Family Practice Advance Access published online on November 13, 2007
Family Practice, doi:10.1093/fampra/cmm062
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The impact of co-morbidity on GPs’ pharmacological treatment decisions for patients with an anxiety disorder
a Centre for Quality of Care Research (WOK)
b Department of General Practice, Radboud University Nijmegen Medical Centre (RUNMC)
c Netherlands Institute for Health Services Research (NIVEL), Utrecht, The Netherlands. Correspondence to Mirrian Smolders, Radboud University Nijmegen Medical Centre (RUNMC), Centre for Quality of Care Research (WOK), PO Box 9101, Code: 114 KWAZO, 6500 HB Nijmegen, The Netherlands; Email: m.smolders{at}kwazo.umcn.nl
Received 9 January 2007; Revised 24 July 2007; Accepted 21 September 2007.
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Abstract |
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Background. Co-morbidity may influence GPs’ treatment decisions for patients with anxiety. However, knowledge about differences in the pharmacological treatment of anxiety disorders in patients with and without co-morbidity is lacking.
Objective. To compare GPs’ pharmacological treatment patterns for anxiety in patients with and without co-morbidity.
Methods. Data were extracted from computerized medical records of 77 general practices participating in the Dutch National Information Network of General Practice (LINH). We used diagnosis and prescription data of patients, aged 18–65 years, with a newly diagnosed anxiety disorder (n = 4604). A mixed model technique was used to determine if there was a difference in the pharmacological treatment of anxiety with and without co-morbidity.
Results. During the year after diagnosing anxiety, anxious patients who also suffered from chronic somatic morbidity or social problems were prescribed more benzodiazepines (effect size [ES] = 0.44, 95% confidence interval [CI] = 0.16–0.72 and ES = 0.67, 95% CI = 0.22–1.25, respectively) but no more antidepressants than patients with anxiety only. Compared to patients with a single diagnosis of anxiety, anxious patients who suffered simultaneously from other psychiatric conditions received twice as many antidepressant prescriptions (ES = 2.07, 95% CI = 1.89–2.56) as well as twice as many benzodiazepine prescriptions (ES = 1.98, 95% CI = 1.84–2.60) during the year after diagnosing anxiety. For all subgroups, the prescription rate of benzodiazepines remained high throughout the year after diagnosing anxiety.
Conclusion. Our results indicate that psychiatric co-morbidity in anxious patients leads to higher prescription levels of both antidepressants and benzodiazepines. Chronic somatic co-morbidity and co-morbid social problems also lead to higher prescription levels of benzodiazepines, but does not seem to influence GPs’ prescribing of antidepressants. The prescription pattern of benzodiazepines was inconsistent with guideline recommendations.
Keywords. Cohort study, family medicine, patient record, prescribing, psychiatry.
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Introduction |
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Co-morbidity is a well-known phenomenon in anxiety, and it is widely observed that the majority of anxiety disorders do not present as a single condition.1 Both clinical and epidemiological studies have documented that anxiety frequently occurs simultaneously with a variety of chronic somatic conditions, such as cancer, cardiac disease, and diabetes.2 In addition, research also showed an association with psychiatric conditions 3–6 as well as a relationship with impairments in social functioning.7,8 Anxiety responds to pharmacologic and behavioural treatments, both individually and in combination. Various studies have raised concerns about prolonged use of pharmacological agents, as well as higher rates of medication use among women and older people.9,10 It is crucial to treat anxiety disorders effectively in patients with other conditions because anxiety increases patients’ sensitivity to somatic distress and worsens the prognosis associated with disorders. Effective treatment of anxiety disorders can have a positive influence on the course of co-morbid conditions and improves overall well being.11 GPs must, therefore, be aware of the importance of treating both conditions concurrently as well as be able to treat anxiety in ill populations. The importance of this issue is underscored by the high rates of anxiety, and high treatment costs and socioeconomic burden for people with anxiety and co-morbid conditions.12–16
