Prolactin-Elevating Antipsychotics and the Risk of Endometrial Cancer.

BACKGROUND: The use of antipsychotics may increase the risk of endometrial cancer through elevation of prolactin levels. We investigated the association between antipsychotics that are known to cause prolactin elevation and the risk of endometrial cancer. METHODS: In data from the United Kingdom Clinical Practice Research Datalink, all women who were newly treated with antipsychotics from 1990-2013 were identified and followed until 2014. Within this cohort of antipsychotic users, a nested case-control analysis was conducted. Main exposure was nonsporadic use of prolactin-elevating antipsychotics, and the active comparator was prolactin-sparing antipsychotics. Cases were women newly diagnosed with endometrial cancer (ICD-10) matched with up to 20 controls on age, calendar year of cohort entry, linkability to the Hospital Episode Statistics repository, and duration of follow-up. Conditional logistic regression models were used to determine the association of prolactin-elevating antipsychotics and endometrial cancer compared with prolactin-sparing antipsychotics. All analyses were adjusted for relevant potential confounders, including smoking, obesity, and diabetes mellitus. RESULTS: The cohort included 65,930 women. During 366,112 person-years of follow-up, there were 139 cases of endometrial cancer (incidence rate: 38/100,000 person-years), which were matched to 1,603 controls. Compared with the use of prolactin-sparing antipsychotics, the use of prolactin-elevating antipsychotics was not associated with an increased risk of endometrial cancer (adjusted odds ratio [aOR] = 1.00; 95% CI, 0.68-1.48). These findings remained similar with different durations of use (≤ 1 year, aOR = 1.07; 95% CI, 0.64-1.78, and > 1 year, aOR = 0.95; 95% CI, 0.58-1.54) and were robust to various sensitivity analyses. CONCLUSIONS: Prolactin-elevating antipsychotics were not associated with an increased risk of endometrial cancer.

Concurrent use of tamoxifen with CYP2D6 inhibitors and the risk of breast cancer recurrence.

Concurrent use of tamoxifen and cytochrome P450 2D6 (CYP2D6) inhibitors, such as selective serotonin reuptake inhibitors, has been shown to decrease plasma concentrations of tamoxifen metabolites. However, it is still unclear whether such concurrent use affects tamoxifen's effectiveness. Thus, the objective of this study is to determine whether concurrent use of tamoxifen with CYP2D6 inhibitors increases the risk of recurrence in patients newly diagnosed with breast cancer. We conducted a nested case-control analysis within a population-based cohort from the UK General Practice Research Database. The cohort included women with a first-ever diagnosis of breast cancer who were prescribed tamoxifen between January 1, 1998 and June 30, 2008. Cases consisted of all patients with a breast cancer recurrence occurring during follow-up. Up to ten controls were matched to each case on year of birth, date of cohort entry, and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RR) of breast cancer recurrence in patients who concurrently used tamoxifen with CYP2D6 inhibitors, compared to patients who only used tamoxifen. The cohort included 9,209 incident users of tamoxifen, of whom 807 were diagnosed with a breast cancer recurrence. Concurrent use was not associated with an increased incidence of breast cancer recurrence (adjusted RR 1.07, 95% 0.88, 1.30). Type and strength of CYP2D6 inhibitors, as well as duration of concurrent use did not affect breast cancer recurrence. These results remained consistent after performing sensitivity analyses. The results of this large population-based study indicate that concurrent use of tamoxifen with CYP2D6 inhibitors does not increase the risk of recurrence.

Economic impact of non-persistence to antidepressant therapy in the Quebec community-dwelling elderly population.

BACKGROUND: In a real-life setting, differences across newer antidepressants in patterns of use remain poorly explored, particularly in the older patients despite the high prevalence of late-life depression. METHODS: An observational retrospective cohort study was conducted in the community-dwelling elderly population of Quebec using health databases to compare the newer antidepressants with respect to non-persistence, associated health care costs and cost/persistence ratio. A random sample of 12,825 outpatients who initiated an antidepressant treatment in 2000 were followed for 12 months. Non-persistence was defined as treatment duration of less than 180 days. Economic variables included direct costs of prescribed medications, medical services and hospitalizations assessed through RAMQ claims databases and Med-Echo hospitalization database. Cost/persistence ratio and incremental cost/persistence ratio were obtained for each antidepressant product; persistence being considered as an indicator of effectiveness. RESULTS: 55.6% of antidepressant treatments were non-persistent. Products associated with low antidepressant costs were often associated with high costs of other medications and health care services, and vice versa. Paroxetine was associated with the lowest non-persistence (50.5%; 95%CI 48.5-52.5) and one of the most favourable cost/persistence ratios (CDN$4869 per persistent treatment). Fluoxetine was associated with the most favourable incremental cost/persistence ratio. LIMITATIONS: Some services and hospitalizations are not included in the administrative databases. No data on indication for treatment were available. These were likely to be non-differential across newer antidepressants. CONCLUSION: As found in other populations, non-persistence with antidepressant treatment is very frequent in the Quebec elderly population. Products associated with poor persistence result in increased health care costs. Hence, intervention programs aimed at improving persistence would optimize the use of health care resources and result in economic advantages.

