Low-dose Antipsychotics Research Articles

Decision-making ability in psychosis: a systematic review and meta-analysis of the magnitude, specificity and correlates of impaired performance on the Iowa and Cambridge Gambling Tasks.

To identify factors which may help or hinder decision-making ability in people with psychosis, we did a systematic review and meta-analysis of their performance on the Iowa and Cambridge Gambling Tasks. Analysis of 47 samples found they had moderately poorer performance than healthy individuals (N = 4264, g = -0.57, 95% confidence interval (CI) -0.66 to -0.48). Few studies (k = 8) used non-psychotic clinical comparator groups, although very low-quality evidence (k = 3) found people with bipolar disorder may perform better. Negative symptoms (k = 13, N = 648, r = -0.17, 95% CI -0.26 to -0.07) and lower IQ (k = 11, N = 525, r = 0.20, 95% CI 0.29-0.10), but not positive symptoms (k = 10, N = 512, r = -0.01, 95% CI -0.11 to 0.08), each had small-moderate associations with poorer decision-making. Lower quality evidence suggested general symptoms, working memory, social functioning, awareness of emotional responses to information, and attentional bias towards gain are associated with decision-making, but not education, executive functioning or overall symptoms. Meta-regression suggested an inverse association between decision-making and depression severity (k = 6, Q = 6.41, R2 100%, p = 0.01). Those taking first-generation (k = 6, N = 305, g = -0.17, 95% CI -0.40 to 0.06, p = 0.147) or low-dose antipsychotics (k = 5, N = 442, g = -0.19, 95% CI -0.44 to 0.06, p = 0.139) had unimpaired decision-making. Although meta-regression found no linear association between dose and performance, non-reporting of the dose was common and associated with larger impairments (k = 46, Q = 4.71, R2 14%, p = 0.03). Those supporting people with psychosis to make decisions, including treatment decisions, should consider the potential effect of these factors. Interventionist-causal trials are required to test whether reducing antipsychotic dose and treating anxiety and depression can improve decision-making in this group.

Very long-term outcome of schizophrenia.

The principal aim is to review recent data concerning the very long-term outcome of schizophrenia and schizophrenia spectrum disorders. We examine factors that influence outcome, including therapeutic interventions. PubMed and Scopus databases were searched for papers published between 2008 and 2017 reporting on prospective studies of schizophrenia or schizophrenia spectrum with a follow-up period ≥5years with adequate outcome information. Additional publications were found in reference lists and authors' reference libraries. The average proportion of patients with symptomatic remission at follow-up ranged between 16.4% in never-treated patients to 37.5% in patients who were systematically treated with antipsychotics. Good outcomes at follow-up were observed in schizophrenia and schizophrenia spectrum patients on low doses of antipsychotics and in patients with no pharmacological treatment at that time. Early detection and intensive treatment of the first episode as well as the availability of continued psychosocial treatment and support over subsequent years appeared associated with better outcomes. The long-term outcome of schizophrenia is highly variable, depending on access to mental healthcare, early detection of psychosis and pharmacological treatment. Recent data support the effectiveness of low-dose antipsychotic treatment for long-term maintenance in some patients. A proportion of first-episode schizophrenia patients, perhaps 20%, do not need long-term maintenance antipsychotic treatment. That proportion may be higher in schizophrenia spectrum patients. The reasons why these patients do not need the long-term treatment are not well understood. Methods to predict the membership in this subgroup are not yet good enough for clinical use in individual patients.

Pharmacotherapy for primary delusional jealousy, a retrospective observational study of 32 cases with Othello syndrome.

