Fewer symptoms vs. more side-effects in schizophrenia? Opposing pathways between antipsychotic medication compliance and quality of life
Introduction
Many patients with either a somatic or a psychiatric disorder do not comply with medication. Based on a review, Cramer and Rosenheck (1998) estimate that, on average, patients who have been prescribed somatic medicine use only 76% of the pills. This percentage is lower in the case of antipsychotics, where only 58% of the prescribed medication is estimated to be actually taken. Keith and Kane (2003) aptly conclude their review by observing that while compliance with medication is difficult for everyone—for example in the field of diabetes, high blood pressure, asthma, or birth control—it is particularly difficult for people with schizophrenia. Four studies have shown that 50% to 75% of patients on antipsychotic medication become non-compliant after one to two years of treatment (Bebbington, 1995, Thomas, 2007, Weiden et al., 1996, Weiden et al., 1991). Obviously, non-compliance makes it difficult to achieve the effects intended for treatment. When a patient stops using antipsychotics, the risk of relapse and admission or readmission increases three to five-fold (Dixon and Lehman, 1995, Fenton et al., 1997, Robinson et al., 2002, Ucok et al., 2006, Weiden et al., 2004). It should be mentioned, however, that in some cases non-compliance may follow clinical deterioration, which can be due to resistance in therapy, making causal attributions on the relationship between non-compliance and relapse difficult. In the same way, the risk of suicide may be 3.75 times higher in non-compliant patients with schizophrenia than it is in those who are compliant (Hawton et al., 2005), though here it is important to realise that depression increases the risk of non-compliance (Elbogan et al., 2005) as well as of suicide.
Although the long-term consequences of non-compliance are often detrimental to patients with schizophrenia, it is less obvious whether those who are compliant experience any short-term improvement in their quality of life. While three studies have found that people suffering from schizophrenia experienced substantially lower quality of life than healthy subjects (Carlsson et al., 2002, Reine et al., 2003, Zissi et al., 1998), few studies have investigated how experienced quality of life was affected by compliance with antipsychotics. One study reported an association between compliance and quality of life in first-episode patients (Coldham et al., 2002). Another initially found a small positive association that however was not borne out by subsequent statistical modelling (Puschner et al., 2006).
Arguably, by reducing symptoms on the one hand and increasing side-effects on the other, compliance with medication involves two mechanisms, each affecting a patient's perceived quality of life in a different direction. Although Puschner et al. (2006) did indeed find that better compliance and higher perceived quality of life were mediated by a reduction in psychopathology, they did not find that better compliance and lower quality of life were mediated by an increase in medication side-effects. This may be because they used the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS, Day et al., 1995)—a good self-report scale of side-effects that nonetheless does not make it possible to quantify their overall burden on a patient. It has been found in other studies, however, that side-effects of antipsychotics are associated with a reduced perceived quality of life (Angermeyer and Matschinger, 2000, Yen et al., 2008), and that they are sometimes a reason for discontinuing medication (Lambert et al., 2004, Robinson et al., 2002).
The objective of this study was to test the hypothesis that medication compliance has two opposing and indirect associations with a patient's perceived quality of life: (1) that, by reducing psychotic symptoms, better compliance is associated with increased quality of life; and (2) that, by increasing adverse medication effects, better compliance is associated with poorer quality of life.
Section snippets
Study population
Participants were respondents in a multi-centre randomized controlled trial that took place in the Dutch city of Rotterdam and investigates the effects of Treatment Adherence Therapy (TAT). TAT is a tailored intervention in which, depending on a patient's individual reasons or causes of non-compliance, four different intervention modules can be applied, for example behavioral interventions or an adapted form of motivational interviewing. For a more detailed description, see Staring et al. (2006)
Patient characteristics
A total of 195 patients were asked to participate in the randomized controlled trial described above. Seventy-nine of them declined to participate. Of the remainder, two were too disorganized in thought and speech to be able to complete the questionnaires. The remaining 114 completed the baseline assessments. Lifetime diagnoses: 79 of these patients (69%) met the criteria of schizophrenia (60 paranoid type, 11 disorganized type, 7 catatonic type, and 1 undifferentiated type), and 35 (31%) met
Discussion of the results
Our results suggest that compliance with antipsychotics in patients with a psychotic disorder involves two different and indirect pathways towards quality of life. While compliance seems to reduce psychotic symptoms—which may increase quality of life—compliance also seems to increase adverse medication effects—which may reduce quality of life. This finding is largely in line with an earlier study which found not only (1) that compliance with antipsychotics had no direct effect on quality of
Role of funding source
Funding for this study was provided by the Dutch Ministry of Health, Welfare, and Sports (ZonMw, research grant number 100-002-017). ZonMw played no further role in the study design or in the collection, analysis and interpretation of data; the writing of the report; or the decision to submit the paper for publication.
Contributors
Authors Mulder, Gaag, and Staring designed the study and wrote the protocol. Staring managed the literature. Authors Duivenvoorden and Staring undertook the statistical analyses. De Haan advised on the study design. Staring wrote the first draft of the manuscript. All authors contributed to revisions and have approved the final manuscript.
Conflict of interest
None.
Acknowledgements
We would like to thank all the participating patients, caregivers, and administrative, medical and paramedical staff at Erasmus University Medical Centre, Parnassia Bavo Group, Delta Psychiatric Centre, ‘De Grote Rivieren’ Community Psychiatric Health Centre, and ‘Riagg Rijnmond’ Community Psychiatric Health Centre.
References (46)
- et al.
Quality of life and standard of living in a randomly selected group of psychiatrically disabled people in Sweden 2 years after a psychitry reform
Eur. Psychiatr.
(2002) - et al.
Impact of present and past anitpsychotic side effects on attitude toward typical antipsychotic treatment and adherence
Eur. Psychiatr.
(2004) - et al.
Improvement of schizophrenic patients' subjective well-being under atypical antipsychotic drugs
Schizophr. Res.
(2001) - et al.
Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder
Schizophr. Res.
(2002) Diagnostic and Statistical Manual of Mental Disorders
(1993)- et al.
Neuroleptics and quality of life. A patient survey
Psychiatr. Prax.
(2000) - et al.
Motivational interviewing in psychotic disorders
Curr. Psychiatr. Rev.
(2006) The content and context of compliance
Int. Clin. Psychopharmacol.
(1995)Comparative fit indexes in structural models
Psychol. Bull.
(1990)- et al.