Number needed to harm: Its limitations in psychotropic drug safety research

Daniel J. Safer, Julie M. Zito

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


Commonly used statistical measures to quantify the likelihood of an adverse drug event (ADE) from clinical trials include risk ratio; odds ratio; and number needed to harm (NNH), the reciprocal of absolute risk. This critical review focused on NNH, specifically on its limitations in controlled trials with psychotropic medication. Data for this evaluation were obtained primarily from articles in MEDLINE from 1988 to 2012. Limitations of NNH were found to include the following: a) arbitrary binary cutoffs for continuous measures, b) limited use of confidence intervals, c) limited adjustments for potential baseline confounders, d) limited adjustments for differences in dose and treatment duration, e) rare consideration of high attrition rates, f) variable use of the term harm, g) oversimplified single harm comparisons, h) frequent biased design and reporting, i) undue emphasis on less severe ADEs, j) application primarily to short-term clinical trials, and k) little or no generalizability in community practice. In sum, the NNH metric supplies very limited information on the risks of psychotropic medication. Postmarketing surveillance of community treatment populations using case-control methodology provides far more useful data on serious ADEs.

Original languageEnglish (US)
Pages (from-to)714-718
Number of pages5
JournalJournal of Nervous and Mental Disease
Issue number8
StatePublished - Aug 1 2013


  • Adverse drug events
  • Clinical trials
  • Likelihood to help or harm (LHH)
  • Number needed to harm (NNH)
  • Number needed to treat (NNT)

ASJC Scopus subject areas

  • Psychiatry and Mental health


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