- Commentary
- Open Access
Individual differences and evidence-based psychopharmacology
- RH Belmaker1Email author,
- Yuly Bersudsky1 and
- Galila Agam1
https://doi.org/10.1186/1741-7015-10-110
© Belmaker et al; licensee BioMed Central Ltd. 2012
- Received: 1 June 2012
- Accepted: 27 September 2012
- Published: 27 September 2012
Abstract
Individual differences in response to pharmacologic treatment limits the usefulness of mean data obtained from randomized controlled trials. These individual differences exist even in genetically uniform inbred mouse strains. While stratification can be of value in large studies, the individual patient history is the most effective currently available guide for personalized medicine in psychopharmacology.
Keywords
- Variance
- clinical trials
- individual differences
- replicability
- measurement error
- variability
Background
The effect of lithium on plasma cAMP response to adrenaline administration (from [2]with permission).
Individual differences in the effect of lithium on plasma cAMP response to adrenaline administration (unpublished data from [2]).
The effect of sodium-dependent myo-inositol cotransporter homozygote knockout or imipramine on immobility after forced swim (from [3]with permission).
Individual differences in the effect of sodium-dependent myo-inositol cotransporter homozygote knockout or imipramine on immobility after forced swim (unpublished data from [3]).
Efficacy of valnoctamide (n = 15) versus placebo (n = 17) as an add-on to risperidone in acute mania (unpublished figure from [6]).
Individual differences in efficacy of valnoctamide (n = 15) versus placebo (n = 17) as an add-on to risperidone in acute mania (unpublished data from [6]).
Conclusion
The truth of course is more likely that most psychiatric disorders, like most medical disorders, are highly heterogeneous [8] and that the best tool we have for dissecting that heterogeneity today is to take a careful history [9]. In the absence of a history, careful follow-up is necessary and often the best treatment for a particular patient will appear only over time. The illusion that what is needed is more head-to-head large trials without differentiating the diagnosis of bipolar depression into subtypes could lead to great expense but also to inappropriate treatment for individual patients. Medicine must return to understanding that individual differences are the essence of medicine as opposed to those sciences that are interested essentially in uncovering the grain of wheat from among all the chaff. We in medicine are interested in each bit of chaff or wheat, whoever and wherever he or she may be. Perhaps Bayes' Theorem might allow us to design more appropriate medical experiments based on this concept of individual differences. Recent papers on 'patient-centered evidence' [10] have emphasized this point as well as the need to report heterogeneity in clinical trials [11].
Authors' information
RHB is a clinical psychopharmacologist and director of a bipolar disorder treatment unit.
YB is a clinical psychiatrist, mood disorder psychopharmacologist and biostatistician.
GA is a biochemist and neuropharmacologist and director of a biochemistry and animal behavior research laboratory.
Declarations
Authors’ Affiliations
References
- Kent DM, Hayward RA: Limitations of applying summary results of clinical trials to individual patients: the need for risk stratification. JAMA. 2007, 298 (10): 1209-1212. 10.1001/jama.298.10.1209.View ArticlePubMedGoogle Scholar
- Ebstein R, Belmaker R, Grunhaus L, Rimon R: Lithium inhibition of adrenaline-stimulated adenylate cyclase in humans. Nature. 1976, 259 (5542): 411-413. 10.1038/259411a0.View ArticlePubMedGoogle Scholar
- Bersudsky Y, Shaldubina A, Agam G, Berry GT, Belmaker RH: Homozygote inositol transporter knockout mice show a lithium-like phenotype. Bipolar Disord. 2008, 10 (4): 453-459. 10.1111/j.1399-5618.2007.00546.x.View ArticlePubMedGoogle Scholar
- Pickrell JK, Pai AA, Gilad Y, Pritchard JK: Noisy splicing drives mRNA isoform diversity in human cells. PLoS Genet. 2010, 6 (12): e1001236-10.1371/journal.pgen.1001236.View ArticlePubMedPubMed CentralGoogle Scholar
- Taniguchi Y, Choi PJ, Li GW, Chen H, Babu M, Hearn J, Emili A, Xie XS: Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science. 2010, 329 (5991): 533-538. 10.1126/science.1188308.View ArticlePubMedPubMed CentralGoogle Scholar
- Bersudsky Y, Applebaum J, Gaiduk Y, Sharony L, Mishory A, Podberezsky A, Agam G, Belmaker RH: Valnoctamide as a valproate substitute with low teratogenic potential in mania: a double-blind, controlled, add-on clinical trial. Bipolar Disord. 2010, 12 (4): 376-382. 10.1111/j.1399-5618.2010.00828.x.View ArticlePubMedGoogle Scholar
- Vieta E, Calabrese JR, Goikolea JM, Raines S, Macfadden W: Quetiapine monotherapy in the treatment of patients with bipolar I or II depression and a rapid-cycling disease course: a randomized, double-blind, placebo-controlled study. Bipolar Disord. 2007, 9 (4): 413-425. 10.1111/j.1399-5618.2007.00479.x.View ArticlePubMedGoogle Scholar
- Lichtenberg P, Belmaker RH: Subtyping major depressive disorder. Psychother Psychosom. 2010, 79 (3): 131-135. 10.1159/000286957.View ArticlePubMedGoogle Scholar
- Belmaker RH: Patient history must be incorporated into any guidelines. Bipolar Disord. 2009, 11 (7): 772-10.1111/j.1399-5618.2009.00743.x. author reply 773View ArticlePubMedGoogle Scholar
- Kent DM, Shah ND: Risk models and patient-centered evidence: should physicians expect one right answer?. JAMA. 2012, 307 (15): 1585-1586. 10.1001/jama.2012.469.View ArticlePubMedGoogle Scholar
- Kent DM, Rothwell PM, Ioannidis JP, Altman DG, Hayward RA: Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials. 2010, 11: 85-10.1186/1745-6215-11-85.View ArticlePubMedPubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/10/110/prepub
Pre-publication history
Copyright
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.