Atypical Depot Research Articles

Ethnic and Age Disparities in Patients Taking Long-acting Injectable Atypical Antipsychotics.

IntroductionThis study will determine whether different ethnicities and different age groups receive equal amounts of long-acting atypical antipsychotics in comparison to their oral equivalents.MethodsSecondary analyses of data from the Los Angeles County Department of Health Services Electronic Health Record (total N=63,134 inpatient visits) were performed. Chi-squared statistics were used to compare ethnicity and age with the use of either risperidone injectable or paliperidone palmitate (r-LAIs) versus risperidone oral.ResultsAmong the 63,134 total inpatient visits, there were 3,011 patient visits that included the use of an atypical antipsychotic. Of these 3,011 visits, 452 (15.0%) were on r-LAIs and 2,559 (85.0%) were on risperidone oral. No statistically significant disparities were identified with the use of r-LAIs as compared to oral risperidone amongst ethnic groups (chi-square = 0.88, df = 3, p = 0.831). However, there was a statistically significant difference with the use of r-LAIs as compared to oral Risperidone amongst age groups, favoring younger patients (chi-square = 13.46, df = 3, p < 0.004).ConclusionOur data indicate a lack of ethnic disparities in prescribing long-acting atypical antipsychotics and an increased percentage of younger patients being treated with atypical depot antipsychotics over their oral equivalents.

Economic analysis of paliperidone long-acting injectable for chronic schizophrenia in Portugal

Objective: Patients with chronic schizophrenia suffer a huge burden, as do their families/caregivers. Treating schizophrenia is costly for health systems. The European Medicines Agency has approved paliperidone palmitate (PP-LAI; Xeplion), an atypical antipsychotic depot; however, its pharmacoeconomic profile in Portugal is unknown. A cost-effectiveness analysis was conducted from the viewpoint of the Portuguese National Health Service.Methods: PP-LAI was compared with long acting injectables risperidone (RIS-LAI) and haloperidol (HAL-LAI) and oral drugs (olanzapine; oral-OLZ) adapting a 1-year decision tree to Portugal, guided by local experts. Clinical information and costs were obtained from literature sources and published lists. Outcomes included relapses (both requiring and not requiring hospitalization) and quality-adjusted life-years (QALYs). Costs were expressed in 2014 euros. Economic outcomes were incremental cost-effectiveness ratios (ICERs); including cost-utility (outcome = QALYs) and cost-effectiveness analyses (outcomes = relapse/hospitalization/emergency room (ER) visit avoided).Results: The base-case cost of oral-OLZ was 4447€ (20% drugs/20% medical/60% hospital); HAL-LAI cost 4474€ (13% drugs/13% medical/74% hospital); PP-LAI cost 5326€ (49% drugs/12% medical/39% hospital); RIS-LAI cost 6223€ (44% drugs/12% medical/44% hospital). Respective QALYs/hospitalizations/ER visits were oral-OLZ: 0.761/0.615/0.242; HAL-LAI: 0.758/0.623/0.250; PP-LAI: 0.823/0.288/0.122; RIS-LAI: 0.799/0.394/0.168. HAL-LAI was dominated by oral-OLZ and RIS-LAI by PP-LAI for all outcomes. The ICER of PP-LAI over oral-OLZ was 14,247€/QALY, well below NICE/Portuguese thresholds (≈24,800€/30,000€/QALY). ICERs were 1973€/relapse avoided and 2697€/hospitalization avoided. Analyses were robust against most variations in input values, as PP-LAI was cost-effective over oral-OLZ in >99% of 10,000 simulations.Conclusion: In Portugal, PP-LAI dominated HAL-LAI and RIS-LAI and was cost-effective over oral-OLZ with respect to QALYs gained, relapses avoided, and hospitalizations avoided.

Risperidone (depot) for schizophrenia.

