Calling for More Research of Medication Effects in Bipolar Disorder: Response to Ketter and Dell’Osso

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Back to table of contents Previous article Next article Letters to the EditorFull AccessCalling for More Research of Medication Effects in Bipolar Disorder: Response to Ketter and Dell’OssoMikael Landén, M.D., Ph.D., Alexander Viktorin, Ph.D.Mikael LandénSearch for more papers by this author, M.D., Ph.D., Alexander ViktorinSearch for more papers by this author, Ph.D.Published Online:1 Aug 2017https://doi.org/10.1176/appi.ajp.2017.17050488rAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We thank Dr. Ketter and Dr. Dell’Osso for the interest in our study (1) published in the April 2017 issue of the Journal and for raising important questions.With respect to the issue of bipolar subtypes, individuals in our study were identified as having bipolar disorder based on a validated search algorithm (2), which required at least two inpatient or outpatient admissions with a discharge diagnosis of bipolar disorder in the Swedish National Patient Register. However, the ICD system used in this register does not reliably distinguish between bipolar I and bipolar II disorder. Therefore, all subtypes of bipolar disorder were included in the analyses. This is a limitation of the study, and more research is needed to examine if the effects observed in the study are limited to, or are more pronounced in, a specific subtype of bipolar disorder. The same limitation affected a previous study of ours (3) published in the Journal in 2014, investigating antidepressant-induced manic switch in patients with bipolar disorder. Therefore, we have read with interest the recent study by Altshuler and colleagues (4), published in the March 2017 issue of the Journal, which observed similar switch and treatment response rates in participants with bipolar II depression associated with lithium monotherapy, sertraline monotherapy, or lithium/sertraline combination therapy.Regarding the issues of dose and administration, the data used in our study include number of pills dispensed, dose per pill, and dispensation dates. Unfortunately, the mean daily dose is not available in the register. Calculating the mean daily dose would therefore need to rely on a number of assumptions regarding each individual’s pattern of consumption that may not be true for every individual. Nevertheless, we ran a new analysis on the cohort used in the study (1). Table 1 presents the distribution of methylphenidate dispensed in the different groups according to the mean dose of methylphenidate per pill dispensed in milligrams and the immediate release, slow release, or combination thereof. There were no discernible differences between the monotherapy group and the group that also received a mood stabilizer.TABLE 1. Descriptive Statistics of Methylphenidate Dispensations in the Study CohortaCharacteristicNo Mood-Stabilizing Medication (N=718)Mood-Stabilizing Medication (N=1,103)Full Sampleb (N=2,307)MeanSDMeanSDMeanSDMean dose per pill (milligrams) Immediate release14.210.617.614.715.712.9 Extended release31.116.332.813.832.114.6N%N%N%Type of release Immediate release only344.7373.4883.8 Extended release only54676.083475.61,76876.6 Combination13819.223221.045119.6aData from the study cohort used in Viktorin et al. (1). The percentages represent rounded numbers.bThe full sample includes a group of 486 subjects with uncertain stabilizer exposure who were excluded from the analyses.TABLE 1. Descriptive Statistics of Methylphenidate Dispensations in the Study CohortaEnlarge tableWe agree with Dr. Ketter and Dr. Dell’Osso that more details are needed in the extent to which stimulants and antidepressants can be safely used, not only regarding dose, medication combinations, and bipolar disorder subtypes, but also regarding interindividual variation in the form of genetic or environmental factors.From the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, and the Seaver Autism Center for Research and Treatment at Mount Sinai, New York.Address correspondence to Dr. Viktorin ([email protected]).The authors’ disclosures accompany the original article.References1 Viktorin A, Rydén E, Thase ME, et al.: The risk of treatment-emergent mania with methylphenidate in bipolar disorder. Am J Psychiatry 2017; 174:341–348Link, Google Scholar2 Sellgren C, Landén M, Lichtenstein P, et al.: Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden. Acta Psychiatr Scand 2011; 124:447–453Crossref, Medline, Google Scholar3 Viktorin A, Lichtenstein P, Thase ME, et al.: The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer. Am J Psychiatry 2014; 171:1067–1073Link, Google Scholar4 Altshuler LL, Sugar CA, McElroy SL, et al.: Switch rates during acute treatment for bipolar II depression with lithium, sertraline, or the two combined: a randomized double-blind comparison. Am J Psychiatry 2017; 174:266–276Link, Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 174Issue 8 August 01, 2017Pages 804-805 Metrics KeywordsStimulantsBipolar DisorderADHDAttention Deficit Hyperactivity DisorderMethylphenidateMood DisordersPDF download History Accepted 1 June 2017 Published online 1 August 2017 Published in print 1 August 2017