Lower drug dose may improve outcomes
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* Simon B. Dimmitt

I concur with the arguments made by McCormack and colleagues in support of starting medication at a very low dose.1 It has been suggested that individualized low-dose pharmacotherapy may improve outcomes in the treatment of chronic disease.2 Side effects and adverse drug reactions are substantially dose-related, and potentially there is a substantial benefit in individualized systematic titration of dosage to optimize the balance of risk and benefit.2

The strategy of using lower doses of drugs with different mechanisms of action in combination, as demonstrated in the treatment of systemic hypertension,3 provides added efficacy and non-additive side effects. Attention to lifestyle and other contributing factors is also necessary to optimize outcomes. For example, instead of increasing the dose of statin and its potential for side effects, coronary risk is more safely reduced by combining a lower dose of statin with weight loss and antiplatelet and antihypertensive pharmacotherapy.2

There is growing evidence that lower dose drug treatment has many potential advantages and is often not less effective. This topic deserves more extensive research. It may be time to review dosing guidelines for a wide range of drugs.

Some letters have been abbreviated for print. See [www.cmaj.ca](http://www.cmaj.ca) for full versions.

## References

1.  McCormack JP, Allen GM, Virani AS. Is bigger better? An argument for very low starting doses. CMAJ 2011;183:65–9.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo4OiIxODMvMS82NSI7czo0OiJhdG9tIjtzOjIyOiIvY21hai8xODMvNS81ODYuMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

2.  Dimmitt SB, Stampfer H. Low drug doses may improve outcomes in chronic disease. Med J Aust 2009;191:511–3.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=19883348&link_type=MED&atom=%2Fcmaj%2F183%2F5%2F586.3.atom) 

3.  Law MR, Wald NJ, Morris JK, et al. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003;326:1427–34.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjEzOiIzMjYvNzQwNC8xNDI3IjtzOjQ6ImF0b20iO3M6MjI6Ii9jbWFqLzE4My81LzU4Ni4zLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==)