Epidemiological studies of medication use and effectiveness in bipolar disorder

Abstract

In the last decades, new treatments for bipolar disorder (BD) have emerged, prompting a decrease in the use of lithium – the former “gold standard” for relapse prevention, and increasing the possibilities for individualized treatment. The aims of this thesis were to: 1) explore the use of relapse prevention in the early phases of bipolar illness, 2) add to the current knowledge concerning the comparative effectiveness of various pharmacological maintenance treatments, including combination therapies, and 3) explore the use of benzodiazepines and non-benzodiazepine hypnotics (so called Z-drugs) in BD. All four studies were population based cohort studies, using data from Swedish national registers.

In Study I, 31 770 individuals with newly diagnosed BD were followed for one year with regard to initiation of relapse prevention. Three months after diagnosis, 72% had initiated such treatment. Patients diagnosed with BD during a long hospitalization were most likely to initiate treatment, followed by patients who had used lithium, anticonvulsants or antipsychotics prior to diagnosis. Our findings indicate that efforts to reduce treatment delay should especially target patients who are naïve to mood-stabilizers and antipsychotics or diagnosed with BD during a brief hospitalization.

In Study II, we followed patients for one year after a hospitalization for a manic episode. The study included follow-up data from 6 502 hospitalizations. We classified patients by various prophylactic drug regimens, based on prescription fills during the first four weeks after hospital discharge, and assessed the one-year rehospitalization risk associated with each regimen. Combination therapy with olanzapine and valproate or lithium was associated with the lowest rehospitalization risk.

Study III had a design similar to Study II, but investigated the risk of treatment failure with various treatment alternatives. Treatment failure was defined as treatment switch/discontinuation or rehospitalization during ongoing treatment. We found that treatment failure was less common in patients on combination therapy, and that combination therapies including lithium, valproate and quetiapine or olanzapine were associated with the lowest risks of treatment failure.

In Study IV, we included 21 883 BD patients with no history of benzodiazepine/Z-drug use in the past year and followed them for one year with regard to benzodiazepine/Z-drug initiation and long-term use (continuous use for ≥6 months). In total, 6 307 patients (29%) initiated benzodiazepine/Z-drug treatment, of whom more than one in five became long-term users. Most notably, patients who initiated treatment with clonazepam or alprazolam had greatly increased odds for long-term use. In addition, long-term use was common among patients who used two or more benzodiazepines and/or Z-drugs.