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Int J Neuropsychopharmacol. 2014 Apr;17(4):553-60. doi: 10.1017/S1461145713001521. Epub 2013 Dec 18.

Norepinephrine transporter occupancy by nortriptyline in patients with depression: a positron emission tomography study with (S,S)-[¹⁸F]FMeNER-D₂.

Author information

1
Clinical Neuroimaging Team, Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
2
Department of Medical Statistics, Shiga University of Medical Science, Shiga, Japan.
3
Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
4
Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
5
Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
6
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.

Abstract

Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder (ADHD). Nortriptyline is a NET-selective tricyclic antidepressant (TCAs) that has been widely used for the treatment of depression. Previous positron emission tomography (PET) studies have reported over 80% serotonin transporter occupancy with clinical doses of selective serotonin reuptake inhibitors (SSRIs), but there has been no report of NET occupancy in patients treated with relatively NET-selective antidepressants. In the present study, we used PET and (S,S)-[18¹⁸F]FMeNER-D₂ to investigate NET occupancies in the thalamus in 10 patients with major depressive disorder taking various doses of nortriptyline, who were considered to be responders to the treatment. Reference data for the calculation of occupancy were derived from age-matched healthy controls. The result showed approximately 50-70% NET occupancies in the brain as a result of the administration of 75-200 mg/d of nortriptyline. The estimated effective dose (ED₅₀) and concentration (EC₅₀) required to induce 50% occupancy was 65.9 mg/d and 79.8 ng/ml, respectively. Furthermore, as the minimum therapeutic level of plasma nortriptyline for the treatment of depression has been reported to be 70 ng/ml, our data indicate that this plasma nortriptyline concentration corresponds to approximately 50% NET occupancy measured with PET, suggesting that more than 50% of central NET occupancy would be appropriate for the nortriptyline treatment of patients with depression.

PMID:
24345533
DOI:
10.1017/S1461145713001521
[Indexed for MEDLINE]
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