This is a copy of an article published in the Cochrane Database of Systematic Reviews © 2016 Cochrane Collaboration Publications. © The Author(s). http://www.cochranelibrary.com/

Indication of depot antipsychotic treatment in the view of slovak psychiatrists

With the increasing number of atypical antipsychotics in depot form, there emerges question about plus and cons of their use in schizophrenia patients. We focused on the opinion of Slovak psychiatrists about use of this treatment in some specific situations of schizophrenia treatment. Research was realized via questionnaire on psychiatrists (n = 47) from ambulant and hospital care, during one conference in June 2015. First part of the questionnaire was focused on the preference of oral or depot form of antipsychotic treatment. Depot form would be indicated by psychiatrists (in more than 89%) when low compliance, anosognosia or frequent episodes. On the contrary, oral antipsychotic treatment is preferred in young patients or employed patients. The type of symptoms (e.g. positive, negative) has relatively small impact on the preference of treatment, where the preferences of each type were the lowest (fewer than 36%). According to the opinion of psychiatrists, depot antipsychotic treatment is not suitable in first episode of disorder (according to 81% of respondents), otherwise in second or third episode it would not be chosen by 6% of asked psychiatrists.From the aspects of the choice between atypical or typical depot, atypical antipsychotics in depot form were favored when presence of adverse reactions (80%), occurrence of negative symptoms (65%) and short duration of disorder (58%). Typical depot was preferred by psychiatrists in patients with chronic states.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Role of miRNAs in Epicardial Adipose Tissue in CAD Patients with T2DM

Background. Epicardial adipose tissue (EAT) is identified as an atypical fat depot surrounding the heart with a putative role in the involvement of metabolic disorders, including obesity, type-2 diabetes mellitus, and atherosclerosis. We profiled miRNAs in EAT of metabolic patients with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) versus metabolically healthy patients by microarray. Compared to metabolically healthy patients, we identified forty-two miRNAs that are differentially expressed in patients with CAD and T2DM from Xinjiang, China. Eleven miRNAs were selected as potential novel miRNAs according to P value and fold change. Then the potential novel miRNAs targeted genes were predicted via TargetScan, PicTar, and miRTarbase, and the function of the target genes was predicted via Gene Ontology (GO) analysis while the enriched KEGG pathway analyses of the miRNAs targeted genes were performed by bioinformatics software DAVID. Then protein-protein interaction networks of the targeted gene were conducted by online software STRING. Finally, using microarray, bioinformatics approaches revealed the possible molecular mechanisms pathogenesis of CAD and T2DM. A total of 11 differentially expressed miRNAs were identified and among them, hsa-miR-4687-3p drew specific attention. Bioinformatics analysis revealed that insulin signaling pathway is the central way involved in the progression of metabolic disorders. Conclusions. The current findings support the fact that miRNAs are involved in the pathogenesis of metabolic disorders in EAT of CAD patients with T2DM, and validation of the results of these miRNAs by independent and prospective study is certainly warranted.

Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic

Purpose:The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots.Methods:An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables.Results:Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates.Conclusions:PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.

Working alliance and its relationship to outcomes in a randomized controlled trial (RCT) of antipsychotic medication.

BackgroundLong acting injections (LAI) have been associated with perceptions of coercion in cross sectional studies but there have been no longitudinal studies of the effects on clinical relationships with newer depot medications.MethodRandomized controlled trial with (50) participants with a diagnosis of schizophrenia randomized to risperidone LAI or oral atypical antipsychotic medication. The main outcome was the Working Alliance Inventory (WAI) with background variables (symptoms, side effect, social functioning, quality of life) measured before randomization and at two years.ResultsAt follow-up (14 risperidone LAI and 16 oral medication) analyses including predictors of missing data and baseline score showed a trend for those on risperidone LAI to reduce WAI score and those on oral medication showing no change. Sensitivity analyses showed (i) a significant detrimental effect of LAI on WAI and (ii) the pattern of results was not affected by change in symptoms over the study.ConclusionThis is the first study to show that the prescription of depot atypical depot medication is associated with detrimental effects on clinical relationships after 2 years of continual treatment.

