Medication adherence in first-episode psychosis and its association with psychopathology.

BACKGROUND: The purpose of the study was to follow-up the individuals with first-episode psychosis (FEP) for a period of 1 year to assess their medication adherence rates and to identify the association between medication adherence and psychopathology.
MATERIALS AND METHODS: In a 1 year longitudinal study, 59 individuals with FEP were assessed for their sociodemographic profile and medication adherence at 1 month and 12-month follow-up period using a semi-structured per forma. Positive and negative symptoms were assessed by positive and negative syndrome scale (PANSS) while the functioning by global assessment of functioning (GAF) scale.
RESULTS: Nearly 85% of the individuals were adherent with medications during the 1-month follow-up period, 32.2% were poorly adherent at the end of 12 months. Among various factors examined for association with medication adherence, positive and negative symptoms, and global functioning of the individuals at the end of 12 months were found to significant associated with poor medication adherence.
CONCLUSION: There is a high rate of medication nonadherence in individuals with FEP at 12-month follow-up, and factors affecting nonadherence should be addressed specifically to improve medication adherence in these individuals.

INTRODUCTION

First-episode psychosis (FEP) is a major health issue worldwide with estimated incidence rate of 34.0 new cases per 100,000 person-years.[1] It is the first presentation of psychotic symptoms or signs and usually occurs in adolescents or young adults. The first line of management is low-dose antipsychotics; treatment with atypical antipsychotics in low doses have exhibited high remission rates.[23] Here, it must be stressed that medication adherence is one of the most important factors independently affecting the remission in FEP.[4] Medication adherence improves the outcome through reducing the risk of relapse and fewer hospitalizations. On the other hand, poor medication adherence is associated with poor symptom improvement, higher level of residual symptoms, higher relapse and hospitalization rates, and poor quality of life.[5] Despite the importance of medication adherence in FEP, many patients do not adhere to the medications. The rate of medication nonadherence varies from 26% to 53% for complete discontinuation at the end of the first year to 33%–63% of inadequate medication adherence.[6]

Various factors have been identified to influence medication adherence such as age, symptom severity, insight, support from the family members, cost of treatment, and availability of treatment services in the proximity.[4] However, most of the studies that have explored the factors influencing the medication adherence in FEP have been from the high-income countries, but similar kind of a study is lacking from low- and middle-income countries (LAMIC) such as India.[7] Identification of these factors affecting medication adherence from the LAMIC would bridge the research gap and would help in identifying the unique factors affecting medication adherence in FEP in these countries. This would lead to the formulation of specific strategies applicable to this region to improve medication adherence in FEP.

Therefore, in this study, we first examined the rate of medication adherence in individuals with FEP over 1 year at two points in time (1 month and 12 months) and examined the demographic and clinical factors associated with poor medication adherence.

MATERIALS AND METHODS

Participants

Participants were recruited from the Schizophrenia Research Foundation-McGill FEP Program, a specialized assessment, treatment, and follow-up program for individuals with FEP in Chennai. Participants were recruited into the study after a written informed consent. The study was approved by the Institutional Review Board. Consecutive sampling methodology was used for recruitment of the study participants.

Inclusion criteria for the study group include age between 16 and 35 years of age, International Classification of Diseases, Tenth Edition diagnosis of psychotic disorder and prior treatment with anti-psychotic medications for not longer than a month. Exclusion criteria include mental retardation, primary neurological or medical disorders, and primary substance use disorder. Individuals with primary psychotic disorder with comorbid substance use were included in the study group. After recruitment into the study, the participants were followed up for the study period of 1 year.

Assessments

Sociodemographic and illness variables

A structured per forma was employed to record the sociodemographic data and illness variables of the study participants during the recruitment into the study.

The participants were administered the following scale at baseline and at the end of 1 year follow-up.

Positive and negative syndrome scale

Positive and negative syndrome scale (PANSS) is a scale for measuring symptoms in schizophrenia.[8] It provides a balanced representation of positive and negative symptoms and measures their relationship to one another and to global psychopathology. It is a 30-item scale, with 7 items in positive symptom domain, 7 in negative symptom domain, and 16 in global psychopathology domains.

Global assessment of functioning

Global assessment of functioning scale is used to rate how serious a mental illness may be.[9] It measures how much a person's symptoms affect his or her day-to-day life on a scale of 0–100. It is designed to help mental health providers understand how well the person can do everyday activities. The score can help to figure out what level of care someone may need and how well certain treatments might work.

Assessment of medication adherence

Medication adherence was evaluated from the information gathered from the participants and their caregivers.[10] Depending on that, participants were classified into the following three groups depending on the number of days the individual has taken medications in the prior month: poor adherence (<25% of the days), intermediate adherence (26%–75% of the days), and good adherent (>75% of the days).

Management and follow-up of the participants

The recruited study participants with FEP were treated according to the established guidelines free of cost. In short, all the individuals were initially started with a second-generation antipsychotic drug such as risperidone or olanzapine with adequate dosage and followed up for an adequate period for improvement. Based on the follow-up assessment, medications were changed according to the guidelines. Along with medications, nonpharmacological management included psychoeducation to the participants and family members and cognitive behavior therapy, when needed.

The regular follow-up of the study participants was carried out by the dedicated research assistants with this project. Medication review and refill were done at the regular interval of 1 month. When the individuals were not able to make for the visit for various reasons, the medications were provided with the caregivers. The medication intake was supervised by the caregivers and their information was used to classify the participants into different medication adherence categories. Regular contact with the study participants was maintained either by phone or home visits by the research assistants to ensure continuous follow-up and to prevent any dropout from the study. For the purpose of this study, we have defined the dropouts as the study participants who have not visited the clinic or whom we were not able to make contact over the phone or by home visits for a period of ≥ 3 months. By this definition, we had continuous contact with all the study participants till the end of the study.

