Helga Gardarsdottir

Initiation of antidepressant therapy: do patients follow the GP's prescription?

BACKGROUND The question whether patients actually start drug taking after having received a first antidepressant prescription is often overlooked. AIM To determine the incidence of patients who do not fill or fill only a single antidepressant prescription at the pharmacy, and to identify associated patient characteristics. DESIGN OF STUDY Retrospective study linking a general practice to a pharmacy dispensing database. SETTING General practice in the Netherlands. METHOD STUDY POPULATION patients who received a first-time antidepressant prescription from a GP. Three patient groups were identified: patients who did not fill the prescription (non-fillers); patients who filled only a single prescription (single Rx-fillers); and patients who filled at least two consecutive prescriptions. Non-fillers and single Rx-fillers were combined into a group of decliners. RESULTS Of all 965 patients, 41 (4.2%) did not fill the prescription, and 229 (23.7%) filled only a single prescription. Patients who consulted their GP for a non-specific indication, rather than for depression, anxiety, panic, or obsessive-compulsive disorder, were almost three times more likely (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.8 to 3.9) to decline treatment. Further, the risk of declining was almost fivefold higher (OR = 4.8, 95% CI = 2.1 to 11.3) in non-Western immigrants, and almost twofold higher (OR = 1.8, 95% CI = 1.2 to 2.8) in patients >60 years of age. CONCLUSION Over one in four patients who receive a first-time antidepressant prescription decline treatment; they either do not initiate drug taking or do not persist with antidepressant use for longer than 2 weeks.

Construction of drug treatment episodes from drug-dispensing histories is influenced by the gap length

OBJECTIVES When constructing drug treatment episodes using drug-dispensing databases, duration and the number of prescriptions belonging to a single treatment episode need to be defined. We investigated how different methods used to construct antidepressant treatment episodes influence their median estimated length. STUDY DESIGN AND SETTING A follow-up study among adult antidepressant drug users, identified from the Dutch PHARMO RLS, starting selective serotonin reuptake inhibitor (SSRI) use in 2001 was conducted. The influence of varying lengths of the prescription overlap and the gap between prescriptions (number of days or percentage of prescription duration) on the median antidepressant treatment episode length were investigated. RESULTS Of the 16,053 SSRI starters, 65.1% were female and mean age was 45.7 (SD: 17.2) years. Median antidepressant treatment episode length doubled when the gap length was expanded from 0 to 10 days. For short gap lengths the episode interquartile range was 40% to 200% larger when overlap was accounted for and when percentage of prescription duration gap length was used. CONCLUSION Differences in median episode length exist between methods that account for or disregard prescription overlap. These differences are of importance for studies that focus on drug exposure-outcome relationships and could have consequences for epidemiological analysis.

Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project

Studies on drug utilization usually do not allow direct cross‐national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases.

The High Impact of Penicillin Allergy Registration in Hospitalized Patients.

BACKGROUND Suspected penicillin allergy (Pen-A) is often not verified or excluded by diagnostic testing. OBJECTIVE To assess the prevalence and impact of Pen-A registration in a Dutch University Medical Center. METHODS In a prospective matched cohort study, all admitted patients (July 2013-July 2014) who underwent a pharmacotherapeutic interview were selected. Patients with a registered Pen-A were matched on age, sex, and department of admission with up to 3 patients without a registered Pen-A. Relative risks (RRs) of receiving a reserve antibiotic, death during hospitalization, and rehospitalization were compared in the 2 cohorts. The number and type of antibiotics prescribed during admission and duration of hospitalization were compared. RESULTS Of 17,959 patients, 1010 (5.6%) patients (66.7% women; median age, 55 years) had a Pen-A registration. These patients had a higher risk of receiving reserve antibiotics (RR, 1.38; 95% CI, 1.22-1.56) and of being rehospitalized within 12 weeks (RR, 1.28; 95% CI, 1.10-1.49). A significantly larger proportion of Pen-A registered patients received reserve antibiotics such as tetracyclines (1.8% vs 0.8%), macrolides/lincosamides/streptogramins (12.5% vs 4.9%), and quinolones (7.9% vs 4.3%) or received 2 or more types of antibiotics during hospitalization (21.7% vs 16.9%). CONCLUSIONS Prevalence of Pen-A registration in hospitalized patients is high, has high impact on antibiotic prescribing, and is associated with a higher risk of readmission. Verification of the Pen-A in hospitalized patients might restrict the use of reserve antibiotics and improve patient outcome.

