Aripiprazole monotherapy in acute mania : 12 - week randomised

Bipolar disorder is a lifelong episodic illness requiring long-term treatment, yet there remains a need for well-tolerated and clinically effective maintenance of effect and continuation therapies. Aripiprazole has a novel pharmacological profile; partial agonism at dopamine D 2 and D 3 and serotonin 5-HT 1A receptors, and antagonism at 5-HT 2A receptors. 1–5 Aripiprazole has been shown to improve symptoms of acute mania in placebo-controlled studies 6,7 and was superior to placebo in maintaining efficacy for up to 100 weeks in patients with bipolar mania. 8,9 This study used a randomised placebo-controlled study design and included an active haloperidol reference arm to evaluate the acute and continued efficacy of aripiprazole monotherapy in patients with bipolar disorder experiencing acute manic or mixed episodes (trial registration NCT00097266). Methods Patients Eligible patients were aged 18 years or older with bipolar I disorder manic or mixed type (with or without psychotic features), as defined by DSM–IV 10 and confirmed by the Mini International Neuropsychiatric Interview (MINI), who were experiencing an acute relapse requiring hospitalisation. In addition, they had a screening and baseline Young Mania Rating Scale (YMRS) 11 Total score 520, with less than a 25% decrease between the two visits. Patients also had a baseline Montgomery–A ˚ sberg Depression Rating Scale (MADRS) 12 Total score 417, with no more than a 4-point increase between the two visits. Female patients of child-bearing potential were required to use acceptable contraceptive measures. Patients were excluded if they had delirium, dementia, amnestic or other cognitive disorders, schizophrenia or schizoaffective disorder , or if they were experiencing their first manic or mixed episode. Also excluded were patients with borderline, paranoid, histrionic, schizotypal, schizoid or antisocial personality disorder. Other exclusions were: serious, unstable medical illness; hospi-talisation for current mania or mixed episode for 43 weeks; previously unresponsive to treatments for manic symptoms (based on clinical judgement that the patient failed treatment with appropriate antimanic therapies (antipsychotic or mood stabiliser such as lithium, valproate, carbamazepine or haloperidol) at a clinically appropriate dose and duration); diagnosis of bipolar II disorder; rapid cycling bipolar disorder (44 manic or depressive episodes/year); DSM–IV-defined substance misuse or substance dependence; clinically assessed significant risk of suicide; recent treatment with long-acting antipsychotics; use of mood stabilisers or antidepressants 2–4 weeks prior to randomisation; and electro-convulsive therapy within the past 3 months. and the USA. All patients provided written informed consent before participation. The study protocol, procedures and …