p=0.013), respectively in patients with bipolar disorder overall compared with healthy control subjects. However, in adjusted models, no statistically significant differences were found in any measure between patients and control individuals. Levels of hsCRP in depressive states were decreased with 40% (95% CI: 5–62%, p=0.029) compared with euthymia and with 48% (95% CI: 17–66%, p=0.006) when compared with hypomanic/manic states after adjustment. BDNF and the other inflammatory markers did not vary according to affective state in adjusted mixed models. LimitationsPatients were all medicated, specifically with high doses of atypical antipsychotics during the manic index episodes. ConclusionsIn a sample recruited during hospitalization for acute mania, levels of hsCRP varied according to affective state with higher levels during manic states compared with depressive states.

Temporal epilepsy and psychosis - Comorbidities

IntroductionThe simultaneous presence of temporal epilepsy and psychosis includes a careful approach to diagnosis and titration of medication.AimTo achieve remission of comorbid diseases resistant to therapy.MethodsPsychotherapy interview and support, laboratory measurements, EEG, cerebral CT and MRI scan, psychological testing.ResultsThe patient was a girl 16 years of age. In 2011, she started experiencing auditory hallucinations of disturbing content, ideas of persecution, and she feared that people were going to kill her, all of which were bothering her deeply. In the family anamnesis, her grandmother and aunt both suffer from schizophrenia. In the first neurological assessment, there were no abberations. The patient was treated with high doses of various antipsychotics, but the hallucinations became unbearable to the extent that she was about to commit suicide. Anticonvulsive therapy was planned, and in the meantime, a second neurological assessment was performed, which confirmed the coexistence of temporal epilepsy. Combined therapy consisting of anticonvulsive and antipsychotic medication markedly abated the hallucinations. However, the patient began to feel cramping of the right arm, as well as experiencing the negative symptoms of psychosis. She wasn’t functioning normally anymore, she was distinctly adynamic, depressive, with a lack of initiative, and poor memory and concentration. Psychological testing confirmed significant cognitive, emotional and personality disorders (of organic source).ConclusionTreatment of the overlapping symptoms of temporal epilepsy and psychosis is complex, along with the presence of intellectual deterioration.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Dyskinésies tardives induites par les antipsychotiques : données actuelles sur leur prévention et prise en charge

IntroductionTardive dyskinesia (TD) is a movement disorder of tongue, jawbone, trunk and/or limbs that may appear after a prolonged use of dopamine receptor blocking agents (after 3 months of treatment or after 1 month for patients over 60), and that are present during at least four consecutive weeks. TD is a frequent side effect of both classical neuroleptics and new generation antipsychotic drugs. The prevalence of iatrogenic TD is between 24 and 32 % after treatment with classical neuroleptics and about 13 % after treatment with a new generation antipsychotic. ObjectiveThis paper presents an updated literature review of data on diagnosis, prevention and treatment of TD. MethodsWe conducted a review of literature using the Medline Browser tool, screening studies from 1950 to 2013 in English or French with keywords « tardive dyskinesia », « tardive dystonia », and « abnormal movements caused by antipsychotic drugs ». ResultsWe first describe and define semeiological features of TD: dystonia, tremor, myoclonus, acathisie, chorea, ballism and athetosia. Secondarily, we resume the main differential diagnoses to exclude when confronted with this kind of movement disorders. Differential diagnoses for dyskinesia can be classified between primary (Parkinson and Huntington diseases) and secondary (Wilson disease, intoxication, metabolic abnormality, cerebrovascular accident) abnormal movements. Psychogenic TD can be evocated if previous pathologies are excluded in case of atypical clinical presentation. We detail the risk factors for TD. Endogenous risk factors are related to the patient's age, underlying psychiatric disease (bipolar disorder or Alzheimer dementia), addiction to alcohol or cocaine, female gender, or neurodevelopmental vulnerability. Iatrogenic risk factors are high doses of antipsychotics, long or intermittent administration, and particular pharmaceutical classes or associations of antipsychotics. As a comprehensive tool, we review the main physiopathological hypotheses to explain the occurrence of TD in some patients: hypersensitivity of D2 neuronal receptor or neurotoxicity associated with oxidative stress mechanisms. We also summarize the current guidelines for prevention and treatment of TD. Three successive curative strategies are suggested in the literature. First, the clinician can adapt the current antipsychotic treatment (switch to a new generation antipsychotic, diminution or cessation of antipsychotic drugs). If this first intervention is not pertinent or ineffective, the clinician can prescribe an antikinetic therapeutic agent, such as tetrabenazine, or an antioxidant. Review of the published studies does not show proof of efficacy of cholinergic or anticholinergic drugs, benzodiazepine or other GABAergic drugs, nor for amantadine. Non-medication therapeutics such as ECT and TMS are discussed, but the level of proof is insufficient to promote them as a curative treatment for TD. In case of high resistance and discomfort for the patient, a neurosurgical intervention should be discussed. These curative interventions are limited, emphasising the importance of TD prevention, by limiting the prescription and doses of antipsychotics, regularly evaluating their side effects and informing the patient of TD's risk. ConclusionWe propose to practitioners a synthesised update of literature concerning a frequent iatrogenic effect of antipsychotics. Nevertheless, no solid guidelines have as yet been established, and further clinical studies are expected in order to better understand this frequent and discomforting side effect.