To determine whether primary delusional jealousy can be treated effectively with antipsychotics or antidepressants, and whether any clinical variables are associated with response to pharmacotherapy, we carried out a retrospective case series observational study by reviewing clinical records of patients with an International Classification of Disease, 9th ed., diagnostic code of 297 (delusional disorders) who were treated at the Department of Psychiatry of a university affiliated hospital from January 2010 to December 2015. Only those records showing obvious delusional jealousy not secondary to other medical conditions, dementia, or schizophrenia were scrutinized thoroughly with respect to types of pharmacotherapy, treatment response, and other demographic and clinical variables likely to be associated with clinical outcomes. All except one of 32 patients, 16 men and 16 women, between 37 and 79 (60.9±10.6) years of age, were treated with low-dose antipsychotics. The general response was favorable as 19 (59.4%) were rated as good and 13 as inadequate responders (seven partial and six limited). Compared with antipsychotic monotherapy, concomitant therapy with antidepressants had a higher rate of good response, although statistically insignificant (75 vs. 53%, P=0.21). Younger age (P=0.01) and presentation at the index visit with their suspected unfaithful spouse were associated with a good response (P=0.036); comorbidity with delusions other than the jealous type was associated with a poor response (P=0.006). The overall outcome for delusional jealousy looks promising if the patients can accept pharmacotherapy in an outpatient setting.

Malignant catatonia and neuroleptic malignant syndrome: How different/similar are they?

IntroductionCatatonia is a neuropsychiatric syndrome that appears in medical, neurological or psychiatric conditions. There are presentation variants: “malignant catatonia” (MC) subtype shares many characteristics with the neuroleptic malignant syndrome (NMS), possibly reflecting common pathophysiology.Objectives/methodsWe present a clinical vignette and review the literature available on online databases about MC/NMS.ResultsWe present a man, 41-years-old, black ethnicity, with no relevant medical history. He had two previous episodes compatible with brief psychosis, the last one in 2013, and a history of adverse reactions to low doses of antipsychotics. Since the last episode he was asymptomatic on olanzapine 2.5 mg id. He acutely presented to the Emergency Room with mutism, negativism, immobility and delusional speech, similar to the previous episodes mentioned and was admitted to a psychiatric infirmary, where his clinical condition worsened, showing muscle rigidity, hemodynamic instability, leukocytosis, rhabdomyolysis and fever. Supportive care was provided, olanzapine was suspended and electroconvulsive therapy (ECT) was initiated. After two months, he was discharged with no psychotic symptoms. He is still under ECT and no antipsychotic medication was reintroduced.Discussion/conclusionMany studies suggest that clinical or laboratory tests do not distinguish MC from NMS and that they are the same entity. These two conditions are life-threatening and key to treatment is a high suspicion level. There is no specific treatment; supportive care and stopping involved medications are the most widely used measures. ECT is a useful alternative to medication.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Clozapine in schizophrenia and its association with treatment satisfaction and quality of life: Findings of the three national surveys on use of psychotropic medications in China (2002–2012)

ObjectiveWe examined the time trends and correlates of clozapine use in schizophrenia patients in China. MethodA total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were interviewed in 2002, 2006 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and quality of life (QOL) were recorded in a standardized fashion. ResultsClozapine was used in 32.9% of the whole sample; with corresponding figures of 39.7%, 32.5% and 26.4% in 2002, 2006 and 2012 (p<0.001). Families of clozapine users had lower satisfaction with treatment than those of the non-clozapine group, without significant differences with respect to patients' treatment satisfaction and mental or physical QOL. In multiple logistic regression analyses, compared to the non-clozapine group, patients on clozapine had an earlier age of onset, longer illness duration, more global illness severity and drug-induced central nervous system, gastrointestinal and other side effects, lower antipsychotic doses, less delusions and hallucinations, more negative symptoms, were more likely male, inpatients, to have a family history of psychiatric disorders, receive treatments in regional centers and receive antipsychotic polypharmacy, but less likely to have health insurance and receive first-generation antipsychotics and benzodiazepines (R2=0.498, p<0.001). ConclusionsClozapine was used in one-third of schizophrenia patients in China, with decreasing frequency since 2002. Patients prescribed clozapine had multiple markers of greater global illness severity/chronicity and decreased satisfaction with treatment by the families, but similar QOL and less delusions and hallucinations than patients not prescribed clozapine.

Co-morbid anxiety disorders in patients with schizophrenia in a tertiary institution in South East Nigeria: prevalence and correlates.

