Striatal D(2) receptor occupancy in bipolar patients treated with olanzapine.
We explored the relationship between striatal dopamine-2 (D(2)) 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, D(2) 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% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) 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.
Attarbaschi
Trawat
T
Department of General Psychiatry, Medical University Vienna, Vienna, Austria.
Sacher
Julia
J
Geiss-Granadia
Thomas
T
Klein
Nikolas
N
Mossaheb
Nilufar
N
Lanzenberger
Rupert
R
Asenbaum
Susanne
S
Dudczak
Robert
R
Kasper
Siegfried
S
Tauscher
Johannes
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001569:Benzodiazepines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D049268:Positron-Emission Tomography / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D001569:Benzodiazepines; D000077152:Olanzapine; D017448:Receptors, Dopamine D2; D017367:Selective Serotonin Reuptake Inhibitors