Juvenile bipolar disorder plagued by non-adherence to therapy

A report has identified treatment non-adherence as a significant problem in the treatment of juvenile bipolar disorder, with regards to both treatment outcomes and limiting the statistical power of treatment efficacy studies. Pharmacotherapy is the cornerstone to the management and treatment of juvenile bipolar disorder. While there is a growing body of evidence to the efficacy of pharmacotherapy, there is little data in the way of the prevalence and correlates of adherence to therapy. To date, only two studies have evaluated adherence to drug therapy in juvenile bipolar disorder and both suggest that nonadherence to prescribed pharmacotherapy for juvenile bipolar disorder is common and that it leads to decreased effectiveness of treatment. Drotar et al. conducted a prospective research trial of combined pharmacotherapy (lithium and divalproex sodium) for juvenile bipolar disorder during an open-label stabilisation phase of treatment. The study involved 107 medically healthy outpatient children and adolescents (70 males) aged between 5 and 17 years who met the symptom criteria for a primary diagnosis of either bipolar I or II disorder. Lithium (intermediate-release preparation) and divalproex were initiated simultaneously at study entry. Drug serum concentrations were measured at weeks 2 and 4 and every 4 weeks thereafter. Medication concentrations were increased over the first 2 weeks so that the target dose range of 20 mg/kg/day of divalproex and 30 mg/kg/day of lithium were achieved. Doses were then adjusted to maintain serum concentrations of between 0.6 and 1.2 mmol/L of lithium and of between 50 and 100 µg/mL of divalproex. Adherence was assessed using a comprehensive protocol that included serum blood levels as the primary measure, clinical judgement, pill count, and patient report. The authors also evaluated clinically relevant correlates of adherence to pharmacotherapy including patient characteristics, medication side effects and family variables. The rates of adherence to treatment identified by assay of serum concentrations were 0.84 for divalproex and 0.66 for lithium. Better treatment adherence to divalproex and lithium was associated with a greater number of side effects, which may reflect therapeutic levels of the medications (note that the number of side effects correlated with clinical response to treatment for divalproex [p<0.01].) In contrast, male sex was associated with worse adherence to both divalproex (p<0.05) and lithium (p<0.05). A lifetime history of parental hospitalisation (p<0.01 for both maternal and paternal) for psychiatric illness and greater familial dysfunction (p<0.05) were both associated with less adequate adherence to divalproex therapy. Furthermore, self-reports and pill counts yielded higher and potentially biased estimates of adherence to pharmacotherapy for bipolar disorder than the data gleaned from serum concentrations of the two agents. “It may be important for clinicians to conduct routine assessments to detect levels of nonadherence to pharmacotherapy in practice settings that are high enough to limit treatment efficacy,” the authors asserted. They concluded that non-adherence to medication treatment for juvenile bipolar disorder is a significant problem, noting that it impacts not only in clinical care but also in research concerning the efficacy of pharmacotherapy. Reference...