Effect of an interdisciplinary educational program on antipsychotic prescribing among nursing home residents with dementia.

OBJECTIVE: To assess the effect of an interdisciplinary educational program in reducing the use of antipsychotics in nursing home residents with dementia. METHODS: We conducted a longitudinal pilot study to test the implementation of a 7-month interdisciplinary educational program in a fixed cohort of residents with dementia receiving antipsychotics. The program included consciousness-raising, educational sessions, and clinical follow-up. Administrators, physicians, pharmacists, nursing staff, and personal care attendants were involved. The effect of the program was assessed over a 6-month period, in terms of the proportion of discontinuations and dose reductions of antipsychotics. Repeated measures for use of other psychotropics and restraints, frequency of disruptive behaviors, and stressful events experienced by nursing staff and personal care attendants were simultaneously assessed. RESULTS: Among the 81 residents still present at the end of the program, there were 40 (49.4%) discontinuations and 11 (13.6%) dose reductions. No significant changes were found in the use of other psychotropics, the use of restraints, or in the number of stressful events experienced by nursing staff and personal care attendants. The frequency of disruptive behaviors decreased significantly over the 6-month period (p<0.001). CONCLUSIONS: Our interdisciplinary educational program led to a substantial reduction in the number of residents receiving antipsychotics and to a decrease in the frequency of disruptive behaviors. Our findings suggest that implementation of recognized practice guidelines could be an effective way to target residents who might not benefit from antipsychotics or who may tolerate a dose reduction.

Use of health care services for psychological distress by immigrants in an urban multicultural milieu.

OBJECTIVE: Research in the United States tends to attribute low rates of use of mental health services by immigrants to economic barriers. The purpose of our study was to examine this issue in the context of Canada's universal health care system. METHODS: A survey of the catchment area of a comprehensive clinic in Montreal interviewed random samples of 924 Canadian-born individuals and 776 immigrants born in the Caribbean (n = 264), Vietnam (n = 234), or the Philippines (n = 278) to assess their health care use for somatic symptoms, psychological distress, and recent life events. RESULTS: Overall rates of use of medical services in the past year were similar in immigrant (78.5%) and nonimmigrant (76.5%) groups. Rates of use of health care services for psychological distress were significantly lower among immigrants (5.5% compared with 14.7%, P < 0.001). This difference was attributable both to a lower rate of use of specialty mental health services by immigrants (2.5% compared with 11.7%, P < 0.001) and to differential use of medical services for psychological distress (3.5% compared with 5.8%, P = 0.02). When level of psychological distress was controlled, Vietnamese and Filipino immigrants were one-third as likely as Canadian-born residents to make use of mental health services. The lower rate of use by immigrants could not be explained by differences in sociodemographics, somatic or psychological symptoms, length of stay in Canada, or use of alternative sources of help. CONCLUSION: Immigrant status is associated with lower rates of use of mental health services, even with universal health insurance. This lower rate of use likely reflects cultural and linguistic barriers to care.

Prevalence, clinical correlates, and treatment of migraine in bipolar disorder.

