Understanding Medication Discontinuation in Depression

Confidence in antidepressant treatment
Sirey and colleagues^18,19 found that perceptions of stigma about depression at the start of treatment predicted subsequent antidepressant adherence 3 months later. Surveys in many countries consistently report that more than three quarters of people believe that antidepressants are addictive and that most prefer psychotherapy or no treatment at all.^20-23 Col and associates²⁴ found that 50% of patients who were depressed believed they did not need their antidepressants when they began to feel better or that the medications could be taken on an as-needed basis. Patients' previous negative experiences with prescribed medication had a negative influence on current adherence behavior.²⁵ Indeed, Brook and colleagues⁸ found that attitude toward antidepressants was the most important predictor in determining reliable adherence behavior. Aikens and coworkers²⁶ went further and modeled the risk as attributable to concerns about medication. Baseline skepticism about starting an antidepressant contributed to a 62% increase in the risk of premature discontinuation over 9 months.

Effectiveness
Ashton and coworkers²⁷ found that the most common reason for discontinuation was lack of efficacy (reported by 44%) in 210 patients who had been previously treated for depression. This appears to confirm the clinical impression that many patients intentionally stop antidepressants as soon as they can. However, many patients stop antidepressants intentionally when they start to feel better. In fact, 2 studies found that a third of patients stop within 3 months, citing feeling better as the reason, and 55% stop when feeling better within 6 months.^28,29 Thus, both successful and unsuccessful treatment often lead to patient-initiated discontinuation.

Adverse effects
Treatment-emergent adverse effects are an important but avoidable (or at least reversible) reason for discontinuing treatment and not wanting to restart. Intentional nonadherence was associated with concerns about adverse effects of antidepressants as well as the associated stigma.³⁰ In a survey of 344 persons taking antidepressants, the most common reason for less than perfect compliance was the risk of adverse effects. The experience of 1 or more bothersome adverse effects meant that an individual was 3 times more likely to stop medication.³¹ Such complications include weight gain (31%), erectile dysfunction (25%), difficulty in reaching orgasm (24%), and fatigue (21%).²⁷

Accidental omissions
If one examines missed doses rather than full discontinuation, then "forgetting to take the tablet" is the most common explanation. This is encouraging because it allows scope for reminder systems (see below). In the large Alberta Mental Health Telephone Survey from Calgary, poor compliance was assessed in 5323 adults. Asked whether they take less medication than they are supposed to, 42% taking a single medication reported noncompliance; forgetfulness may have been the most common reason for missed medication (64.9%).³² Similarly, Ashton and associates²⁷ found that difficulty in remembering to take medication accounted for 43% of cases of poor compliance. Forgetting to take all doses is related to regimen complexity, cognitive impairment, duration of institutionalization, and ironically, depression.³³

REDUCING ANTIDEPRESSANT NONADHERENCE
Evidence-based adherence studies in depression
There are numerous potential ways of improving adherence behavior, from simple to complex (Table 3). Unfortunately, data from large-scale studies in medical settings hint that dramatic effects on adherence behavior are rare.³⁴ Only a few strategies have been rigorously tested for patients with depression.^35-37 Vergouwen and colleagues³⁸ reviewed 6 studies of interventions involving mental health outpatients and 13 studies comprising primary care patients. Of those studies conducted in psychiatric settings, 5 tested education as an adherence-enhancing intervention, and 3 of these did not demonstrate any appreciable effect.^39-41 However, 2 studies demonstrated significantly better adherence in patients who received verbal and/or written information about side effects of antidepressant medication.^42,43 One study tested the influence of dosing complexity as well as the effectiveness of allowing patients to choose their own dosage regimen.⁴⁴ Adherence was significantly better in those patients who were allowed to choose.

Of the 13 primary care studies reviewed, 3 tested educational interventions but 2 of these involved only a leaflet. None were successful at improving adherence.^45-47 Since early 2003, 8 more studies have been published.⁴⁸ The largest was a randomized study involving 1031 patients with depression. This study looked at an educational program and therapeutic drug monitoring in patients who took sertraline(Drug information on sertraline) for 24 weeks.⁴⁹ Neither of the interventions resulted in a significant increase in adherence rate. Also of note, Bambauer and colleagues⁷ found that a simple intervention of faxed alerts regarding patient adherence was not successful in improving antidepressant adherence. Despite these disappointments, collaborative care packages have been more successful and demonstrated a benefit in 14 of 28 studies that used adherence as an outcome.⁴⁸