Anxiety disorders occur commonly in schizophrenia but are often overlooked by psychiatrists. Their presence may compound the challenges faced by these patients and may contribute to poor outcome. The purpose of this study was to determine the prevalence of anxiety disorders among the participants with schizophrenia, and the association between this co-morbidity and disability. A total of 367 participants were recruited from the out-patient department of Federal neuropsychiatric hospital Enugu, Nigeria. Socio-demographic questionnaire, schedules for clinical assessment in neuropsychiatry, positive and negative syndrome scale and the 12-item version of the World Health Organization disability assessment schedule were administered. A total of 189 females (51.5%) and 178 (48.5%) males were studied. A lifetime prevalence of 12.3% was reported for anxiety disorder. Anxiety disorder was more likely in females (ϰ(2)=4.93, p<0.03). Specific prevalence for anxiety disorder in schizophrenia was generalized anxiety disorder 6.3%, obsessive compulsive disorder 3.3%, and phobic anxiety disorder 2.7%. Anxiety disorder was associated with increased disability (t=3.50, p<0.001) and psychopathology (t=3.40, p<0.001) among the participants studied. Phobias were associated with prescription of low doses of antipsychotics (ϰ(2)=4.08, p<0.04). There was a low rate of identification of anxiety disorder in routine clinical practice (k=0.08, p<0.001). Co-morbid anxiety disorders are common in schizophrenia and they are associated with increased disability and psychopathology. The results emphasize the need to screen for anxiety disorders in patients with schizophrenia.

Acupuncture for schizophrenia.

Acupuncture, with many categories such as traditional acupuncture, electroacupuncture, laser acupuncture, and acupoint injection, has been shown to be relatively safe with few adverse effects. It is accessible and inexpensive, at least in China, and is likely to be widely used there for psychotic symptoms. To review the effects of acupuncture, alone or in combination treatments compared with placebo (or no treatment) or any other treatments for people with schizophrenia or related psychoses. We searched Cochrane Schizophrenia Group's Trials Register (February 2012), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO and clinical trials registries. We also inspected references of identified studies and contacted relevant authors for additional information. We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, comparing acupuncture added to standard dose antipsychotics with standard dose antipsychotics alone, acupuncture added to low dose antipsychotics with standard dose antipsychotics, acupuncture with antipsychotics, acupuncture added to Traditional Chinese Medicine (TCM) drug with TCM drug, acupuncture with TCM drug, electric acupuncture convulsive therapy with electroconvulsive therapy. We reliably extracted data from all included studies, discussed any disagreement, documented decisions and contacted authors of studies when necessary. We analysed binary outcomes using a standard estimation of risk ratio (RR) and its 95% confidence interval (CI). For continuous data, we calculated mean differences with 95% CI. For homogeneous data we used fixed-effect model. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. After an update search in 2012 the review now includes 30 studies testing different forms of acupuncture across six different comparisons. All studies were at moderate risk of bias.When acupuncture plus standard antipsychotic treatment was compared with standard antipsychotic treatment alone, people were at less risk of being 'not improved' (n = 244, 3 RCTs, medium-term RR 0.40 CI 0.28 to 0.57, very low quality evidence). Mental state findings were mostly consistent with this finding as was time in hospital (n = 120, 1 RCT, days MD -16.00 CI -19.54 to -12.46, moderate quality evidence). If anything, adverse effects were less for the acupuncture group (e.g. central nervous system, insomnia, short-term, n = 202, 3 RCTs, RR 0.30 CI 0.11 to 0.83, low quality evidence).When acupuncture was added to low dose antipsychotics and this was compared with standard dose antipsychotic drugs, relapse was less in the experimental group (n = 170, 1 RCT, long-term RR 0.57 CI 0.37 to 0.89, very low quality evidence) but there was no difference for the outcome of 'not improved'. Again, mental state findings were mostly consistent with the latter. Incidences of extrapyramidal symptoms - akathisia, were less for those in the acupuncture added to low dose antipsychotics group (n = 180, 1 RCT, short-term RR 0.03 CI 0.00 to 0.49, low quality evidence) - as dry mouth, blurred vision and tachycardia.When acupuncture was compared with antipsychotic drugs of known efficacy in standard doses, there were equivocal data for outcomes such as 'not improved' using different global state criteria. Traditional acupuncture added to TCM drug had benefit over use of TCM drug alone (n = 360, 2 RCTs, RR no clinically important change 0.11 CI 0.02 to 0.59, low quality evidence), but when traditional acupuncture was compared with TCM drug directly there was no significant difference in the short-term. However, we found that participants given electroacupuncture were significantly less likely to experience a worsening in global state (n = 88, 1 RCT, short-term RR 0.52 CI 0.34 to 0.80, low quality evidence).In the one study that compared electric acupuncture convulsive therapy with electroconvulsive therapy there were significantly different rates of spinal fracture between the groups (n = 68, 1 RCT, short-term RR 0.33 CI 0.14 to 0.81, low quality evidence). Attrition in all studies was minimal. No studies reported death, engagement with services, satisfaction with treatment, quality of life, or economic outcomes. Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia.

