Statu quo: ¿qué nos dicen los estudios observacionales?

Randomized, controlled clinical trials offer the best methodological conditions to ensure internal validity, meeting strict inclusion criteria and mechanisms for controlling bias. However, in addition to the associated high cost, the patients and treatments studied are not always representative of those in real-life clinical settings, a significant percentage of whom present comorbid conditions and varying levels of severity. Furthermore, they often receive combination treatments, which is especially relevant in bipolar disorder. Pragmatic and observational studies provide a model that is able to decrease this gap, increasing its external validity, i.e. the ability of results to be transferred to routine clinical practice. Among the pragmatic studies, STEP-BD in the USA has demonstrated a significant percentage of comorbidities, the prevalent lack of treatment compliance and the limited usefulness of antidepressants during depressive phases, whereas evidence for using antipsychotics such as quetiapine during maintenance phases has been strengthened. On a European level, multicenter observational studies, such as EMBLEM and WAVE-BD, in addition to finding similar low compliance rates with significant implications for development and direct costs, demonstrated the usefulness of atypical antipsychotics for manic, mixed and even depressive phases. A high incidence of polypharmacy was also revealed, with antidepressant prescription rates remaining elevated during all phases of the disorder. This finding was confirmed in similar studies in Spain, such as SIN-DESPRES, MANACOR and EXPASEN, which also explored the usefulness and tolerability of new antipsychotics in treating bipolar disorder.