OBJECTIVE: To investigate the prevalence, clinical correlates, and treatment of migraine in bipolar disorder. BACKGROUND: The relationship between migraine and mood disorders has been of long-standing interest to researchers and clinicians. Although a strong association has been demonstrated consistently for migraine and major depression, there has been less systematic research on the links between migraine and bipolar disorder. METHODS: A migraine questionnaire (based on International Headache Society criteria) was administered to 108 outpatients with bipolar disorder. Information on the clinical course of bipolar illness was also collected. RESULTS: The overall lifetime prevalence of migraine was 39.8% (43.8% among women and 31.4% among men). In the subgroup of patients with bipolar II disorder, the lifetime prevalence of migraine was 64.7%. The bipolar with migraine group was younger, tended to be more educated, was more likely to be employed or studying, and had fewer psychiatric hospitalizations. Their initial presentation for psychiatric treatment was more often for symptoms of depression, rather than hypomania or mania. They were more likely to have a family history of migraine and psychiatric disorders, and a greater number of affected relatives. They were less likely to use mood stabilizers, and more likely to use atypical antidepressants. Migraine was assessed by a neurologist in only 16% of affected patients. The prevalence of the use of specific antimigraine medications (triptans) was 27.9%. CONCLUSIONS: This study confirms the higher prevalence of migraine among those with bipolar disorder compared to the general population. Migraine in patients with bipolar disorder is underdiagnosed and undertreated. Bipolar disorder with migraine is associated with differences in the clinical course of bipolar disorder, and may represent a subtype of bipolar disorder.

Delirium in older emergency department patients discharged home: effect on survival.

OBJECTIVES: To determine whether prevalent delirium is an independent predictor of mortality in older patients seen in emergency departments (EDs) and discharged home without admission. DESIGN: Prospective study with 18 months of follow-up. SETTING: EDs in two Montreal hospitals. PARTICIPANTS: From a cohort study of prognosis for delirium (107 delirious and 161 nondelirious subjects), 30 delirious and 77 nondelirious subjects aged 66 and older who were discharged home without admission were identified. MEASUREMENTS: Detailed interviews with patients and their proxies and review of medical charts were performed at enrollment. Trained lay interviewers determined delirium status using the Confusion Assessment Method. Subjects were followed up at 6-month intervals for a total of 18 months. Dates of death were obtained from the Ministère de la Santé et des Service Sociaux (Ministry of Health and Social Services). Survival analysis was performed using the Cox proportional hazards modeling adjusting for potential confounding variables. RESULTS: The analysis revealed a statistically significant association between delirium and mortality after adjustments for age, sex, functional level, cognitive status, comorbidity, and number of medications for the first 6 months of follow-up (hazard ratio = 7.24; 95% confidence interval = 1.62-32.35). The subjects whose delirium was not detected by the ED physician or nurse had the highest mortality over 6 months (30.8%). The mortality of delirious subjects detected in the ED was similar to that of the nondelirious subjects (11.8 vs 14.3%). CONCLUSION: The results of this study suggests that nondetection of delirium in the ED may be associated with increased mortality within 6 months after discharge. Further research is necessary to examine the effectiveness of improving detection on subsequent prognosis of older patients with delirium.

Treatment seeking for obsessive-compulsive disorder: role of obsessive-compulsive disorder symptoms and comorbid psychiatric diagnoses.

Previous research has indicated that individuals afflicted with obsessive-compulsive disorder (OCD) have a very low rate of seeking help from mental health professionals. From standardized psychiatric interviews of 7,214 residents of Edmonton, Canada, we identified 172 subjects with a lifetime diagnosis of OCD; 63 (36.6%) had consulted a doctor about their symptoms. Total number of OCD symptoms (odds ratio [OR] = 2.23) and severe obsessions of violence and other unpleasant thoughts (OR = 2.52) were significantly associated with treatment seeking in multivariate analysis. The absence of association between compulsions and treatment seeking was corroborated by a very low prevalence of treatment seeking (17.3%) in individuals suffering from compulsions only. Our findings suggest that there is a need to teach the public about compulsions, and such a strategy may enhance future public health education programs.

Suboptimal duration of antidepressant treatments in the older ambulatory population of Quebec: association with selected physician characteristics.

OBJECTIVES: To assess the association between selected physician characteristics and suboptimal duration of antidepressant use in the older outpatient population. DESIGN: Follow-up of patients who were prescribed an antidepressant treatment by a cohort of physicians in Quebec. SETTING: Community-based older outpatient population in Quebec. PARTICIPANTS: Retrospective cohort of 1,301 general practitioners (GPs) and 236 psychiatrists followed from 1991 to 1997. MEASUREMENTS: Treatment duration of less than 180 days in 1996/97. RESULTS: Premature interruption of antidepressant treatment was very frequent (44.7%). GPs, physicians who practice in metropolitan or urban regions, and those who have a proportion of older patients in their practice of less than 50% show a higher rate of premature interruption. These associations could not be accounted for by the choice of products, dosage, or patient characteristics. CONCLUSION: We have identified physician characteristics that are associated with suboptimal duration of antidepressant use and conclude that further interventions should target subgroups of physicians.