Faculty Opinions recommendation of Long-term treatment with finasteride results in a clinically significant reduction in total prostate volume compared to placebo over the full range of baseline prostate sizes in men enrolled in the MTOPS trial.

A recent meta-analysis of antidepressant trials is the largest conducted to date. Although it claims to prove antidepressant effectiveness beyond dispute, the main outcome is response rates, which are derived from continuous data in a process that can inflate differences between groups. The standardised mean difference of 0.3 is in line with other meta-analyses that show small differences between antidepressants and placebo that are unlikely to be clinically significant. Other factors likely to exaggerate the effects are discussed, and evidence on associations between antidepressant effects and severity and outcomes of long-term treatment is considered. Clinicians need to have open discussions with patients about the limitations of antidepressant research, the lack of evidence that antidepressants correct a chemical imbalance or other brain abnormality, and the range of adverse effects and mental and physical alterations they can produce.

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Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5533 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5533-5533 ◽

Cited By ~ 18

Author(s):

Charlie Gourley ◽

Michael Friedlander ◽

Ursula A. Matulonis ◽

Vadim Shirinkin ◽

Frédéric Selle ◽

...

Keyword(s):

Ovarian Cancer ◽

Parp Inhibitor ◽

Final Analysis ◽

Term Treatment ◽

Tolerability Profile ◽

Treatment Benefit ◽

Platinum Based Chemotherapy ◽

Long Term Treatment ◽

Clinically Significant

5533 Background: In Study 19 (NCT00753545), a RCT in 265 pts with PSR SOC, the oral PARP inhibitor olaparib significantly improved progression-free survival (PFS) vs placebo (PBO), with the greatest benefit seen in pts with a BRCA1/2 mutation ( BRCAm); an interim overall survival (OS) analysis suggested an advantage for olaparib-treated pts (DCO: Sep 30, 2015; Ledermann et al, 2016). We report a planned final analysis of the long-term benefit of olaparib in pts with PSR SOC in Study 19. Methods: Pts who had received ≥2 prior regimens of platinum-based chemotherapy and were in response to their most recent regimen received olaparib (400 mg bid; capsules) or PBO until disease progression. Retrospective germline or tumor testing resulted in a known BRCAm status for 254/265 pts (96%). Results: At final DCO (May 9, 2016) median OS follow-up was 78.0 months. A long-term treatment benefit and the final hazard ratio (HR) for OS vs PBO (unadjusted for crossover: 13% of PBO pts – full analysis set [FAS]; 23% of PBO pts – BRCAm subgroup) is shown (Table). Details of BRCAwt pts on treatment for ≥6 years will be presented. No new safety signals or changes in olaparib tolerability profile were seen. Conclusions: The Study 19 final analysis shows that olaparib provides clinically significant, long-term treatment benefit in pts with PSR SOC. A durable benefit was seen in ≥10% of BRCAm and BRCAwt pts, who continued to receive and benefit from olaparib for ≥6 years–unprecedented in the relapsed ovarian cancer setting. Olaparib is well tolerated in this pt population and the analysis suggests olaparib confers an OS benefit in BRCAm pts. Clinical trial information: NCT00753545. [Table: see text]

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Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended Release in Adults With ADHD

CNS Spectrums ◽

10.1017/s109285290000242x ◽

2005 ◽

Vol 10 (S20) ◽

pp. 35-43 ◽

Cited By ~ 39

Author(s):

Richard H. Weisler ◽

Joseph Biederman ◽

Thomas J. Spencer ◽

Timothy E. Wilens

Keyword(s):

