Promoting treatment adherence in patients with bipolar disorder
Consider your patients’ perspectives and goals when choosing interventions
Other factors that may contribute to medication nonadherence in BD patients include comorbid substance abuse or personality disorders, both of which are associated with more frequent relapse.15 Marriage has a beneficial affect on adherence.15 A good support system may contribute to treatment adherence; in a study of 107 children and adolescents with BD, nonadherent patients were more likely to experience family dysfunction and have a parental history of psychiatric hospitalization.22
Adherence and BD course
Treatment adherence decreases the suicide rate among BD patients. Angst et al23 evaluated the rate of suicide among 406 patients with BD and unipolar depression who were followed for 40 years. They found that 11% committed suicide; untreated patients had significantly higher standardized mortality rates than of those who were treated with lithium, antipsychotics, or antidepressants. Other studies confirm this finding.15
Repeated relapse may predict poorer cognitive performance. Lopez-Jaramillo et al24 showed that patients with BD who had more manic episodes performed poorer on cognitive tests assessing attention, memory, and executive functioning compared with patients with less episodes and with normal subjects.
Medication adherence in BD is a priority because of potential neurodegeneration in BD and the neuroprotective effects of mood stabilizers and some atypical antipsychotics (Box).
As emerging studies document morphologic brain changes associated with bipolar disorder (BD), researchers have been relating these changes to the duration and progression of illness. A longer duration of illness is associated with a smaller total gray matter volume on brain MRI of BD patients compared with unipolar patients and normal controls.a Brain MRI analysis of grey and white matter in elderly patients with longstanding BD who underwent neuropsychological testing to rule out dementia showed a decreased concentration of grey matter in the anterior limbic areas as well as reduced fiber tract coherence in the corpus callosum when compared with normal controls.b
Additionally, microstructural brain changes have been associated with acute mood states, in particular bipolar depression.c Lithium, valproate, olanzapine, and clozapine are neuroprotective in cultures of human-derived neuroblastoma cells, by enhancing the cells’ proliferation and survival.d
Source:
a. Frey BN, Zunta-Soares GB, Caetano SC, et al. Illness duration and total brain gray matter in bipolar disorder: evidence for neurodegeneration? European Neuropsychopharm. 2008;18:717-722.
b. Haller S, Xekardaki A, Delaloye C, et al. Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder. J Psychiatry Neurosci. 2011;36(1):100140.
c. Zanetti MV, Jackowski MP, Versace A, et al. State-dependent microstructural white matter changes in bipolar I depression. Eur Arch Psychiatry Clin Neurosci. 2009;259(6):316-328.
d. Aubry J, Schwald M, Ballmann E, et al. Early effects of mood stabilizers on the Akt/GSK-3ß signaling pathway and on cell survival and proliferation. Psychopharmacology. 2009;205:419-429.
Increasing adherence
Pharmacologic strategies. Adherence in BD often is difficult when patients require a complex medication regimen to control their illness. Patients and clinicians may prefer to use once-daily dosing drug formulations, which can provide consistent serum levels and fewer adverse effects. Divalproex extended-release (ER) allows once-daily dosing and improved tolerability by reducing fluctuations in valproic acid serum concentrations compared with the delayed-release formulation. In a retrospective chart review,25 most patients (62%) who switched to divalproex ER from divalproex delayed-release preferred the ER formulation; 52% showed clinical improvement, 81% did not experience side effects, and 8% demonstrated higher adherence after switching.25 Similarly, an extended-release formulation of carbamazepine is approved for treating acute mania.
Many atypical antipsychotics are FDA-approved for acute mania, acute bipolar depression, and/or maintenance (Table 2). Long-acting injectable formulations (LAIs) may be used as maintenance treatment if nonadherence is an issue. LAI risperidone, which is FDA-approved for maintenance treatment of bipolar I disorder (BDI), was found to be safe and effective in stable BD patients who were switched from an oral antipsychotic.26 Asenapine is provided in a rapidly absorbed, sublingual form and is FDA-approved for treating acute mania or mixed episodes associated with BDI.27 Overall, however, only slightly more than one-half of BD patients are adherent to atypical antipsychotics.15
Although antidepressant use in BD is controversial, Sajatovic17 found 44% of depressed BDI patients were treated with antidepressants. Novel extended-release antidepressant formulations—including controlled-release fluvoxamine, paroxetine, extended-release bupropion and venlafaxine, once-weekly fluoxetine, rapidly dissolving mirtazapine, and transdermal selegiline—can optimize drug delivery, minimize side effects, and delay onset of action.1