Previous studies have shown that patients with a psychiatric disorder frequently go unrecognized if they have additional somatic conditions.17–19 In contrast, the co-occurrence of anxiety and depression has been found to facilitate recognition of anxiety disorders.20,21 There are several reasons to suspect that, in addition to differences in diagnosing anxiety disorders in patients with and without co-morbid conditions, there are also differences in GPs’ decisions about pharmacological treatment of anxiety disorders in patients with and without co-morbidity. First, somatic co-morbid conditions may complicate GPs’ treatment decisions about anxiety. In the anxious patient with somatic co-morbidity, the GP must develop a pharmacologic approach that will be effective and yet will have a favourable side-effect profile relative to the patient's other conditions and treatments. Important principles in prescribing psychopharmacologic agents to anxious patients with somatic co-morbidity are an awareness of the effects of the co-morbid conditions on the actions and pharmacokinetics of the agent, effects of the agent on the co-morbid conditions and potential drug interactions.22
Conversely, the co-occurrence of anxiety and other psychiatric morbidity may provide GPs more opportunities to treat patients with psychotropic drugs. A recent study reported that treatment with psychotropic drugs is offered more frequently to patients with a combined depressive and anxiety disorder, compared with patients diagnosed with an anxiety disorder only.23 Little is known about whether and how other psychiatric conditions actually influence GPs’ pharmacological treatment of anxiety disorders. With relatively few exceptions,24 the impact of co-existing psychosocial problems on the prescription of antidepressants and benzodiazepines in patients with anxiety disorders has been under-investigated.
We recently conducted a study to examine the impact of co-morbidity on GPs’ pharmacological treatment decisions for patients with depression.25 We found that chronic somatic or psychiatric co-morbidity in depressed patients led to higher GP prescription levels of antidepressants and benzodiazepines, whereas co-morbid social problems did not seem to influence GPs’ pharmacological treatment of depression. The current study was designed to compare the pharmacological treatment patterns of anxiety disorders in general practice patients with and without concurrent chronic somatic, psychiatric or social morbidity. The results could reveal insight into the prescription behaviour of GPs treating anxious patients with and without co-morbidity. This insight could serve as a trigger for quality improvement activities and provides valuable information on where to target quality improvement efforts with respect to the medical treatment of anxiety. In the present study, in accordance with observations of our previous study, we hypothesized (i) that anxious patients with co-morbid chronic somatic conditions or other psychiatric conditions are prescribed both more antidepressants and benzodiazepines than patients with a single diagnosis of anxiety and (ii) that anxious patients with co-morbid social problems receive the same pharmacological treatment as patients with an unimorbid anxiety disorder.
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Methods |
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Setting and study population
The study population for this cohort study was identified within a national representative computerized GP-based network in The Netherlands, i.e. the National Information Network of General Practice (LINH).26 In this network, the GP staff routinely record encoded patient information using a computerized medical record system. To ensure completeness of data, participating practices must have a (nearly) paperless office. Within this network, data are continuously extracted twice a year from the computerized medical records used in the practices to file patient information.
Practices were selected according to the availability of reliable and valid data on diagnoses and prescriptions in the database in the years 2001–2003. Practices that did not have complete data as well as practices that did not have data for a period of 16 consecutive months were excluded. The maximum allowable period of missing data was 4 weeks.
Procedure and data collection
GPs recorded diagnostic information and therapeutic actions according to the International Classification of Primary Care (ICPC)27 and medical drug prescriptions according to the Anatomical Therapeutic Chemical (ATC) Classification System.28 Data concerning the pharmacological treatment of anxiety disorders with and without concurrent other conditions were extracted from the electronic patient records at patient level using specially developed software. These data included ICPC codes of a number of chronic somatic, psychiatric and social conditions as well as prescriptions with ATC codes for antidepressants and benzodiazepines. The pharmacological treatment of anxiety disorders was followed for 1 year after diagnosing a new episode of anxiety by the GP.