Extended Release ◽

Vital Signs ◽

Cardiovascular Effects ◽

Term Treatment ◽

Healthy Adults ◽

Hyperactivity Disorder ◽

Long Term Treatment ◽

Clinically Significant ◽

Combined Subtype

AbstractObjective: To assess long-term cardiovascular effects of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.Methods: 223 otherwise healthy adults (≥18 years of age) with ADHD combined subtype were exposed to ≤24 months of MAS XR (20–60 mg/day). Resting sitting diastolic blood pressure (DBP) and systolic blood pressur (SBP) and pulse were measured at baseline and weekly, then monthly during long-term treatment. Twelve-lead electrocardiograms were obtained at screening/baseline, weekly, then at 3-and 6-month intervals up to 24 months.Findings: With MAS XR 20–60 mg/day, mean changes in DBP (1.3±9.2 mm Hg; P=.O42), SBP (2.3±12.5 mmHg; P=.OO6), and pulse (2.1±13.4 bpm; P=.019) were small and not clinically significant. A clinically insignificant increase in QTcB (corrected by Bazett's formula) interval (7.2 msec; P<.001) was observed at 24 months. No subject exhibited QTcB interval >480 msec (QTcF [corrected by Fridericia's formula] >454 msec). Seven subjects discontinued due to a car-diovascular adverse event (hypertension, n=5, palpitation/tachycardia, n=2); none of these events was reported as serious. Few subjects with normal baseline vital signs (using approved parameters at the time of study initiation) exhibited clinically significant abnormalities at end point; several subjects with borderline baseline values exhibited shifts to abnormal values during MAS XR therapy.Conclusion: Cardiovascular effects of long-term MAS XR (≤60 mg/day) were minimal in otherwise healthy adults with ADHD. Nevertheless, vital signs should be monitored prior to and during treatment with any stimulant.

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Oral Butorphanol Tartrate for the Long-Term Treatment of Out-Patients with Moderate to Severe Cancer Pain

Journal of International Medical Research ◽

10.1177/030006058100900207 ◽

1981 ◽

Vol 9 (2) ◽

pp. 124-127 ◽

Cited By ~ 2

Author(s):

Jaime De La Garza

Keyword(s):

Blood Pressure ◽

Cancer Pain ◽

Open Study ◽

Analgesic Efficacy ◽

Term Treatment ◽

Long Term Treatment ◽

Clinically Significant ◽

Oral Doses ◽

Median Pain

The safety, tolerance and analgesic efficacy of multiple oral doses of butorphanol tartrate for the long-term treatment of cancer pain were evaluated in this open study. Thirty-five patients were treated with various doses (1 to 12 tablets per day) for 4 to 147 days. The median pain relief was fair, good, very good or excellent in 51% of the patients and poor in 49% of the patients. Global assessments were very similar. No clinically significant changes in blood pressure, weight, blood and urine chemistries were observed. Seventeen patients reported side-effects (only sedation and dry mouth) ranging from mild to severe.

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Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment

Acta Endocrinologica ◽

10.1530/eje-12-0121 ◽

2012 ◽

Vol 167 (1) ◽

pp. 17-25 ◽

Cited By ~ 37

Author(s):

Atanaska Elenkova ◽

Rabhat Shabani ◽

Krassimir Kalinov ◽

Sabina Zacharieva

Keyword(s):

Arterial Pressure ◽

Pulmonary Arterial Pressure ◽

Term Treatment ◽

Safe Alternative ◽

Increased Risk ◽

Long Term Treatment ◽

Echocardiographic Examination ◽

Pulmonary Arterial ◽

Clinically Significant

BackgroundIn contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited.ObjectiveTo assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy.DesignCase–control study.MethodsA transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls.ResultsClinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17–4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22–5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects.ConclusionsLong-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.

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172 A Phase 3, Multicenter Study to Assess the Long-Term Safety, Tolerability, and Efficacy of Olanzapine/Samidorphan in Patients with Schizophrenia

CNS Spectrums ◽

10.1017/s1092852920000887 ◽

2020 ◽

Vol 25 (2) ◽

pp. 309-310

Author(s):

Sergey Yagoda ◽

Christine Graham ◽

Adam Simmons ◽

Christina Arevalo ◽

Yansong Cheng ◽

...

