A randomized, double-blind, placebo-controlled phase 2 study of the augmentation of a nicotinic acetylcholine receptor partial agonist in depression is there a relationship to leptin levels?

Journal of Clinical Psychopharmacology

Volumn 35, Issue 1, 2015, Pages 51-56

  Fava, Maurizio ^a   Ramey, Tanya ^b   Pickering, Eve ^b   Kinrys, Gustavo ^a   Boyer, Stacey ^b   Altstiel, Larry ^b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b PFIZER INC   (United States)

Author keywords

BMI; CP 601, 927; Depression; Leptin; MADRS score

Indexed keywords

ANTIDEPRESSANT AGENT; BIOLOGICAL MARKER; CITALOPRAM; CP 601927; ESCITALOPRAM; FLUOXETINE; LEPTIN; NICOTINIC AGENT; PAROXETINE; PLACEBO; SERTRALINE; UNCLASSIFIED DRUG; ANTIDEPRESSIVE AGENTS; BIOLOGICAL MARKERS; NICOTINIC AGONISTS; RECEPTORS, NICOTINIC;

ADULT; ARTICLE; BECH-RAFAELSEN MELANCHOLIA SCALE; BODY MASS; CONTROLLED STUDY; DEPRESSION; DOUBLE BLIND PROCEDURE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG STRUCTURE; DRUG WITHDRAWAL; FEMALE; HAMILTON DEPRESSION RATING SCALE; HUMAN; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MALE; MONTGOMERY ASBERG DEPRESSION RATING SCALE; NAUSEA; OPEN STUDY; PHASE 2 CLINICAL TRIAL; POST HOC ANALYSIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; BLOOD; CHEMISTRY; CLINICAL TRIAL; DEPRESSIVE DISORDER, MAJOR; DOUBLE-BLIND METHOD; DRUG PARTIAL AGONISM; FOLLOW-UP STUDIES; HUMANS; MIDDLE AGED; MULTICENTER STUDY;

ADULT; ANTIDEPRESSIVE AGENTS; BIOLOGICAL MARKERS; DEPRESSIVE DISORDER, MAJOR; DOUBLE-BLIND METHOD; DRUG PARTIAL AGONISM; FEMALE; FOLLOW-UP STUDIES; HUMANS; LEPTIN; MALE; MIDDLE AGED; NICOTINIC AGONISTS; RECEPTORS, NICOTINIC; TREATMENT OUTCOME;

EID: 84925751237     PISSN: 02710749     EISSN: 1533712X     Source Type: Journal    
DOI: 10.1097/JCP.0000000000000245     Document Type: Article

References (22)

1. Gaynes BN, Warden D, Trivedi MH, et al. What did STAR∗D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009;60:1439-1445.
2. Fava M, Rush AJ. Current status of augmentation and combination treatments for major depressive disorder: a literature review and a proposal for a novel approach to improve practice. Psychother Psychosom. 2006;75: 139-153.
3. Charles HC, Lazeyras F, Krishnan KR, et al. Brain choline in depression: in vivo detection of potential pharmacodynamic effects of antidepressant therapy using hydrogen localized spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry. 1994;18:1121-1127.
4. Stoll AL, Cohen BM, Hanin I. Erythrocyte choline concentrations in psychiatric disorders. Biol Psychiatry. 1991;29:309-321.
5. Brody AL, Mandelkern MA, Costello MR, et al. Brain nicotinic acetylcholine receptor occupancy: effect of smoking a denicotinized cigarette. Int J Neuropsychopharmacol. 2009;12:305-316.
6. BrodyAL, MandelkernMA, London ED, et al. Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors. Arch Gen Psychiatry. 2006;63:907-915.
7. News WP. Remaining TC-5214 Phase III Efficacy Studies Do Not Meet Endpoint. Available at: http://www.worldpharmanews.com/ astrazeneca/2013-remaining-tc-5214-phase-iii-efficacy-studies-do-notmeet-endpoint. Accessed April 24, 2014.
8. Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther. 1977;229 (2):327-336.
9. Mineur YS, Einstein EB, Seymour PA, et al. alpha4beta2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties. Behav Pharmacol. 2011;22(4):291-299.
10. TargumSD, PollackMH, Fava M. Redefining affective disorders: relevance for drug development. CNS Neurosci Ther. 2008;14:2-9.
11. Hamilton M. Rating depressive patients. J Clin Psychiatry. 1980;41 (12 Pt 2):21-24.
12. Consensus Development Panel. Gastrointestinal surgery for severe obesity. Ann Intern Med. 1991;115(12):956-961.
13. FinucaneMM, StevensGA, CowanMJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377(9765):557-567.
14. Kloiber S, Ripke S, KohliMA, et al. Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels. Eur Neuropsychopharmacol. 2013;23:653-662.
15. Uher R, Mors O, Hauser J, et al. Body weight as a predictor of antidepressant efficacy in the GENDEP project. J Affect Disord. 2009;118 (1-3):147-154.
16. Caro JF, Kolaczynski JW, Nyce MR, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet. 1996;348:159-161.
17. Martin SS, Qasim A, Reilly MP. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol. 2008;52:1201-1210.
18. Shimizu H, Oh IS, Okada S, et al. Leptin resistance and obesity. Endocr J. 2007;54:17-26.
19. Lu XY, Kim CS, Frazer A, et al. Leptin: a potential novel antidepressant. Proc Natl Acad Sci U S A. 2006;103:1593-1598.
20. Yamada N, Katsuura G, Ochi Y, et al. Impaired CNS leptin action is implicated in depression associated with obesity. Endocrinology. 2011;152: 2634-2643.
21. Burghardt PR, Love TM, Stohler CS, et al. Leptin regulates dopamine responses to sustained stress in humans. J Neurosci. 2012;32: 15369-15376.
22. Abernethy DR, Greenblatt DJ. Pharmacokinetics of drugs in obesity. Clin Pharmacokinet. 1982;7:108-124.