Acupuncture for schizophrenia.

Background Acupuncture, with many categories such as traditional acupuncture, electroacupuncture, laser acupuncture, and acupoint injection, has been shown to be relatively safe with few adverse effects. It is accessible and inexpensive, at least in China, and is likely to be widely used there for psychotic symptoms. Objectives To review the effects of acupuncture, alone or in combination treatments compared with placebo (or no treatment) or any other treatments for people with schizophrenia or related psychoses. Search methods We searched Cochrane Schizophrenia Group’s Trials Register (February 2012), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO and clinical trials registries. We also inspected references of identified studies and contacted relevant authors for additional information. Selection criteria We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, comparing acupuncture added to standard dose antipsychotics with standard dose antipsychotics alone, acupuncture added to low dose antipsychotics with standard dose antipsychotics, acupuncture with antipsychotics, acupuncture added to Traditional Chinese Medicine (TCM) drug with TCM drug, acupuncture with TCM drug, electric acupuncture convulsive therapy with electroconvulsive therapy. Data collection and analysis We reliably extracted data from all included studies, discussed any disagreement, documented decisions and contacted authors of studies when necessary. We analysed binary outcomes using a standard estimation of risk ratio (RR) and its 95% confidence interval (CI). For continuous data, we calculated mean differences with 95% CI. For homogeneous data we used fixed-effect model. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. Main results After an update search in 2012 the review now includes 30 studies testing different forms of acupuncture across six different comparisons. All studies were at moderate risk of bias. When acupuncture plus standard antipsychotic treatment was compared with standard antipsychotic treatment alone, people were at less risk of being 'not improved' (n = 244, 3 RCTs, medium-term RR 0.40 CI 0.28 to 0.57, very low quality evidence). Mental state findings were mostly consistent with this finding as was time in hospital (n = 120, 1 RCT, days MD -16.00 CI -19.54 to -12.46, moderate quality evidence). If anything, adverse effects were less for the acupuncture group (e.g. central nervous system, insomnia, short-term, n = 202, 3 RCTs, RR 0.30 CI 0.11 to 0.83, low quality evidence). When acupuncture was added to low dose antipsychotics and this was compared with standard dose antipsychotic drugs, relapse was less in the experimental group (n = 170, 1 RCT, long-term RR 0.57 CI 0.37 to 0.89, very low quality evidence) but there was no difference for the outcome of 'not improved'. Again, mental state findings were mostly consistent with the latter. Incidences of extrapyramidal symptoms - akathisia, were less for those in the acupuncture added to low dose antipsychotics group (n = 180, 1 RCT, short-term RR 0.03 CI 0.00 to 0.49, low quality evidence) - as dry mouth, blurred vision and tachycardia. When acupuncture was compared with antipsychotic drugs of known efficacy in standard doses, there were equivocal data for outcomes such as 'not improved' using different global state criteria. Traditional acupuncture added to TCM drug had benefit over use of TCM drug alone (n = 360, 2 RCTs, RR no clinically important change 0.11 CI 0.02 to 0.59, low quality evidence), but when traditional acupuncture was compared with TCM drug directly there was no significant difference in the short-term. However, we found that participants given electroacupuncture were significantly less likely to experience a worsening in global state (n = 88, 1 RCT, short-term RR 0.52 CI 0.34 to 0.80, low quality evidence). In the one study that compared electric acupuncture convulsive therapy with electroconvulsive therapy there were significantly different rates of spinal fracture between the groups (n = 68, 1 RCT, short-term RR 0.33 CI 0.14 to 0.81, low quality evidence). Attrition in all studies was minimal. No studies reported death, engagement with services, satisfaction with treatment, quality of life, or economic outcomes. Authors' conclusions Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia.

