Abstract
Background Bipolar depression is more pervasive than mania, but has fewer evidence-based treatments.
Methods Using data from multicenter, randomized, double-blind, placebo-controlled trials and meta-analyses, we assessed the number needed to treat (NNT) for response and the number needed to harm (NNH) for selected side effects for older and newer acute bipolar depression treatments.
Results The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC, NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability (NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently demonstrated in randomized controlled trials.
Limitations NNT and NNH are categorical metrics; only selected NNHs were assessed; limited generalizability of efficacy (versus effectiveness) studies.
Conclusion For acute bipolar depression, older approved treatments may have utility in high-urgency situations, whereas lamotrigine and antidepressants may have utility in low-urgency situations. Newly approved lurasidone may ultimately prove useful in diverse situations. New drug development needs to focus on not only efficacy but also on tolerability.
| Original language | English |
|---|---|
| Pages (from-to) | S24-S33 |
| Journal | Journal of Affective Disorders |
| Volume | 169 |
| Issue number | S1 |
| DOIs | |
| Publication status | Published - Dec 1 2014 |
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Keywords
- Antidepressants
- Antidepressants
- Antipsychotics
- Armodafinil
- Bipolar depression
- Bipolar disorder
- Lamotrigine
- Lurasidone
- Mood stabilizers
- Number needed to harm
- Number needed to treat
- Olanzapine plus fluoxetine
- Quetiapine
ASJC Scopus subject areas
- Psychiatry and Mental health
- Clinical Psychology
- Medicine(all)
Cite this
Balancing benefits and harms of treatments for acute bipolar depression. / Ketter, Terence A.; Miller, Shefali; Dell'Osso, Bernardo; Calabrese, Joseph R.; Frye, Mark A.; Citrome, Leslie.
In: Journal of Affective Disorders, Vol. 169, No. S1, 01.12.2014, p. S24-S33.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Balancing benefits and harms of treatments for acute bipolar depression
AU - Ketter, Terence A.
AU - Miller, Shefali
AU - Dell'Osso, Bernardo
AU - Calabrese, Joseph R.
AU - Frye, Mark A.
AU - Citrome, Leslie
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Background Bipolar depression is more pervasive than mania, but has fewer evidence-based treatments.Methods Using data from multicenter, randomized, double-blind, placebo-controlled trials and meta-analyses, we assessed the number needed to treat (NNT) for response and the number needed to harm (NNH) for selected side effects for older and newer acute bipolar depression treatments.Results The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC, NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability (NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently demonstrated in randomized controlled trials.Limitations NNT and NNH are categorical metrics; only selected NNHs were assessed; limited generalizability of efficacy (versus effectiveness) studies.Conclusion For acute bipolar depression, older approved treatments may have utility in high-urgency situations, whereas lamotrigine and antidepressants may have utility in low-urgency situations. Newly approved lurasidone may ultimately prove useful in diverse situations. New drug development needs to focus on not only efficacy but also on tolerability.
AB - Background Bipolar depression is more pervasive than mania, but has fewer evidence-based treatments.Methods Using data from multicenter, randomized, double-blind, placebo-controlled trials and meta-analyses, we assessed the number needed to treat (NNT) for response and the number needed to harm (NNH) for selected side effects for older and newer acute bipolar depression treatments.Results The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC, NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability (NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently demonstrated in randomized controlled trials.Limitations NNT and NNH are categorical metrics; only selected NNHs were assessed; limited generalizability of efficacy (versus effectiveness) studies.Conclusion For acute bipolar depression, older approved treatments may have utility in high-urgency situations, whereas lamotrigine and antidepressants may have utility in low-urgency situations. Newly approved lurasidone may ultimately prove useful in diverse situations. New drug development needs to focus on not only efficacy but also on tolerability.
KW - Antidepressants
KW - Antidepressants
KW - Antipsychotics
KW - Armodafinil
KW - Bipolar depression
KW - Bipolar disorder
KW - Lamotrigine
KW - Lurasidone
KW - Mood stabilizers
KW - Number needed to harm
KW - Number needed to treat
KW - Olanzapine plus fluoxetine
KW - Quetiapine
UR - http://www.scopus.com/inward/record.url?scp=84919668795&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919668795&partnerID=8YFLogxK
U2 - 10.1016/S0165-0327(14)70006-0
DO - 10.1016/S0165-0327(14)70006-0
M3 - Article
VL - 169
SP - S24-S33
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
SN - 0165-0327
IS - S1
ER -