Premature Treatment Discontinuation Research Articles

Extended Treatment Duration for Hepatitis C Virus Type 1: Comparing 48 Versus 72 Weeks of Peginterferon-Alfa-2a Plus Ribavirin

The treatment of patients infected with hepatitis C virus (HCV) type 1 remains a challenge necessitating innovative strategies to improve treatment outcome. The extension of treatment duration beyond 48 weeks is one possible strategy to address this problem. The efficacy and safety of 48 weeks (group A, N = 230) vs 72 weeks (group B, N = 225) of treatment with pegylated-interferon-alfa-2a (180 microg/wk) plus ribavirin (800 mg/day) were studied in treatment-naive patients with HCV type 1 infection. On-treatment and sustained virologic response (SVR) 24 weeks after stopping treatment was assessed by qualitative reverse-transcription polymerase chain reaction (sensitivity 50 IU/mL). Overall, no significant differences could be observed in the treatment outcome between both groups. End-of-treatment and SVR rates in groups A and B were 71% vs 63% and 53% vs 54%, respectively. Patients with undetectable HCV-RNA levels already at weeks 4 and 12 had excellent SVR rates ranging from 76% to 84% regardless of treatment group, whereas patients shown to be still HCV-RNA positive at week 12 achieved significantly higher SVR rates when treated for 72 instead of 48 weeks (29% vs 17%, P = .040). A particular benefit from extended treatment duration was seen in patients with low-level viremia (<6000 IU/mL) at week 12. The frequency and intensity of adverse events was similar between the 2 groups. Extended treatment duration generally is not recommended in HCV type 1 infection and should be reserved only for patients with slow virologic response defined as HCV-RNA positive at week 12 but negative at week 24.

P.250 Australian trial in acute hepatitis C: preliminary findings

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-α) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P < .0001), a low baseline gamma-glutamyltransferase (GGT) level (P < .0001), a high baseline alanine aminotransferase level (P = .002), and a low baseline viral load (P = .04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2– and 3–infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment. (HEPATOLOGY 2003;37:600-609.)

P.251 Long term outcome of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-α) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P < .0001), a low baseline gamma-glutamyltransferase (GGT) level (P < .0001), a high baseline alanine aminotransferase level (P = .002), and a low baseline viral load (P = .04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2– and 3–infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment. (HEPATOLOGY 2003;37:600-609.)

P.249 Recurrence or persistence of HCV RNA detectable only by TMA during antiviral therapy

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-α) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P < .0001), a low baseline gamma-glutamyltransferase (GGT) level (P < .0001), a high baseline alanine aminotransferase level (P = .002), and a low baseline viral load (P = .04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2– and 3–infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment. (HEPATOLOGY 2003;37:600-609.)

P.8.a.017 A flexible dose open label trial evaluating the efficacy and safety of quetiapine as adjunctive pharmacotherapy for the treatment of generalized anxiety disorder (GAD)

Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD.We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile.We report on the open-label phase of a two-phase randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD.Subjects with moderate to severe GAD received open-label treatment with pharmaceutical-grade chamomile extract 1500 mg/day for up to 8 weeks. Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8. Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, and the Psychological General Well Being Index. Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined.Of 179 subjects, 58.1% (95% CI: 50.9% to 65.5%) met criteria for response, while 15.6% prematurely discontinued treatment. Significant improvement over time was also observed on the GAD-7 rating (β = −8.4 [95% CI = −9.1 to −7.7]). A similar proportion of subjects demonstrated statistically significant and clinically meaningful reductions in secondary outcome ratings of anxiety and well-being. Adverse events occurred in 11.7% of subjects, although no serious adverse events occurred.Chamomile extract produced a clinically meaningful reduction in GAD symptoms over 8 weeks, with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile. Future comparative effectiveness trials between chamomile and conventional drugs may help determine the optimal risk/benefit of these therapies for patients suffering from GAD.

