Adequate adherence to medication confers benefits on patients with psychotic illness, but is difficult to achieve. Efficacy of medication influences adherence in patients in advanced phases of illness and may have a similar influence on patients with a first episode of psychosis (FEP). We assessed medication adherence and efficacy in 216 FEP patients at program entry and at 3 and 6 months later. “Efficacy” was evaluated as the ability of medication to reduce positive or negative symptoms to below established thresholds for clinical remission at each evaluation. Adherence was defined as adequate (> 75%) or not. Resolution of negative symptoms by month 3 of treatment was associated with inadequate adherence at months 3 and 6. In contrast, rapid resolution of positive symptoms showed no relationship to adherence. In a multivariate analysis taking into account other determinants of adherence in FEP, the role of early negative symptom remission was confirmed, and we found that a 3-month sustained remission of positive symptoms was associated with adequate adherence. Medication efficacy may promote adherence if it produces sustained remission of positive symptoms. However, many patients who benefit from medication, particularly those with rapid improvement of negative symptoms, fail to adhere to the treatment.
Medication adherence improves outcomes in psychotic illness, reducing the risk of relapse and rehospitalization (Valenstein et al., 2002, Ascher-Svanum et al., 2006a, Ascher-Svanum et al., 2006b and Law et al., 2008). For patients with first episode psychosis (FEP), adherence is associated with faster remission of positive symptoms, fewer recurrences and better social/occupational functioning (Robinson et al., 1999, Malla et al., 2006 and Lambert et al., 2010). However, many patients with FEP do not adhere to a medication regimen: 26 to 53% of early psychosis patients leave treatment in the first year (Favre et al., 1997, Novak-Grubic and Tavcar, 2002 and Robinson et al., 2002) and between 33 and 63% display inadequate levels of adherence (Coldham et al., 2002, Mojtabai et al., 2002, Kamali et al., 2006 and Quach et al., 2009). Several studies have found that poor adherence predicts subsequent poor adherence (Verdoux et al., 2000, Lacro et al., 2002, Ascher-Svanum et al., 2006a and Ascher-Svanum et al., 2006b), increasing the importance of understanding this phenomenon in FEP.
Adherence to medication is influenced by numerous factors, including patient-related elements (age and gender; attitudes; symptoms), relationship elements (alliance with caregivers; family support) and health care system elements (cost of care; ease of access; (Velligan et al., 2009)). Many of these factors have been associated with adherence in FEP (see (Miller, 2008 and Masand et al., 2009) for review). However, several studies have pointed to a crucial role for attitudes and beliefs about medications. Mutsatsa et al. concluded that attitudes and insight were more important determinants of adherence in FEP than adverse effects or demographics (Mutsatsa et al., 2003). More specifically, Perkins et al. found that positive attitudes towards medications and beliefs that they are beneficial were highly associated with adherence (Perkins et al., 2006).
These results raise questions about how medication attitudes are formed. Studies of multi-episode patients suggest that perceived medication efficacy is an important factor in both attitudes and adherence. In a qualitative study asking patients to list influences on adherence, efficacy was the most often cited factor (Kikkert et al., 2006). Data from a series of antipsychotic clinical trials showed that lack of efficacy, as perceived by the patient, was the most common reason for discontinuation (Liu-Seifert et al., 2005). Although patients and clinicians may have different ways of evaluating efficacy, several studies have found that reduction of symptoms is relevant to patients: Karow et al. found that improvements in both subjective well-being and in symptoms were associated with improvements in adherence (Karow et al., 2007), symptom improvement in the first 2 weeks of a treatment trial predicted completion of a 6-month protocol (Liu-Seifert et al., 2005) and failure of treatment response was associated with non-adherence and study discontinuation in a year-long trial with first episode patients (Perkins et al., 2008).
In the present study, we examined the interaction between medication efficacy and adherence very early in treatment, when patients are learning about medications and attitudes are being formed. Because of the association mentioned above between early symptom reduction and remaining in treatment, one might predict that rapid relief of symptoms would be interpreted as proof that medications are useful and would promote adherence. On the contrary, patients who experience rapid elimination of symptoms may be more likely to minimize or dismiss their illness experiences, and see medication as unnecessary (Fenton et al., 1997 and Clatworthy et al., 2007). Our aim was to test which of these observations applies to patients being treated for FEP. We hypothesized that rapid improvement of symptoms would be associated with subsequent adherence, especially if improvement was sustained.
