Relapse in patients with schizophrenia has devastating repercussions, including worsening symptoms, impaired functioning, cognitive deterioration and reduced quality of life. This progressive decline exacerbates the burden of illness on patients and their families. Relapse prevention is identified as a key therapeutic aim; however, the absence of widely accepted relapse definition criteria considerably hampers achieving this goal. We conducted a literature review in order to investigate the reporting of relapses and the validity of hospitalization as a proxy for relapse in patients with schizophrenia. The primary aim was to assess the range and validity of methods used to define relapse in observational or naturalistic settings. The secondary aim was to capture information on factors that predicted or influenced the risk of relapse. A structured search of the PubMed database identified articles that discussed relapse, and hospitalization as a proxy of relapse, in patients with schizophrenia. National and international guidelines were also reviewed. Of the 150 publications and guidelines identified, 87 defined relapse and 62% of these discussed hospitalization. Where hospitalization was discussed, this was as a proxy for, or a component of, relapse in the majority of cases. However, hospitalization duration and type varied and were not always well defined. Scales were used to define relapse in 53 instances; 10 different scales were used and multiple scales often appeared within the same definition. There were 95 references to factors that may drive relapse, including non-adherence to antipsychotic medication (21/95), stress/depression (11/95) and substance abuse (9/95). Twenty-five publications discussed the potential of antipsychotic therapy to reduce relapse rates—continuous antipsychotic therapy was associated with reduced frequency and duration of hospitalization. Non-pharmacological interventions, such as psychoeducation and cognitive behavioural therapy, were also commonly reported as factors that may reduce relapse. In conclusion, this review identified numerous factors used to define relapse. Hospitalization was the factor most frequently used and represents a useful proxy for relapse when reporting in a naturalistic setting. Several factors were reported to increase the risk of relapse, and observation of these may aid the identification of at-risk patients.

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The observed time to relapse superiority of paliperidone palmitate over oral antipsychotics provides further evidence for the value of long-acting injectable antipsychotic therapies in the treatment of schizophrenia, including during the early stages of illness.

Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse. An open-label, randomized, active-controlled, 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone, olanzapine, or conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety evaluations included adverse events (AEs) reported for the duration of the study, Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital signs. A total of 666 patients (n ¼ 329 RLAI, n ¼ 337 quetiapine) were evaluable for effectiveness measures. Baseline demographics were similar between treatment groups. Kaplan-Meier estimate of time-to-relapse was significantly longer with RLAI (po0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain affected 7% of patients with RLAI and 6% with quetiapine, with mean end point increases of 1.25 ± 6.61 and 0 ± 6.55 kg, respectively. There were no significant betweengroup differences in weight gain. ESRS total scores decreased similarly after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in 10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%) patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of patients with RLAI and 11% with quetiapine. To our knowledge, this is the first report of a randomized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy. Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients randomized to RLAI compared with those randomized to oral quetiapine. Both antipsychotics were generally well tolerated.

Studies on the predictive value of the electroencephalogram (EEG) concerning the risk of seizure recurrence have shown contradictory results. We prospectively studied the predictive value of the standard EEG and EEG with sleep deprivation for seizure relapse in adult patients presenting with a first unprovoked seizure. EEGs were performed on 157 adult patients within the first 48 hours of the first seizure. Additional EEGs with sleep deprivation were obtained in 60 cases. The standard EEG was abnormal in 70.7% and significantly associated with an increased risk of seizure recurrence [risk ratio 4.5, 95% confidence interval (CI) 1.8; 11.3, p=0.001]. Subgroup analysis revealed the highest recurrence rates for patients with focal epileptiform activity (risk ratio 2.2, CI 1.2; 4.2, p=0.01). EEGs with sleep deprivation were abnormal in 48.3% of all cases and revealed epileptiform discharges in 13.3% of the patients who had no epileptiform activity in the standard EEG. Routine EEG revealed abnormalities in 60 of 94 patients who presented with normal neurologic status on admission. Further neuroradiological examinations detected previously unknown brain lesions in 19 of these cases, particularly cerebrovascular disease (CVD, n=7), brain tumors (n=6), and posttraumatic scars (n=4). In conclusion, the EEG is important for the early detection of focal nonepileptic and epileptic abnormalities after a first unprovoked seizure in adult patients and may provide valuable information on previously unknown disorders, particularly CVD and cerebral tumors. The abnormal EEG is a highly significant predictor for seizure recurrence. An additional EEG with sleep deprivation is helpful in cases when standard EEG does not reveal epileptiform discharges.