Reducing antipsychotics in dementia

The prescribing of low-dose antipsychotics for challenging behaviour for people with dementia gained prominence following media attention and the publication of the Banerjee report in 2006[1]. The report identified that there are an estimated 180,000 people with dementia on antipsychotic drugs. However, in only about one-third of cases were the drugs beneficial. There were 1,800 […]

Antipsychotic combination using low-dose antipsychotics is as efficacious and safe as, but cheaper, than optimal-dose monotherapy in the treatment of schizophrenia

The use of antipsychotic combination has been increasing during the last decade. This study aimed to compare the efficacy and safety of low-dose amisulpride plus low-dose sulpiride with full-dose amisulpride in the treatment of acute schizophrenia. In this 6-week, double-blind, fixed-dose study, patients were randomized to antipsychotic combination (400 mg/day amisulpride plus 800 mg/day sulpiride, N=46) or monotherapy (800 mg/day amisulpride, N=46) groups. Efficacy measurements included the Positive and Negative Syndrome Scale (PANSS) and subscales, and other scales. Safety and quality of life were also assessed. Response was defined as a 30% reduction in the PANSS total score. Both groups were similar in terms of the following: (a) clinical characteristics at baseline, (b) response rates, and (c) score changes in all psychopathology measures, quality of life, and all side-effect scales after 6 weeks of treatment. There were also no significant between-group differences in changes in other safety measurement. However, the combination strategy did reduce treatment costs. The current study suggests that an antipsychotic combination of low-dose antipsychotics is as efficacious and safe as, but cheaper than, optimal-dose monotherapy in the treatment of schizophrenia.

Optimal Extent of Dopamine D2 Receptor Occupancy by Antipsychotics for Treatment of Dopamine Supersensitivity Psychosis and Late-Onset Psychosis

Several studies have proposed an optimal dopamine D2 receptor occupancy by antipsychotics (OOc) to establish optimal pharmacological treatment of schizophrenia. However, there are limitations to the use of the OOc, especially in application to patients with treatment-resistant schizophrenia, including dopamine supersensitivity psychosis (DSP) or late-onset psychosis (LOP). It has been suggested that D2 receptor density is up-regulated by chronic treatment of antipsychotics in DSP, whereas it may be low in LOP owing to age-related reduction. In estimation of the proposed OOc, these alterations have not been taken into account, which may be one of the factors contributing to the limited application of this index. We here hypothesize that there is an optimal range in the number of D2 receptors available for dopamine binding to elicit adequate neurotransmission in the treatment of patients with schizophrenia. We then estimated the OOc under the assumption that the range is constant while D2 density is variable. The results showed that the OOc and plasma level of antipsychotics increase with an increase in the D2 density but decrease with a decrease in the D2 density. That is, if the range of OOc is 65% to 78% in a standard D2 density, it becomes 82% to 89% under 2-fold up-regulated density and 42% to 63% under a 40% reduced density. The results also indicated that the reduction of the plasma antipsychotic level is greater during a given time period in patients with higher D2 density, as they need a higher antipsychotic dose to achieve the raised OOc, which would account for the clinical features of DSP, for example, acute exacerbation after a discontinuation of antipsychotics. On the other hand, in patients with lower D2 density, only a lower antipsychotic dose will achieve the OOc, and a small increase in the dose will result in a greater increase in occupancy and induce extrapyramidal adverse effects more easily. Furthermore, the reduction of the plasma antipsychotic level during the time period is smaller, which prolongs extrapyramidal adverse effects after discontinuation of antipsychotics in LOP. We also attempted to develop a strategy for the prevention and treatment of patients with DSP or LOP by focusing on D2 density.

