The DOI matches its Crossref record.
Pharmacodynamics of milnacipran in young and elderly volunteers
Open accessAbstract
Aims To investigate the pharmacodynamics of milnacipran in healthy young and elderly volunteers. Methods Randomized double‐blind crossover designs were employed and a standardized psychometric battery was administered pre and post dose for both studies. In the first study 10 healthy young volunteers received milnacipran 12.5 mg, 25 mg, 50 mg, 100 mg as a single dose or matched placebo. The test battery was administered at baseline and at 1, 2, 4 and 6 h post dose. The second study compared the effects of milnacipran 75 mg (50 mg+25 mg) per day, amitriptyline 50 mg (25 mg+25 mg) per day and placebo for 3 days’ dosing in healthy volunteers aged over 65 years. The test battery was administered at baseline and at 2, 10 and 24 h post dose. The psychometric battery included critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT) and tests of short‐term memory (STM), subjective sedation (LARS) and subjective sleep (LSEQ). Results Milnacipran produced no significant dose related effects in the young volunteers. For the elderly, milnacipran significantly (P<0.05) raised CFF scores compared with placebo but had no significant effects on any of the other measures used. Amitriptyline, in contrast, significantly (P<0.05) lowered CFF threshold, lengthened CRT and increased error on the CTT. On the subjective variables, LARS and LSEQ, amitriptyline increased ratings both of sedation and of difficulty in waking from sleep. Conclusions The results showed that milnacipran at single doses of up to 100 mg in healthy young volunteers is free from disruptive effects on cognitive function and psychomotor performance. In addition, milnacipran 75 mg (50+25 mg) appears to be free of negative effects on cognitive function in elderly volunteers, where it seemingly improves performance on CFF. In contrast, the tricyclic antidepressant amitriptyline, used here as a positive internal control, significantly impaired performance in the elderly on the majority of psychometric measures used in this study. This finding not only validated the sensitivity of this current test battery but also indicates the potential behavioural toxicity of amitriptyline in clinical use in the elderly.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Sedation and trouble waking were significantly worse for amitriptyline (50mg), compared to placebo, in healthy participants.
“This hangover effect was confirmed by (Hindmarch et al., 2000) who demonstrated that sedation and trouble waking were significantly worse for amitriptyline (50mg), compared to placebo.”
From Antidepressants and their effect on sleep (2005) · cites this paper as Hindmarch et al., 2000
Amitriptyline, trimipramine, nortriptyline, dothiepin and doxepin have all been associated with sedation.
“Amitriptyline (Hindmarch et al., 2000), trimipramine (Sonntag et al., 1996), nortriptyline (Hammack et al., 2002), dothiepin (Blacker et al., 1988) and doxepin (Hajak et al., 2001) have all been associated with sedation, while imipramine (Volkers et al., 2002) and desipramine (Shipley et al., 1985) are less likely to be linked with sedation, but have been associated with insomnia; the evidence is”
From Antidepressants and their effect on sleep (2005) · cites this paper as Hindmarch et al., 2000
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 42
- Kitamura Y, 1995, Pharmacological study of milnacipran, a novel antidepressant., Jpn J Neuropsychopharmacol, 17, 25
- Matsubara R, 1993, Effect of chronic treatment with milnacipran, a novel antidepressant, on the β‐adrenergic receptor‐adenylate cyclase system and serotonin2 receptor in the rat cerebral cortex., Jpn J Neuropsychopharmacol, 15, 119