Measures
The ICPC distinguishes separate chapters for somatic symptoms and diagnoses (e.g. ear complaints, pneumonia), psychological symptoms and diagnoses (e.g. depressed feeling, schizophrenia) and social problems (e.g. relation problems, work problems). In each chapter, ICPC codes between 01 and 29 are assigned to symptoms and complaints, whereas ICPC codes between 70 and 99 represent diagnoses and diseases. The ICPC contains one chapter on psychological problems and mental disorders (chapter P). In the ICPC, two codes deal with anxiety: P74, anxiety disorder and P01, feeling anxious/nervous/tense.27
In our study, patients having an episode P74 and/or P01 were considered to be diagnosed with anxiety, while patients without such episodes were not. An episode of anxiety was considered as ‘new’ if patients were not diagnosed with anxiety by their GP during the preceding 4 months. A co-morbid condition was defined as having at least one diagnosed chronic somatic, psychiatric or social condition in the 4 months preceding or the 4 months following the diagnosis of a new episode of anxiety.
The presence of concurrent chronic somatic morbidity was determined on the basis of ICPC-coded diagnoses of chronic somatic conditions recorded by GPs. In accordance with the chronic conditions list from Statistics Netherlands (CBS, Centraal Bureau voor de Statistiek), the following nine categories of chronic somatic morbidity were distinguished: neurological conditions (ICPC chapter N); musculoskeletal conditions (ICPC chapter L); cardiovascular conditions (ICPC chapter K); respiratory conditions (ICPC chapter R); skin conditions (ICPC chapter S); endocrine, metabolic, and nutritional conditions (ICPC chapter T); digestive conditions (ICPC chapter D); a category of malignant chronic somatic conditions (codes from various ICPC chapters) and a rest category of other non-malignant chronic somatic conditions (codes from various ICPC chapters).
The presence of concurrent psychiatric morbidity was determined on the basis of ICPC-coded diagnoses of mental or psychiatric conditions (ICPC chapter P) recorded by GPs. The following six categories of psychiatric morbidity were distinguished: depressive feelings/depressive disorder, surmenage, acute stress reaction, sleep disturbance, drug abuse and other mental symptom/complaint.
The presence of concurrent social morbidity was determined on the basis of ICPC-coded diagnoses of social conditions (ICPC chapter Z) recorded by GPs. The following five categories of social morbidity were distinguished: problem working conditions/problem with being unemployed, relation problem with partner/child/parent/other family member or friend, problem with partner/child/parent or other family member being ill, loss or death of partner/child/parent or other family member and other social problem.
The ATC classification system is a five-level hierarchical coding system dividing drugs into 14 main groups according to the organ or system on which they act (the first level). Subgroups to the 14 main groups refer to specific therapeutic, pharmacological and chemical characteristics (the second, third and fourth levels, respectively). The fifth level refers to the drug substances. Each level is given an ATC code.29 Psychotropics are classified into the group of agents for the treatment of nervous system disorders (N group). In our study, we classified psychotropic agents as either antidepressants or benzodiazepines. Antidepressants are part of the psychoanaleptic category (NO6), whereas benzodiazepines are part of the psycholeptic category (NO5). The drugs called antidepressants in our study are those with ATC codes NO6AA, NO6AB, NO6AF, NO6AG and NO6AX. The drugs called benzodiazepines in this study are those with ATC codes NO5BA and NO5CD.
For the analysis regarding the psychotropics prescribed, we included only patients with mono-morbid pathology concerning the three subgroups of chronic somatic, psychiatric or social morbidity. Within each of these three subgroups, patients could suffer from more conditions simultaneously.