Statistical analysis

Statistical analysis was performed using SPSS version 16 (SPSS Inc., Chicago, US). Groups were compared by Chi-square test for categorical variable and analysis of variance (ANOVA) for continuous variables. The statistical significance was set at P < 0.05 using a two-tailed statistic.

RESULTS

The sociodemographic profile of the participants is presented in Table 1. The mean age of the participants was 29.5 ± 4.9 years with more female participants. Nearly, 60% of the participants were not married at the time of recruitment into the study with a high unemployment rate (66%).

Table 1

Socio demographic and illness variable of study subjects with first episode psychosis (n=59)

Variables	n (%); Mean±SD
Age (in years)	29.5±4.9
Education (in years)	11.1±3.4
Gender
Male	24 (40.7)
Female	35 (59.3)
Employment
Unemployed	39 (66.1)
Employed	13 (22.0)
Others	07 (11.9)
Marital Status
Married	24 (40.7)
Others	35 (59.3)
Housing Type
Urban	46 (78)
Rural	13 (22)
Family Type
Nuclear	47 (79.7)
Joint	12 (20.3)
Diagnosis
Schizophrenia	41 (69.5)
Other psychoses	18 (31.5)
Age at Onset	27.9±10.6

Among the 59 participants of the FEP program, at the end of 1 month, 3.4% (2) of them demonstrated poor adherence (<25%), 10.2% (6) were intermediately adherent (25%–75%), and 86.4% (51) good adherent (>75%). On completion of 1 year, 32.2% (19) were poor adherent, 8.5% (5) of them were intermediately adherent, and 59.3% (35) were good adherent [Figure 1].

Figure 1

Level of medication adherence in individuals with first-episode psychosis at baseline and 1 year of follow-up (n = 59)

One-way ANOVA was done to assess the differences among the three groups on sociodemographic and illness variables. The groups did not differ significantly in the sociodemographic profile. The poor-adherent group had significantly poorer level of functioning when compared to the other groups. Furthermore, the total PANSS score was significantly higher in the poor adherent group at 1 month and 1 year. The group also significantly differed in their subdomains of PANSS at the end of 1 year [Table 2].

Table 2

Comparison of individuals with first episode psychosis classified as three groups based on medication adherence into good, intermediate and poor medication adherent (n=59)

Variable	F	p
Age	1.14	0.33
Age at onset	0.75	0.46
Education (in years)	0.77	0.47
Prodrome (in weeks)	1.54	0.22
PANSS - Positive symptoms at one year	4.11	0.02*
PANSS - Negative symptoms at one year	4.01	0.02*
PANSS - Total at one year	3.66	0.03*
GAF at one year	4.4	0.01*

DISCUSSION

The aim of the present study was to assess the rate of medication adherence in individuals with FEP in a longitudinal follow-up and to examine the various factors that could predict the adherence to medications in these individuals. Adherence to treatment prescription is a critical aspect of health care. It is a complex and multi-factorial phenomenon determined by different factors in different patients. In psychotic illness, medication adherence improves outcomes, reduces risk of relapse, and rehospitalization.[1112]

The rate of poor adherence in our study is comparable to other studies that have examined the prevalence of adherence in FEP – 26%–53% of patient leave treatment in the first year[131415] and 33%–63% display inadequate levels of adherence.[10161718]

In our results, we observed that age, age of onset of illness, educational status in years, and prodromal phase were not significantly associated with poor adherence rates. This is in contrast with other studies which have shown that age, age of onset, premorbid functioning, and insight are significantly associated with nonadherence at the end of 1 year.[451920] However, in another study, age, education, and socioeconomic status were not consistent predictors of medication adherence in individuals with FEP.[21]

In our study, higher positive and negative symptom scores at the end of 12 months have been shown to be associated with medication nonadherence in individuals with FEP. In contrast, in a study by Steger et al. where they examined the effect of symptom resolution on medication adherence in FEP and found that early resolution of negative symptoms but not the resolution positive symptoms predict medication adherence.[22] With the resolution of the positive and negative symptoms and improvement in daily functioning, they no longer feel the need to continue medication, and it is also possible that reduction in a motivation, apathy and similar symptoms may allow patients to feel capable of managing their illness. Furthermore, another issue among early phase patients is that those who have a good response to treatment is in the belief that treatment is no longer necessary.[23] As examined by Rangaswamy et al., in FEP, symptoms resolution is seen at 3 months and medication discontinuation happens; since the relapse is usually after a 12-month period, this long gap could contribute further to a false sense of security that treatment is no longer necessary.[24]

The major strengths of the current study are the prospective study design with 1-year follow-up of the participants, standardized assessment of psychopathology at predetermined intervals and low attrition rate. The major limitations are the small sample size because of the restrictive inclusion and exclusion criteria, inclusion of only psychopathology assessment to study the association with medication adherence, assessment done only at baseline and 12 months, and no specific scale was used to assess the medication adherence. Moreover, we have not assessed the relationship between the medications, side effects, and treatment adherence.

The future studies assessing the medication adherence in FEP should include other factors such as insight, medication adverse effects, and family support and to examine the interaction between various factors. This could lead to prediction models for medication adherence in FEP and possible targets to improve medication adherence.

CONCLUSION

Medication adherence is an important component for better outcomes in individuals with FEP. The results indicate that nearly one-third of them are not adherent to medications at the end of 1-year follow-up. The major factors associated with medication nonadherence are better improvements in psychopathology and functioning. This can lead to relapse and other complications. Hence, psychoeducation on the importance of continued medication should play a pivotal role in the treatment management of FEP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.