Liver Injury and Changes in Hepatitis C Virus (HCV) RNA Load Associated with Protease Inhibitor-Based Antiretroviral Therapy for Treatment-Naive HCV-HIV-Coinfected Patients: Lopinavir-Ritonavir versus Nelfinavir

Highly active antiretroviral therapy (HAART) initiation in patients coinfected with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) has been associated with transaminase and HCV viral load flares. Previous studies have included highly variable antiretroviral regimens. We compared effects of 2 protease inhibitor-based regimens on alanine aminotransferase (ALT) levels and HCV loads in HCV-HIV-coinfected patients initiating HAART. Seventy HIV-infected patients with positive baseline results of HCV enzyme-linked immunosorbant assay from a treatment trial comparing lopinavir-ritonavir with nelfinavir were evaluated during a 48-week period. HCV and HIV titers were analyzed at baseline, at weeks 24 and 48 of treatment, and during flares in the ALT level of >5 times the upper limit of normal. A total of 57 of 70 patients tested positive for HCV RNA at baseline. HCV titers for patients in lopinavir-ritonavir and nelfinavir groups, respectively, were as follows: baseline, 6.07 and 6.22 log IU/mL; week 24 of treatment, 6.68 and 6.48 log IU/mL; and week 48 of treatment, 6.32 and 6.44 log IU/mL. Of patients with a CD4+ cell count of <100 cells/mm3 at baseline, 5 of 11 in the nelfinavir group and 0 of 10 in the lopinavir-ritonavir group had an increase in the HCV load of >0.5 log IU/mL from baseline to week 48. The mean ALT level increased by 45 U/L at 24 weeks and 18 U/L at 48 weeks in the nelfinavir group but decreased by 18 U/L at 24 weeks and 7 U/L at 48 weeks in the lopinavir-ritonavir group. Eight patients in the nelfinavir group and 2 patients in the lopinavir-ritonavir group had grade 3 or 4 flares in the ALT level. HAART initiation is associated with increased HCV loads and ALT levels. A low baseline CD4+ cell count is associated with persistent increases in the HCV RNA load in nelfinavir-treated patients. These results warrant careful interpretation of abnormalities in the ALT load after HAART initiation in HCV-HIV-coinfected patients to prevent premature discontinuation of treatment.

Service quality and attrition: an examination of a pediatric obesity program.

To examine the demographic, illness, and quality of care determinants of service attrition in a pediatric obesity program, and to elucidate factors that may promote families' return to care. Cross-sectional survey with semi-structured interviews. A regional children's hospital in the United States. Caregivers of 163 patients, consecutively enrolled in a pediatric obesity treatment program between January 1998 and September 2000, were contacted by telephone and offered participation in a survey of clinical care experiences. A total of 120 (74%) families participated. Service attrition as defined as premature discontinuation of treatment before completing phase I of a multi-phase treatment program. Multivariate results indicated that service attrition was associated with both insurance status and perceived quality of care. Patients with government-subsidized insurance were more likely to defect from services than those with commercial insurance. Perceived quality of care was highly associated with attrition after controlling for demographic and health parameters. Caregiver-reported reasons for service attrition included difficulty with adequate insurance coverage (53%), the child's desire to leave the program (50%), and the program taking too much time (32%). The most frequent suggestions to facilitate families' return to the program were: (i) assistance with insurance coverage; (ii) following up with families; and (iii) increasing engagement with the child. This study found few demographic differences between patients completing the program and those defecting from services. Both families completing the program and those discontinuing prematurely rated the overall quality of the program as high. However, lower quality of care was related to increased service attrition even after controlling for the effects of demographic and health parameters. Although a considerable number of patients discontinued services, very few reported that they would not return to the program. The results provide further support for ongoing audit and examination of families' care perceptions in preventing attrition and promoting service recovery.

Treatment of Inflammatory Acne with a Combination Therapy with Lymecycline and Adapalene Followed by Maintenance Treatment with Adapalene

Oral antibiotics, especially tetracyclines, are commonly used to treat moderate to moderately severe acne vulgaris. There are hints suggesting that a combination treatment with oral tetracyclines and topical retinoids can cause a greater and prompter improvement of acne than monotherapy with tetracyclines. We evaluated the clinical activity of a 12-week combined therapy with oral lymecycline (300mg/day for 2 weeks and then 150mg/day) and topical adapalene (gel or cream) in 419 patients with inflammatory acne. A significant reduction in the number of acne lesions was noted at 4 and 12 weeks (P&lt;0.0001). Thereafter, 400 patients underwent a maintenance treatment with adapalene alone for 12 weeks. At week 24 a relevant improvement of acne lesions still persisted (P&lt;0.0001) in most patients. Only 16 patients relapsed and required additional use of oral lymecycline which proved again successful. No substantial differences were noted in the magnitude of clinical response between patients treated with adapalene gel and those treated with cream formulation. Treatment was well tolerated. Local adverse reactions occurred in 11.7 % of patients and resulted in premature discontinuation of treatment in 1.4 %. Systemic (gastrointestinal) untoward effects developed in 1.2 % of patients and caused treatment interruption in 0.7 % of cases. No serious adverse events occurred.

