Antidepressants and the risk of death in older patients with depression: A population-based cohort study.

BACKGROUND: Antidepressants are frequently used in older patients with depression, but little is known about the comparative safety of individual agents. The objective of the study was to determine the comparative risk of death of antidepressants in older patients with depression. METHODS AND FINDINGS: We carried out a cohort study from 2004 to 2015 utilizing the German Pharmacoepidemiological Research Database, a population-based database supplied by statutory health insurance providers covering approximately 17% of the general population and all geographical regions. We included 376,846 patients aged 65+ years with a diagnosis of depression who initiated treatment with one of 13 antidepressants (ADs). In total 27,019 patients died during follow-up corresponding to a rate of 119.7 per 1,000 person years. We used proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of death for twelve ADs compared to citalopram. In the primary analysis, we found an increased risk of death associated with the use of amitriptyline (HR 1.15, 95%CI: 1.10-1.20). However, opipramol, trimipramine, doxepin, mirtazapine, fluoxetine, paroxetine, duloxetine, venlafaxine, and St. John's wort were found to be associated with a lower risk of death. The increased risk of amitriptyline diminished after exclusion of patients with a history of cancer (HR 0.88, 95%CI: 0.82-0.94) and after high-dimensional propensity score (HdPS) adjustment (HR 1.04, 95%CI: 0.95-1.14). In older patients and in those with dementia, differences in risk between most individual ADs and citalopram were smaller. After adjustment by HdPS, the decreased risks for fluoxetine, paroxetine, venlafaxine and mirtazapine compared to citalopram disappeared. CONCLUSIONS: This study suggests that ADs recommended as first-line treatment in patients with depression have a similar safety profile with regard to the risk of death, especially in very old patients and in those with dementia. Further research is needed to investigate the risk of death for individual ADs in specific subgroups such as patients with cancer or cardiovascular disease.

Characteristics and drug use patterns of older antidepressant initiators in Germany.

PURPOSE: The purpose of this study was to investigate characteristics, drug use patterns, and predictors for treatment choice in older German patients initiating antidepressant (AD) treatment. METHODS: Using the German Pharmacoepidemiological Research Database, we identified a cohort of AD initiators aged at least 65 years between 2005 and 2011. Potential indications, co-morbidity, and co-medication as well as treatment patterns such as the duration of the first treatment episode were assessed. In addition, a logistic regression model was used to identify independent predictors for initiating treatment with tricyclic ADs (TCAs) compared to selective serotonin reuptake inhibitors (SSRIs). RESULTS: Overall, 508,810 individuals were included in the cohort. About 55 % of patients initiated AD treatment with TCAs, followed by 22 % receiving SSRIs. During the study period, a decrease of treatment initiation with TCAs was observed. Higher age and male sex as well as being diagnosed with depression were highly associated with SSRI treatment, whereas pain and sleeping disorders were strong predictors for initiating TCA treatment. The duration of the first treatment episode was substantially longer in SSRI users compared to TCA initiators (median 119 vs. 43 days). CONCLUSIONS: Potential indications and drug use patterns in older German AD initiators varied substantially for different drug classes and single agents. Given the anticholinergic and sedative properties of TCAs, the frequent use of this drug class though probably related to indications such as pain was remarkable.

Comparative risk of death in older adults treated with antipsychotics: A population-based cohort study.

Although the use of antipsychotics has been associated with an increased risk of death, data on the safety of individual substances is scarce. We thus aimed to compare the risk of death in new users of individual antipsychotics aged =>65 years and conducted a cohort study in the German Pharmacoepidemiological Research Database between 2005 and 2011. Patients were followed from initiation of treatment until death, 90 days after cohort entry, end of insurance or the end of the study period. Multivariable cox regression was used to estimate confounder adjusted hazard ratios (aHR) of death for 14 individual antipsychotics compared to risperidone. In sensitivity analyses, we also applied high-dimensional propensity score (HDPS) methods to explore possible unmeasured confounding. In a cohort of 137,713 new users of antipsychotics, a higher risk of death was found for haloperidol (aHR: 1.45; 95% confidence interval: 1.35-1.55), levomepromazine (aHR: 1.34; 1.16-1.54), zuclopenthixol (aHR: 1.32; 1.02-1.72) and to a lesser extent for melperone (aHR: 1.13; 1.07-1.19) compared to risperidone. Lower risks were observed for quetiapine, prothipendyl, olanzapine, tiapride, clozapine, perazine and flupentixol. In subgroup analyses, levomepromazine and chlorprothixene were only associated with a higher risk of death in patients aged =>80 years and with dementia. The application of HDPS methods did not substantially change the results. In conclusion, our study suggests that initiation of haloperidol, levomepromazine, zuclopenthixol and chlorprothixene treatment is associated with an increased risk of death compared to risperidone and should be avoided in older patients except in palliative care when treatment alternatives are available.

Treatment patterns and characteristics of older antipsychotic users in Germany.

