316 Original article

Community pharmacists’ support improves antidepressant adherence in the community Shmuel H. Klanga, Yuval Ben-Amnonb, Yaeli Cohena and Yoram Barakc The treatment goal of major depressive disorder (MDD) is achieving and maintaining remission. One of the major obstacles in attaining remission is poor adherence to the medication regimen. Community pharmacists (CPs) are accessible to primary care patients and are in a unique position to help improve adherence. The aim was to compare the effectiveness of pharmacist intervention with standard care for patients with MDD. This was an exploratory controlled trial conducted in 17 general pharmacies with clinical pharmacists in Israel. Participants were patients with MDD prescribed escitalopram by their general practitioner. CP medication review was initiated at enrollment, with face-to-face pharmacist adherence support at treatment initiation and every month throughout the study. Treatment as usual (TAU) was derived from computerized medical charts for the same pharmacies during the same time period. Comparison with published ‘historical’ controls was also carried out. No blinding was possible. Continuous antidepressant treatment at 6 months as reflected in computerized pharmacy records was the primary outcome. Within a 1-year period, 173 patients were enrolled. There were 49 men (28%) and 124 women (72%) in the CP group, mean age 53.9 ± 18.9 years. There were 4079 men (32%) and 8667 women (68%) in the TAU group, mean

age 50.4 ± 17.8 years. Ninety-six patients (55%) completed 6 months of antidepressant treatment. At 1 month, the adherence rate was 71% in the CP arm and at 6 months, the rates were 55% versus published norms of 42% (P = 0.004). At 1 month, the adherence rate was 57% (N = 7256) in the TAU arm and at 6 months, the rate was 15.2% (N = 1934) (compared with CP rates: P < 0.0001). There were no differences between sites in adherence rates. CPs participating in this study reported higher levels of confidence in supporting MDD patients at the end of the study. This is the first trial of pharmacist adherence support in Israel, and shows benefits for patients in the community with MDD. Int Clin Psychopharmacol 30:316–319 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Introduction

estimated to be 45.9% for antidepressants, the greatest of all psychotropics analyzed (Bulloch and Patten, 2010).

The treatment goal of major depressive disorder (MDD) is achieving and maintaining remission (Stotland, 2012). There are many obstacles in the path to reach this goal, one of the major obstacles being poor adherence to the medication regimen in MDD as well as many other chronic conditions (Viswanathan et al., 2012). Poor or nonadherence is reported widely in various care settings and across cultures. However, poor adherence is especially prevalent in primary care. The rates of antidepressant prescribing by general physicians far exceed that of psychiatrists. It is therefore of public health relevance that efforts should be made to increase adherence in this patient population. To date, the majority of studies on adherence have been on various clinical populations and the relevance of their results to the general population is unknown. The degree of nonadherence with antidepressants, antipsychotics, anxiolytics, mood stabilizers, and sedatives in the general population of Canada was studied by Bulloch and Patten (2010). The prevalence of use over the last 12 months was estimated to be 5.8% for antidepressants. Nonadherence was 0268-1315 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

International Clinical Psychopharmacology 2015, 30:316–319 Keywords: adherence, depression, pharmacist a

Clalit Health Services, bLundbeck and cAbarbanel MHC and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel Correspondence to Yoram Barak, MD, MHA, Psychogeriatric Department, Abarbanel Mental Health Center, 15 KKL Street, 59100 Bat-Yam, Israel Tel/fax: + 972 3 5552738; e-mail: [email protected] Received 17 December 2014 Accepted 16 June 2015

There have been attempts to increase adherence to antidepressants involving manipulation of variables related to patients, settings, costs, and physicians – with varying levels of success (Llorca et al., 2011). Pharmacists wishing to help their patients to adequately manage their antidepressant drug treatment face important barriers. Potential solutions include tools designed to help pharmacists better detect and intervene (Guillaumie et al., 2015). Community pharmacists (CPs) are accessible to primary care patients and are in a unique position to help improve adherence. Several studies have reported mixed results for CPs interventions to increase adherence among MDD patients. Recently, a systemic review of different types of pharmacist interventions used to enhance patient adherence to antidepressant medications was published. A total of 119 peer-reviewed papers were retrieved; 94 were excluded on the basis of abstract review and 13 after full-text analysis, resulting in 12 studies suitable for DOI: 10.1097/YIC.0000000000000090

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Pharmacists improve antidepressant adherence Klang et al. 317

inclusion and intensive review. A cumulative patient adherence improvement ranged from 15 to 27%. This review suggests that pharmacist intervention is effective in the improvement of patient adherence to antidepressants (Al-Jumah and Qureshi, 2012). Despite the very positive results reported by Al-Jumah and Qureshi (2012), another review published recently (Rubio-Valera et al., 2011) identified six relevant studies. Although most of the individual studies had shown nonstatistically significant results, when pooled, a statistically significant effect was observed favoring a pharmacist intervention. Thus, the potential for CPs to become a significant part of the multidisciplinary team needs be examined further.

