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Title Multimorbidity and polypharmacy among depressed elderly: specifications for highly prevalent diseases and medications
Keywords chronic disease polypharmacy multi-morbidity
Researchers F. Holvast
Prof. dr. P.F.M. Verhaak
Nature of the research wetenschap/research
Fields of study GP medicine
Background / introduction
Depression at older age often coincides with other chronic morbidity.(1)( (2) (3, 4). This results in diagnostic and treatment problems in general and in problems with medication specifically.

In earlier analyses (5) we found that depressed patients had a 16% (95% CI 10-24%) higher rate of chronic somatic diseases and had higher odds for multi-morbidity (OR 1.55; 95% CI 1.33-1.81) compared to mentally healthy controls. No difference existed between depressed patients and patients with other psychological diagnoses. Compared to mentally healthy controls, depressed patients had a 46% (95% CI 39-53%) higher rate of chronically used drugs and had higher odds for polypharmacy (OR 2.89; 95% CI 2.41-3.47). Comparable trends were found comparing depressed patients to patients with other psychological diagnoses (26%; OR 1.75; both p<.001).

Up till now, these analyses have been carried out for the complete dataset (± 4500 patients), and all somatic diseases regarded as chronic by the RIVM have been included. However, from literature it is known that depression most frequently occurs together with arthritis, diabetes, COPD/Asthma, stroke, cancer, heart failure or heart disease (4).

In the current study we will analyze the relationship between multimorbidity, polypharmacy and depression for patients with one of these specific chronic condition, namely: malignancies, coronary heart disease, heart failure, stroke, peripheral arthritis, COPD/asthma and diabetes. In this way, guidelines for (future) general practitioners can be specified for these prevalent chronic conditions
Research question / problem definition
Can the increased risk for polypharmacy and an elevated drug burden index be demonstrated for all chronic conditions in the same degree or are some conditions more at risk than others?
Workplan
Design
In order to determine the odds of depressed elderly on adherence as compared to non-depressed elderly, a case – control design including three groups (see below) will be followed.

Inclusion
Patients older than 60 years with a GP diagnosis of major depression (ICPC = P76) or depressive symptoms (ICPC P03) in 2012 are matched with a control group of patients older than 60 years who presented with a psychological symptom or disorder (but not major depression) in 2012 and a matched control group of patients older than 60 year who did not present with any psychological symptom or disorder in 2012. The three groups are matched on age, gender ??. All these characteristics are available in the database.
For the specification per separate disorder, subgroups will be created of patients combining each of the index disorders with at least one other chronic condition. The following numbers of patients are available for each index disorder:


Depressed
(N=1512) Psychological diagnoses
(N=1457)
Controls
(N=1508)
p-value*
Malignancy 284 (18.8) 272 (18.7) 242 (16.0) .086
Coronary heart disease 228 (15.1) 213 (14.6) 198 (13.1) .279
Peripheral arthritis 353 (23.3) 313 (21.5) 317 (21.0) .264
COPD 205 (13.6) 3 194 (13.3) 3 115 (7.6) 1,2 <.001
Asthma 138 (9.1) 121 (8.3) 113 (7.5) .267
Diabetes Mellitus 270 (17.9) 276 (18.9) 287 (19.0) .654
Stroke 129 (8.5) 126 (8.6) 104 (6.9) .143
Heart failure 62 (4.1) 51 (3.5) 49 (3.2) .437

Available data
Data on 2012 have been retrieved from NIVEL Primary Care Database and the pharmaceutical database SFK. Within the NIVEL Primary Care Database, GPs in ± 200 family practices register and code all health problems presented within a consultation according to the International Classification of Primary Care (ICPC). Pharmacy dispensing data are collected nationwide in the Netherlands by the Foundation for Pharmaceutical Statistics (SFK). Data from both sources have been linked anonymously as has been done before (13). This linking is done by birthday, gender, geographical postcode and prescribed prescriptions. In a similar way, linking to the population registry of Statistics Netherlands is possible. For the 2011-2012 linking, this resulted in the combination of 122 pharmacies to 213 general practices.
From the NIVEL Primary Care Database we have information on:
• patients’ acute and chronic disorders (morbidity)
• medicines prescribed by the GP, for each different disorder
• number of contacts/year
• adverse events with medication
• age, gender of the patient
From the pharmaceutical database SFK we get information on:
• dispensed drugs. Patients who keep adhere to prescribed medicines, patients who start to get the medication but stop after one fill and patients who never fill their prescription

1512 patients, older than 60 years, with a diagnosis by the GP of major depression (ICPC P76) or depressive symptoms (ICPC P03) in 2012 have been included, matched with 1497 patients with other psychological diagnoses and 1508 healthy controls .


Outcome measures
Multimorbidiy (defined as having two or more chronic conditions)
Polypharmacy (defined as using five or more medications chronically)
Drug Burden Index: a quantification of the cumulative anticholinergic and sedative drug load
.
Determinants
The principal determinant is the mental health status of patients.
The second determinant are practice characteristics: size, region, urbanization, presence of a practice nurse (POH-GGZ and/or POH-Somatiek). Zijn de 7 chronische ziekten dan niet ook determinanten?

Data analysis

Multivariable multilevel logistic regression analyses will be performed with multimorbidity respectively polypharmacy as dependent variables with mental health status on the first level, and practice characteristics as determinants on the second level for each of the seven specified chronic disorders
References
1 Caughey GE, Roughead EE, Shakib S, McDermott RA, Vitry AI, Gilbert AL. Comorbidity of chronic disease and potential treatment conflicts in older people dispensed antidepressants. Age Ageing. 2010;39(4):488-94.
2. Iosifescu DV, Nierenberg AA, Alpert JE, Smith M, Bitran S, Dording C, et al. The impact of Medical Comorbidity on acute treatment in major depressive disorder. American Journal of Psychiatry. 2008;160:2122-7.
3. Nuyen J, Volkers AC, Verhaak PF, Schellevis FG, Groenewegen PP, Van den Bos GA. Accuracy of diagnosing depression in primary care: the impact of chronic somatic and psychiatric co-morbidity. Psychol Med. 2005;35(8):1185-95.
4. Sinnige J, Braspenning J, Schellevis F, Stirbu-Wagner I, Westert G, Korevaar J. The prevalence of disease clusters in older adults with multiple chronic diseases--a systematic literature review. PLoS One. 2013;8(11):e79641.
5 Holvast F, Hattem BA van, Sinnige J, Schellevis F, Taxis K, Burger H, Verhaak, PFM. Late-life depression and the association with multimorbidity and polypharmacy – a cross-sectional study. Accepted by Family Practice
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