Analysis
First, we calculated the number of patients with a new episode of anxiety. After that, we determined the incidence of anxiety disorders with and without co-morbidity. In addition, we calculated the number of patients with an anxiety disorder who suffered simultaneously from chronic somatic, psychiatric or social morbidity. Finally, we calculated the number of anxious patients with and without co-morbidity who received psychotropic medication treatment during the year after their diagnosis of an anxiety disorder. A mixed model was conducted to compare the psychotropic medication treatment of anxiety in patients with and without concurrent chronic somatic, psychiatric or social morbidity. We compared the prescription of antidepressants and benzodiazepines separately, as well as the prescription of all psychotropic agents. Our model included correction for the possible effects of practice, gender, age and the interaction between gender and age. The mixed model produced estimates of means—referred to as ‘estimated mean number of prescriptions'—standard errors of differences, effect sizes (ESs) and 95% confidence intervals (CIs). We applied this model only to the total subgroups of chronic somatic, psychiatric or social co-morbidity. Due to the small number of patients included in subgroups with a specific co-morbid condition, we presented only descriptive statistics (mean number of prescriptions) for these subgroups without statistically testing for differences among subgroups. To show the changes in the levels of prescription of psychotropics over the course of 1 year after diagnosing an anxiety disorder, this year was divided into two periods: 0–3 months after diagnosing anxiety and 4–12 months after diagnosing anxiety. The number of psychotropic drug prescriptions was expressed as quarterly mean number of prescriptions per patient. SAS version 8.0 was used for the statistical analysis. Significance was accepted at the 5% level.
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Results |
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Study population characteristics
Table 1 compares the practice characteristics of the LINH study population (n = 95) with the Dutch population of GPs. Solo practices were under-represented, whereas practices in rural area were slightly over-represented. Seventy-seven practices met the inclusion criteria.
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From these 77 practices, a total number of 4604 patients, aged 18–65 years, with a newly diagnosed anxiety disorder were included. Table 2 illustrates the demographic and clinical characteristics of the 4604 patients with a newly diagnosed anxiety disorder. The majority of the patients had a co-morbid condition. Chronic somatic conditions occurred most frequently simultaneously with anxiety. The most prevalent concurrent chronic somatic disease category was musculoskeletal. Depression was by far the most common concurrent psychiatric condition. Social conditions that occurred most frequently simultaneously with anxiety were relation problems and problems with (un)employment. About 16% of the patients suffered from multiple concurrent conditions, including chronic somatic, psychiatric and/or social co-morbidity. Finally, 3862 patients were included in the analysis of psychotropic drug prescription.
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Pharmacological treatment of anxiety disorders in patients with and without co-morbidity
Table 3 shows the mixed model estimates of the base rate of both psychotropic and all medication prescriptions per patient for patients with and without co-morbidity. Multimorbidity was associated with a higher total prescription rate throughout the year after diagnosing anxiety (ES chronic somatic co-morbidity = 5.74, 95% CI = 4.84–6.64; ES psychiatric co-morbidity = 5.37, 95% CI = 5.12–6.95, and ES social co-morbidity = 1.55, 95% CI = 0.54–3.21). During the year after diagnosing an anxiety disorder, the prescription rate of psychotropic agents did not differ for anxious patients with and without concurrent chronic somatic morbidity. Compared to patients with a single diagnosis of anxiety, anxious patients with concurrent other psychiatric or social conditions were prescribed more psychotropic agents during the year after diagnosing anxiety (ES = 4.68, 95% CI = 4.47–5.71 and ES = 0.78, 95% CI = 0.09–1.74, respectively).
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There was a variation in prescribing patterns between practices. The prescribing rate per patient for all medication prescriptions during the year after diagnosing anxiety ranged from 5.18 to 27.80 (interquartile range 9.41–14.00). For psychotropics, the prescribing rate per patient during the year after diagnosing anxiety ranged from 1.43 to 16.5 (interquartile range 3.16–5.94).
Tables 4–6
show the mixed model estimates of quarterly mean number of antidepressant and benzodiazepine prescriptions per patient for patients with and without co-morbidity. Most antidepressants and benzodiazepines for both anxious patients with and without a co-morbid condition were prescribed in the first months after diagnosing an anxiety disorder. In the following 9 months, the prescription rate of psychotropics declined considerably for all subgroups, but especially the number of benzodiazepine prescriptions remained high.