The study was approved by the CHS ethical committee. All participants had signed a written informed consent form after a detailed explanation of the study was provided to them.

Despite the data presented in the above-mentioned reviews, few studies have explored CP’s actual counseling practices in response to antidepressant adherencerelated issues. A recent Australian study reported that the majority of CPs provided information on the risks and benefits of antidepressant treatment. However, there remains scope for improvement in CPs’ counseling practice, particularly in providing key educational messages relating to adherence-related messages (Chong et al., 2013).

Inclusion criteria

The aim of the present study was to prospectively evaluate the influence of enhanced involvement of CPs’ management of depression to improve adherence to escitalopram treatment in primary care settings.

Exclusion criteria

Methods Overall design

This study is a 24-week, prospective, nonrandomized, open-label, naturalistic observational study. The study was carried out at 17 sites selected randomly across the country at which the health maintenance organization [Clalit Health Services (CHS)] family medicine clinics have an in-house pharmacy. The study evaluated the influence of enhanced involvement of CPs in the management of MDD treatment with patients who had been prescribed escitalopram by their family physician independent of participation in this study. All were using escitalopram either for the first time or had a previous episode for which antidepressant treatment ended at least 1 year previously. Patients were monitored for general safety and efficacy of treatment by their physicians according to good clinical practice guidelines. All patients prescribed escitalopram by their family physician were approached by the site CP when they first came to the pharmacy and were offered participation in the study. Escitalopram was selected as it is described as the first antidepressant by 78% of Israeli family physicians. CHS is Israel’s largest healthcare organization, with 4.2 million members. CHS provides medical services to its members through 550 primary care clinics, 200 specialty clinics, and 460 pharmacies.

Primary endpoint

Time to treatment discontinuation for any reason was defined as the primary outcome measure. This was measured as the time from first prescription dispensed to last prescription dispensed. Switching to a different antidepressant during the study period was not considered as nonadherence.

(1) Patients with a depressive episode [MDD according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV)] and had been prescribed escitalopram. (2) Age: 18 years and older. (3) Willing to provide informed consent and sign the informed consent form after a detailed explanation of the study design and aims was provided.

(1) Contraindications to escitalopram. (2) History of severe drug allergy or hypersensitivity or known hypersensitivity to escitalopram. (3) Pregnant or breast-feeding. (4) Female patient of childbearing potential, not using adequate contraception. (5) Concomitant treatment with psychoactive compounds (except for benzodiazepines or hypnotics). Details of CPs involvement

A 3-day training session was conducted at the 17 selected pharmacies with the aim of preparing the pharmacists for supporting depressed patients according to the patientcentered model. The CPs monitored the prescriptions dispensed. CPs also provided support on an ongoing basis to the patients, emphasizing the flow of information related to the antidepressant treatment and its implications. In brief, patients who were prescribed escitalopram went to the pharmacy for dispensation. CPs provided the initial information about the study process following a detailed explanation of the study design and aims. Participants who signed an informed consent form following the detailed explanation were then provided an overview of MDD and antidepressant treatment by the CPs following the guidelines acquired at the prestudy training sessions. After 21 days (a week before the stipulated date for renewing prescription), the CPs reminded the patients about the importance of renewing the prescription and enquired about the general status of the patient. If the patient did not come to renew the prescription or if the patient notified the pharmacists that he/she had no intention of renewing prescription, the

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318 International Clinical Psychopharmacology 2015, Vol 30 No 6

pharmacist enquired after the reason for not renewing the prescription according to the flowchart that was provided to him/her during the prestudy training sessions and then the CPs completed the Case Report Form accordingly. Statistical analyses

The possible effect of the pharmacists’ involvement on adherence to the prescribed medication was evaluated as the difference between the two groups with respect to the proportion of compliance during the first 24 weeks. The difference between the proportions of the two groups was tested for significance using a normal (Z) test. Significance was evaluated at a 5% level using a twotailed test. The mean and 95% confidence limits were evaluated for the proportion in each group and for the difference between the groups. In addition, the proportion of compliant individuals by month was calculated in lifetables.

Results Demographics

Fig. 1

200 180

173 (100%)

160 140

124 (71%)

120

109 (63%) 101 (58%) 96 (55%)

100

105 (60%)

99 (57%)

80 60 40 20 0 Months

0

1

2

3

4

5

6

Adherence throughout the study.

