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Looking backwards: a possible new path for drug discovery in psychopharmacology

Abstract

The history of psychopharmacology is littered with type II errors — the rejection of effective compounds in the specious belief that they were inefficacious because they had failed to beat placebo in a controlled trial. Revisiting some of these drugs to establish their receptor profile, and then determining what patentable compounds now on the shelf match that profile, might represent a possible future pathway to drug discovery. This article looks at the special circumstances in which numerous potentially effective drugs were withdrawn in the United States.

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Figure 1: Antineurotic drugs evaluated by the NAS/NRC Psychiatry Panel, 1966–1968: 13 out of 18 were subsequently withdrawn by the FDA.

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References

  1. Shorter, E. Fading beauties: searching for value in psychopharmacology. Scrip Magazine 52–53 (September 2001).

  2. Drug Efficacy Study. Final Report to the Commissioner of Food and Drugs, Food and Drug Administration, from the Division of Medical Sciences, National Research Council (National Academy of Sciences, Washington DC, 1969).

  3. Impact of NAS/NRC report on future of drug regulation. The Pink Sheet 5 (July 14, 1969).

  4. Bryan, P. A. & Stern, L. H. The drug efficacy study, 1962–1970. FDA Papers 4, 14–17 (1970).

    Google Scholar 

  5. Temple, R. Re-Evaluation of Marketed Drugs: the DESI Program (3rd International Conference of Drug Regulatory Agencies, Stockholm, Sweden, 1984).

    Google Scholar 

  6. Temin, P. Taking your Medicine: Drug Regulation in the United States (Harvard Univ. Press, Cambridge, 1980).

    Book  Google Scholar 

  7. Nelson hearings on psychotropics open with NIMH. The Pink Sheet T&G-6 (July 14, 1969).

  8. Edwards' new thinking on Rx combos emerges from House subcommittee. The Pink Sheet 28 (May 10, 1971).

  9. Smith Kline & French Laboratories. A Chronology and Review of the National Academy of Sciences/National Research Council Drug Efficacy Study (Smith Kline & French, Philadelphia, 1971).

  10. NAS should reconvene drug evaluation panel chairmen. The Pink Sheet T&G-6 (October 19, 1970).

  11. National Academy of Sciences/National Research Council. NAS/NRC Report on Captodiame FDA Accession Number 1740 (1968).

  12. Ashby, W. R. et al. A clinical trial of covatin on elderly patients with anxiety and restlessness. J. Ment. Sci. 105, 504–507 (1959).

    Article  CAS  Google Scholar 

  13. Ellermann, M. Virkningen af covatin (et nyt dagsedativum) pa et ambulant patientmateriale. Nordisk Medicin 10, 1531 (1955).

    Google Scholar 

  14. Pentney, B. H. et al. Captodiame in anxiety states in general practice. The Practitioner 185, 218–221 (1960).

    CAS  PubMed  Google Scholar 

  15. National Academy of Sciences/National Research Council. NAS/NRC Report on Butabarbital FDA Accession Number 1720 (1968).

  16. National Academy of Sciences/National Research Council. NAS/NRC Report on Deprol FDA Accession Number 1729 (1968).

  17. National Academy of Sciences/National Research Council. NAS/NRC Report on Potassium–Magnesium Aspartate FDA Accession Number 1314 (1968).

  18. Wright, J. An Interview with Dr Jonathan Wright Tahoma Clinic [online] (cited Oct 10 2002) <http://www.tahoma-clinic.com/male.shtm> (2002).

    Google Scholar 

  19. Hass, A. E. & Coppinger, P. L. Introductions and Discontinuations of New Drugs in the United States and the United Kingdom (Food and Drug Administration, Office of Planning and Evaluation, Study 78 Appendix A, September 1989).

    Google Scholar 

  20. Formica, P. E. The housewife syndrome. Treatment with the potassium and magnesium salts of aspartic acid. Curr. Therap. Res. 4, 98–106 (1962).

    CAS  Google Scholar 

  21. National Academy of Sciences/National Research Council. NAS/NRC Report on Emylcamate FDA Accession Number 1739 (1968).

  22. Melander, B. O. et al. 3-Methyl-3-pentanol carbamate compositions. US Patent 2,972,564 (1961).

  23. Striatran advertisement. JAMA 174, 234–235 (1960).

  24. Shubin, H. & Steinberg, N. A study of a new tranquilizer in general practice: emylcamate in 400 patients. Curr. Therap. Res. 3, 527–533 (1963).

    Google Scholar 

  25. Listica advertisement. Dis. Nervous Syst. 22, 543–545 (1961).

  26. National Academy of Sciences/National Research Council. NAS/NRC Report on Hydroxyphenamate FDA Accession Number 1737 (1968).

  27. Mclaughlin, B. E. et al. A double blind study involving Listica, Librium and placebo as an adjunct to supportive psychotherapy in a psychiatric clinic. Dis. Nervous Syst. 22, S41–S42 (1961).

    Google Scholar 

  28. Greenspan, E. B. Use of hydroxyphenamate in some forms of cardiovascular disease. Dis. Nervous Syst. 22, S33–S34 (1961).

    Google Scholar 

  29. Alexander, L. Discussion comment. Dis. Nervous Syst. 22, S53 (1961).

    Google Scholar 

  30. PMA President Stetler's statement on efficacy study disclosures. The Pink Sheet 9 (June 14, 1971).

  31. Justice's narcotics bill called 'stupid'; Brill urged government-supported drug data. The Pink Sheet 10 (August 4, 1969).

  32. Cooper, J. D. (ed.) The Efficacy of Self-Medication (The Smithsonian Institution, Interdisciplinary Communications Program, Washington DC, 1973).

    Google Scholar 

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National Academy of Sciences

National Association of Science Writers

National Institute of Mental Health

National Research Council

Pharmaceutical Research and Manufacturers Association

The Pink Sheet

US Food and Drug Administration

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Shorter, E. Looking backwards: a possible new path for drug discovery in psychopharmacology. Nat Rev Drug Discov 1, 1003–1006 (2002). https://doi.org/10.1038/nrd964

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