Facial ulcer treated with olanzapine

A 69-year-old woman presented with a nonhealing ulcer on her right cheek. On histological examination of a biopsy, no evidence of granuloma formation or malignancy was found, and the overall picture was felt to be consistent with dermatitis artefacta (DA). The patient was referred to a joint psychodermatology clinic, where treatment with risperidone was started. However, at follow-up the ulcer remained unchanged, and treatment was changed to olanzapine 2.5 mg twice daily. Within 10 months, the large facial ulcer, which had been refractory to treatment for several years, had completely healed. Anxiolytics, antidepressants and low-dose antipsychotics have been shown to be helpful in the management of DA. Successful treatment with olanzapine has been described. The good clinical response to olanzapine may be attributed to its anti-impulsive effect, antihistaminic properties and low risk of parkinsonian side-effects.

What Do We Really Know About the Treatment of Delirium with Antipsychotics? Ten Key Issues for Delirium Pharmacotherapy

Despite the significant burden of delirium among hospitalized adults, no pharmacologic intervention is approved for delirium treatment. Antipsychotic agents are the best studied but there are uncertainties as to how these agents can be optimally applied in everyday practice. We searched Medline and PubMed databases for publications from 1980 to April 2012 to identify studies of delirium treatment with antipsychotic agents. Studies of primary prevention using pharmacotherapy were not included. We identified 28 prospective studies that met our inclusion criteria, of which 15 were comparison studies (11 randomized), 2 of which were placebo-controlled. The quality of comparison studies was assessed using the Jadad scale. The DRS (N = 12) and DRS-R98 (N = 9) were the most commonly used instruments for measuring responsiveness. These studies suggest that around 75% of delirious patients who receive short-term treatment with low-dose antipsychotics experience clinical response. Response rates appear quite consistent across different patient groups and treatment settings. Studies do not suggest significant differences in efficacy for haloperidol versus atypical agents, but report higher rates of extrapyramidal side effects with haloperidol. Comorbid dementia may be associated with reduced response rates but this requires further study. The available evidence does not indicate major differences in response rates between clinical subtypes of delirium. The extent to which therapeutic effects can be explained by alleviation of specific symptoms (e.g. sleep or behavioral disturbances) versus a syndromal effect that encompasses both cognitive and noncognitive symptoms of delirium is not known. Future research needs to explore the relationship between therapeutic effects and changes in pathophysiological markers of delirium. Less than half of reports were rated as reasonable quality evidence on the Jadad scale, highlighting the need for future studies of better quality design, and in particular incorporating placebo-controlled work.

A pharmacy led program to review anti-psychotic prescribing for people with dementia

BackgroundAnti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics.MethodsThis project was conducted within primary care in Medway Primary Care Trust (PCT) in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people with dementia prescribed anti-psychotics. Second, a trained specialist pharmacist conducted targeted clinical medication reviews in people with dementia initiated on anti-psychotics by primary care, identified by the data search.ResultsData were collected from 59 practices. One hundred and sixty-one (15.3%) of 1051 people on the dementia register were receiving low-dose anti-psychotics. People with dementia living in residential homes were nearly 3.5 times more likely to receive an anti-psychotic [25.5% of care home residents (118/462) vs. 7.3% of people living at home (43/589)] than people living in their own homes (p < 0.0001; Fisher’s exact test). In 26 practices there was no-one on the dementia register receiving low-dose anti-psychotics.Of the 161 people with dementia prescribed low-dose anti-psychotics, 91 were receiving on-going treatment from local secondary care mental health services or Learning Disability Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or the dosage was reduced, in 43 instances (61.4%) following the pharmacy-led medication review.ConclusionsIn total 15.3% of people on the dementia register were receiving a low-dose anti-psychotic. However, such data, including the recent national audit may under-estimate the usage of anti-psychotics in people with dementia. Anti-psychotics were used more commonly within care home settings. The pharmacist-led medication review successfully limited the prescribing of anti-psychotics to people with dementia.

P-1463 - Menopause and schizophrenia: wich links?