Within a 1-year period, 173 patients were enrolled. There were 49 men (28%) and 124 women (72%) in the CP group, mean age 53.9 ± 18.9 years (range: 21–91). During the same 1-year period of recruitment, 12 746 patients were prescribed escitalopram by their family physician in the same 17 centers where the study was carried out. These are defined as the ‘treatment-as-usual’ (TAU) group. There were 4079 men (32%) and 8667 women (68%) in the TAU group, mean age 50.4 ± 17.8 years (range: 22–89). Outcome

Within a 1-year period, 173 patients were enrolled and 96 patients (55%) completed 6 months of antidepressant treatment. CPs initiated pharmacist medication review at enrollment, followed by face-to-face pharmacist adherence support throughout the study period. See Fig. 1 for adherence throughout the study. The primary outcome measure was adherence to antidepressant treatment at 6 months. At 1 month, the adherence rate was 71% in the pharmacist arm and at 6 months, the rates were 55% versus 1-month adherence rates of 57% (N = 7256) in the TAU arm; at 6 months, the rate was 15.2% (N = 1934) in the TAU arm (compared with CP rates: P < 0.0001).

Discussion In the present study, continued treatment rates compared with TAU were improved in the CP group (55% at 6 months vs. 15.2%) as well as when compared with published norms. Given the similarity in age and sex between the CP and TAU groups and the large sample size of the TAU group, here, we show a significant advantage to CPs interventions for community-treated

patients with MDD. Reported rates of noncompliance with medical treatments prescribed for MDD vary considerably from 30% to (a questionable) 97% (Pampallona et al., 2002). These rates contrasted with an observed 76% compliance in physical disorders (Cramer and Rosenheck, 1998). Other research has claimed that depressed patients are three times more likely to be noncompliant with medical treatment recommendations in general compared with nondepressed patients (DiMatteo et al., 2000). Only a small number of studies used reliable methods to assess pharmacists’ training needs in terms of mental illness and treatment options (Mey et al., 2014). Little has been published specifically in relation to depression and anxiety in community pharmacy practice (Liekens et al., 2012a, 2012b). In the present study, CPs trained in depression care and initiated enrollment only after completing an intensive course. The effectiveness of pharmacists’ care in patients with heart failure, diabetes, hypertension, dyslipidemia, and chronic pain is well established (Bruhn et al., 2013). However, there are few studies using standardized methods to assess effectiveness in patients with depression. A recent study in 68 MDD patients showed a statistically significant difference between groups, with a median reduction in the Beck Depression Inventory score of 2.5 points in the TAU group and 13.5 points in the pharmacists’ care (Marques et al., 2013). Other studies have reported similar results, with a focus on financial advantages to CPs support (Finley et al., 2011). Our work is similar in some way to the study by Rubio-Valera et al.

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Pharmacists improve antidepressant adherence Klang et al. 319

(2013). These authors aimed to evaluate the impact of a CP intervention on primary care patients who had initiated antidepressant treatment. Newly diagnosed primary care patients were randomized to usual care (N = 92) or pharmacist intervention (N = 87). Patients were followed up at 6 months. Adherence was continuously registered from the computerized pharmacy records. Patients in the intervention group were more likely to remain adherent at 3 and 6 months of follow-up, but the difference was not statistically significant. They concluded that a brief intervention in community pharmacies does not improve the adherence of depressed patients (Rubio-Valera et al., 2013). We suggest that the different outcome in the present study is because of both the ‘pre’ enrollment training of CPs and the active role of CPs in the present study. The present study has several limitations that need be acknowledged. Blinding was not possible. We evaluated the outcome only in terms of adherence and not in terms of symptomatic improvement or quality of life. A single drug was used and that within the setting of one health providing organization. Participants were not randomized and the same pharmacists provided the intervention as well as the ‘usual care,’ and there are inherent flaws of just using the prescription fill method to assess adherence. Nevertheless, the random selection of pharmacies across the country, the large sample examined, and the popularity of the drug chosen (Barak and Aizenberg, 2006) contribute toward the validity of our findings. Furthermore, the CPs’ positive effects on adherence are substantiated by the relatively high adherence rates at 6 months of the present study versus published norms [55 vs. 42% (P = 0.004)] (Kostev et al., 2008). In conclusion, the present study emphasizes the role that CPs can play in improving adherence to antidepressant treatment in the community.

Acknowledgements Conflicts of interest

This study was supported by an unrestricted grant from Lundbeck Israel.

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Community pharmacists' support improves antidepressant adherence in the community.

The treatment goal of major depressive disorder (MDD) is achieving and maintaining remission. One of the major obstacles in attaining remission is poo...
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