Two Sudden and Unexpected Deaths of Patients with Schizophrenia Associated with Intramuscular Injections of Antipsychotics and Practice Guidelines to Limit the Use of High Doses of Intramuscular Antipsychotics.

Intravenous haloperidol has been associated with torsades de pointes (TdP). These two sudden deaths were probable adverse drug reactions (ADRs) following intramuscular (IM) antipsychotics. The autopsies described lack of heart pathology and were highly compatible with the possibility of TdP in the absence of risk factors other than the accumulation of antipsychotics with a high serum peak after the last injection, leading to death within hours. The first case was a 27-year-old African-American male with schizophrenia but no medical issues. His death was probably caused by repeated IM haloperidol injections of 10 mg (totaling 35 mg in 2 days). The second case involves a 42-year-old African-American female with metabolic syndrome. Her probable cause of death was the last ziprasidone IM injection of 20 mg in addition to (1) three extra haloperidol doses (2 hours before the ziprasidone injection, 5 mg oral haloperidol; approximately 21 hours earlier, 5 mg oral haloperidol; and 2 days prior, one 10 mg IM haloperidol injection), (2) 10 mg/day of scheduled oral haloperidol for 6 days before death, and (3) a long-acting paliperidone injection of 156 mg 18 days before death. The study of haloperidol glucuronidation and its impairment in some African-Americans is urgently recommended.

Use of antipsychotics and risk of venous thromboembolism in postmenopausal women. A population-based nested case-control study.

Despite continued uncertainty of venous thromboembolism (VTE) caused from antipsychotic agents, this safety issue has not been examined in postmenopausal women, a population with high usages of antipsychotics and at high risk for VTE. We assessed whether antipsychotic use was associated with an increased VTE risk in women after menopause. We conducted a nested case-control study of all Taiwanese women aged ≥ 50 years (n = 316,132) using a nationwide healthcare claims database between 2000 and 2011. All newly diagnosed VTE patients treated with an anticoagulant or thrombectomy surgery were identified as cases (n = 2,520) and individually matched to select controls (n = 24,223) by cohort entry date, age, cancer diagnosis and major surgery procedure. The odds ratios (ORs) and 95 % confidence interval (CI) of VTE associated with antipsychotics were estimated by multivariate conditional logistic regressions. Current use of antipsychotics was associated with a 1.90-fold (95 % CI = 1.64-2.19) increased VTE risk compared with nonuse in postmenopausal women. The VTE risk existed in a dose-dependent fashion (test for trend, p<0.001), with a more than quadrupled risk for high-dose antipsychotics (adjusted OR = 4.60; 95 % CI = 2.88-7.33). Current parenteral administration of antipsychotics also led to a 3.46-fold increased risk (95 % CI = 2.39-5.00). Conversely, there was no increased VTE risk when antipsychotics were discontinued for > 30 days. In conclusion, current use of antipsychotics is significantly associated with a dose-dependent increased risk of VTE in postmenopausal women, especially for those currently taking high-dose or receiving parenteral antipsychotics.

Antipsychotic Prescribing Patterns in First-episode Schizophrenia: A Five-year Comparison.

ObjectiveEarly treatment choice is critical in first-episode schizophrenia-spectrum disorders. The purpose of this study was to describe prescribing trends of antipsychotics use in patients with first-episode schizophrenia in 2005 and 2010, respectively.MethodsWe reviewed the medical records of newly treated patients with schizophrenia from a university psychiatric hospital in 2005 (n=47) and 2010 (n=52). We defined patients as receiving a high antipsychotic dose if their ratio of prescribed daily dose (PDD) to defined daily dose (DDD) was greater than 1.5.ResultsThe rates of high-dose antipsychotic prescription were 61.7% and 53.8% in 2005 and 2010, respectively. The rates of antipsychotic polypharmacy were 34.6% in 2005 and 34.0% in 2010. The most common first-prescribed antipsychotics were (in descending order of prescription frequency) olanzapine, risperidone, aripiprazole, and haloperidol in 2005 and risperidone, quetiapine, paliperidone, and olanzapine in 2010. High-dose antipsychotics were significantly associated with antipsychotic poly-pharmacy (odds ratio=23.97; p<0.01). More individuals were treated with mood stabilizers in 2010 than in 2005 (p=0.003).ConclusionThe practice of prescribing high-dose antipsychotics and associated antipsychotic polypharmacy were common even for initial treatment of first-episode schizophrenia in 2005 and 2010. In 2010, the list of the most common first-prescribed antipsychotics changed, and the use of mood stabilizers increased in non-affective schizophrenia.