Keyword(s):

Clinical Laboratory ◽

Study Drug ◽

Term Treatment ◽

Extension Study ◽

Open Label ◽

Phase 3 ◽

Long Term Treatment ◽

Open Label Extension ◽

Clinically Significant

Abstract:Background: ALKS 3831, a combination of olanzapine and samidorphan (OLZ/SAM), is in development for the treatment of schizophrenia and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. We report the safety, tolerability, and efficacy of OLZ/SAM in patients with schizophrenia in a phase 3, 52-week, open-label extension study.Methods:Patients aged 18–70 years who completed a previous phase 3, 4-week, inpatient acute efficacy study were switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Study assessments included adverse events (AEs), weight, clinical laboratory testing, and Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S) scores.Results:281 patients were enrolled; 277 (mean age, 41.4 years) received ≥1 dose of study drug, and 183 (66.1%) completed the extension study. The most common reasons for discontinuation were withdrawal by patient (15.5%), loss to follow-up (6.9%), and AEs (5.8%). AEs were reported in 136 (49.1%) patients; most were mild in severity. The most common AEs were increased weight (13.4%), somnolence (8.3%), nasopharyngitis (4.0%), and headache (4.0%). Mean weight increase from baseline in patients completing 52 weeks of treatment was 1.86 kg, a 2.79% increase. No clinically significant changes in mean laboratory parameters were observed. Mean (SD) changes from baseline to week 52 in PANSS total score and CGI-S score were –16.2 (15.41) and –0.9 (0.92), respectively (both P<0.001).Discussion:OLZ/SAM was generally well tolerated with a safety profile that supports long-term treatment. During this 52-week extension study, there were improvements in schizophrenia symptoms.Funding Acknowledgements:This study was funded by Alkermes, Inc.

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Desmopressin Tablets in the Treatment of Severe Nocturnal Enuresis in Adolescents

PEDIATRICS ◽

10.1542/peds.94.6.841 ◽

1994 ◽

Vol 94 (6) ◽

pp. 841-846

Author(s):

Arne Stenberg ◽

Göran Läckgren

Keyword(s):

Nocturnal Enuresis ◽

Term Treatment ◽

Dose Titration ◽

Optimal Dosage ◽

Double Blind ◽

Long Term Study ◽

Titration Period ◽

Long Term Treatment ◽

Clinically Significant

Background. In recent years the treatment of primary nocturnal enuresis (PNE) with desmopressin (DDAVP) has been promising. The route of administration until now had been intranasal, but because the tablets were introduced for the treatment of diabetes insipidus they have also become available for the treatment of PNE. Objectives. To find the optimal dosage of desmopressin tablets and to compare desmopressin's efficacy with placebo in a group of adolescents with severe monosymptomatic enuresis. The long-term safety of desmopressin was also studied in the same group of patients. Methods. The effect of oral desmopressin (1-deamino-8-D-arginine-vasopressin) (DDAVP® tablets, Minirin®) was investigated in 25 adolescents (ages 11 to 21 years) with severe monosymptomatic nocturnal enuresis. The first part of the dose-ranging study comprised a single-blind dose titration period, followed by a double-blind, crossover efficacy period comparing desmopressin with placebo. The final part was an open long-term study consisting of two 12-week treatment periods. The efficacy of the drug was measured in reductions of the number of wet nights per week. Results. During the first dose-titration period, the majority of the patients were given desmopressin 400 µg, and the number of wet nights decreased from a mean of 4.9 to 2.8. During the double-blind period, a significant reduction of wet nights was observed (1.8 vs 4.1 for placebo). During the two long-term periods, 48% and 53% of the patients could be classified as responders (0 to 1 wet night per week) and 22% and 23.5% as intermediate responders (2 to 3 wet nights per week). No weight gain was observed due to water retention. After cessation of the drug, 44% of the patients had a significant decrease in the number of wet nights. Conclusions. Oral desmopressin has a clinically significant effect on patients with PNE, and therapy is safe when administered as long-term treatment.

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