Influences on Therapist’s Decisions for Neuroleptic Treatment in Schizophrenia: The Role of Characteristics of the Patient and the Physician

We investigated factors influencing physicians' treatment decisions regarding 4 antipsychotic treatment strategies for schizophrenia (conventional oral/conventional depot/atypical oral/atypical depot). We analysed the influence of the patient's compliance with medication, socio-economic status (occupational prestige/educational attainment), as well as the influence of gender, age and practice setting (psychiatric/general hospital/private practice) of the prescribing physician.We examined the influence of these factors by means of case vignettes. 4 vignettes were constructed with varying levels for compliance and socio-economic status. For each vignette, physicians had to choose one treatment strategy from the 4 alternatives. Data were collected using a survey (n=1 342) of physicians in Germany and analysed using a weighted least-squares regression model and a random-effect logit model.Compliance and status had interactive effects on treatment selection. Low compliance was associated with an increase in selections of depot medication. For high-status, noncompliant patients, physicians selected mainly atypical oral and atypical depot antipsychotics. Low-status, noncompliant patients were mostly given conventional and atypical depot antipsychotics. Noncompliant, low-status patients received conventional depot antipsychotics 4 times as often as noncompliant, high-status patients. The physician's age and practice setting were also related to the treatment selection.Therapeutic decisions are influenced by patients' and the physicians' characteristics. There might be barriers for patients with low compliance and low socio-economic status that prevent them from being prescribed newer medications. Not all physicians seem to have the same choices of treatment options available to them.

C.05.03 The role of novel atypical depot formulations in helping to improve long-term outcomes in schizophrenia

C.05.03 The role of novel atypical depot formulations in helping to improve long-term outcomes in schizophrenia

P03-282 - Patients’ attitudes to antipsychotic depot medication

IntroductionThe advantages of conventional depots (CDs) in treating schizophrenia have been demonstrated in several studies. Indeed, the use of CDs continues to have a great importance in our psychiatric sectors due to the unavailability of atypical depot formulations.ObjectiveThe aim of this work was to assess the perspectives of patients with schizophrenia towards CDs.MethodsWe conducted a cross-sectional survey using fifty schizophrenic/schizoaffective outpatients treated by CDs for at least 3 months. The questionnaire included sociodemographic data, data concerning the disease and perspectives of CDs.Results80% of the patients were males. The mean age was 30.7 years. 40% were married and 70% unemployed.76% were diagnosed as schizophrenic patients (58% undifferentiated, 18% disorganized) and 24% as schizoaffective patients. The average duration of the disease was 15.5 years. The time of the last hospitalization went back to 10.1 years on average.For all the patients, the initiative of CDs’ prescription was taken by the psychiatrist by reason of the poor adherence (72%) and the inefficiency of the previous treatment (38%). 80% of the patients preferred CDs to oral neuroleptics because the former: -allowed avoidance of oblivion (70%),-were more effective (60%),-made relapses less frequent (50%),-ensured distant intakes of treatment (50%),-were better tolerated (40%),-improved patient's autonomy (32.5%).ConclusionThe patients in our study have high regard for CDs, which explains their adherence success.Their autonomy and their tolerance of neuroleptics might be improved by using atypical depot formulations.

P03-89 - Psychiatric nurses’ attitudes to antipsychotic depot injections

IntroductionThe use of conventional depots (CDs) continues to have a great importance in our psychiatric sectors due to the unavailability of atypical depot formulations.ObjectiveThe aim of this work was to assess psychiatric nurses’ perspectives of CDs.MethodsForty nurses from our psychiatric department completed a questionnaire which included both open and multiple choice questions concerning the following topics:-CDs and improvement in adherence to treatment,-efficacy and tolerance of CDs,-interest and indications of CDs.Results*Psychiatric nurses (PNs) reported that CDs allowed avoidance of oblivion (83%) and regular intake of treatment (54%). But, several PNs believed that the injections of CDs were complex (67%) and the majority considered that CDs did not have positive impact on patient adherence (85%).*PNs thought that CDs :-were more effective (fewer relapses 56%) and better tolerated than oral formulations.-did not require more precautions (80%).-provided more security to the patient (no risk of toxicity 97%).*PNs reported lots of indications: lack of family support (75%), multiple relapses (72%), poor adherence (70%) and self or hetero-aggressive behavior at relapse (52%).They supported the advantages of CDs: improving social life (85%) and patient's autonomy (68%) and permitting remission (25%).ConclusionThe findings suggest that PNs have positive attitude towards efficacy and tolerance of CDs but negative ideas about their indications, which could be the cause of patient stigmatization. That's why providing a clear piece of information seems necessary.

