Frequency of dosing. In an early study in a psychiatric outpatient practice in the United Kingdom, Myers & Branthwaite randomized patients into groups that received their treatment once daily or three times daily, or chose one of the two schedules. Adherence was assessed by pill count and interview (12). There was no overall difference in reported adherence between patients receiving once-daily or three-times-daily doses, but those who elected to take their medication three times daily reported better adherence than the others. This suggests that the element of personal control over choice of dose, rather than the frequency of dosing itself was influential. A recent study has suggested that prescribing a once-weekly dose of enteric-coated fluoxetine may lead to better adherence than a once-daily dose (13); thus substantial gains in convenience may also improve adherence.
Education. Lin et al. reported that patients were more likely to continue to take their medication during the first month of treatment if they had received specific educational messages, namely that they should take their medication daily, that they might notice no benefit for the first 2 - 4 weeks, that they should continue even if they felt better and that they should not stop medication without consulting their doctor. They also received advice about how to seek answers to questions about medication (14). The impact of such advice has not been evaluated prospectively.
Drug type. There has been considerable interest in the question of whether or not different antidepressant drugs are associated with better or worse adherence. A naturalistic study of claims data of 2000 patients suggested that adherence may be poorer in patients treated with tricyclic antidepressants, and that the provision of family, group or individual psychotherapy may improve adherence (15).
Several meta-analyses of randomized trials have also addressed this question. Montgomery & Kasper reviewed 67 trials and reported that the number of patients who discontinued their treatment because of side-effects was 5% lower in patients treated with selective serotonin reuptake inhibitors (SSRIs) than in patients treated with tricyclics (16). Anderson & Tomenson reviewed 62 trials and also found a marginally lower discontinuation rate in patients treated with SSRIs, but commented that the difference was probably too small to be of clinical significance (17). Hotopf et al. reporting the results of another meta-analysis suggested that even this small difference might be due to the preponderance of older tricyclic drugs used in most of the early trials, and that it would disappear if the comparison were made with newer tricyclic and heterocyclic medicines (18). Although the generalizability of meta-analysis may be limited by the characteristics of the patient samples in the trials reviewed, these results suggest that drug type may not be a particularly influential variable.
Co-medication. Furukawa et al. conducted a meta-analysis of trials comparing combinations of antidepressants and benzodiazepines with antidepressants prescribed alone for periods of up to 8 weeks and reported a marginal benefit of co-prescribing benzodiazepines. Any potential benefit must be offset against the possible clinical disadvantages such as the development of dependence on benzodiazepines (19).
Psychiatric co-morbidity and personality traits. Keeley et al. reported from a small study in family practice, that patients with more frequent somatoform symptoms were more likely to be nonadherent to drug treatment (20). Ekselius et al. reported that sensation-seeking personality traits were associated with lower blood-levels of antidepressant drug, though not with lower self-reported adherence, in patients participating in a randomized trial (21).