Duration of Antidepressant Drug Treatment and Its Influence on Risk of Relapse/Recurrence: Immortal and Neglected Time Bias

Several observational studies have found a higher risk of recurrence/relapse of depression for patients who discontinue antidepressant use compared with those who continue. This study demonstrated that measurement of follow-up time can be subject to immortal and neglected time bias. Data were obtained from the 2001 Second Dutch National Survey of General Practice. The study population was composed of antidepressant users with a registered depression diagnosis, divided into early discontinuers and continuing users. Two methods were used to measure time to relapse/recurrence. Method 1, used in previously mentioned studies, measured the beginning of follow-up 6 months after starting antidepressant therapy. Method 2 constructed individual treatment episodes for each patient and measured follow-up from actual end-of-treatment episode. The Cox proportional hazards model produced a risk ratio of 1.58 (95% confidence interval: 1.02, 2.45) for method 1, suggesting a higher risk of relapse/recurrence for early discontinuers. In method 2, a statistically nonsignificant risk ratio of 0.77 (95% confidence interval: 0.49, 1.21) was produced, indicating no difference in risk of relapse/recurrence. The authors found the method used in previous studies subject to bias. Applying a different method, accounting for immortal and neglected time bias, eliminated the protective effects of longer treatments.

An algorithm to identify antidepressant users with a diagnosis of depression from prescription data.

Antidepressants are used for many indications besides depression. This makes investigating depression treatment outcomes in prescription databases problematic when the indication is unknown. The aim of our study is to develop an algorithm to identify antidepressant drug users from prescription data that suffer from depression.

Does the length of the first antidepressant treatment episode influence risk and time to a second episode

Antidepressant treatment in primary care is inconsistent with treatment recommendations, and many patients discontinue treatment within 6 months. How this affects treatment outcomes is unknown. The aim of this study was to assess how length of the first antidepressant episode influences risk and time to a second treatment episode within 5 years. The study population included 9423 adults (67% women; mean age, 47.3 years) who initiated selective serotonin reuptake inhibitor use in 1998 or 1999. Based on the length of the first antidepressant treatment episode, patients were divided into early discontinuers (<6 months), continuing users (6-12 months), and persistent users (>12 months). The Cox proportional hazards model was used to estimate risk ratios (RRs) for the association between the length of the first antidepressant treatment episode and time to reinitiating antidepressant treatment. Time to a second treatment episode did not differ significantly between continuing users and early discontinuers (RR, 0.99; 95% confidence interval, 0.92-1.07). Persistent users showed a higher risk of experiencing a second treatment episode than early discontinuers (RR, 1.23; 95% confidence interval, 1.15-1.32). In conclusion, the risk of experiencing a second antidepressant treatment episode did not differ for those who used antidepressants for 6 to 12 months and those who discontinued early. In general, there is limited information on how length of an antidepressant treatment episode influences the risk of reinitiating treatment of patients in primary care. More research is needed to investigate the effectiveness of antidepressant drug treatment patterns in preventing relapse or recurrence in primary care populations.

Hip/femur fractures associated with the use of benzodiazepines (anxiolytics, hypnotics and related drugs) : a methodological approach to assess consistencies across databases from the PROTECT-EU project

Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed.

Seasonal patterns of initiating antidepressant therapy in general practice in the Netherlands during 2002–2007

BACKGROUND Studies on seasonality in antidepressant prescribing showed prescribing peaks during autumn and winter. Since then, new antidepressants have become available and indications have broadened, possibly contributing to a change in prescribing practices. This study investigates seasonal patterns of initiating antidepressant use in general practice during 2002-2007 in the Netherlands. METHOD Data were obtained from the Netherlands Information Network of General Practice. The study population was composed of adult patients initiating antidepressant use from 21 December 2001 to 20 December 2007, with no antidepressant use during at least two years prior to initiation. Seasonal distribution of initiating antidepressant use was investigated for the four seasons. The difference in frequency of initiating use between the seasons, normalized for general practice contacts, was tested using Chi-square testing. RESULTS The majority of the study population (N=16,289) was female (64.0%) with a mean age (standard deviation (SD)) of 50.5 (18.0) years. Significant seasonal variation (p<0.01) was found in initiation of antidepressant use, with about 5-35% more patients initiating use during winter than summer. Significant (p<0.01) seasonality of initiating antidepressant use was seen in all patient groups, except within age groups 18-30 years and >60 years. LIMITATIONS Our study investigated only general practitioner prescribing thus additional prescriptions from psychiatrists are missed. CONCLUSIONS The seasonal influence on initiation of antidepressant drug use has not changed with the introduction of the newer antidepressants and is in line with seasonality of depression onset, with most patients initiating use during the winter and fewest during the summer.

Understanding inconsistency in the results from observational pharmacoepidemiological studies : the case of antidepressant use and risk of hip/femur fractures

Results from observational studies on the same exposure–outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs.