The Safety of Fluoxetine - An Update

1988 ◽  
Vol 153 (S3) ◽  
pp. 77-86 ◽  
Author(s):  
Glenn L. Cooper
Keyword(s):  
Tricyclic Antidepressants ◽  
Term Treatment ◽  
Major Depressive ◽  
Serious Adverse Events ◽  
Double Blind ◽  
The Core ◽  
Antidepressant Agent ◽  
Long Term Treatment ◽  
One Year

Fluoxetine is a new antidepressant agent which is a selective inhibitor of neuronal serotonin uptake; it has minimal affinity for muscarinic, dopaminergic, histaminic, serotonergic, or noradrenergic receptors (Stark et al, 1985). This specificity of activity suggests that fluoxetine may have a side-effect profile which is different from previously available antidepressants.The safety of fluoxetine has been extensively studied: several hundred patients have received the drug continuously for more than one year - some have had therapy for 5 years or more. Previous reviews of the safety of fluoxetine (Wernicke, 1985; Zerbe, 1986) have described a smaller population of patients than is now available.This review is drawn from data pooled from comparative clinical trials, which included 4336 patients: fluoxetine - 2938, tricyclic antidepressants (TCAs) - 599, and placebo - 799 patients. The TCAs studied were amitriptyline, imipramine, and doxepin. Most patients were adults with major depressive disorder, and the most common study design was a 6-week comparative double-blind phase, followed by unblinded long-term treatment. While the core of this study is a data base of 2938 fluoxetine-treated patients, all serious adverse events reported in over 7500 fluoxetine-treated patients worldwide, as of mid-1987, have been included.

scholarly journals Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
David H. Adams ◽  
Lu Zhang ◽  
Brian A. Millen ◽  
Bruce J. Kinon ◽  
Juan-Carlos Gomez
Keyword(s):  
Weight Gain ◽  
Adverse Events ◽  
Term Treatment ◽  
Phase 3 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Treatment Groups ◽  
Long Term Treatment ◽  
Blind Comparison

We tested the hypothesis that long-term treatment with pomaglumetad methionil would demonstrate significantly less weight gain than aripiprazole in patients with schizophrenia. In this 24-week, multicenter, randomized, double-blind, Phase 3 study, 678 schizophrenia patients were randomized to either pomaglumetad methionil (n=516) or aripiprazole (n=162). Treatment groups were also compared on efficacy and various safety measures, including serious adverse events (SAEs), discontinuation due to adverse events (AEs), treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), and suicide-related thoughts and behaviors. The pomaglumetad methionil group showed significantly greater weight loss at Week 24 (Visit 12) compared with the aripiprazole group (−2.8 ± 0.4 versus 0.4 ± 0.6;P<0.001). However, change in Positive and Negative Syndrome Scale (PANSS) total scores for aripiprazole was significantly greater than for pomaglumetad methionil (−15.58 ± 1.58 versus −12.03 ± 0.99;P=0.045). The incidences of SAEs (8.2% versus 3.1%;P=0.032) and discontinuation due to AEs (16.2% versus 8.7%;P=0.020) were significantly higher for pomaglumetad methionil compared with aripiprazole. No statistically significant differences in the incidence of TEAEs, EPS, or suicidal ideation or behavior were noted between treatment groups. In conclusion, long-term treatment with pomaglumetad methionil resulted in significantly less weight gain than aripiprazole. This trial is registered with ClinicalTrials.govNCT01328093.

Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide

1994 ◽  
Vol 131 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Josef Marek ◽  
Václav Hána ◽  
Michal Kršek ◽  
Vlasta Justová ◽  
France Catus ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Slow Release ◽  
Serum Levels ◽  
Term Treatment ◽  
Somatostatin Analogue ◽  
Tumour Mass ◽  
Long Term Treatment ◽  
Active Acromegaly ◽  
One Year

