Abstract
Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original. Methods: Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. Results: The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p <.001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days. Conclusions: Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 250-256 |
| Number of pages | 7 |
| Journal | Biological Psychiatry |
| Volume | 74 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 15 2013 |
| Externally published | Yes |
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Keywords
- Antidepressant
- experimental therapeutics
- glutamate
- ketamine
- major depressive disorder
- treatment-resistant depression
ASJC Scopus subject areas
- Biological Psychiatry
Cite this
Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. / Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; Aan Het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.
In: Biological Psychiatry, Vol. 74, No. 4, 15.08.2013, p. 250-256.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression
AU - Murrough, James W.
AU - Perez, Andrew M.
AU - Pillemer, Sarah
AU - Stern, Jessica
AU - Parides, Michael K.
AU - Aan Het Rot, Marije
AU - Collins, Katherine A.
AU - Mathew, Sanjay J.
AU - Charney, Dennis S.
AU - Iosifescu, Dan V.
PY - 2013/8/15
Y1 - 2013/8/15
N2 - Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original. Methods: Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. Results: The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p <.001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days. Conclusions: Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.
AB - Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original. Methods: Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. Results: The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p <.001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days. Conclusions: Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.
KW - Antidepressant
KW - experimental therapeutics
KW - glutamate
KW - ketamine
KW - major depressive disorder
KW - treatment-resistant depression
UR - http://www.scopus.com/inward/record.url?scp=84880767967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880767967&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2012.06.022
DO - 10.1016/j.biopsych.2012.06.022
M3 - Article
VL - 74
SP - 250
EP - 256
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 4
ER -