Perceptions on efficacy and side effects of conventional depot antipsychotics (CDA) and atypical depot antipsychotics (ADA): Psychiatrists versus patients in Hong Kong

Objectives. We compared the satisfaction level of psychiatrists and psychiatric patients towards conventional (CDA) and atypical (ADA) depot antipsychotics on symptom management, role functioning, and side effects. Method. Patients from an out-patient clinic of a public hospital and psychiatrists from public hospitals participated in the survey in 2007–2008. A total of 153 patients were interviewed by a tailor-made questionnaire and 72 psychiatrists self-administered a similar questionnaire. Results. Both groups shared similar attitudes towards clinical effectiveness and treatment efficacy of ADA and CDA. More patients were ambivalent towards relapse prevention of CDA than psychiatrists (30.7 vs. 16.7%, P<0.044) and three quarters of psychiatrists believed that ADA are associated with less side effects. More than half of the patients showed negative attitudes towards the effectiveness of CDA on improving quality of life (52.40%), work (57.50%), and recreation (55.50%). Psychiatrists were more aware of the limitation of CDA and severity of side effects of CDA. They did not, however, seem to incorporate patients' opinions and research findings into their clinical practice. Conclusion. Evidence-based practice and shared decision-making model between clinicians and mental patients should be advocated. More investigations should be devoted to examine the efficacy of ADA as the alternative to CDA.

Olanzapine pamoate - blockbuster or damp squib?

In the past two decades, there has been a small revolution in the treatment of schizophrenia and related psychoses. During the 1990s, new 'atypical' antipsychotics such as clozapine, risperidone, olanzapine and quetiapine were introduced, largely freeing patients of the considerable burden of acute extrapyramidal adverse effects and tardive dyskinesia. In the current decade, we have seen the introduction of a dopamine partial agonist (aripiprazole) and the first atypical depot injection - risperidone long acting injection (RLAI). Olanzapine (as olanzapine pamoate) is the second of the new drugs to be marketed as a long-acting depot. Leslie Citrome, in this journal (1), opined that long-acting olanzapine may be 'an option to consider for a patient who has a history of response to olanzapine but for whom adherence has been difficult' Is depot olanzapine needed? How much is it likely to be used?

Comparación de la eficacia de las formas farmacéuticas de liberación retardada (depot) y las orales de los antipsicóticos típicos y atípicos comercializados en España para pacientes diagnosticados de esquizofrenia

Currently in Spain, 4 depot antipsychotics are available: flufenazine, pipotiazine, zuclopentixol and risperidone. The objectives of the present study are: a) to evaluate the efficacy of depot vs. oral forms of typical and atypical antipsychotics available in Spain for treating patients with schizophrenia; b) to compare the efficacy of different depot antipsychotics; c) to evaluate cost-effectiveness of typical and atypical depot and oral antipsychotics. Systematic review of the literature between January 1980 and March 2007. Pharmaceutical companies of depot preparations were contacted aiming to include unpublished material. A total of 15 studies were included (13 journal manuscripts and 2 posters provided by the industry). Concordance between evaluators was moderate-high. The quality of selected studies was moderate-low. There were no differences in the efficacy between depot and oral risperidone. Efficacy of depot risperidone was higher than oral olanzapine (there were no differences regarding tolerability) and higher and better tolerated than oral zuclopentixol. The evidence was controversial when comparing the efficacy of depot and oral flufenazine. There were no differences when comparing the efficacy between depot flufenazine and oral pimozide. Depot zuclopentixol was more efficient than the oral preparation for treating patients with schizophrenia and violent behaviour. Finally, there were no differences regarding the efficacy and tolerability between depot pipotiazine and depot flufenazine and between depot clopentixol and depot flufenazine. There is few high-quality scientific evidence comparing depot and oral antipsychotics or different depot antipsychotics available in Spain. Selected evidence does not allow to conclude that depot antipsychotics are more effective and better tolerated than oral ones.

