Elsevier

Schizophrenia Research

Volume 159, Issue 1, October 2014, Pages 95-100
Schizophrenia Research

The impact of second-generation antipsychotic adherence on positive and negative symptoms in recent-onset schizophrenia

https://doi.org/10.1016/j.schres.2014.07.008Get rights and content

Abstract

Objective

The aim of the study was to explore the extent to which initial severity of positive or negative symptoms in patients with recent-onset schizophrenia is related to medication nonadherence during the first outpatient year.

Methods

The study involved 64 first-episode schizophrenia patients treated with the second-generation oral antipsychotic medication, risperidone, for 12 months. Symptoms were evaluated using the SANS and SAPS completed every 3 months. Pearson correlations between medication adherence and symptoms were examined over each 3-month interval during 12 months of follow-through treatment. Possible causality was inferred from cross-lagged panel analyses.

Results

As expected, higher levels of adherence with antipsychotic medication were generally associated with lower levels of concurrent reality distortion (mean of SAPS delusions and hallucinations). Greater adherence during the 3-month baseline interval was generally associated with lower levels of avolition–apathy as well as alogia throughout the first outpatient year. However, medication adherence was not significantly associated with decreases in avolition–apathy or alogia over time. Cross-lagged panel analyses based on correlation coefficients are consistent with a causal relationship between initial medication adherence and lower levels of alogia. A test of mediation confirmed that an indirect path through reality distortion mediated the relationship between medication nonadherence and alogia.

Conclusions

The associations between greater medication adherence and lower levels of negative symptoms appeared to be accounted for by the relationship of both variables to positive psychotic symptoms. The findings suggest that the impact of second-generation antipsychotic medication on suppression of negative symptoms might be mediated via a reduction in positive symptoms.

Introduction

Patients with prominent negative symptoms who are also medication non-adherent typically have poorer outcomes (Morken et al., 2008, Tsang et al., 2010). It is possible that patients with negative symptoms lack distress about having schizophrenia and are therefore less motivated to participate in treatment. Given that medication nonadherence in schizophrenia patients is perhaps the single most preventable cause of psychotic relapse, examination of this relationship is very important. However, only a very few studies have empirically examined this question, and the findings have been equivocal.

Individuals with schizophrenia who had significantly higher overall SANS scores and higher avolition–apathy and alogia SANS item scores, were shown to have lower levels of first-generation depot antipsychotic medication adherence (Tattan and Creed, 2001). The authors hypothesized that the lethargy and lack of motivation associated with avolition and apathy led to the greater nonadherence with clinic visits required for depot antipsychotic medication injections, and speculated that alogia could interfere with treatment and developing greater insight into the need for treatment. The presence of higher levels of negative symptoms on the PANSS (Kay et al., 1987) was shown to be moderately positively correlated with lower oral antipsychotic medication adherence (Kao and Liu, 2010). Baloush-Kleinman et al. (2011) found that higher levels of negative symptoms were not directly related to antipsychotic medication adherence, but did indirectly impact medication adherence by influencing attitudes towards medication, which in turn were associated with lower adherence. Using structural equation modeling to test the Health Belief Model, they found that the presence of negative symptoms predicted negative attitudes (related to insight, medication costs, and medication benefits) towards medication, which then in turn predicted nonadherence. In contrast, findings for a large first-episode schizophrenia sample suggested that negative symptoms do not interfere with medication adherence, but on the contrary are associated with continued adherence to the antipsychotic medication regimen (Steger et al., 2012). In that study, resolution of positive symptoms was associated with continued medication adherence.

No effective treatments for negative symptoms of schizophrenia have been clearly established. Current antipsychotic medications are apparently ineffective or only minimally effective in treating negative symptoms of schizophrenia (Erhart et al., 2006, Moller, 2007, Carpenter and Davis, 2012, Levine and Leucht, 2012). There have been some reports of limited efficacy of clozapine, iloperidone, asenapine, amisulpride, and risperidone for reduction of negative symptoms, but the specificity for treatment of negative symptoms has not been clearly established (Danion et al., 1999, Makinen et al., 2008, Hanson et al., 2010, Levine and Leucht, 2012, Levine and Leucht, 2013).

