Zeba M. Khan

Antidepressant-Induced Sexual Dysfunction

OBJECTIVE: To review the evidence regarding antidepressant-induced sexual dysfunction and address implications for treatment strategy and health plan coverage policies for antidepressant medications. DATA SOURCES: Primary articles were identified by a MEDLINE and HealthSTAR search to identify English-language studies published between January 1986 and July 2000. Search terms included sexual dysfunction or sexual function and antidepressants, fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, venlafaxine, nefazodone, bupropion, and mirtazapine. A cross-check of references cited in 10 published reviews yielded additional in-scope articles. STUDY SELECTION AND DATA EXTRACTION: Approximately 200 articles were identified, including 8 randomized controlled trials and numerous open-label studies, case series, and case reports. Of the randomized controlled trials, only 5 were designed to evaluate the incidence of sexual dysfunction associated with antidepressant treatment. Three additional randomized controlled trials included a structured assessment of sexual dysfunction within an efficacy trial. Data extraction excluded case reports, letters, and other limited study designs. A panel survey augmented published reports. DATA SYNTHESIS: Sexual dysfunction is a relatively common adverse effect of many of the antidepressants in common use today. Rates of sexual dysfunction observed in clinical practice may be higher than those reported in the product information for several agents. Selective serotonin-reuptake inhibitors (SSRIs) appear to be the class of antidepressants most likely to cause sexual dysfunction. Published studies suggest that between 30% and 60% of SSRI-treated patients may experience some form of treatment-induced sexual dysfunction. Bupropion and nefazodone appear to be much less likely to cause sexual dysfunction (≤10% of patients). Mirtazapine also appears to be associated with a low rate of sexual adverse effects. Panel results largely reflect the consensus of the literature. CONCLUSIONS: Sexual dysfunction is a common adverse effect of antidepressant treatment. Physicians should monitor their patients for antidepressant-induced sexual adverse effects, as these may affect compliance with therapy and ultimate treatment success. In addition to the consequences for patient health and well-being, managed-care organizations should be concerned with sexually related adverse effects of antidepressants, insofar as additional healthcare resources may be required to treat depressed patients in whom these adverse effects arise.

Impact of smoking status on workplace absenteeism and productivity

OBJECTIVES To: evaluate the impact of smoking status on objective productivity and absenteeism measures; evaluate the impact of smoking status on subjective measures of productivity; and assess the correlation between subjective and objective productivity measures. DESIGN Prospective cohort study in a workplace environment. SUBJECTS Approximately 300 employees (100 each of former, current, and never smokers) at a reservation office of a large US airline. MAIN OUTCOME MEASURES Objective productivity and absenteeism data were supplied by the employer. Subjective assessments of productivity were collected using a self report instrument, the Health and Work Questionnaire (HWQ). RESULTS Current smokers had significantly greater absenteeism than did never smokers, with former smokers having intermediate values; among former smokers, absenteeism showed a significant decline with years following cessation. Former smokers showed an increase in seven of 10 objective productivity measures as compared to current smokers, with a mean increase of 4.5%. While objective productivity measures for former smokers decreased compared to measures for current smokers during the first year following cessation, values for former smokers were greater than those for current smokers by 1–4 years following cessation. Subjective assessments of “productivity evaluation by others” and “personal life satisfaction” showed significant trends with highest values for never smokers, lowest for current smokers, and intermediate for former smokers. CONCLUSIONS Workplace productivity is increased and absenteeism is decreased among former smokers as compared to current smokers. Productivity among former smokers increases over time toward values seen among never smokers. Subjective measures of productivity provide indications of novel ways of productivity assessment that are sensitive to smoking status.

Recommendations for Evaluating Compliance and Persistence With Hypertension Therapy Using Retrospective Data

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. The World Health Organization Global Burden of Disease Study estimates that nonoptimal blood pressure [(BP) ie, systolic BP of >115 mm Hg] is responsible annually for 7.1 million deaths and the loss of 64.3 disability-adjusted life years worldwide.1 The associated economic burden of hypertension is also substantial. The average annual medical care cost for individuals with hypertension has been estimated at

Quality of Life in Geriatric Depression: A Comparison of Remitters, Partial Responders, and Nonresponders

3900 (in year 2000 US dollars) in Canada,2 with similar values (

Excess risk of diabetes in persons with hypertension.