Treatment of Waldenstrom's macroglobulinemia with single-agent thalidomide or with the combination of clarithromycin, thalidomide and dexamethasone

To evaluate the activity of thalidomide in Waldenstrom's macroglobulinemia (WM), 20 patients were treated on a dose schedule that escalated from 200 mg/d to 600 mg/d. On an intention-to-treat basis, five (25%) patients achieved a partial response, which was noted within 3 months of treatment. Adverse effects were common and prevented dose escalation of thalidomide in 75% of patients and led to premature discontinuation of treatment in 35%. We subsequently evaluated the oral combination of clarithromycin (500 mg twice per day), low-dose thalidomide (200 mg once daily), and dexamethasone (40 mg once per week). Our preliminary analysis on 12 previously treated patients indicate activity of this regimen in WM: three patients achieved a partial response and two patients demonstrated monoclonal protein reduction of greater than 25%. This combination was associated with a variety of side effects due not only to thalidomide, but also to corticosteroids and to clarithromycin. Our preliminary data indicate that this combination may be a useful salvage regimen for some patients with heavily pretreated macroglobulinemia. Semin Oncol 30:265-269. © 2003 Elsevier Inc. All rights reserved.

Prediction of treatment outcome in patients with chronic hepatitis C: Significance of baseline parameters and viral dynamics during therapy

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-α) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 ( P < .0001), a low baseline gamma-glutamyltransferase (GGT) level ( P < .0001), a high baseline alanine aminotransferase level ( P = .002), and a low baseline viral load ( P = .04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2– and 3–infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment. (H EPATOLOGY 2003;37:600-609.)

Selective phosphodiesterase type-5 inhibitor treatment of serotonergic reuptake inhibitor antidepressant-associated sexual dysfunction: a review of diagnosis, treatment, and relevance.

Sexual dysfunction related to antidepressants, particularly serotonin reuptake inhibitors is a major cause of premature treatment discontinuation. This places patients at increased risk for recurrence, relapse, chronicity, and mortality (eg, suicide). The clinical assessment requires a comprehensive evaluation of sexual function, including libido, arousal, orgasm, and resolution prior to affective disorder, disturbances associated with the emergence of depression, and changes or dysfunctions associated with antidepressant treatment. Other factors to be included for evaluating sexual dysfunction include inquiry for concurrent medical conditions, somatic treatments, lifestyle risk factors, and response to antidepressants. Current treatment approaches to antidepressant-associated sexual dysfunction have relied on open-label reports, literature reviews, and clinical wisdom. Without double-blind, placebo-controlled studies to support them, too much non-evidence-based treatment may be offered to patients. Advances into nonadrenergic-noncholinergic novel signal transduction, specifically phosphodiesterase type-5 inhibitors, offer new opportunities for developing evidence-based treatments for this side effect and improving depression disease management outcomes.

Topiramate treatment for SSRI-induced weight gain in anxiety disorders.

Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been associated with significant weight gain, a problem that frequently leads to noncompliance and premature discontinuation of treatment. Topiramate is a novel anticonvulsant that has also been used as a mood stabilizer and augmentation agent in mood disorders. Topiramate has been observed to have an interesting side effect of weight loss in some individuals. In this study, topiramate was added to the treatment regimen of patients with a primary DSM-IV anxiety disorder who had experienced substantial SSRI-induced weight gain, in an attempt to induce weight loss. Topiramate was added to SSRI treatment in 15 anxiety disorder patients, starting at a dose of 50 mg/day and titrating up to a target daily dose of 100 mg/day, with a maximum dose of 250 mg/day. Subjects' weight was measured at baseline and after 5 and 10 weeks of treatment. Before topiramate treatment, SSRI-treated subjects in this sample had gained a mean of 13.0 +/- 8.4 kg (28.6 +/- 18.5 lb). After the addition of a mean dose of 135.0 +/- 44.1 mg/day of topiramate for approximately 10 weeks, subjects lost a mean of 4.2 +/- 6.0 kg (9.3 +/- 13.3 lb). Topiramate may have a role in managing SSRI-induced weight gain in anxiety disorder patients.

