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Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression

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2009
1230.pdf (208.1Kb)
Authors
Vezmar, Sandra
Miljković, Branislava
Vučićević, Katarina
Timotijević, Ivana
Prostran, Milica
Todorović, Zoran
Pokrajac, Milena
Article (Published version)
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Abstract
Although often necessary for obtaining remission following major depressive disorder, combined antidepressant treatment Is frequently associated with drug interactions and enhanced adverse drug effects. We investigated pharmacokinetic interactions following combined fluvoxamine and amitriptyline treatment and their impact on therapeutic efficacy and tolerability. Twenty-two inpatients with major depression [Hamilton Depression Scale (HAM-D) rating >= 18] were treated with either amitriptyline (75 mg/day), fluvoxamine (100 mg/day) or both. Blood samples, for determination of amitriptyline, its major metabolite nortritpyline, and fluvoxamine, were obtained after single dose administration and in steady-state. Therapeutic efficacy was evaluated using HAM-D and adverse drug effects were evaluated using the clinical global impression scale. Following combined treatment, steady-state plasma levels of nortriptyline were significantly decreased compared to monotherapy. HAM-D scores after two-w...eek treatment showed that there was a better response to combined treatment. There was no significant difference in severity of adverse effects among groups. We observed a pharmcokinetic interaction between fluvoxamine and amitritpyline resulting in impaired metabolism of the later. However, no signifcant impact of the interaction on treatment safety was observed. Moreover, concomitant use of amitriptyline at 75mg/day and fluvoxamine at 100 mg/day was well tolerated with a more prompt and stronger onset of clinical response compared to monotherapy in patients with major depression.

Keywords:
amitriptyline / fluvoxamine / efficacy / safety / interaction
Source:
Journal of Pharmacological Sciences, 2009, 110, 1, 98-104
Publisher:
  • Japanese Pharmacological Soc, Kyoto
Funding / projects:
  • Eksperimentalna i kliničko-farmakološka istraživanja mehanizma dejstva i interakcija lekova u nervnom i kardiovaskularnom sistemu (RS-145001)

DOI: 10.1254/jphs.09013FP

ISSN: 1347-8613

PubMed: 19444001

WoS: 000266351400011

Scopus: 2-s2.0-66349112356
[ Google Scholar ]
16
15
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1232
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Vezmar, Sandra
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
AU  - Timotijević, Ivana
AU  - Prostran, Milica
AU  - Todorović, Zoran
AU  - Pokrajac, Milena
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1232
AB  - Although often necessary for obtaining remission following major depressive disorder, combined antidepressant treatment Is frequently associated with drug interactions and enhanced adverse drug effects. We investigated pharmacokinetic interactions following combined fluvoxamine and amitriptyline treatment and their impact on therapeutic efficacy and tolerability. Twenty-two inpatients with major depression [Hamilton Depression Scale (HAM-D) rating >= 18] were treated with either amitriptyline (75 mg/day), fluvoxamine (100 mg/day) or both. Blood samples, for determination of amitriptyline, its major metabolite nortritpyline, and fluvoxamine, were obtained after single dose administration and in steady-state. Therapeutic efficacy was evaluated using HAM-D and adverse drug effects were evaluated using the clinical global impression scale. Following combined treatment, steady-state plasma levels of nortriptyline were significantly decreased compared to monotherapy. HAM-D scores after two-week treatment showed that there was a better response to combined treatment. There was no significant difference in severity of adverse effects among groups. We observed a pharmcokinetic interaction between fluvoxamine and amitritpyline resulting in impaired metabolism of the later. However, no signifcant impact of the interaction on treatment safety was observed. Moreover, concomitant use of amitriptyline at 75mg/day and fluvoxamine at 100 mg/day was well tolerated with a more prompt and stronger onset of clinical response compared to monotherapy in patients with major depression.
PB  - Japanese Pharmacological Soc, Kyoto
T2  - Journal of Pharmacological Sciences
T1  - Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression
VL  - 110
IS  - 1
SP  - 98
EP  - 104
DO  - 10.1254/jphs.09013FP
ER  - 
@article{
author = "Vezmar, Sandra and Miljković, Branislava and Vučićević, Katarina and Timotijević, Ivana and Prostran, Milica and Todorović, Zoran and Pokrajac, Milena",
year = "2009",
abstract = "Although often necessary for obtaining remission following major depressive disorder, combined antidepressant treatment Is frequently associated with drug interactions and enhanced adverse drug effects. We investigated pharmacokinetic interactions following combined fluvoxamine and amitriptyline treatment and their impact on therapeutic efficacy and tolerability. Twenty-two inpatients with major depression [Hamilton Depression Scale (HAM-D) rating >= 18] were treated with either amitriptyline (75 mg/day), fluvoxamine (100 mg/day) or both. Blood samples, for determination of amitriptyline, its major metabolite nortritpyline, and fluvoxamine, were obtained after single dose administration and in steady-state. Therapeutic efficacy was evaluated using HAM-D and adverse drug effects were evaluated using the clinical global impression scale. Following combined treatment, steady-state plasma levels of nortriptyline were significantly decreased compared to monotherapy. HAM-D scores after two-week treatment showed that there was a better response to combined treatment. There was no significant difference in severity of adverse effects among groups. We observed a pharmcokinetic interaction between fluvoxamine and amitritpyline resulting in impaired metabolism of the later. However, no signifcant impact of the interaction on treatment safety was observed. Moreover, concomitant use of amitriptyline at 75mg/day and fluvoxamine at 100 mg/day was well tolerated with a more prompt and stronger onset of clinical response compared to monotherapy in patients with major depression.",
publisher = "Japanese Pharmacological Soc, Kyoto",
journal = "Journal of Pharmacological Sciences",
title = "Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression",
volume = "110",
number = "1",
pages = "98-104",
doi = "10.1254/jphs.09013FP"
}
Vezmar, S., Miljković, B., Vučićević, K., Timotijević, I., Prostran, M., Todorović, Z.,& Pokrajac, M.. (2009). Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression. in Journal of Pharmacological Sciences
Japanese Pharmacological Soc, Kyoto., 110(1), 98-104.
https://doi.org/10.1254/jphs.09013FP
Vezmar S, Miljković B, Vučićević K, Timotijević I, Prostran M, Todorović Z, Pokrajac M. Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression. in Journal of Pharmacological Sciences. 2009;110(1):98-104.
doi:10.1254/jphs.09013FP .
Vezmar, Sandra, Miljković, Branislava, Vučićević, Katarina, Timotijević, Ivana, Prostran, Milica, Todorović, Zoran, Pokrajac, Milena, "Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression" in Journal of Pharmacological Sciences, 110, no. 1 (2009):98-104,
https://doi.org/10.1254/jphs.09013FP . .

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