The aim of this study was to investigate the characteristics and treatment patterns of older antipsychotic (AP) users in Germany. We carried out a cohort study in the German Pharmacoepidemiological Research Database and identified new AP users aged at least 65 years between 2005 and 2011. Possible indications, comedication, and information on persistence and adherence, concurrent multiple use, and switch of APs were assessed. Overall, 298,847 individuals were included in the cohort. Almost 70% entered the cohort with a typical antipsychotic (TAP). Melperone (23.4%) was used most frequently, followed by promethazine (18.3%), sulpiride (11.0%), and risperidone (10.3%). AP users had a low prevalence of schizophrenia and bipolar disorders in contrast to dementia. Initiators of atypical antipsychotics had more treatment episodes compared with TAPs (median 3 vs. 2), but lower median persistence (14 vs. 22 days). Persistence was also lower in patients with, rather than without, dementia. The overall percentage of concurrent multiple use and switch to other APs was low with 5.6%, but higher in patients with, rather than without, dementia. In conclusion, APs were used for a broad range of indications, mostly other than schizophrenia and bipolar disorders. Low persistence and a high number of treatment episodes suggest frequent 'as-needed' treatment, especially in dementia patients.

[Utilization patterns of dementia patients in the light of statutory health insurance data]. / Inanspruchnahmeverhalten von Demenzpatie- nten im Spiegel von GKV-Daten.

In describing the patterns of utilization of healthcare services by dementia patients in comparison to age- and sex-matched controls the study was to provide information on special care needs of patients with dementia concerning somatic diseases. A representative sample of insured individuals from 1998 to 2002 (the "Versichertenstichprobe AOK Hessen/KV Hessen") provided the database. Patients with dementia were defined according to the ICD-coded billing diagnoses. Regarding general practitioner visits, patients with dementia have approx. 11 additional contacts per year compared to their controls. A smaller percentage of patients with dementia present to a specialist (excluding neurologists/psychiatrists). Furthermore, the two groups differ as to the kind of specialists visited, which in turn is associated with different service and prescription patterns. The study was not able to clarify whether the differences are possibly due to the GPs' prioritization of treatment of dementia patients. Both physicians and nurses should be sensitized to the possibility that dementia patients may not be able to explicitly mention existing diseases and impairments (such as cardiovascular and sensory disorders, pain). Moreover, physicians and other professionals involved in the management of dementia patients should be trained to pay special attention to the particular care-related problems (pressure ulcers, infections or inadequate fluid intake).

First patient-centered drug information service in Germany--a descriptive study.

BACKGROUND: The majority of patients have unmet drug information needs, and patients' knowledge of their own treatment is often poor. This is a major obstacle to a more patient-centered healthcare system. OBJECTIVE: To explore patterns of patients' unmet drug information needs and outcomes of counseling patients by a drug and therapy information center (DTIC). METHODS: We established the first German DTIC for patients. In this descriptive study, data obtained on callers within 24 months were analyzed. Questionnaires for gathering information about callers' characteristics and the outcome of the advice were sent to all patients using the service after consultation. Data on all inquiries and evaluation sheets were documented and analyzed by a standardized database. RESULTS: During 24 months, 2049 telephone calls were recorded. Patients' unmet information needs were mainly related to adverse drug reactions/drug interactions (31.0%) and therapy information (27.2%). In 81.0% of the cases, patients' uncertainties regarding their prescribed medications were reduced, 37.9% discussed the advice with their physician, and 18.3% reported a reduction of physician visits as a result of our advice. The patient-physician relationship remained mainly (70.6%) unaffected after our intervention. CONCLUSIONS: The DTIC is useful as a source of medical expert advice. The service can help to reduce medication problems based on inadequate information and therefore avoid unnecessary healthcare utilization. With the knowledge provided, patients can participate in decisions affecting their own health. This procedure encourages greater confidence in the merits of drug therapy.

Prescriptions of systemic antibiotics for children in Germany aged between 0 and 6 years.

Limited information is available about systemic antibiotic use among children in Germany. We therefore assessed prescription patterns by office-based physicians to analyse antibiotic consumption in early childhood. A total of 331 children < 6 years were eligible for inclusion. The number of antibiotic prescriptions, consumed daily doses, number of treatment courses, types of antibiotics and diagnoses for prescribing were determined. The prevalence of systemic antibiotic treatment was 42.9%. Antibiotic consumption was highest between 2 and 3 years of age (55.8%). The percentage of children receiving one, two or three courses of antibiotic treatment was 49.3, 28.2 and 16.2%, respectively. Acute otitis media (32.2%), upper respiratory tract infections (18.9%), tonsillitis (15.9%) and acute bronchitis (15.4%) were principal indications for treatment. Macrolides were most frequently prescribed (48.1%), followed by penicillin V (21.3%), broad-spectrum penicillins (14.3%), sulfonamides (10.5%) and cephalosporins (5.8%). Antibiotics not recommended for particular indication were selected in 5-43% of cases. The considerable prescription of systemic antibiotics to children in many European countries is also the case in Germany. A noteworthy trend emerged for suboptimal prescribing with second-line antibiotics. As such treatment may be associated with the development of bacterial resistance, improved guidelines for antibiotic treatment should be drawn up and enforced.