European Neuropsychopharmacology (v.17, #S2)

Contents (iii).

Patients with schizophrenia show low employment rates and low Quality of Life (QoL), and rehabilitation aims to maximise daily functioning, improve social interactions, and develop employment prospects. Evaluation of long-term treatment effectiveness should address these issues. Choice of medication can influence patient compliance and adverse experience of side effects may act as a barrier to rehabilitation. The Schizophrenia Trial of Aripiprazole (STAR), in which patients were randomised to receive 26 weeks of the atypical antipsychotic, aripiprazole (n  = 284) or standard of care medication (n  = 271) showed that aripiprazole demonstrated significantly better effectiveness in terms of Investigator Assessment Questionnaire (IAQ) total score. Like other atypical antipsychotic agents, aripiprazole shows a low rate of extrapyramidal adverse events. In addition, unlike the majority of other agents, aripiprazole treatment has a low risk of weight gain, translating into health-related QoL benefits. In summary, newer, atypical agents may improve efficacy, patient satisfaction, and aid long-term rehabilitation.
Keywords: Atypical antipsychotics; Rehabilitation; Schizophrenia;

Risk factors for schizophrenia — All roads lead to dopamine by Marta Di Forti; Julia M. Lappin; Robin M. Murray (S101-S107).
Schizophrenia is a debilitating disease of major public health importance, the incidence of which shows prominent worldwide variation (up to fivefold) and is about 40% greater in men than in women. Furthermore, epidemiological studies have shown that the incidence is higher among those who grow up in urban areas and among migrants. Recent evidence indicates that, although the neurochemical origins of schizophrenia do not necessarily lie in dopamine dysregulation, this operates as the final common pathway underlying positive psychotic symptoms and may also play a role in negative and cognitive symptoms. The last few years have seen the development of a plausible model in which schizophrenia is seen as the consequence of the actions of a number of component causes, such as genes or early environmental hazards that subtly alter subsequent neurodevelopment, thereby predisposing the child to later dopamine dysregulation.
Keywords: Dopamine; Neurodevelopment; Schizophrenia;

Long-term treatment of stable schizophrenia focuses on treatment effectiveness, addressing direct efficacy plus treatment adherence, treatment burden, and impact on factors such as weight gain. With the introduction of atypical antipsychotics such as aripiprazole, reduced side effects may lead to improved long-term treatment. The Clinical Trials of Intervention Effectiveness (CATIE) study where 1500 patients were randomised to atypical antipsychotics (olanzapine, quetiapine, risperidone, ziprasidone), or the typical antipsychotic drug perphenazine showed high discontinuation rates of 74% after 18 months, but extrapyramidal side effects were lower after atypical antipsychotic treatment compared with perphenazine. Twenty-six weeks of aripiprazole treatment, assessed in 284 patients in the Schizophrenia Trial of Aripiprazole (STAR) showed that aripiprazole had similar discontinuation rates to the atypical antipsychotics standard of care. In the CATIE study, weight gain was common during treatment. In contrast, STAR demonstrated a favourable weight profile for aripiprazole, with a mean weight loss of 0.41 kg. Results from these naturalistic trials help define the effectiveness of atypical antipsychotics for long-term treatment.
Keywords: Atypical antipsychotics; Rehabilitation; Schizophrenia;

Rapid-acting intramuscular (IM) formulations of atypical antipsychotics offer a significant advance over IM haloperidol in the short-term management of acute schizophrenic episodes. Several short-term open-label randomised studies, typically enrolling two- to three-hundred patients, have compared an atypical antipsychotic with haloperidol. These studies show that IM ziprasidone, IM olanzapine and IM aripiprazole are at least as effective and better tolerated than IM haloperidol, with lower extrapyramidal side effects. Successful transitions from an IM to oral formulation of the same agent have been performed in double-blind randomised trials assessing haloperidol, olanzapine, ziprasidone and aripiprazole. Avoiding over-sedation is now recognised as important, and randomised clinical trial data indicate that oral ziprasone, quetiapine, and IM olanzapine have high dose-related sedative potential while oral risperidone and IM aripiprazole have low sedative potential. In summary, IM formulations of atypical antipsychotics are recommended as first-line treatment of acute agitation with subsequent transition to an oral formulation of the same agent for ongoing management.
Keywords: Schizophrenia; Atypical antipsychotics; Acute agitation; Intramuscular; Sedation;

Foreword: Improved understanding and treatment of schizophrenia by Julia M. Lappin; Marta Di Forti; Robin M. Murray (v-vi).