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Prescription of psychotropics for anxiety and concurrent chronic somatic conditions
Table 4 presents the estimated mean number of antidepressant and benzodiazepine prescriptions for anxious patients with and without concurrent chronic somatic morbidity. Compared to patients with a single diagnosis of anxiety, anxious patients who suffered simultaneously from chronic somatic morbidity were prescribed more benzodiazepines (ES = 0.44, 95% CI = 0.16–0.72) but no more antidepressants during the year after diagnosing their anxiety disorder. All subgroups with anxiety and a co-morbid chronic somatic condition, except this with skin morbidity, received considerably more benzodiazepine prescriptions than patients with anxiety only. Compared to patients with a single diagnosis of anxiety, anxious patients with concurrent digestive morbidity were prescribed markedly more antidepressants during the year after diagnosing anxiety.
Prescription of psychotropics for anxiety and concurrent other psychiatric conditions
Table 5 presents the estimated mean number of antidepressant and benzodiazepine prescriptions for anxious patients with and without concurrent other psychiatric morbidity. Compared to patients with a single diagnosis of anxiety, anxious patients who suffered from concurrent other psychiatric conditions received twice as many antidepressant prescriptions (ES = 2.07, 95% CI = 1.89–2.56) as well as twice as many benzodiazepine prescriptions (ES = 1.98, 95% CI = 1.84–2.60) during the year after diagnosis of their anxiety disorder. The higher prescription rate of psychotropic agents for patients with an anxiety disorder and concurrent other psychiatric morbidity was observable in all our subgroups. Even though the prescription rate of benzodiazepines declined during the course of the year, it remained high.
Prescription of psychotropics for anxiety and concurrent social conditions
Table 6 presents the estimated mean number of antidepressant and benzodiazepine prescriptions for anxious patients with and without concurrent social problems. In comparison to patients with a single diagnosis of anxiety, anxious patients who suffered simultaneously from social problems were prescribed more benzodiazepines (ES = 0.67, 95% CI = 0.22–1.25) but no more antidepressants during the year after diagnosing their anxiety disorder. In particular, the prescription rate of benzodiazepines for anxious patients who suffered simultaneously from problems with a family member being ill remained remarkably high in the following 9 months. They received three times as many prescriptions for benzodiazepines than patients with anxiety only.
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Discussion |
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Summary of main findings and comparison with existing literature
Our study confirmed that the majority of anxiety disorders examined in primary care do not occur in single form, but are co-morbid with other conditions. Results obtained in this study only partly confirmed our first hypothesis on the influence of chronic somatic conditions on the psychotropic prescription by GPs for patients with an anxiety disorder. The results indicated that anxious patients with concurrent chronic somatic conditions received more benzodiazepine prescriptions but no more antidepressant prescriptions than patients with anxiety only. We also found that anxious patients who suffered simultaneously from other psychiatric morbidity were prescribed both more antidepressants and more benzodiazepines than patients with a single diagnosis of anxiety. These results are consistent with our second hypothesis. In contrast to our third hypothesis on the influence of co-morbid social problems on GPs’ pharmacological treatment patterns of anxiety disorders, we found that anxious patients with concurrent social problems were prescribed more benzodiazepines but no more antidepressants than patients with anxiety only. Finally, our results showed that the prescription rate of benzodiazepines remained high throughout the year after diagnosing anxiety.
These results are not fully consistent with our prior research on the impact of co-morbidity on GPs’ pharmacological treatment decisions for depressed patients.25 In our previous study, we found that depressed patients with concurrent chronic somatic conditions received more prescriptions for both antidepressants and benzodiazepines than patients with depression only. Our more robust results extend and confirm earlier findings that patients with a combined anxiety and depressive disorder received more prescriptions for psychotropic drugs.23 Furthermore, these results also clearly comport with our prior research findings.25 Co-occurring psychiatric disorders seemed to lead to higher prescription rates of both antidepressants and benzodiazepines. Our results are not entirely consistent with a recently published case–control study which demonstrated that concurrent social problems did not influence GPs’ prescribing patterns for patients with anxiety.24
Strengths and limitations of the study
The main strength of this study was our ability to examine a national sample of primary care practices and patients and to explore, in a longitudinal way, an important health care issue in primary care. The findings of our study are likely to be generalizable to other settings and countries.