BackgroundNonadherence is common among patients with schizophrenia, although the rates vary according to means of assessment and patient population. Failure to adhere to medication can have a major impact on the course of illness and treatment outcomes, including increasing the risk of relapse and rehospitalization. Understanding psychiatrists’ perception of the causes and consequences of nonadherence is crucial to addressing adherence problems effectively.MethodsThe Europe, the Middle East, and Africa (EMEA) Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES) survey was conducted by questionnaire during January–March 2010 among psychiatrists treating patients with schizophrenia in 36 countries. The survey comprised 20 questions. In addition to recording the demographic details of the 4722 respondents (~12% response rate), it canvassed their preferred methods of assessing adherence, their perceptions of adherence rates, reasons for nonadherence, and strategies to improve adherence.ResultsPsychiatrists estimated that 53% of their patients with schizophrenia were partially/nonadherent during the previous month. They estimated only one-third of patients who deteriorated after stopping medication were able to attribute this to nonadherence. Psychiatrists assessed adherence most often by patient interview. Lack of insight was viewed as the most important cause of medication discontinuation, followed by patients feeling better and thinking their medication unnecessary, and experiencing undesirable side effects. Considerably fewer psychiatrists viewed insufficient efficacy, cognitive impairment, or drug/alcohol abuse as the most important reasons for their patients stopping medication.ConclusionPsychiatrists throughout EMEA recognize the impact of partial/nonadherence to medication, with patient enquiry being the most commonly used means of assessment. There remains a need for more proactive management of patients with schizophrenia, particularly in increasing patient insight of their illness in order to improve adherence and minimize the consequences of relapse. Strategies focused on raising awareness of the importance of adherence are also warranted, with the aim of improving patient outcomes in schizophrenia.

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BackgroundDiscontinuation of antipsychotic treatment for schizophrenia can interrupt improvement and exacerbate the illness. Reasons for discontinuing treatment are multifactorial and include adherence, efficacy and tolerability issues. Poor adherence may be addressed through non-pharmacological approaches as well as through pharmacological ones, ie ensured delivery of medication, such as that achieved with long-acting injectable (LAI) antipsychotics. However, attitudes of healthcare professionals (HCPs) towards LAI antipsychotics may influence their prescribing decisions and may influence medication choices offered to patients. We therefore conducted a survey to investigate factors driving LAI use as well as physician and nurse attitudes to LAI antipsychotics and to different injection sites.MethodsAn independent market research agency conducted the survey of HCPs across Europe. Participants were recruited by telephone and completed the survey online. Using conjoint analyses (a multivariate statistical technique analysing preferences on the basis of ranking a limited number of attributes which are presented repetitively), attitudes to oral versus LAI medication and gluteal versus deltoid injection routes were assessed.ResultsA total of 891 HCPs across Europe were surveyed. Of these, 40% would choose LAI antipsychotics for first episode patients whereas 90% would select LAI antipsychotics for chronic patients with two to five psychotic episodes. Dominant elements in antipsychotic choice were low sedation but no tardive dyskinesia, no or mild pain at injection and low risk of embarrassment or impact upon therapeutic alliance. Eighty-six per cent of respondents considered that having the choice of a deltoid as well as gluteal administration site was beneficial over not having that choice. Two thirds of respondents said they agreed that medication administration via the deltoid muscle may reduce social embarrassment associated with LAI antipsychotics and most respondents (61%) believed that administration of LAI antipsychotics into the deltoid muscle as opposed to the gluteal muscle may be more respectful to the patient.ConclusionsIn this survey of physicians and nurses, attitudes towards LAI antipsychotics compared with oral medication were generally positive. Respondents considered that the availability of a deltoid administration route would offer increased choice in LAI antipsychotic administration and may be perceived as more respectful and less socially embarrassing.