Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression

2009
Authors
Vezmar, Sandra
Miljković, Branislava

Vučićević, Katarina

Timotijević, Ivana
Prostran, Milica

Todorović, Zoran
Pokrajac, Milena
Article (Published version)
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Show full item recordAbstract
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 / interactionSource:
Journal of Pharmacological Sciences, 2009, 110, 1, 98-104Publisher:
- Japanese Pharmacological Soc, Kyoto
Funding / projects:
DOI: 10.1254/jphs.09013FP
ISSN: 1347-8613
PubMed: 19444001
WoS: 000266351400011
Scopus: 2-s2.0-66349112356
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PharmacyTY - 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 . .