Search

Previous studies have investigated the occupancy of the serotonin reuptake transporter (SERT) after clinical doses of citalopram and other selective serotonin reuptake inhibitors. In the present study, the occupancies of SERT after multiple doses of escitalopram and citalopram were compared using the radioligand [(123)I]ADAM and single photon emission computed tomography (SPECT).Fifteen healthy subjects received escitalopram 10 mg/day (n = 6) or citalopram 20 mg/day (n = 9) for a total of 10 days. SERT occupancies in midbrain were determined with SPECT and [(123)I]ADAM at three different time points: at baseline (no medication) and at 6 and 54 h after last drug intake.At 6 h after the last dose, mean SERT occupancies were 81.5 +/- 5.4% (mean+/-SD) for escitalopram and 64.0 +/- 12.7% for citalopram (p0.01). At 54 h after the last dose, mean SERT occupancies were 63.3 +/- 12.1% for escitalopram and 49.0 +/- 11.7% for citalopram (p0.05). The plasma concentrations of the S-enantiomer were of the same magnitude in both substances. For both drugs, the elimination rate of the S-enantiomer in plasma was markedly higher than the occupancy decline rate in the midbrain.The significantly higher occupancy of SERT after multiple doses of escitalopram compared to citalopram indicates an increased inhibition of SERT by escitalopram. The results can also be explained by an attenuating effect of R-citalopram on the occupancy of S-citalopram at the SERT.

Die Diagnose und Behandlung der Manie bei bipolaren Storungen stellt eine grose Herausforderung dar. Traditionell werden vorwiegend Lithium oder Valproat als Mittel der ersten Wahl verwendet. Aufgrund des begrenzten therapeutischen Wirkspektrums dieser Medikamente werden jedoch haufig auch typische Neuroleptika zur Behandlung der Manie eingesetzt. Diese sind in dieser Indikation zwar nachweislich wirksam, ihre Anwendung ist aber haufig mit erheblichen Nebenwirkungen, insbesondere extrapyramidalen Symptomen, verbunden. Daher werden fur die Behandlung der Manie bei bipolar erkrankten Patienten aufgrund der aktuellen Datenlage zunehmend atypische Antipsychotika bevorzugt. In dieser Ubersicht werden die Ergebnisse kontrollierter Studien mit verschiedenen atypischen Antipsychotika in der Maniebehandlung dargestellt und jene Aspekte diskutiert, die bei der Wahl geeigneter Atypika eine Rolle spielen.

We explored the relationship between striatal dopamine-2 (D2) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5–45 mg/day olanzapine for at least 14 days. After that period, D2 receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson–Angus Scale (SAS) and Barnes–Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28–50%, 10 mg to 40–68%, 15 mg to 69%, 20 mg to 57–66%, 30 mg to 66% and 45 mg to 80% D2 receptor occupancy; and a significant correlation between plasma levels and occupancy (R2 = .55, P = .001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D2 occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.