Comparing the efficacy of long-acting pharmaceutical forms (depot) versus oral forms of the atypical and conventional antipsychotics marketed in Spain for treating patients with schizophrenia

Introduction and objectivesCurrently in Spain, 4 depot antipsychotics are available: flufenazine, pipotiazine, zuclopentixol and risperidone. The objectives of the present study are: a) to evaluate the efficacy of depot vs. oral forms of typical and atypical antipsychotics available in Spain for treating patients with schizophrenia; b) to compare the efficacy of different depot antipsychotics; c) to evaluate cost-effectiveness of typical and atypical depot and oral antipsychotics. MethodsSystematic review of the literature between January 1980 and March 2007. Pharmaceutical companies of depot preparations were contacted aiming to include unpublished material. ResultsA total of 15 studies were included (13 journal manuscripts and 2 posters provided by the industry). Concordance between evaluators was moderate-high. The quality of selected studies was moderate-low. There were no differences in the efficacy between depot and oral risperidone. Efficacy of depot risperidone was higher than oral olanzapine (there were no differences regarding tolerability) and higher and better tolerated than oral zuclopentixol. The evidence was controversial when comparing the effi cacy of depot and oral flufenazine. There were no differences when comparing the efficacy between depot flufenazine and oral pimozide. Depot zuclopentixol was more effi cient than the oral preparation for treating patients with schizophrenia and violent behaviour. Finally, there were no differences regarding the effi cacy and tolerability between depot pipotiazine and depot flufenazine and between depot clopentixol and depot flufenazine. ConclusionsThere is few high-quality scientific evidence comparing depot and oral antipsychotics or different depot antipsychotics available in Spain. Selected evidence does not allow to conclude that depot antipsychotics are more effective and better tolerated than oral ones.

Upcoming Agents for the Treatment of Schizophrenia

Since the introduction of a group of atypical antipsychotics in the 1990s, there has been a decline in the rate of new antipsychotics being introduced into clinical practice. However, with increasing safety and efficacy concerns over currently available drugs and a dearth of options available for atypical depot formulations, there is a considerable need for the development of new formulations and agents. This review examines the profile of seven antipsychotic drugs currently in the premarketing stage of development and summarizes their mechanism of action, clinical potential and safety.Asenapine is an antipsychotic with activity for multiple receptors and has potential to improve negative and cognitive symptoms of schizophrenia. Bifeprunox is a partial dopamine D2 and serotonin 5-HT(1A) receptor agonist showing a less than convincing efficacy profile, but which may offer safety advantages over available agents by means of a reduced risk of metabolic complications. Iloperidone is a D2 and 5-HT(2A) receptor antagonist requiring further studies to establish its effectiveness. It has a high affinity for alpha(1)-adrenoceptors, which can lead to associated haemodynamic adverse effects. Nemonapride is essentially a typical antipsychotic drug, similar in structure to sulpiride, which has been available for some time in Japan. It has efficacy against positive symptoms and has shown some antidepressant and anxiolytic properties, although efficacy data for it are somewhat limited. Norclozapine (N-desmethylclozapine) is a major metabolite of clozapine formed by its demethylation. Its partial agonist activity at D2 receptors has raised interest in it as an antipsychotic in its own right. In addition, it appears to have muscarinic agonist activity, which is believed to be responsible for the observed positive effects it has on cognition. It was envisaged to be effective as an adjunct to other agents or at high doses in the treatment of refractory schizophrenia, although a recent randomized, controlled study showed that it was no more effective than placebo in patients with schizophrenia experiencing an acute psychotic episode. Olanzapine pamoate depot injection has shown comparable efficacy to oral olanzapine in several studies. However, it has provoked considerable safety concerns by its association with inadvertent intravascular injection events in numerous patients. This accidental intravascular administration of olanzapine pamoate leads to excessive sedation, confusion, dizziness and altered speech. Post-injection observation periods and postmarketing surveillance are planned following the introduction of the depot. Paliperidone palmitate is the palmitate ester of paliperidone, the major metabolite of risperidone, and is formulated as a long-acting injection for intramuscular use. Its pharmacology is comparable to risperidone, having D2 and 5-HT(2A) receptor antagonist activity. Efficacy studies have shown positive results, and because paliperidone has no antagonistic activity at cholinergic receptors, it has low potential for anticholinergic adverse effects, including cognitive dysfunction. However, with higher doses, the frequency of extrapyramidal side effects and orthostatic hypotension have been shown to be greater than with placebo.