Our findings depend on the quality of the registration by the GPs. Participating GPs were experienced in working with electronic medical records and with ICPC. While there is no gold standard measure for assessing anxiety and a comprehensive range of concurrent conditions, the validity of assessments is enhanced given that our findings correspond reasonably well to other studies in terms of the proportion of anxious patients diagnosed with a particular concurrent psychiatric condition.30,31
In interpreting the results of this study, it is important to bear in mind that we looked only at the prescription behaviour of GPs without questioning them about their practices and habits regarding the prescription of psychotropic agents. This may possibly have led to an underestimation on the capacity of GPs to manage patients with anxiety. GPs might possibly choose for treatment by combined medications (polypharmacy) in order to obtain specific reaction in anxious patients with concurrent other psychiatric morbidity. An earlier survey of expert judgement on therapeutic use of benzodiazepines and other psychotherapeutic medications showed that expert pharmacotherapists tended to recommend combining medications, especially as second-line medication choices, in case the response to the first-line agent was not satisfactory.32
It is possible that a few concurrent conditions, e.g. sleep problems, are purely anxiety symptoms. Although we used a narrow definition of concurrent morbidity, it cannot be ruled out that some patients with anxiety only were incorrectly assigned to one of the subgroups with concurrent conditions.
In accordance with reality, the diagnostic subgroups in our study were not mutually exclusive. Although thorough analysis of the overlap did not reveal a strong degree of overlap between two or more specific subgroups, the precise influence of overlapping subgroups is not known.
Implications for clinical practice and future research
It is encouraging that GPs do not ignore the pharmacological treatment of anxiety in their patients who also suffer from concurrent somatic morbidity. This is of crucial clinical importance because appropriate treatment of anxiety can reduce both the patient and socioeconomic burden that are associated with multimorbidity.
Although it was not the primary aim of this study to assess adherence to guidelines by GPs, there were some indications that psychotropic drug treatment was not always conducted in accordance with treatment recommendations.33 In the range of treatments provided by GPs, especially the large-scale use of benzodiazepines was striking. To a certain extent, higher prescription rates of psychotropic drugs for patients with multiple psychiatric conditions were acceptable as various psychiatric conditions required same treatment patterns (e.g. anxiety and sleep problems). Unlike the guideline recommendations, experts considered benzodiazepines, especially when combined with an antidepressant, a mainstay in the treatment of panic disorder.32 However, for some conditions, e.g. drug abuse, benzodiazepines are considered inappropriate. In addition, the significant higher prescription rate of benzodiazepines for anxious patients with a co-morbid chronic somatic condition was inappropriate. Furthermore, all our study groups received long-term prescriptions for benzodiazepines. Evidence-based guidelines advise against long-term prescriptions of benzodiazepines, because long-term benzodiazepine use appears to provoke more severe adverse effects, including memory impairment, tolerance and dependence. Benzodiazepines are only considered to be effective for a limited period of time.34,35 Given the lack of effectiveness and potential hazards of (long term) use of psychotropic drugs, GPs should be cautious in prescribing these drugs, especially in the long term.
According to the guidelines published by the Dutch College of General Practitioners (NHG),33 both pharmacologic and nonpharmacologic therapies may be considered appropriate anxiety treatment. To complement our findings, future research could examine GP's nonpharmacologic management of anxiety with and without co-morbidity, and subsequently make a comparison between anxiety care delivered and care recommended in guidelines on anxiety.
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Declaration |
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Funding: National Association of General Practitioners (LHV). However, the views expressed here are those of the authors and not necessarily those of the funding body.
Conflict of interest: None.
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Notes |
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Smolders M, Laurant M, van Rijswijk E, Mulder J, Braspenning J, Verhaak P, Wensing M and Grol R. The impact of co-morbidity on GPs’ pharmacological treatment decisions for patients with an anxiety disorder. Family Practice 2007; Pages 1–9 of 9.
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References |
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1 Bakish D. The patient with comorbid depression and anxiety: the unmet need. J Clin Psychiatry (1999) 60(Suppl 6):20–24.