In the past, some authors postulated that many women with schizophrenia showed signs of “hypoestrogenism”, suggesting that women became psychotic mainly before or during menstruation. Kraepelin created the diagnostic category “Menstrual Psychosis”. Understand a possible relationship between menopause/estrogens and the development of schizophrenia. Bibliographic search in Pubmed and textbooks. Several authors observed a relationship between estrogen levels and psychotic symptoms. Some facts contribute to this hypothesis like late-onset schizophrenia being more frequent in women, a second peak for onset of the disease, psychosis in temporal relationship with ovary surgery, puerperium and oscillations throughout the menstrual cycle, lower doses of antipsychotics during pregnancy. For some authors, estrogens also exert a “protective” effect over psychotic symptoms, beyond other several known effects on various psychopathological aspects, namely through antidopaminergic actions as well as modulation of apoptosis and improvement of depressive and negative symptoms. Although some evidence confirms this theory, the estrogen hypothesis is not universally accepted, some authors claiming the existence of other biological, emotional and social factors that should be considered in menopause. The etiology of the gender differences in schizophrenia is not yet well understood, but hormone-gene interactions may explain part of the mechanism. The psychiatric interview should explore menstrual irregularities or galactorrhoea, and, with increasing evidence, serum levels of prolactin and estrogens may become part of the routine tests. In the future, treatment with hormone replacement therapy may be a possibility for these patients.

Pharmacothérapie des troubles de la personnalité

Drug treatment of personality disorders is less developed than are psychological treatments in this area, but they are a logical prolongation of psychobiological models of personality and temperament, and respond to the need of many clinicians in front of difficult patients. The results obtained in the field of pharmacotherapy of personality disorders can be classified according to DSM-IV axis-II categorization. In anxious personalities (cluster C), some isolated studies suggest a favourable effect of antidepressants on obsessive-compulsive dimension, on avoidant personality disorder, and on inhibition and trait-anxiety, especially when serotoninergic agents are used. Few studies have been conducted in cluster A personality disorders, and some are in favour of the interest of low doses of antipsychotic drugs in this group. Most studies have been conducted in cluster B, and especially in antisocial and borderline personality disorders. Partial positive results have been obtained using various classes of drugs for dealing with aggression and impulsive behaviors, including lithium, beta-blockers, carbamazepine, valproate, antipsychotic drugs, and also SSRIs. Self-harm and suicidal behaviors seem to be partially but significantly improved by antidepressants and low doses of antipsychotics. Overall, the pharmacotherapy of personality disorder may lead in the future to the development of effective treatments, in complement to psychotherapy, for actually severe, chronic, and disabling disorder.

Gender differences in Singaporean Chinese patients with schizophrenia

The purpose of this study was to compare gender differences in age of onset of illness, clinical features and prescription patterns in Chinese schizophrenia patients in Singapore. A cross-sectional study was conducted which recruited 903 subjects diagnosed with schizophrenia from the Institute of Mental Health between 2005 and 2008. Information on age of onset of schizophrenia, body mass index (BMI), psychiatric family history and current medication was collected via a standardised collection form. Symptom severity was assessed with Positive and Negative Syndrome Scale (PANSS). Differences in age of onset of schizophrenia illness, clinical features and prescription patterns were compared between gender groups. Among sporadic schizophrenia cases, female subjects demonstrated a bimodal distribution in age of onset of illness, and had a significantly later age of illness onset compared with male subjects. For subjects with family history of psychiatric disorder, no significant gender differences were found in age of onset of illness. Female subjects had significantly higher BMI, higher proportion of diabetes mellitus, lower negative symptom scores and were prescribed more atypical antipsychotics and antidepressants compared with male subjects. Male subjects after age 50 were prescribed a lower antipsychotic dose, but this difference was not observed in female subjects. In conclusion, we found differences in age of onset of schizophrenia, severity of negative symptoms and prescription patterns between the male and female gender groups in Chinese schizophrenia patients in Singapore. These differences were consistent with findings from Caucasian population, and could possibly be explained by influences of oestrogen.

Adjunctive benzodiazepine treatment of hospitalized schizophrenia patients in Asia from 2001 to 2008

