0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letters to the Editor   |    
Dr. Valenstein and Colleagues Reply
MARCIA VALENSTEIN; JOHN F. McCARTHY; KAREN L. AUSTIN; JOHN F. GREDEN; ELIZABETH A. YOUNG; FREDERIC C. BLOW
Am J Psychiatry 2006;163:2197-2197.

To the Editor: Given the research evidence, we understand Dr. Terao’s surprise regarding the infrequent use of lithium and the more common use of a second antidepressant or an atypical antipsychotic as antidepressant augmenting agents in U.S. clinical settings. Only our familiarity with clinical treatments in the United States and the literature on providers’ treatment preferences tempered our own surprise at these findings (1).

Dr. Terao suggests the observed low use of lithium may have resulted because providers “automatically” diagnose patients who are prescribed lithium as having bipolar disorder rather than depressive disorders, and the latter were excluded from study analyses. He notes that lithium has an FDA indication for bipolar disorder but not for antidepressant augmentation. He further suggests that the definition of antidepressant augmentation, which required >60 days of overlap between an augmenting agent and an antidepressant, might have excluded patients who initiated but discontinued lithium in <60 days because of rapid treatment responses.

Unfortunately, we do not believe that these methodological issues explain our findings.

First, U.S. physicians commonly use medications “off-label” for non-FDA approved indications. Few would feel compelled to re-diagnose depressed patients as having bipolar I disorder—a diagnosis that requires a manic episode and has different prognostic and treatment implications—to be concordant with FDA indications. However, physicians may make subtle diagnostic “shifts” when there are less distinct boundaries. Thus, we included patients in our cohort who received both depression and bipolar II diagnoses. Even then, rates of lithium use were low.

We required ≥60 days of overlap between potential augmenting agents and antidepressant medications to avoid misclassifying patients as receiving augmentation when they were actually switching or cross-tapering medications. We assumed that physicians generally continue augmentation when patients have a good response. When we reduced the required days of overlap, rates of lithium augmentation remained low. Only 1,672 (0.68%) of the 244,859 patients in our study had ≥30 days overlap of lithium and an antidepressant and only 2,035 (0.8%) received any lithium at all during the year.

The data, in our judgment, continue to indicate that lithium augmentation is seldom used in clinical practice. The reasons are uncertain. Concerns about safety, tolerability, convenience and stigma may play a role. Lithium may be less effective when coupled with selective serotonin reuptake inhibitors than with tricyclic agents (2), and the lithium use is not actively promoted by large pharmaceutical companies. Rigorous randomized controlled trials that directly compare lithium and the more popular augmenting agents are urgently needed.

1.Fredman SJ, Fava M, Kienke AS, White CN, Nierenberg AA, Rosenbaum JF: Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current "next-step" practices. J Clin Psychiatry 2000; 61:403–408
 
2.Birkenhager TK, van den Broek WW, Mulder PG, Bruijn JA, Moleman P: Comparison of two-phase treatment with imipramine or fluvoxamine, both followed by lithium addition, in inpatients with major depressive disorder. Am J Psychiatry 2004; 161:2060–2065
 
+

References

1.Fredman SJ, Fava M, Kienke AS, White CN, Nierenberg AA, Rosenbaum JF: Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current "next-step" practices. J Clin Psychiatry 2000; 61:403–408
 
2.Birkenhager TK, van den Broek WW, Mulder PG, Bruijn JA, Moleman P: Comparison of two-phase treatment with imipramine or fluvoxamine, both followed by lithium addition, in inpatients with major depressive disorder. Am J Psychiatry 2004; 161:2060–2065
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Books
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 12.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 9.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 12.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 1.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 12.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles
The history of lithium therapy. Bipolar Disord 2009;11 Suppl 2():4-9.
A review of FDA-approved treatment options in bipolar depression. CNS Spectr 2013;18 Suppl 1():4-20; quiz 21.