Oral Agents: First-Line Therapy for Erectile Dysfunction

Oral agents are relatively non-invasive, reversible, readily administered and well tolerated; hence, they are emerging as first-line treatments for patients with erectile dysfunction. Two medications have been licensed in Europe: the dopamine agonist sublingual apomorphine, which influences central regulatory mechanisms, and the phosphodiesterase type 5 (PDE5) inhibitor sildenafil citrate, which affects local regulation of erectile function by potentiating the effects of nitric oxide. Two other potent, selective, reversible PDE5 inhibitors (tadalafil and vardenafil) are under regulatory review in Europe, the United States and other countries. In double-blind, placebo-controlled trials, these compounds significantly enhanced erectile function and increased the likelihood of successful sexual intercourse largely irrespective of etiology or severity of erectile insufficiency. Apomorphine and PDE5 inhibitors also significantly improved scores in the erectile function, orgasmic function, intercourse satisfaction and overall satisfaction domains of the International Index of Erectile Function. Oral agents were well tolerated; adverse events were generally mild or moderate, prompting premature treatment discontinuation in a small minority of patients. The chief adverse effects with apomorphine were nausea and headache, and with PDE5 inhibitors, headache, dyspepsia and flushing. Because of a potential pharmacodynamic interaction between PDE5 inhibitors and nitrates or nitric oxide donors that has been associated with hypotension, concomitant nitrate use is an absolute contraindication. However, the actual incidences of myocardial infarction in sildenafil and tadalafil patients are similar to those in placebo controls.

Phase II randomized multicenter study evaluating a treatment regimen alternating docetaxel and cisplatin–vinorelbine with a cisplatin–vinorelbine control group in patients with stage IV non-small-cell lung cancer: GFPC 97.01 study

BackgroundThe potential absence of cross-resistance between cisplatin and docetaxel in non-small-cell lung cancer (NSCLC) suggests that alternating regimens of cisplatin-based chemotherapy and docetaxel might increase the activity of chemotherapy in stage IV NSCLC. Patients and methodsRandomized, multicenter, non-comparative phase II study in patients with stage IV NSCLC (Eastern Cooperative Oncology Group performance status of 0–2). Patients randomized to alternating treatment group (A) received docetaxel 100 mg/m2 on days (D) 1 and43 alternating with cisplatin 100 mg/m2 on D22 and vinorelbine 30 mg/m2 on D22, D29 and D36. Those randomized to the control group (B) received cisplatin 80 mg/m2 on D1, D22 and D43 and vinorelbine 30 mg/m2 once a week from D1 to D57. Treatment was continued for a further 6 weeks in the event of objective response or stabilization. ResultsSeventy patients were enrolled (group A: 38, group B: 32). More premature treatment discontinuations due to toxicity were observed in group A (median number of cycles: 3) than in group B (median number of cycles: 5). The intention-to-treat objective response rate was 10.8% [95% confidence interval (CI) 0.8% to 20.8%] in group A compared with 25% (95% CI 10% to 40%) in group B, the median time to treatment failure being 10.2 weeks and 17.3 weeks, respectively. The median survival and 1-year survival were 29.1 weeks and 39% in group A compared with 41.6 weeks and 42% in group B. Febrile neutropenia occurred in 5.9 and 4.9% of the cycles in group A and group B, respectively. Non-hematological toxicity was moderate in the two groups. ConclusionsThe addition of docetaxel alternating with cisplatin–vinorelbine did not enhance the activity of this combination. The development of sequential regimens might be a more promising way of exploiting the absence of cross-resistance between these two drugs.

A retrospective study of hyposensitization in canine atopy based on a polyclonal ELISA test.

Compliance with the treatment protocol and the most significant reasons encountered in general practice for the discontinuation of treatment in hyposensitized dogs are examined. The data are based on (1) a review of order forms for the hyposenzitization mixture and information sheets for an ELISA test and (2) telephone interviews with dog owners. Most of the owners (81%) gave their dogs allergen injections at home. Non-compliance was defined as discontinuation of treatment in the induction period; 33.9% of the owners became non-compliant. A large proportion of non-compliant owners (51.2%) claimed to be unaware of the length of the induction period. Furthermore, 70.2% of the owners were not aware that treatment would most likely need to be lifelong if it was to remain effective. Although 67.5% of the owners perceived that their dogs had beneficial effects from hyposensitization, only 36.3% of the dogs were receiving maintenance injections at the time of the telephone interview, considerably reducing the long-term benefit from treatment. Canine atopy is a chronic disease characterized by remission and relapses. Since no control group was available in this study, the beneficial outcome of treatment reported by the owners could be partly due to the natural course of the disease. Nevertheless, the results indicated that the long-term effect of hyposensitization in canine atopy will be reduced by premature discontinuation of treatment in the maintenance period. The discontinuation of treatment could be a reflection of the treatment becoming less effective, owing to the development of new hypersensitivities or to a reduction in the placebo effect that may occur in 'new' treatments. However, poor client education and follow-up seem to be important reasons for both noncompliance and discontinuation of the treatment in the maintenance period.