2 Sareen J, Cox BJ, Clara I, Asmundson GJ. The relationship between anxiety disorders and physical disorders in the U.S. National Comorbidity Survey. Depress Anxiety (2005) 21(4):193–202.[CrossRef][Web of Science][Medline]
3 de Graaf R, Bijl RV, Spijker J, Beekman AT, Vollebergh WA. Temporal sequencing of lifetime mood disorders in relation to comorbid anxiety and substance use disorders—findings from the Netherlands Mental Health Survey and Incidence Study. Soc Psychiatry Psychiatr Epidemiol (2003) 38(1):1–11.[CrossRef][Web of Science][Medline]
4 Kessler RC, Nelson CB, McGonagle KA, Liu J, Swartz M, Blazer DG. Comorbidity of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey. Br J Psychiatry Suppl (1996) (30):17–30.
5 Merikangas KR, Angst J, Eaton W, et al. Comorbidity and boundaries of affective disorders with anxiety disorders and substance misuse: results of an international task force. Br J Psychiatry Suppl (1996) (30):58–67.
6 Verhaak PF, Schellevis FG, Nuijen J, Volkers AC. Patients with a psychiatric disorder in general practice: determinants of general practitioners’ psychological diagnosis. Gen Hosp Psychiatry (2006) 28(2):125–132.[CrossRef][Web of Science][Medline]
7 Ormel J, VonKorff M, Ustun TB, Pini S, Korten A, Oldehinkel T. Common mental disorders and disability across cultures. Results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA (1994) 272(22):1741–1748.
8 Rodriguez BF, Bruce SE, Pagano ME, Keller MB. Relationships among psychosocial functioning, diagnostic comorbidity, and the recurrence of generalized anxiety disorder, panic disorder, and major depression. J Anxiety Disord (2005) 19(7):752–766.[CrossRef][Web of Science][Medline]
9 Meijer WE, Heerdink ER, Leufkens HG, Herings RM, Egberts AC, Nolen WA. Incidence and determinants of long-term use of antidepressants. Eur J Clin Pharmacol (2004) 60(1):57–61.[CrossRef][Web of Science][Medline]
10 Willison DJ, Kirshen AJ, Anderson G. Long-term use of benzodiazepines among community dwelling seniors in Ontario—area variation and patient-level predictors. Pharmacoepidemiol Drug Saf (1998) 7(Suppl 2):147.
11 McWilliams LA, Cox BJ, Enns MW. Mood and anxiety disorders associated with chronic pain: an examination in a nationally representative sample. Pain (2003) 106(1–2):127–133.[CrossRef][Web of Science][Medline]
12 Bijl RV, Ravelli A. Psychiatric morbidity, service use, and need for care in the general population: results of The Netherlands Mental Health Survey and Incidence Study. Am J Public Health (2000) 90(4):602–607.
13 Hecht H, von Zerssen D, Wittchen HU. Anxiety and depression in a community sample: the influence of comorbidity on social functioning. J Affect Disord (1990) 18(2):137–144.[CrossRef][Web of Science][Medline]
14 Kessler RC, Frank RG. The impact of psychiatric disorders on work loss days. Psychol Med (1997) 27(4):861–873.[CrossRef][Web of Science][Medline]
15 Roy Byrne PP, Stang P, Wittchen HU, Ustun B, Walters EE, Kessler RC. Lifetime panic-depression comorbidity in the National Comorbidity Survey. Association with symptoms, impairment, course and help-seeking. Br J Psychiatry (2000) 176:229–235.
16 Wittchen HU, Lieb R, Wunderlich U, Schuster P. Comorbidity in primary care: presentation and consequences. J Clin Psychiatry (1999) 60(Suppl 7):29–36.[Web of Science][Medline]
17 Coulehan JL, Schulberg HC, Block MR, Janosky JE, Arena VC. Medical comorbidity of major depressive disorder in a primary medical practice. Arch Intern Med (1990) 150(11):2363–2367.
