Determining the duration of antidepressant treatment: application of signal detection methodology and the need for duration adaptive designs (DAD).
BACKGROUND
With remission now the treatment goal, antidepressant trial duration has increased. However, most patients do not remit and are exposed to prolonged, ineffective treatment.


METHODS
Conditional probabilities and signal detection methodology were contrasted in early detection of nonremitters in three comparator, 12-week antidepressant trials conducted in late- or mid-life depression.


RESULTS
The mid- and late-life samples did not differ in rates or time-to-onset of remission or accuracy of early identification of nonremission. Using conditional probabilities, there were marked differences in predictive power depending on the remission criterion. With signal detection methods, sensitivity and specificity of early identification were uniform across the differing medication conditions, remission criteria, and the three studies. By week 6, > or = 60% of ultimate nonremitters were identified, while maintaining a false positive rate < or = 20%.


CONCLUSIONS
The goals of providing maximal opportunity to achieve remission, while minimizing exposure to ineffective treatment can be satisfied by use of duration adaptive designs (DAD). While use of conditional probabilities has been the traditional method for early detection of nonremitters, this approach is inferior to use of signal detection methods. The findings also contradicted the widely held view that patients with late-life depression require longer treatment duration.
Sackeim
Harold A
HA
Department of Biological Psychiatry, New York State Psychiatric Institute, New York 10032, USA. has1@columbia.edu
Roose
Steven P
SP
Lavori
Philip W
PW
D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005473:Fluoxetine / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D009661:Nortriptyline / Q000008:administration & dosage* / Q000009:adverse effects; D010552:Personality Assessment / Q000706:statistics & numerical data; D011336:Probability; D011594:Psychometrics; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012189:Retrospective Studies; D020280:Sertraline / Q000008:administration & dosage* / Q000009:adverse effects; D017603:Signal Detection, Psychological
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D009661:Nortriptyline; D020280:Sertraline