Subjective health measures and acute treatment outcomes in geriatric depression

Prior research suggests that elderly patients are less likely to respond to antidepressant treatment if they have low self-rated health. However, successful treatment for depression has been associated with improvement in self-rated health and other health measures. To examine measures of self-rated health, physical disability, and social function as predictors of treatment response in late-life depression, and to assess these same health measures as treatment outcomes. We hypothesized that greater impairment in these measures would predict poorer treatment response, and that these measures would show significant improvements with recovery from depression. Subjects were enrolled in a depression intervention study for people aged 60 and older with recurrent unipolar major depression; they were assessed with measures of self-rated health, physical disability, and social functioning at baseline and at the end of treatment. Baseline measures were compared between the 88 remitters, 11 non-remitters, and seven dropouts. Additionally, changes in the measures were examined in subjects who recovered from the index depressive episode. Subjects with poorer self-rated health at baseline were more likely both to drop out of treatment and to not respond to adequate treatment. This relationship was independent of demographic measures, severity of depression, physical and social functioning, medical illness, personality, hopelessness, overall medication use, and side effects or non-compliance with treatment. Although this finding is preliminary because of the small number of dropouts and non-remitters, it suggests that lower self-rated health may independently predict premature discontinuation of treatment for depression. Additionally, subjects who recovered from depression showed significant improvements in self-rated health, physical disability, and social functioning.

A lithium clinic for bipolar patients: 2‐year outcome of the first 148 patients

Objective: This paper describes the outcome for the first 148 patients referred to a lithium clinic. Method: Two‐year follow‐up data from treatment charts are reported for all patients entering a lithium clinic in the study period. Results: Lithium was given as the only mood stabilizer in 132 (89.2%) of the cases. Thirty‐two (21.6%) patients were readmitted with a new affective disorder episode. Twenty‐nine (19.6%) patients discontinued treatment prematurely. Variables predicting the recurrence of new affective disorder episodes as well as premature discontinuation of treatment were identified. Conclusion: The majority of bipolar patients received lithium for prophylaxis against recurrent affective disorder episodes. The outcome was moderate but comparable to the 30–40% improvement usually reported in follow‐up studies of bipolar patients given long‐term prophylactic treatment with lithium. Better long‐term treatment results for bipolar patients depend on both the development of more effective mood stabilizing drugs or drug combinations and the improvement of patients' adherence to treatment.

A lithium clinic for bipolar patients: 2-year outcome of the first 148 patients.

This paper describes the outcome for the first 148 patients referred to a lithium clinic. Two-year follow-up data from treatment charts are reported for all patients entering a lithium clinic in the study period. Lithium was given as the only mood stabilizer in 132 (89.2%) of the cases. Thirty-two (21.6%) patients were readmitted with a new affective disorder episode. Twenty-nine (19.6%) patients discontinued treatment prematurely. Variables predicting the recurrence of new affective disorder episodes as well as premature discontinuation of treatment were identified. The majority of bipolar patients received lithium for prophylaxis against recurrent affective disorder episodes. The outcome was moderate but comparable to the 30-40% improvement usually reported in follow-up studies of bipolar patients given long-term prophylactic treatment with lithium. Better long-term treatment results for bipolar patients depend on both the development of more effective mood stabilizing drugs or drug combinations and the improvement of patients' adherence to treatment.

Étude comparative de l’efficacité et de la tolérance de l’étidronate et de l’alendronate au cours de l’ostéoporose postménopausique. Influence de l’adjonction d’un traitement hormonal substitutif

Objectives. To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). Patients and methods. In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than one year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/day. Results. Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean ±SD) increased significantly both in the etidronate group (+2.1%±0.7%/year) and in the alendronate group (+5.3%±0.9%/year). The increase was significantly greater with alendronate (P<0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5%±1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+1.2%±0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P<0.01). Conclusion. Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.

Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. Effect of adding hormone replacement therapy

Objectives. To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). Patients and methods. In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than 1 year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/d. Results. Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean ± SD) increased significantly both in the etidronate group (+2.1% ± 0.7%/year) and in the alendronate group (+5.3% ± 0.9%/year). The increase was significantly greater with alendronate ( P < 0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5% ± 1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+1.2% ± 0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P < 0.01). Conclusion. Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.