18 Freeling P, Rao BM, Paykel ES, Sireling LI, Burton RH. Unrecognised depression in general practice. Br Med J (Clin Res Ed) (1985) 290:1880–1883.[Medline]
19 Tylee A, Freeling P, Kerry S, Burns T. How does the content of consultations affect the recognition by general practitioners of major depression in women? Br J Gen Pract (1995) 45:575–578.[Web of Science][Medline]
20 Pini S, Berardi D, Rucci P, et al. Identification of psychiatric distress by primary care physicians. Gen Hosp Psychiatry (1997) 19:411–418.[CrossRef][Web of Science][Medline]
21 Sartorius N, Ustun TB, Lecrubier Y, Wittchen HU. Depression comorbid with anxiety: results from the WHO study on psychological disorders in primary health care. Br J Psychiatry Suppl (1996) (30):38–43.
22 Cunningham LA. Depression in the medically ill: choosing an antidepressant. J Clin Psychiatry (1994) 55(Suppl A):90–97.[Web of Science][Medline]
23 van Rijswijk E, Borghuis M, van De Lisdonk E, Zitman F, van Weel C. Treatment of mental health problems in general practice: a survey of psychotropics prescribed and other treatments provided. Int J Clin Pharmacol Ther (2007) 45:23–29.[Web of Science][Medline]
24 van Rijswijk E, Lucassen P, van De Lisdonk E, Zitman F, van Weel C. Do co-existing psychosocial problems influence the prescription of psychotropic medication in depressive and anxiety disorders? Eur J Gen Pract (2006) 12(1):37–39.[CrossRef][Medline]
25 Smolders M, Laurant M, van Rijswijk E, et al. Depressed and a co-morbid condition: more psychotropics prescribed! (2006) Submitted.
26 Verheij R, Jabaaij L, De Bakker D, et al. Cijfers uit het Landelijk Informatie Netwerk Huisartsenzorg: contacten, verwijzingen en voorschrijven in de huisartspraktijk (LINH Year-Report 2001; Figures from the Dutch Continuous Morbidity Registration Network in General Practice: Encounters, Referrals, and Prescriptions in General Practice. (2002) Utrecht, Nijmegen: LHV, NHG, NIVEL, WOK.
27 Lamberts H, Wood M. International Classification of Primary Care (ICPC) (1990) Oxford: Oxford University Press.
28 WHO. Collaborating Centre for Drugs Statistics Methodology Guidelines ATC Classification and DDD Assignment (1996) 1st edn. Oslo: WHO/NCM.
29 Pahor M, Chrischilles EA, Guralnik JM, Brown SL, Wallace RB, Carbonin P. Drug data coding and analysis in epidemiologic studies. Eur J Epidemiol (1994) 10:405–411.[CrossRef][Web of Science][Medline]
30 Bijl RV, Ravelli A, van Zessen G. Prevalence of psychiatric disorder in the general population: results of The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Soc Psychiatry Psychiatr Epidemiol (1998) 33:587–595.[CrossRef][Web of Science][Medline]
31 Merikangas KR, Angst J, Eaton W, et al. Comorbidity and boundaries of affective disorders with anxiety disorders and substance misuse: results of an international task force. Br J Psychiatry Suppl (1996) (30):58–67.
32 Uhlenhuth EH, Balter MB, Ban TA, Yang K. International study of expert judgement on therapeutic use of benzodiazepines and other psychotherapeutic medications: V. Treatment strategies in panic disorder, 1992–1997. J Clin Psychopharmacol (1998) 18(6, Suppl 2):27S–31S.[CrossRef][Web of Science][Medline]
33 Terluin B, van Heest FB, van der Meer K, et al. Guideline anxiety disorders Dutch College of General Practitioners (first revision). Huisarts Wet (2004) 47(1):26–37.
34 Furukawa TA, Streiner DL, Young LT. Antidepressant plus benzodiazepine for major depression. Cochrane Database Syst Rev (2001) (2):CD001026.
35 van Marwijk HW, Grundmeijer HGLM, Brueren MM, et al. Guideline depression Dutch college of general practitioners. Huisarts Wet (2000) 37:482–490.
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