Marek J, Hána V. Kršek M. Justová V, Catus F, Thomas F. Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide. Eur J Endocrinol 1994;131:20–6. ISSN 0804–4643 Thirteen patients with active acromegaly despite previous surgery were treated with 30 mg lanreotide im twice a month for 9 months. In 10 subjects the treatment continued to 19 months. GH serum levels of all patients decreased significantly from an initial value of 32.0 (29.4) μg/l [median (standard error of median)] to 10.0 (3.6) and 19.1 (5.7) after 3 and 9 months of treatment, respectively. In the 10 patients with the treatment longer than one year the decrease in GH was from 46.8 (29.4) μg/l to 12.5 (5.0) and 16.1 (5.3) after 13 and 19 months, respectively. IGF-I serum levels decreased significantly from 1193 (73)μg/l to 782 (99) and 621 (103) after 3 and 9 months, respectively, and were normalized in 3 patients. In the 10 patients treated for longer than one year, levels decreased significantly from 1318 (74)μg/l to 653 (170) and 742 (180) after 13 and 19 months, respectively. IGF BP-3 levels were reduced to the normal range in 6 patients and decreased from 8.7 (1.5)mg/l to 6.4 (0.8) and to 5.4 (1.0) after 3 and 9 months, respectively. In the patients with the 19 months treatment the decrease was from 9.3 (1.6) mg/l to 3.9 (0.9) and 4.8 (0.9) after 13 and 19 months, respectively. The IGF BP-3 to IFG I ratio increased in 7 patients. This elevation significantly correlated with the decrease in bioassayable somatomedin. Prolactin serum levels fell in all patients with increased prolactin secretion. Testosterone plasma levels increased in 4 out of 5 men without replacement therapy. Clinical improvement was observed in all patients. A reduction of tumour mass was observed in five patients and complete disappearance of the tumour in one subject. All patients complained of mild abdominal pain and softened stools for several days following the injections. However, these side effects never required interruption of treatment. Asymptomatic microlithiasis was seen in only one patient after 13 months, which led to treatment being suspended for a period of 3 months after which it was resumed. Fasting serum insulin and insulin area under the curve (AUC) after oral glucose tolerance test (OGTT) fell in all patients. Fasting blood glucose, fructosamine and glucose AUC after OGTT slightly increased during the treatment, but all blood glucose levels (fasting and during OGTT) remained within normal ranges. Lanreotide appears to be a safe and effective treatment in patients with active acromegaly unresolved by surgery. The long-acting formulation avoids the drawbacks associated with either repeated daily injections or continuous infusions of somatostatin analogues. Josef Marek, Third Department of Medicine, Charles University, U nemocnice 1, 128 21 Praha 2, The Czech Republic

scholarly journals 139 Early Response with Valbenazine and Long-Term Symptom Reduction in Patients with Tardive Dyskinesia: Post Hoc Analysis of the KINECT 3 Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 288-289
Author(s):  
Stanley N. Caroff ◽  
Jean-Pierre Lindenmayer ◽  
Stephen R. Marder ◽  
Stewart A. Factor ◽  
Khodayar Farahmand ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Early Response ◽  
Term Treatment ◽  
Score Change ◽  
Double Blind ◽  
Early Improvement ◽  
Long Term Treatment ◽  
Post Hoc ◽  
Improvement Score

Abstract:Study Objective:Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from a long-term study (KINECT 3; NCT02274558), the effects of once-daily valbenazine (40 mg, 80 mg) on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS) in participants who were early responders based on subjective measures, including patient self-report (Patient Global Impression of Change [PGIC]) or clinician judgment (Clinical Impression of Change-Tardive Dyskinesia [CGI-TD]).Methods:Data from KINECT 3 (6-week double-blind, placebo-controlled [DBPC] period; 42-week double-blind extension) were analyzed post hoc. Long-term outcomes included mean change from baseline to Week 48 in AIMS total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48. These AIMS outcomes were assessed in participants who achieved early improvement, defined as a PGIC or CGI-TD score of ≤3 (“minimally improved” or better) at Week 2 (first post-baseline visit of the DBPC period). Participants who initially received placebo were not included in the analyses.Results:In participants who received only valbenazine (40 or 80 mg) during KINECT 3 and had available Week 2 assessment, 50% (72/143) had early PGIC improvement (score ≤3) and 43% (61/142) had early CGI-TD improvement (score ≤3). Baseline characteristics were generally similar between participants who achieved early PGIC or CGI-TD improvement and those who did not. Based on available assessments at Week 48, mean AIMS total score change from baseline in participants with early PGIC improvement was similar to those who did not reach the early PGIC improvement threshold (-4.1 [n=35] vs -3.5 [n=41]). Mean AIMS total score change from baseline in participants with early CGI-TD improvement was similar to those who did not achieve early CGI-TD improvement (-4.2 [n=31] vs -3.5 [n=45]). AIMS response at Week 48 was also similar in those who achieved early PGIC and CGI-TD improvement (40% and 42%, respectively) compared to those who did not achieve early PGIC and CGI-TD improvement (39% and 38%, respectively).Conclusions:Results from this long-term valbenazine trial indicate that many participants achieved at least minimal patient- and clinician-reported improvement at Week 2. AIMS outcomes at Week 48 demonstrated long-term reductions in TD severity regardless of early response. More research is needed to understand the association between early improvement and long-term treatment effects, but early non-improvement based on subjective measures may not be predictive of long-term treatment failure.Presented:International Congress of Parkinson’s Disease and Movement Disorders; September 22-26, 2019; Nice, France.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

