Michael Berk has performed a useful RCT. Yes, they do exist. He works with young people (15 — 25) in an acute ward. Those who present in mania are treated with an antipsychotic (quetiapine) and Lithium. The question then is, as both have some evidence as maintenance treatment, which one should you use?

This is from the abstract. The answer is … the older drug. Lithium.

To investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania.

Maintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry – ACTRN12607000639426.)

In total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology (Brief Psychotic Rating Scale (BPRS), P = 0.005, Clinical Global Impressions – Bipolar, severity, P = 0.006), psychotic symptoms (BPRS, positive symptoms, P = 0.047) and functioning (Global Assessment of Functioning Scale, P = 0.001; Social and Occupational Functioning Scale, P = 0.001). Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine.

It may be that this is an effect for the young. It may be that this is because the patients were sufficiently unwell to get admitted in Victoria, were there is always a bed shortage. But the older drug has more efficacy than the newer drug… despite the network meta analyses, in a head to head trial.