Benzodiazepines are commonly prescribed to patients with schizophrenia in many countries, but as little is known about such treatment in Asia, we evaluated their adjunctive use for 6761 in-patients diagnosed with schizophrenia in nine Asian countries using a cross-sectional study design in 2001, 2004 and 2008. Multivariate logistic regression and multivariate linear regression analyses were performed to assess predictors of benzodiazepine use and dose, respectively. Overall, 54% of the patients received adjunctive benzodiazepines at an average daily dose equivalent to 30.3 mg diazepam, with minor changes over the years sampled. Benzodiazepine use was highest in Taiwan and Japan, lowest in Thailand and China, and was associated with fewer years ill, presence of delusions (OR 1.24), hallucinations (OR 1.22), disorganized speech (OR 1.17), social or occupational dysfunction (OR 1.16), and use of mood stabilizers (OR 3.15), antiparkinsonian (OR 1.79) or antidepressant drugs (OR 1.33), and lower doses of antipsychotics (all p=0.016 to <0.001). Benzodiazepine doses were highest in Taiwan and China, lowest in Korea and Singapore; higher doses were associated with being young, male, physically aggressive, receiving mood stabilizers, and having electroconvulsive treatment (all p=0.019 to <0.001). Benzodiazepine use was associated with neurological and systemic adverse effects. In conclusion, benzodiazepine use was common in Asian patients with schizophrenia. Predictors of benzodiazepine use and dose differed in this population. Critical clinical guidelines should be developed specifically for Asian countries to address sound practices in regard to use of benzodiazepines for psychotic disorders.

Reconnaître les symptômes psychiatriques iatrogènes liés aux antipsychotiques

This article proposes a review of atypical multicentre studies for drug-induced movement disorders (and related psychiatric symptoms) and supersensitivity psychosis. A well-conducted antipsychotic treatment consists of regular attempts to reduce the dose by finding the minimal therapeutic dose. To achieve optimal antipsychotic treatment, it is important to distinguish psychiatric symptoms associated with drug-induced movement disorder(s) (DIMD) or supersensitivity psychosis from true relapse. Persistent DIMD have been found to be a predictor of supersensitivity psychosis or tardive dyskinesia (DT). DIMD-associated psychiatric symptoms can be classified into three types: directly induced by DIMD; resulting from confounding DIMD with psychiatric symptoms; and supersensitivity symptoms associated with DIMD. Without this distinction, the beneficial effects of antipsychotics are masked by emergent DIMD psychiatric symptoms (as was confounded in the CATIE study). A constant decline in the prevalence of TD (hyperkinetic, involuntary and purposeless movement disorder) has been observed since the introduction of atypical antipsychotics. The neurotoxic effects of classical antipsychotics are well documented and their discontinuation is required. However, the risk of TD still exits with atypical antipsychotics and continued surveillance of emerging cases is very important for clinicians. Moreover, a regular evaluation of DIMD and associated psychiatric symptoms is crucial. It is important to underline the fact that DIMD persists with antipsychotics, with significantly higher total PANSS scores than in patients without DIMD. Supersensitivity psychosis is a drug-induced psychotic relapse (6 weeks following the decrease or withdrawal of an antipsychotic). Discontinuation syndromes can produce psychiatric symptoms (and be confounded with true relapse), but can be improved more quickly after reintroduction of treatment. Interestingly, various data suggest that lower doses of antipsychotics could prevent such symptoms. Anticonvulsants can be efficient adjuvants in the treatment of psychosis. In the United States, many patients received valproate or gabapentin treatment. These adjuvants, by antikindling effect, can facilitate minimal maintenance drug treatment and be efficient for anxiety. Resistant schizophrenia can be related to supersensitivity psychosis; gabapentin and lamotrigine are effective in this case.

Is late‐onset schizophrenia a subtype of schizophrenia?

To determine whether late-onset schizophrenia (LOS, onset after age 40) should be considered a distinct subtype of schizophrenia. Participants included 359 normal comparison subjects (NCs) and 854 schizophrenia out-patients age >40 (110 LOS, 744 early-onset schizophrenia or EOS). Assessments included standardized measures of psychopathology, neurocognition, and functioning. Early-onset schizophrenia and LOS groups differed from NCs on all measures of psychopathology and functioning, and most cognitive tests. Early-onset schizophrenia and LOS groups had similar education, severity of depressive, negative, and deficit symptoms, crystallized knowledge, and auditory working memory, but LOS patients included more women and married individuals, had less severe positive symptoms and general psychopathology, and better processing speed, abstraction, verbal memory, and everyday functioning, and were on lower antipsychotic doses. Most EOS-LOS differences remained significant after adjusting for age, gender, severity of negative or deficit symptoms, and duration of illness. Late-onset schizophrenia should be considered a subtype of schizophrenia.