Clinical value of early partial symptomatic improvement in the prediction of response and remission during short-term treatment trials in 3369 subjects with bipolar I or II depression.
OBJECTIVE
To evaluate the clinical value of early partial symptomatic improvement in predicting the probability of response during the short-term treatment of bipolar depression.


METHODS
Blinded data from 10 multicenter, randomized, double-blind, placebo-controlled trials in bipolar I or II depression were used to determine if early improvement (≥20% reduction in depression symptom severity after 14 days of treatment) predicted later short-term response or remission. Sensitivity, specificity, efficiency, and positive and negative predictive values (PPV, NPV) were calculated using an intent to treat analysis of individual and pooled study data.


RESULTS
1913 patients were randomized to active compounds (aripiprazole, lamotrigine, olanzapine/olanzapine-fluoxetine, and quetiapine), and 1456 to placebo. In the pooled positive studies, early improvement predicted response and remission with high sensitivity (86% and 88%, respectively), but rates of false positives were high (53% and 59%, respectively). Pooled negative predictive values for response/remission (i.e. confidence in knowing the drug will not result in response or remission) were 74% and 82%, respectively, with low rates of false negatives (14% and 12%, respectively).


CONCLUSIONS
Early improvement in an individual patient does not appear to be a reliable predictor of eventual response or remission due to an unacceptably high false positive rate. However, the absence of early improvement appears to be a highly reliable predictor of eventual non-response, suggesting that clinicians can have confidence in knowing when a drug is not going to work during short-term treatment. Patients who fail to demonstrate early improvement within the first two weeks of treatment may benefit from a change in therapy.
Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH, USA. kemp.david@gmail.com
David E
DE
Kemp
Stephen J
SJ
Ganocy
Martin
M
Brecher
Berit X
BX
Carlson
Suzanne
S
Edwards
James M
JM
Eudicone
Gary
G
Evoniuk
Wim
W
Jansen
Andrew C
AC
Leon
Margaret
M
Minkwitz
Andrei
A
Pikalov
Hans H
HH
Stassen
Armin
A
Szegedi
Mauricio
M
Tohen
Arjen P P
AP
Van Willigenburg
Joseph R
JR
Calabrese
D018687:Antidepressive Agents, Second-Generation; D018692:Antimanic Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D000077213:Lamotrigine; D000077152:Olanzapine; D010879:Piperazines / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000627:therapeutic use; D012074:Remission Induction; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use
D018687:Antidepressive Agents, Second-Generation; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D015363:Quinolones; D014227:Triazines; D005473:Fluoxetine; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000068180:Aripiprazole; D000077152:Olanzapine; D000077213:Lamotrigine