Antidepressant response to aripiprazole augmentation associated with enhanced FDOPA utilization in striatum: a preliminary PET study.
Several double blind, prospective trials have demonstrated an antidepressant augmentation efficacy of aripiprazole in depressed patients unresponsive to standard antidepressant therapy. Although aripiprazole is now widely used for this indication, and much is known about its receptor-binding properties, the mechanism of its antidepressant augmentation remains ill-defined. In vivo animal studies and in vitro human studies using cloned dopamine dopamine D2 receptors suggest aripiprazole is a partial dopamine agonist; in this preliminary neuroimaging trial, we hypothesized that aripiprazole's antidepressant augmentation efficacy arises from dopamine partial agonist activity. To test this, we assessed the effects of aripiprazole augmentation on the cerebral utilization of 6-[(18)F]-fluoro-3,4-dihydroxy-l-phenylalanine (FDOPA) using positron emission tomography (PET). Fourteen depressed patients, who had failed 8 weeks of antidepressant therapy with selective serotonin reuptake inhibitors, underwent FDOPA PET scans before and after aripiprazole augmentation; 11 responded to augmentation. Whole brain, voxel-wise comparisons of pre- and post-aripiprazole scans revealed increased FDOPA trapping in the right medial caudate of augmentation responders. An exploratory analysis of depressive symptoms revealed that responders experienced large improvements only in putatively dopaminergic symptoms of lassitude and inability to feel. These preliminary findings suggest that augmentation of antidepressant response by aripiprazole may be associated with potentiation of dopaminergic activity.
Washington University School of Medicine, Department of Psychiatry, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110, USA; Saint Louis University School of Medicine, Department of Neurology & Psychiatry, 1438 South Grand Boulevard, St. Louis, MO 63104, USA. Electronic address: cconway@wustl.edu.
Charles R
CR
Conway
Saint Louis University School of Medicine, Department of Neurology & Psychiatry, 1438 South Grand Boulevard, St. Louis, MO 63104, USA.
John T
JT
Chibnall
Department of Nuclear Medicine, Friedrich-Alexander University, Erlangen/Nuremberg, Germany.
Paul
P
Cumming
Washington University School of Medicine, Departments of Radiology and Psychiatry, St. Louis, MO 63110, USA; Avid Radiopharmaceuticals, Philadelphia, PA 19104, USA.
Mark A
MA
Mintun
Washington University School of Medicine, Department of Psychiatry, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110, USA.
Marie Anne I
MA
Gebara
Washington University School of Medicine, Department of Psychiatry, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110, USA.
Dana C
DC
Perantie
Washington University School of Medicine, Department of Anatomy and Neurobiology, St. Louis, MO 63110, USA.
Joseph L
JL
Price
Washington University School of Medicine, Department of Psychiatry, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110, USA.
Martha E
ME
Cornell
Washington University School of Medicine, Department of Radiology, Division of Nuclear Medicine, St. Louis, MO 63110, USA.
Jonathan E
JE
McConathy
Washington University School of Medicine, Department of Psychiatry, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110, USA.
Sunil
S
Gangwani
Washington University School of Medicine, Departments of Psychiatry, Neurology, and Radiology, St. Louis, MO 63110, USA.
Yvette I
YI
Sheline
D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068180:Aripiprazole; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D018401:Sample Size; D016037:Single-Blind Method; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D000928:Antidepressive Agents; D018491:Dopamine Agonists; D010879:Piperazines; D015363:Quinolones; D015283:Citalopram; D004295:Dihydroxyphenylalanine; D000068180:Aripiprazole; D004298:Dopamine
Aripiprazole; Caudate; Dopamine; Positron emission tomography; Treatment-resistant depression