The aim of this report is to explore the extent to which the severity of negative symptoms in patients with recent-onset schizophrenia is related to medication nonadherence during the first outpatient year. A secondary aim is to explore potential “causal” relationships between oral antipsychotic medication adherence and negative symptoms. We hypothesized that the presence of negative symptoms is a primary contributing factor in decreased medication adherence.

Section snippets

Participants

This study involved patients with a recent first episode of schizophrenia drawn from two National Institute of Mental Health-funded longitudinal protocols (“Sample 3” and “Sample 4”) conducted at the Aftercare Research Program at the University of California, Los Angeles (Nuechterlein et al., 1992, Nuechterlein et al., 2008, Subotnik et al., 2011). All patients received treatment with second-generation antipsychotic medication, regular visits with the treating psychiatrist, individual case

Results

The demographic and clinical characteristics of the study participants are representative of the greater Los Angeles region (presented in Table 1). Participant symptom levels during the four time intervals are presented in Table 2.

Discussion

In this sample of first-episode schizophrenia patients, higher levels of antipsychotic medication adherence were associated with lower levels of positive symptoms as well as lower levels of two forms of negative symptoms. Specifically, greater adherence to the second-generation oral antipsychotic medication, risperidone, was associated with lower levels of reality distortion (delusions and hallucinations), avolition–apathy, and alogia in zero-order bivariate correlations. However, contrary to

Role of funding source

This research was primarily funded by the National Institute of Mental Health (NIMH research grant MH037705 and NIMH Center grant P50 MH066286 to K.H. Nuechterlein). Medication and supplemental support was provided by Janssen Scientific Affairs, Inc., through an investigator-initiated grant. An investigator-initiated grant from Genentech, Inc., provided supplemental funding to support the data analyses presented here.

Contributors

Keith H. Nuechterlein, Kenneth L. Subotnik, and Joseph Ventura participated in the overall design of the longitudinal studies described here, and Elisha R. Agee, Denise Gretchen-Doorly, Gerhard S. Hellemann, and Kathleen F. Villa, planned the data analyses reported in this manuscript. Gerhard S. Hellemann, Kenneth L. Subotnik, and Elisha R. Agee conducted the data analyses. Laurie R. Casaus and John S. Luo were the psychiatrist investigators who supervised the medication administration. All

Conflict of interest

Kenneth L. Subotnik, Ph.D., has received research funding from Janssen Scientific Affairs, LLC, and Genentech, Inc. through grants to Drs. Nuechterlein and Ventura. He is a consultant to Otsuka America Pharmaceutical, Inc. Keith H. Nuechterlein, Ph.D., has received funding from Janssen Scientific Affairs, LLC, Brain Plasticity, Inc., and Genentech, Inc. He has served as a consultant to Genentech, Inc., Janssen Scientific Affairs, and Otsuka America Pharmaceutical, Inc. Joseph Ventura, Ph.D.,

Acknowledgements

We gratefully acknowledge the caring UCLA Aftercare Research Program case managers Kimberly Baldwin, M.F.T., Rosemary Collier, M.A., Nicole R. DeTore, M.A., Yurika Sturdevant, Psy.D., and Luana Turner, Psy.D.. We also thank the medication adherence raters, Elizabeth Arreola, B.A., Manjot Bains, Miriam Barillas, B.A., Ashton Christian, Kassandra Coronel, Jing Gong, Liset Cristino Crespin, M.S.W., Angie Sung Hyun Lim, Lilian Medina, B.A., Sabiha Kaiser, B.S., Steven Kwong, B.S., Angie Lim, B.S.,

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