AUTHORS' CHRONICLES

Medication-adherence and persistence with first- and second-generation antipsychotics in schizophrenia

Adhesión farmacológica y continuidad del tratamiento con antipsicóticos de primera y segunda generación en la esquizofrenia

Subho Chakrabarti¹

¹ Institute of Medical Education and Research, Chandigarh, India

Subho Chakrabarti describes for SIIC his article published in Indian Journal of Psychological Medicine 36:33-39, 2014.

Chandigarh, India (special for SIIC)

Treatment non-adherence is highly prevalent in schizophrenia and leads to a number of adverse clinical and social outcomes. With the advent of second-generation antipsychotics (SGAs) similar in efficacy to first-generation antipsychotics (FGAs) but with a lesser propensity for extrapyramidal side-effects, it was anticipated that these newer antipsychotic medications would improve medication-adherence in schizophrenia. However, despite a large body of evidence on the matter it still remains somewhat unresolved. Though randomized-controlled trials of efficacy, meta-analyses, and large-scale effectiveness studies have found no differences in adherence between SGAs and FGAs, contrary evidence indicating that patients on SGAs are more likely to take their medications also exists. Two related constructs are often used to describe medication-taking behaviour. While adherence is defined as the extent to which patients' medication-taking corresponds with agreed upon advice from clinicians, persistence or continuation of treatment is the time-period from initiation to discontinuation of medication-treatment. Unlike the equivocal findings regarding differences in medication-adherence between SGAs and FGAs, most efficacy and effectiveness trials have shown that patients on SGAs are more likely to persist with taking their medications.

Therefore, the present study attempted to compare adherence as well as persistence with treatment between patients with schizophrenia on SGAs and FGAs. Over a 6-month period, 40 patients with DSM-IV schizophrenia on SGAs (mainly olanzapine and risperidone) were compared with 30 patients on FGAs (mainly trifluoperazine). Symptom-severity was rated using the Positive and Negative Syndrome Scale (PANSS), while the Compliance Rating Scale (CRS) was used as a clinician-rated measure of medication-adherence and the Drug Attitude Inventory-10-item version (DAI-10) as a patient-reported measure of adherence. Extrapyramidal and other side effects were assessed by appropriate scales. Patients were examined twice; baseline assessments covered the preceding 3-month period and a second assessment after 3 months of follow-up covered the 3-month period between baseline and follow-up assessments. At baseline, the FGA group had significantly lower family incomes, a greater number of past relapses and hospitalizations, longer treatment duration, higher numbers of psychotropics and higher prevalence of extrapyramidal side-effects. Mean scores on the CRS and the DAI-10 were used to categorize as patients as adherent or non-adherent with treatment. At baseline, there were no differences between the two antipsychotic groups in mean scores and proportion of adherent/non-adherent patients.

However, over 3 months of follow-up about 20% of patients on FGAs became non-adherent whereas 15% of the patients on SGAs moved from the non-adherent to the adherent category. Consequently, at the end of the 3-month period and for the entire 6-month duration of the study medication-adherence was significantly greater in the SGA group based on mean CRS and DAI-10 scores, as well the proportion of patients who were categorized as adherent/non-adherent. Further analysis of adherence and persistence revealed that these differences obtained between the two antipsychotic groups were primarily driven by differences between the olanzapine and the FGA group during 3 months of follow-up and over the 6-month study-period. Differences in adherence and continuation rates between the two antipsychotic groups were reflected in the significantly greater decline in PANSS scores over 3 months of follow-up and for the 6-month study period for patients on SGAs. For the whole group, higher family income and supervision of treatment by relatives emerged as significant correlates of adherence, but accounted for a very small proportion of the variance. In the FGA group, there were positive correlations between DAI-10 scores and the CRS scores.

The principal finding of this study was that though patients on SGAs or FGAs did not differ on medication-adherence in the first 3 months prior to intake, over the next 3 months of follow-up 20% of the FGA group discontinued treatment, while 15% patients on SGAs became more adherent with their treatment. These differences in treatment-persistence between the two groups led to patients on SGAs being rated as more adherent at the end of this 3 months of follow-up and for the entire 6-month study-duration. Differences between the two groups resulted mainly from the higher persistence and adherence rates with olanzapine versus FGAs. Due to this improved medication persistence and adherence, patients on SGAs registered a decline in symptom-severity whereas patients on FGAs had a worsening of symptoms during follow-up.

Following large-scale naturalistic studies of antipsychotic treatment such as the Clinical Antipsychotic Trials of Intervention Effectiveness study (CATIE), the CUTLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia study) and the EUFEST (European First Episode Schizophrenia Trial), the consensus was that there were no differences in medication-adherence between SGAs and FGAs. However, other effectiveness trials have found better adherence among patients on SGAs, as have quite a few controlled trials and certain meta-analytic studies. In contrast to the somewhat equivocal findings regarding medication-adherence with FGAs and SGAs, findings on medication-persistence have been relatively consistent; the majority of trials have found greater treatment-persistence among SGAs. The existing literature also suggests that among SGAs, patients on olanzapine and clozapine are more likely to persist with their treatment for a longer period. The current study provides a clue to the discrepancy between adherence and persistence between antipsychotic groups in previous studies. Since the assessment of adherence often involves a cross-sectional assessment over a shorter time-frame, results may vary depending on the point of time when the adherence assessments are carried out. On the contrary, the estimation of treatment-persistence involves longitudinal assessments over longer periods, which could account for the greater consistency of results regarding SGA-FGA differences. The findings of the present study were limited by the small numbers in both groups, baseline differences between the two antipsychotic groups and the relatively short period of prospective follow-up. Nevertheless, the finding that patients on certain SGAs like olanzapine are more likely to continue with their treatment than those on FGAs indicates that there may still be further scope for methodologically sound research in this area of immense clinical relevance.