Antidepressant reformulations: Who uses them, and what are the benefits?

Health Affairs

Volumn 28, Issue 3, 2009, Pages 734-745

  Huskamp, Haiden A ^a   Busch, Alisa B ^a,b   Domino, Marisa E ^c   Normand, Sharon Lise T ^a,d  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MCLEAN HOSPITAL   (United States)

^c University of North Carolina at Chapel Hill   (United States)

^d HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMFEBUTAMONE; ANTIDEPRESSANT AGENT; CITALOPRAM; ESCITALOPRAM; MIRTAZAPINE; PAROXETINE; VENLAFAXINE;

ADULT; AGED; ARTICLE; DRUG COST; DRUG EFFICACY; DRUG FORMULATION; DRUG TOLERANCE; DRUG WITHDRAWAL; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MALE; TREATMENT DURATION;

ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; DEPRESSIVE DISORDER, MAJOR; DRUG COMPOUNDING; DRUG COSTS; DRUG UTILIZATION REVIEW; ECONOMIC COMPETITION; HUMANS; PATENTS AS TOPIC; SEROTONIN UPTAKE INHIBITORS; TREATMENT OUTCOME; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 66749127324     PISSN: 02782715     EISSN: 15445208     Source Type: Journal    
DOI: 10.1377/hlthaff.28.3.734     Document Type: Article

References (25)

1. Pharmaceutical Business Review Online, "Pharma Turns to Reformulation to Maximize ROI," 8 December 2006, http://www.pharmaceutical- business-review.com/article-feature.asp?guid=877C0956-lBF3-4982-986F- 805E7DCD60C9 (accessed 9 October 2008).
2. The original product's patent is not extended. Additional exclusivity applies only to the reformulation. Most types of reformulations (for example, controlled-release forms) would receive three years of exclusivity. Lexapro, marketed as a new chemical entity, received five.
3. H.A. Huskamp et al., "Generic Entry, Reformulations, and Promotion of SSRIs in the U.S.," PharmacoEconomics 26, no. 7 (2008): 603-616.
4. See, for example, M. Angell, The Truth about Drug Companies: How They Deceive Us and What to Do about It (New York: Random House, 2004).
5. A.I. Wertheimer and T.M. Santella, "Pharmacoevolution: The Benefits of Incremental Innovation," http://www.who.int/intellectualproperty/ submissions/Pharmacoevolution.pdf (accessed 19 February 2009).
6. A review (across medication classes) of compliance studies that used electronic monitoring found that number of doses per day is inversely related to compliance. A.J. Claxton, J. Cramer, and C. Pierce, "A Systematic Review of the Associations between Dose Regimens and Medication Compliance," Clinical Therapeutics 23, no. 8 (2001): 1296-1310. (Pubitemid 32804122)
7. Forest Laboratories, "Lexapro, the Single-Isomer of Celexa, Receives FDA Approvable Letter," 24 January 2009, http://www.frx.com/news/ PressRelease.aspx?ID=250711 (accessed 19 February 2009).
8. See the online Appendix for a complete list of studies described in this paragraph, at http://content.healthaffairs.org/cgi/content/full/28/3/734/DC1.
9. See, for example, S. Svensson and P.R. Mansfield, "Escitalopram: Superior to Citalopram or a Chiral Chimera?" Psychotherapy and Psychosomatics 73, no. 1 (2004): 10-16. (Pubitemid 37524098)
10. The only antidepressant prior authorization requirement during the ten-year period was implemented in February 2005 (for Celexa). The observation window for our two main analyses ended before that date.
11. See, for example, Agency for Healthcare Research and Quality, Depression in Primary Care, Vol 2: Treatment of Major Depression (Rockville, Md.: U.S. Department of Health and Human Services, 1993).
12. K. Rost et al., "Clinical Improvement Associated with Conformance to HEDIS-Based Depression Care," Mental Health Services Research 7, no. 2 (2005): 103-112. (Pubitemid 40762550)
13. AHRQ, Treatment of Major Depression.
14. Additional detail on each of the three analyses is available in the online Appendix, as in Note 8.
15. We estimated similar models of the probability of reformulation use among new antidepressant users. Results were similar, so we do not present results for incident users.
16. National Committee for Quality Assurance, "HEDIS 2008 Summary Table of Measures, Product Lines, and Changes," http://www.ncqa.org/Portals/0/ HEDISQM/HEDIS2008/2008-Measures.pdf (accessed 14 October 2008).
17. R.B. D'Agostino Jr., "Propensity Score Methods for Bias Reduction in the Comparison of a Treatment to a Non-Randomized Control Group," Statistics in Medicine 17, no. 19 (1998): 2265-2281. (Pubitemid 28466823)
18. We performed a 1-11 matched analysis without replacement on the basis of the estimated propensity score of each patient. Additional detail provided in the online Appendix, as in Note 8.
19. Depression diagnosis variables were excluded, since all were diagnosed with major depression.
20. Most SSRIs have indications for treating both anxiety and depression; most other antidepressants do not.
21. J.S. Crowley, D. Ashner, and L. Elam, State Medicaid Outpatient Prescription Drug Policies: Findings from a National Survey, 2005 Update, October 2005, http://www.kff.org/medicaid/upload/State-Medicaid-Outpatient- Prescription-Drug-Policies-Findings-from-a-National-Survey-2005-Update-report. pdf (accessed 19 February 2009).
22. R.G. Frank et al., "New Analyses of Costs and Effectiveness in CATIE" (Working paper, Harvard University, 2008).
23. Reformulation manufacturers must demonstrate bioequivalence and safety.
24. In deciding when to introduce, manufacturers balance time needed to shift demand onto the reformulation against the limited exclusivity period. See S. Kina, "Optimal Regulation of Pharmaceutical Line Extensions" (Working paper, Harvard University, 2009).
25. A similar result was found in A. Lleras-Muney and F.R. Lichtenberg, "The Effect of Education on Medical Technology Adoption: Are the More Educated More Likely to Use New Drugs" NBER Working Paper no.9185 (Cambridge, Mass.: National Bureau of Economic Research, September 2002).