BACKGROUND: This study analyzed regularity in the daily dosage of antidepressants taken by patients with bipolar disorder and identified the factors associated with irregularity.

METHODS: Daily self-reported medication dosage taken and mood ratings were available from 144 patients who received treatment as usual. All 144 patients took the same antidepressant for at least 100 days. One hundred eleven of these patients were also taking a mood stabilizer. Approximate entropy (ApEn) was used to measure serial regularity in daily dosage. Regularity is the tendency that values within a time series remain the same on incremental comparisons. Drug holidays (missing three or more consecutive days) were also determined. Generalized estimating equations (GEE) were used to estimate if any demographic or clinical variables were associated with regularity.

RESULTS: Although the mean percent of days missing doses was only 18.6%, there was a wide range of regularity in the daily antidepressant dosage. Drug holidays were common, occurring in 41% of the analyses. Factors significantly associated with irregularity were as follows: total number of psychotropic medications (p = 0.005), pill burden (p = 0.005), and depression (p = 0.015). Neither the percent of days missing doses nor the drug holidays were associated with any demographic or clinical factors. For patients taking both antidepressants and mood stabilizers, there was no significant difference in regularity in daily dosage between these drugs.

DISCUSSION: There can be considerable irregularity in daily dosage despite a low percent of days missing doses. Medication regimen complexity and depressed mood are associated with increased irregularity. Daily regularity in drug dosage may be more dependent on the individual than on the specific drug. Research on the clinical impact of irregularity in daily dosage of antidepressants is needed.