Within psychiatry, like in other areas of medicine, randomised controlled trials (RCTs) represent the gold standard for obtaining information on how treatment affects health [1]. In relation to mania, a new systematic review and random-effects model network meta-analysis identified 72 double-blind placebo-controlled RCTs of 23 drugs, showing that antipsychotics, carbamazepine, lithium, tamoxifen and valproate were superior to placebo in terms of response for acute mania although only aripiprazole, olanzapine, quetiapine and risperidone had a lower all-cause discontinuation than placebo [2]. Achieving results from RCTs with high internal and external validity [1] is a major challenge within psychiatry because of the nature of psychiatric illnesses, including mania [3, 4]. The complex and labile symptomatic presentations, a tendency for patients to deny illness and reject treatment, and diagnostic heterogeneity severely complicate the design and conduct of experimental treatment trials in bipolar disorder [5]. In this way, most real-life patients with bipolar disorder are excluded due to several factors including psychotic symptoms, comorbidity, severity, suicide risk and poor illness insight, cooperation and adherence to medication [5, 6]. It is estimated that as few as one in ten patients with bipolar disorder presenting as potential research subjects will be recruited into a long-term trial involving a placebo condition [5]. For these reasons, it is unsurprising that only few RCTs exist on placebo controlled or comparative treatment of different drugs for mania during psychiatric hospitalisation when patients are severely ill, with decreased illness insight and willingness to accept treatment.

This narrative review aims to propose a pragmatic clinical algorithm for optimised pharmacological treatment of mania during hospitalisation that goes beyond the incomplete evidence from RCTs.