Regularity in Daily Mood Stabilizer Dosage Taken by Patients with Bipolar Disorder

Abstract

Objective:

The aim of this study was to investigate regularity in the daily mood stabilizer dosage taken by patients with bipolar disorder, and identify factors associated with irregularity.

Methods:

Self-reported daily mood and medication data were available from 206 patients who took the same mood stabilizer for ≥100 days. Approximate entropy (ApEn) was used to measure serial regularity in daily mood stabilizer dosage. Generalized estimating equations (GEE) were used to estimate if demographic or clinical variables were associated with ApEn.

Results:

There was a wide range of regularity in the daily mood stabilizer dosage. The mean percent of days of missing doses was 13.6%. The number of psychotropic medications (p=0.007), pill burden (p=0.004) and percent of days with depressed mood (p=0.013) were associated with more irregularity, while the percent of days euthymic (p=0.014) was associated with less irregularity. The percent of days missing doses was not associated with the number of medications, pill burden or mood ratings.

Discussion:

Patients may have irregularity in daily dosage in spite of a low percent of days missing doses. Psychotropic medication regimen complexity and depression are associated with increased dosage irregularity. Research is needed on how irregularity in daily dosage impacts the continuity of drug action of mood stabilizers.

Key words

bipolar disorder - mood stabilizers - dosage

• References

• 1 DiMatteo MR. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Med Care 2004; 42: 200-209
• 2 Lingam R, Scott J. Treatment non-adherence in affective disorders. Acta Psychiatr Scand 2002; 105: 164-172
• 3 Scott J, Pope M. Nonadherence with mood stabilizers: prevalence and predictors. J Clin Psychiatry 2002; 63: 384-390
• 4 Sajatovic M, Valenstein M, Blow F et al. Treatment adherence with lithium and anticonvulsant medications among patients with bipolar disorder. Psychiatr Serv 2007; 58: 855-863
• 5 Berk L, Hallam KT, Colom F et al. Enhancing medication adherence in patients with bipolar disorder. Hum Psychopharmacol 2010; 25: 1-16
• 6 Busby KK, Sajatovic M. REVIEW: Patient, treatment, and systems-level factors in bipolar disorder nonadherence: A summary of the literature. CNS Neurosci Ther 2010; 16: 308-315
• 7 Gutiérrez-Rojas L, Jurado D, Martínez-Ortega JM et al. Poor adherence to treatment associated with a high recurrence in a bipolar disorder outpatient sample. J Affect Disord 2010; 127: 77-83
• 8 Keck Jr PE, McElroy SL, Strakowski SM et al. 12-month outcome of patients with bipolar disorder following hospitalization for a manic or mixed episode. Am J Psychiatry 1998; 155: 646-652
• 9 Hassan M, Lage MJ. Risk of rehospitalization among bipolar disorder patients who are non-adherent to antipsychotic therapy after hospital discharge. Am J Health Syst Pharm 2009; 66: 358-365
• 10 Schuepbach D, Novick D, Haro JM et al. Determinants of voluntary vs. involuntary admission in bipolar disorder and the impact of adherence. Pharmacopsychiatry 2008; 41: 29-36
• 11 Scott J, Pope M. Self-Reported adherence to treatment with mood stabilizers, plasma levels, and psychiatric hospitalization. Am J Psychiatry 2002; 159: 1927-1929
• 12 Gonzalez-Pinto A, Mosquera F, Alonso M et al. Suicidal risk in bipolar I disorder patients and adherence to long-term lithium treatment. Bipolar Disord 2006; 8: 618-624
• 13 Sajatovic M, Velligan DI, Weiden PJ et al. Measurement of psychiatric treatment adherence. J Psychosom Res 2010; 69: 591-599
• 14 Baldessarini RJ, Perry R, Pike J. Factors associated with treatment nonadherence among US bipolar disorder patients. Hum Psychopharmacol 2008; 23: 95-105
• 15 González-Pinto A, Reed C, Novick D et al. Assessment of medication adherence in a cohort of patients with bipolar disorder. Pharmacopsychiatry 2010; 43: 263-270
• 16 Jónsdóttir H, Opjordsmoen S, Birkenaes AB et al. Medication adherence in outpatients with severe mental disorders: relation between self-reports and serum level. J Clin Psychopharmacol 2010; 30: 169-175
• 17 Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353: 487-497
• 18 Kikkert MJ, Barbui C, Koeter MW et al. Assessment of medication adherence in patients with schizophrenia: the Achilles heel of adherence research. J Nerv Ment Dis 2008; 196: 274-281
• 19 Pomykacz B, Mao M, Weiss RD et al. A review of brief medication-adherence instruments used in patients with schizophrenia and bipolar disorder. Harv Rev Psychiatry 2007; 15: 259-263