- 10.1016/0028-3908(92)90146-G · DOI
- 10.1016/0028-3908(85)90157-1 · DOI
- 10.1097/00004850-199609004-00004 · DOI
- 10.1159/000118596 · DOI
- Clerc GE, 1990, Therapeutic contribution of milnacipran and clomipramine during a 3‐month treatment: Results of a comparative study., Psychiatr Psychobiol, 5, 137
- 10.1097/00004850-199609004-00005 · DOI
- 10.1016/0924-977X(91)90712-4 · DOI
- 10.1007/BF02245454 · DOI
- 10.1016/0165-0327(90)90081-I · DOI
- 10.1177/026988119400800407 · DOI
- 10.1002/hup.470060408 · DOI
- De Vane CL, 1997, Pharmacokinetics of the newer antidepressants: Clinical relevance., Am J Med, 6, 13S
- 10.1002/hup.470080108 · DOI
- 10.1002/hup.470080607 · DOI
- 10.1002/(SICI)1520-6394(1997)6:1<10::AID-DA2>3.0.CO;2-9 · DOI
- 10.2165/00003495-198937050-00006 · DOI
- 10.1097/00004850-199703000-00005 · DOI
- 10.1097/00004850-199609004-00007 · DOI
- 10.1001/archpsyc.1982.04290050061012 · DOI
- 10.1056/NEJM198205063061804 · DOI
- 10.1136/bmj.1.6052.10 · DOI · Paper page
- 10.1111/j.1365-2125.1995.tb04441.x · DOI
- Hindmarch IA, 1975, 1, 4–benzodiazepine temazepam (K3917) its effects on some psychological parameters of sleep and behaviour, Arzneimittel–Forsch (Drug Res), 11, 1836
- 10.1159/000119466 · DOI
- 10.1111/j.1365-2125.1980.tb01745.x · DOI
- 10.1126/science.153.3736.652 · DOI · Paper page
- 10.1159/000118146 · DOI
- 10.1037/h0032103 · DOI
- FrewerLJ HindmarchIThe effects of time of day age and anxiety on a choice reaction time task. InPsychopharmacology and Reaction Time eds Hindmarch I Aufdembrinke B Ott H. John Wiley and Sons Chichester 1988: pp 103–143
- 10.1007/s002130050553 · DOI
- 10.1111/j.1365-2125.1980.tb01731.x · DOI
- GnanadesikanRMethods for Statistical Data Analysis of Multivariate Observations.New York. John Wiley & Sons 1977
- HindmarchIAntidepressant drugs and cognitive function. InQuo Vadis‐ Diagnosis and Treatment of Depression eds Biziere K Garattini S Simon P. McGraw‐Hill Paris 1987;356‐365
- 10.1093/aje/136.7.873 · DOI
- 10.1093/occmed/45.6.323 · DOI
- 10.1176/ajp.154.10.1369 · DOI
- 10.1016/S0140-6736(98)04087-2 · DOI
- 10.1097/00004850-199703000-00005 · DOI
- 10.1097/00004850-199409000-00001 · DOI
- 10.1177/0269881193007001041 · DOI
Cited by
Sorted by citations
Antidepressants and their effect on sleep
Mayers, A. G., & Baldwin, D. S. (2005) · Human Psychopharmacology: Clinical and Experimental · doi:10.1002/hup.726 · Cited by 323
Metadata
- Authors
- Hindmarch, I., Rigney, U., Stanley, N., & Briley, M.
- Affiliations
- Institut de Recherche Pierre Fabre (France) (FR)
- Corresponding author
- Rigney, U.
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2000-02
- Volume
- 49
- Issue
- 2
- Pages
- 118-125
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC2014900
- OpenAlex
- W1640525623
- Cited by
- 41
- References
- 0
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2020: 1 · 2018: 3 · 2017: 1 · 2016: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- milnacipran, pharmacodynamics, cognitive function, psychomotor performance, older adults, amitriptyline, tricyclic antidepressants, critical flicker fusion, choice reaction time, compensatory tracking, short-term memory, sedation, sleep disorders, dose-response relationship, healthy volunteers, serotonin reuptake inhibitors
- MeSH terms
- Milnacipran, Adult, Age Factors, Aged, Aged, 80 and over, Amitriptyline, Antidepressive Agents, Cognition, Cyclopropanes, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Memory, Short-Term, Neuropsychological Tests, Psychomotor Performance, Treatment Outcome, Cross-Over Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