A Pharmacovigilance Study in First Episode of Psychosis: Psychopharmacological Interventions and Safety Profiles in the PEPs Project.

Background:The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice.Methods:Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period.Results:The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, P<.001).Conclusions:These data indicate that the overall pharmacologic prescription for treating a first episode of psychosis in Spain follows the clinical practice guideline recommendations, and, together with security issues, support future research of determinate pharmacological strategies for the treatment of early phases of psychosis, such as the role of clozapine, long-acting injectable antipsychotics, antipsychotic combination, and the use of benzodiazepines.

Cognitive neuropsychological functioning in New Zealand Māori diagnosed with schizophrenia.

Previous research suggests that New Zealand Māori may have an elevated rate of schizophrenia. However, there is limited evidence on important clinical features of the illness in this population. This study examined cognitive neuropsychological functioning in 54 adult Māori diagnosed with schizophrenia and 56 Māori controls. This study also examined associations between cognition, medication and symptoms of psychosis in the schizophrenia group. The groups were matched on socio-demographic variables, handedness and premorbid cognitive ability. Participants were assessed on neuropsychological tests of attention, executive ability, motor, premorbid ability, verbal/non-verbal memory and verbal fluency (English/Māori versions). The Positive and Negative Syndrome Scale was used to assess psychotic symptoms. Information on cultural identity, duration of illness, duration of untreated psychosis, medication and substance abuse was collected. The performance of the schizophrenia group was significantly lower than the control group on all the neuropsychological tests, except the test of attention. The effect sizes were moderate to large: 0.78 for motor function; 1.3 for executive ability, verbal fluency and visual memory; 1.6 for verbal learning and 1.8 for verbal memory. These differences remained after adjustment for multiple comparisons and covariates. A higher dose of antipsychotic medication and a higher anticholinergic load were associated with greater verbal memory impairment (r = -0.38 and r = -0.38, respectively). A longer duration of illness was associated with greater impairment of verbal memory (rho = -0.48), verbal learning (rho = -0.41) and visual memory (rho = -0.44). The findings for the schizophrenia group show a profile of generalised cognitive impairment with greater impairment of verbal memory. The cognitive impairment in this group was independent of psychotic symptoms, but was associated with a higher antipsychotic dose, higher anticholinergic load and longer duration of illness. These findings have implications for clinical prescribing practices and rehabilitation for New Zealand Māori diagnosed with schizophrenia.

Case report: Effectiveness of inhalative loxapin in the treatment of therapy refractory agitation

Agitation is a common symptom occurring in different psychiatric disorders. As a state of severe excitement and tension, agitation may also be associated with aggressive behavior. Thus, there is a great need for treatment options, in particular drug therapies, that have a rapid short-term effect. We treated a 26-year-old patient with mixed personality disorder with antisocial and impulsive features (ICD-10:F61) who frequently presented himself with states of severe agitation and aggression and urgently demanded medication to calm down. In the course of treatment, high doses of several antipsychotics (i. e. quetiapine 1000 mg/d, haloperidole 40 mg/d, olanzapine 50 mg/d) and benzodiazepins (i. e. diazepam 40 mg/d) were given as acute medication, but didn’t show any significant effect on the described states. In the subsequent inpatient care, the patient received inhalative loxapine (Adasuve 9,1 mg) for the first time. Following the first drug administration, there was a rapid and strong improvement of agitation and aggression that lasted for more than 24 hours. In this period, no other medication was required. However, the patient also reported side effects in terms of a marked sedation and sleepiness. Also in subsequent administrations of inhalative loxapine, there was a reliable improvement of symptoms for at least four hours. After discharge from hospital, a comparable effect was obtained by an off-label pnr medication with oral loxapine (up to 3 × 25 mg/d). This case demonstrates that inhalative loxapine may be a beneficial treatment option for agitation in psychiatric patients also beyond the official approval for schizophrenia and bipolar disorder.