• 20 Velligan D, Sajatovic M, Valenstein M et al. Methodological challenges in psychiatric treatment adherence research. Clin Schizophr Relat Psychoses 2010; 4: 74-91
• 21 Levy G. Medication non-compliance: When hard science meets soft science. International Congress Series 2001 1220; 125-133
• 22 Bauer M, Glenn T, Keil M et al. Brief depressive symptoms in patients with bipolar disorder: analysis of long-term self-reported data. Aust N Z J Psychiatry 2012; 46: 1068-1078
• 23 Bauer M, Grof P, Gyulai L et al. Using technology to improve longitudinal studies: self-reporting with chronorecord in bipolar disorder. Bipolar Disord 2004; 6: 67-74
• 24 Bauer M, Wilson T, Neuhaus K et al. Self-reporting software for bipolar disorder: validation of ChronoRecord by patients with mania. Psychiatry Res 2008; 159: 359-366
• 25 Pincus SM. Approximate entropy as a measure of system complexity. Proc Natl Acad Sci USA 1991; 88: 2297-2301
• 26 Pincus SM, Gladstone IM, Ehrenkranz RA. A regularity statistic for medical data analysis. J Clin Monit 1991; 7: 335-345
• 27 Pincus SM, Goldberger AL. Physiological time-series analysis: what does regularity quantify?. Am J Physiol 1994; 266: H1643-H1656
• 28 Pan W, Connett JE. Selecting the working correlation structure in generalized estimating equations with application to the lung health study. Statistica Sinica 2002; 12: 475-490
• 29 Harter JG, Peck CC. Chronobiology. Suggestions for integrating it into drug development. Ann N Y Acad Sci 1991; 618: 563-571
• 30 Osterberg LG, Urquhart J, Blaschke TF. Understanding forgiveness: minding and mining the gaps between pharmacokinetics and therapeutics. Clin Pharmacol Ther 2010; 88: 457-459
• 31 Urquhart J. Patient non-compliance with drug regimens: measurement, clinical correlates, economic impact. Eur Heart J 1996; 17 (Suppl A): 8-15
• 32 Bauer M, Glenn T, Grof P et al. The association between concurrent psychotropic medications and self-reported adherence with taking a mood stabilizer in bipolar disorder. Hum Psychopharmacol 2010; 25: 47-54
• 33 Johnson FR, Ozdemir S, Manjunath R et al. Factors that affect adherence to bipolar disorder treatments: a stated-preference approach. Med Care 2007; 45: 545-552
• 34 Ingersoll KS, Cohen J. The impact of medication regimen factors on adherence to chronic treatment: a review of literature. J Behav Med 2008; 31: 213-224
• 35 Gianfrancesco FD, Sajatovic M, Tafesse E et al. Association between antipsychotic combination therapy and treatment adherence among individuals with bipolar disorder. Ann Clin Psychiatry 2009; 21: 3-16
• 36 Sajatovic M, Bauer MS, Kilbourne AM et al. Self-reported medication treatment adherence among veterans with bipolar disorder. Psychiatr Serv 2006; 57: 56-62
• 37 Cramer JA, Rosenheck R. Enhancing medication compliance for people with serious mental illness. J Nerv Ment Dis 1999; 187: 53-55
• 38 Gaudiano BA, Weinstock LM, Miller IW. Improving treatment adherence in bipolar disorder: a review of current psychosocial treatment efficacy and recommendations for future treatment development. Behav Modif 2008; 32: 267-301
• 39 Urquhart J. Ascertaining how much compliance is enough with outpatient antibiotic regimens. Postgrad Med J 1992; 68 (Suppl. 03) S49-S58
• 40 Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296-1310
• 41 Saini SD, Schoenfeld P, Kaulback K et al. Effect of medication dosing frequency on adherence in chronic diseases. Am J Manag Care 2009; 15: e22-e33
• 42 Richter A, Anton SE, Koch P et al. The impact of reducing dose frequency on health outcomes. Clin Ther 2003; 25: 2307-2335
• 43 Levy G. A pharmacokinetic perspective on medicament noncompliance. Clin Pharmacol Ther 1993; 54: 242-244
• 44 Bialer M. Extended-release formulations for the treatment of epilepsy. CNS Drugs 2007; 21: 765-774
• 45 van Berge Henegouwen MT, van Driel HF, Kasteleijn-Nolst Trenité DG. A patient diary as a tool to improve medicine compliance. Pharm World Sci 1999; 21: 21-24
• 46 Lam DH, Watkins ER, Hayward P et al. A randomized controlled study of cognitive therapy for relapse prevention for bipolar affective disorder: outcome of the first year. Arch Gen Psychiatry 2003; 60: 145-152
• 47 Garber MC, Nau DP, Erickson SR et al. The concordance of self-report with other measures of medication adherence: a summary of the literature. Med Care 2004; 42: 649-652
• 48 Kupka RW, Altshuler LL, Nolen WA et al. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Bipolar Disord 2007; 9: 531-535
• 49 Judd LL, Akiskal HS, Schettler PJ et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002; 59: 530-537