3787) for the United States.3 The increase in medical care costs is greater for those with moderate-to-severe BP elevation (diastolic BP >104 mm Hg) than for those with mild disease.4 Although a broad range of hypertension medications have been demonstrated to reduce BP, and BP control is an achievable goal,5 reports suggest that up to two thirds of patients with hypertension are not successfully treated, that is, achieve BP control.6–8 According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), BP control rates are far below the “healthy people” goal of 50% set in 2000.9 A major (and modifiable) reason for lack of BP control is failure by patients to use medications as prescribed.10 Appropriate use of medications includes compliance, taking medications at the prescribed frequency/interval and dose/dosing regimen, and persistence, continuing their use for the specified treatment time period, which, in the case of hypertension therapy, is usually lifelong.11 Poor compliance with hypertension medications is associated with adverse health outcomes.12 Studies have demonstrated that poor BP control is associated with greater healthcare costs.13 For example, in the United States, inadequate control of hypertension has been estimated to result in &40 000 cardiovascular events, >8000 …

Economic Analysis of Carboplatin Versus Cisplatin in Lung and Ovarian Cancer

The authors examined patterns of improvement in quality of life (QOL) in elderly patients with recurrent major depression (MDD) after acute treatment. One hundred elderly (age 60-88 years) patients with recurrent MDD were randomized to receive either bupropion sustained-release (100 mg-300 mg/day) or paroxetine (10 mg-40 mg/day) for 6 weeks. Treatment with both paroxetine and bupropion was associated with improvements in QOL. Lower perceived Physical- and Social-Functioning QOL ratings at baseline were associated with lower treatment response. Improvement in depression symptom ratings correlated significantly with improvement in QOL on many domains, but accounted for less than one-quarter of the total variance. Remitters showed significantly (P<0.001) greater improvement than both Partial Responders and Nonresponders on various measures. Findings support the importance of treating elderly depressed patients to full remission to maximize impact on both emotional and physical QOL domains.

Risk of diabetes in a real-world setting among patients initiating antihypertensive therapy with valsartan or amlodipine

PROBLEM Persons with hypertension appear to be at increased risk of diabetes, an important predictor of cardiovascular disease. Whether, and to what extent, this risk may vary across subgroups defined on the basis of important clinical characteristics has not been well characterized. METHODS Study population included members of Kaiser Permanente Northwest Region, a large health maintenance organization, aged > or = 35 years and free of diabetes in 1998. Persons in the study population were stratified based on whether or not they had hypertension, and onset of diabetes was ascertained over a 6-year period beginning January 1999. Excess risk of diabetes was characterized in terms of risk differences between persons with and without hypertension, and was estimated on an overall basis and for subgroups defined on the basis of age, sex, and body mass index (BMI). RESULTS Study population totaled 104,368; 44% had hypertension. Relative risk (RR) of developing diabetes was 2.7 (95% CI: 2.6-2.8) for those with vs. without hypertension [21.0 (95% CI: 20.7-21.4) vs. 7.8 (95% CI: 7.6-8.0) per 1000 person-years, respectively]. Adjusted for age, sex, and BMI, RR of diabetes was 1.8 (95% CI: 1.7-1.9). With one exception (men, aged > or = 75 years), risk of diabetes was higher across all age and BMI strata for both men and women with vs. without hypertension; differences in risk were greatest among those with high BMI (> or = 35 kg/m(2)). Across BMI strata, RR of developing diabetes was generally higher at younger ages. CONCLUSION All persons with hypertension, irrespective of age, sex, and BMI, are at elevated risk of developing diabetes. Men and women with hypertension who are overweight or obese are at substantially elevated risk of diabetes, regardless of age, and should be monitored especially closely for the development of this disease.