scholarly journals 50 Adjunctive Buprenorphine/Samidorphan Combination in Patients with Major Depressive Disorder: Phase 3 Long-term Extension Study Results

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 203-204 ◽  
Author(s):  
Michael Thase ◽  
Arielle D. Stanford ◽  
Asli Memisoglu ◽  
William Martin ◽  
Amy Claxton ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Safety Profile ◽  
Rating Scale ◽  
Remission Rate ◽  
Term Treatment ◽  
Adjunctive Treatment ◽  
Major Depressive ◽  
Long Term Treatment

AbstractIntroductionBuprenorphine/samidorphan (BUP/SAM), a combination of BUP (a µ-opioid receptor partial agonist and κ-antagonist) and SAM (a sublingually bioavailable µ-opioid antagonist), is an investigational opioid system modulator for depression. BUP/SAM has shown efficacy versus placebo as an adjunctive treatment for major depressive disorder (MDD) and a consistent safety profile in previously reported, placebo-controlled clinical studies.1,2Study Objective(s)1. To characterize the safety profile following long-term treatment with BUP/SAM2. To explore depression symptoms and remission rates in patients with MDD following long-term treatment with BUP/SAMMethodsFORWARD-2 (Clinicaltrials.gov ID: NCT02141399) enrolled patients who had participated in 1 of 4 controlled studies as well as de novo patients. All patients had a confirmed diagnosis of MDD, had a history of inadequate response to standard antidepressant therapies (ADTs), and had been treated with an adequate dose of an established ADT for ≥8weeks before BUP/SAM initiation. ADT dosage could be titrated, but the ADT could not be changed. During the study, patients received open-label, sublingual BUP/SAM 2mg/2mg as adjunctive treatment for up to 52weeks. Safety (primary objective) was assessed via adverse events (AEs), vital signs, laboratory analytes, and electrocardiography. Suicidal ideation or behavior (SIB) was evaluated by the Columbia Suicide Severity Rating Scale. Abuse potential, dependence, and withdrawal were assessed by AEs and the Clinical Opiate Withdrawal Scale. Exploratory efficacy endpoints included mean Montgomery–Åsberg Depression Rating Scale (MADRS) scores and remission rate (MADRS ≤10).ResultsOf 1454 total patients, 49% completed the 52-week study, 11% discontinued due to an AE, and 40% discontinued because of other reasons as of the interim data cutoff date (April 30, 2017). Most AEs were of mild/moderate severity. Serious AEs were reported in 3.2% of patients. AEs occurring in ≥10% of patients were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of increased risk of SIB with BUP/SAM. Incidence of euphoria-related events was low (1.2%). After abrupt discontinuation of BUP/SAM, there was little evidence of withdrawal. BUP/SAM was not associated with meaningful changes in laboratory or metabolic parameters or in bodyweight. The mean MADRS score decreased from 22.9 (±9.7) at baseline to 9.8 (±8.8) after 52weeks. The remission rate at 52weeks was 52.5%.ConclusionsLong-term treatment with BUP/SAM did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low. BUP/SAM maintained an antidepressant effect for up to 52weeks of treatment in patients with MDD.Funding Acknowledgements: Alkermes, Inc.

scholarly journals Reducing the Toxicity of Long-Term Glucocorticoid Treatment in Large Vessel Vasculitis

2020 ◽  
Vol 22 (12) ◽  
Author(s):  
Andriko Palmowski ◽  
Frank Buttgereit
Keyword(s):  
Adverse Events ◽  
Takayasu Arteritis ◽  
Term Treatment ◽  
Large Vessel Vasculitis ◽  
Large Vessel ◽  
Serious Adverse Events ◽  
Glucocorticoid Treatment ◽  
Long Term Treatment ◽  
Higher Doses