Wenn Arzneimittel nicht eingenommen werden - der Einfluss verschiedener Antipsychotika auf das Complianceverhalten schizophrener Patienten

The effectiveness of pharmacotherapy partly depends on patients' compliance. However noncompliance with pharmacotherapy occurs frequently. It is particularly a problem in diseases requiring long-term treatment. On average chronically ill patients only take about half of their medication as prescribed. Especially patients with chronic psychiatric diseases, such as schizophrenia, are known to have low compliance rates. Atypical antipsychotics or depot medication are believed to improve compliance. In our systematic literature review we identified ten studies analysing the differences in compliance rates between atypical and typical antipsychotics. However our analyses did not show a difference in compliance rates except for clozapine. The higher compliance rates for clozapine might be explained by the regular monitoring and thus frequent patient contact. A positive effect of depot antipsychotics on compliance could be explained by the easy detection of noncompliant patients.

Use of long-acting injectable risperidone before and throughout pregnancy in schizophrenia

Data on the use of long-acting injectable (LAI) risperidone, the first atypical depot antipsychotic, during pregnancy are limited. A 35-year-old woman with schizophrenia was given LAI risperidone before and throughout her pregnancy. She gave birth to a female infant weighing 2230 g at 36 weeks and 6 days of pregnancy, following premature rupture of the membranes. The baby had no congenital malformation and was healthy 8 months postnatal. To our knowledge, this is the first reported use of LAI risperidone throughout an entire pregnancy. In this paper, we discuss the rationale and problems of LAI risperidone use in pregnancy, based on a literature review.

Symptom control, functioning and satisfaction among Swiss patients treated with risperidone long-acting injectable

Objective: To investigate antipsychotic efficacy and tolerability of risperidone long-acting injectable (RLAI) in Swiss patients with schizophrenia or other psychotic disorders, changed directly from their previous antipsychotic medication. Methods: Patients symptomatically stable for ≥1 month on their previous medication and considered to require a treatment change, received 25 mg RLAI (increased to 37.5 or 50 mg, if required) every 2 weeks for 6 months. Results: Of 60 patients enrolled (68.3% male, average age 40.4 years), most (81.7%) had DSM-IV schizophrenia (mainly paranoid). Previous treatments were with atypical antipsychotics (58.3% of patients), depot (38.3%) and conventional oral (13.3%) neuroleptics. Mean total PANSS scores were significantly reduced from baseline to treatment endpoint (76.1 vs. 64.4, P<0.001), as were all PANSS subscale and symptom factor scores. The CGI, GAF, and patient satisfaction with treatment were also significantly improved at endpoint (P<0.001). At endpoint, 37.0% of patients rated their satisfaction as “very good” compared with only 4.3% at baseline. Mean scores for total ESRS and Parkinsonism subscales were significantly reduced at endpoint (P<0.001). Conclusion: Treatment with RLAI significantly improved disease symptoms, functioning, patient satisfaction, and reduced movement disorders. It provides an important option for long-term treatment of patients with psychotic disorders.

Antipsychotic agents. Gradually improving treatment from the traditional oral neuroleptics to the first atypical depot

Relapse is one of the key factors in the long-term outcome of schizophrenia. The consequences of relapse are diverse and often unpredictable, and the time to recovery and degree of recovery worsen with each successive relapse. There is now overwhelming evidence that advances in antipsychotic drug treatment have led to significant reductions in the rate of relapse. This review charts the developments that have taken place in antipsychotic therapy from the introduction of depot formulations, through atypical agents, to the development of the first long-acting atypical antipsychotic. Depot formulations of conventional antipsychotics were developed in the 1960s and led to fewer relapses and episodes of hospitalization, compared with oral equivalents. Meta-analysis has confirmed that patients receiving depot antipsychotics experience significantly greater global improvement than those receiving the respective oral agents. Conventional antipsychotics are, however, associated with a range of potentially serious adverse events. The atypical antipsychotics were introduced in the 1990s and have significant advantages over conventional agents with regard to positive and negative symptoms. There is also evidence that atypical agents can reduce the risk of relapse. Importantly, atypical antipsychotics have an improved safety profile compared with older agents, particularly with regard to extrapyramidal symptoms. One disadvantage of atypical agents has been that they are only available in an oral form. The recent development of a long-acting injectable formulation of risperidone means that a new treatment option is available to physicians.