Strategies to improve adherence with medications in chronic, ‘silent’ diseases representing high cardiovascular risk

AbstractObjective: To conduct an economic analysis on the use of carboplatin versus cisplatin over multiple courses in patients with lung [nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] or ovarian cancer. Design: This 1-year study was a prospective, multicentre, cost-minimisation evaluation. Direct medical resource utilisation and costs associated with carboplatin and cisplatin administration over 3 to 6 courses of treatment were measured and compared. The perspective of this evaluation was that of the payer. Setting: A convenience sample of 16 sites representing a mix of cancer centres, outpatient clinics, medical centres and managed-care sites in a general practice oncology setting participated. Patients and interventions: Patients were included in this study if they were newly diagnosed with NSCLC, SCLC or ovarian cancer, had not received prior chemotherapy, received either carboplatin or cisplatin as their treatment (additional chemotherapy agents were allowed), and received at least 3 courses of carboplatin or cisplatin therapy up to a maximum of 6 courses. Patients receiving more than 6 courses of therapy were included in this study, but data collection on those patients stopped after the sixth course.Individuals involved with data collection at all sites were trained via on-site and/or teleconference training. Site visits were made to assure reliability of at least 0.80. Data were collected and compiled via a fax transmission process that scans directly through optical mark and character recognition into a computer database. Outcome measures included costs of: medications, emergency room visits, physician/clinic/laboratory visits, home healthcare visits, transfusions, special procedures, consultations, hospitalisations and other/miscellaneous costs. Main outcome measures and results: Of 220 patients, 164 met the study criteria (response rate = 74.2%) with 95 patients in the carboplatin group (NSCLC = 45 SCLC = 18, ovarian = 32) and 69 in the cisplatin group (NSCLC = 36, SCLC = 21, ovarian = 12). The average number of courses were: NSCLC = 4.3 and 4.2, SCLC = 4.3 and 4.8, and ovarian = 4.7 and 5.1, respectively, for carboplatin and cisplatin. The total costs (treatment and toxicity) associated with the use of carboplatin were higher in NSCLC, similar in SCLC but lower in ovarian cancer. Conclusions: These results indicate that overall treatment costs may vary depending on cancer type, even when the same drugs are used. The total costs (treatment plus toxicity costs) associated with the use of carboplatin were higher than those of cisplatin in patients with NSCLC, similar in SCLC, but lower in ovarian cancer.

Impact of patient programs on adherence and persistence in inflammatory and immunologic diseases: a meta-analysis

In the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, the risk of new-onset diabetes was reported to be 23% lower among patients initiating therapy with valsartan versus amlodipine. The objective of our study was to examine whether this finding is generalizable to ‘real-world’ clinical practice. A retrospective cohort design and a large US health insurance database were employed for analyses. Study subjects included all hypertensive patients, aged ⩾35 years, who were free from diabetes and who initiated treatment with valsartan (n=9999) or amlodipine (n=18 698) between January 1999 and March 2005. Unadjusted absolute risks of diabetes were 21.4 (95% confidence interval (CI) 18.9–24.3) and 26.3 (95% CI 24.3–28.3) per 1000 patient-years for valsartan and amlodipine, respectively; the corresponding relative risk (RR) for valsartan was 0.82 (95% CI 0.70–0.94). Multivariate analyses – controlling for age, sex, presence of hypercholesterolemia, cardiovascular disease and kidney disease, and pretreatment medical care expenditures – yielded similar results (RR=0.79, 95% CI 0.68–0.92). Our study thus corroborates the finding from VALUE that diabetes risk is lower for patients who receive valsartan versus amlodipine, and extends this finding to a ‘real-world’ setting.

A survey of African Americans at a community health fair.

Given the burden of illness related to diabetes, hypertension and dyslipidemia, it is very important to achieve glycemic control, optimal blood pressure and low-density lipoprotein cholesterol (LDL-C) in order to avoid severe long-term complications. Patients’ adherence with, and persistence to, the treatment regimen is a critical factor in achieving this goal. Medication taking behavior in these chronic, nonsymptomatic (‘silent’) diseases is generally low, although a wide range of results have been reported. The literature has shown that nonadherence to medications is a multidimensional phenomenon; relating factors can be grouped into the following categories: health system related, social/economic, condition-related, therapy-related and patient-related factors. Although several interventions exist to improve patients’ medication-taking behavior, none appear to be clearly superior to others. The key steps to improve adherence are to identify individual barriers and to develop patient-specific self-management plans to overcome them (called ‘patient-centric’ approach). When developing intervention strategies one should always remember that ‘one size does not fit all’. Well designed (but not randomized), observational studies (for example, patient registries) may be required with sufficient follow-up periods and multiple adherence measurements in order to advance the field.