Abstract Purpose While glucocorticoids (GCs) are effective in large vessel vasculitis (LVV), they may cause serious adverse events (AEs), especially if taken for longer durations and at higher doses. Unfortunately, patients suffering from LVV often need long-term treatment with GCs; therefore, toxicity needs to be expected and countered. Recent Findings GCs remain the mainstay of therapy for both giant cell arteritis and Takayasu arteritis. In order to minimize their toxicity, the following strategies should be considered: GC tapering, administration of conventional synthetic (e.g., methotrexate) or biologic (e.g., tocilizumab) GC-sparing agents, as well as monitoring, prophylaxis, and treatment of GC-related AEs. Several drugs are currently under investigation to expand the armamentarium for the treatment of LVV. Summary GC treatment in LVV is effective but associated with toxicity. Strategies to minimize this toxicity should be applied when treating patients suffering from LVV.

scholarly journals Relapse recovery

2019 ◽  
Vol 7 (2) ◽  
pp. e653 ◽  
Author(s):  
Orhun H. Kantarci ◽  
Burcu Zeydan ◽  
Elizabeth J. Atkinson ◽  
Brittani L. Conway ◽  
Carmen Castrillo-Viguera ◽  
...  
Keyword(s):  
Term Treatment ◽  
Benign Disease ◽  
Good Recovery ◽  
Class Iii ◽  
Early Recovery ◽  
Double Blind ◽  
Delayed Treatment ◽  
Long Term Treatment ◽  
Edss Score

ObjectiveTo determine whether basing the decision to initiate immediate vs delayed disease-modifying therapy (DMT) on extent of recovery after initial relapse affects long-term disability accumulation in a multiple sclerosis (MS) evidence-based setting.MethodsWe analyzed the double-blind, placebo-controlled interferon beta-1a 30 mc once a week in clinically isolated syndrome and 10-year-follow-up extension trial. Good recovery after presenting relapse was defined as (1) full early recovery within 28 days of symptom onset (Expanded Disability Status Scale [EDSS] score of 0 at enrollment maintained ≥6 months) and (2) delayed good recovery (EDSS score > 0 at enrollment and improvement from peak deficit to 6th-month or 1-year visit ≥ median). Time from recovery assignment to future disability (EDSS score ≥ 2.5 or ≥4.0) was studied on a relapse-recovery-stratified age axis and immediate vs 3-year delayed treatment initiation with Kaplan-Meier statistics and hazard ratios (HRs).ResultsOne hundred seventy-five/328 patients had good recovery (94 immediate and 81 delayed treatment); 153 did not have good recovery (77 immediate and 76 delayed treatment). HRs for EDSS score ≥2.5 outcome were: delayed treatment without good recovery as reference (HR = 1.0), delayed treatment with good recovery (HR6th-month: 0.67, p = 0.207; HR1st-year: 0.40, p = 0.027), immediate treatment without good recovery (HR6th-month: 0.56, p = 0.061; HR1st-year: 0.40, p = 0.011), and immediate treatment with good recovery (HR6th-month: 0.43, p = 0.014; HR1st-year: 0.48, p = 0.034). Placebo patients were switched to long-term treatment after 3 years, and insufficient EDSS score ≥4.0 outcome events were available to study.ConclusionsIn patients with MS presenting without good recovery after the initial relapse, immediate DMT initiation favorably influences the likelihood of more ambulatory-benign disease akin to patients with good recovery after the initial relapse.Classification of evidenceThis study provides Class III evidence that for patients with MS without good recovery after the initial relapse, immediate DMT initiation increases the likelihood of a benign disease course.

scholarly journals Mitochondrial and Oxidative Impacts of Short and Long-term Administration of HAART on HIV Patients

2020 ◽  
Vol 15 (2) ◽  
pp. 110-124
Author(s):  
Joy E. Ikekpeazu ◽  
Oliver C. Orji ◽  
Ikenna K. Uchendu ◽  
Lawrence U.S. Ezeanyika
Keyword(s):  
Treatment Group ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Hiv Patients ◽  
Long Term Treatment ◽  
Term Administration ◽  
Short And Long Term ◽  
One Year

Background and Objective: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.

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