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Safety and tolerability of vortioxetine (15 and 20 mg) in patients with major depressive disorder: results of an open-label, flexible-dose, 52-week extension study.

Jacobsen PL, Harper L, Chrones L, Chan S, Mahableshwarkar AR - Int Clin Psychopharmacol (2015)

Bottom Line: Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache.In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine were safe and well tolerated.After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period.

View Article: PubMed Central - PubMed

Affiliation: aTakeda Development Center Americas Inc., Deerfield, Illinois bCNS Healthcare, Orlando, Florida, USA.

ABSTRACT
Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery-Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ-4.2), the Clinical Global Impression Scale-Severity of Illness (Δ-1.2), and the Sheehan Disability Scale (Δ-4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine were safe and well tolerated. After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period.

No MeSH data available.


Related in: MedlinePlus

Mean HAM-A total scores by study visit for the OLE study (NCT01152996) and three DB feeder studies (OC). DB, double blind; HAM-A, Hamilton Anxiety Scale; OC, observed case; OLE, open-label extension.
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Figure 4: Mean HAM-A total scores by study visit for the OLE study (NCT01152996) and three DB feeder studies (OC). DB, double blind; HAM-A, Hamilton Anxiety Scale; OC, observed case; OLE, open-label extension.

Mentions: Measures of depression (MADRS), anxiety (HAM-A), global symptoms (CGI-S), and overall functioning (SDS) were assessed at the baseline visit in the short-term DB lead-in study and at the baseline visit in the OLE study. For all the measures of effectiveness, regardless of the study of origin, improvements achieved during the DB period were maintained, and additional improvements were observed during the OLE study. Among the patients in the OLE study, the mean MADRS total score (±SD) decreased from 32.8±4.3 at the start of the initial DB studies to 19.9±10.7 at the OLB, and it was further reduced during the OLE study to 9.0±9.0 by week 52 (OC; Fig. 3). A similar improvement in measures of anxiety was observed during the extension study. The mean HAM-A total score, which decreased from 18.8±5.5 at the start of the initial DB studies to 11.5±6.6 at the start of the OLE study, further decreased to 6.3±5.8 (OC) by week 52 (Fig. 4). The improvements seen in the short-term study for CGI-S were maintained, and improvement continued in the long-term study. The mean CGI-S total score decreased throughout the study from 4.6±0.6 at the start of the DB studies to 3.3±1.2 at the start of the OLE study. At week 52, the mean score was 2.0±1.1 (OC), corresponding to a change from the OLE baseline of −1.2±1.3 (Fig. 5). The mean SDS total score decreased during the OLE study from 11.3±7.7 at OLB to 5.7±6.4 (OC) at week 52 (Fig. 6).


Safety and tolerability of vortioxetine (15 and 20 mg) in patients with major depressive disorder: results of an open-label, flexible-dose, 52-week extension study.

Jacobsen PL, Harper L, Chrones L, Chan S, Mahableshwarkar AR - Int Clin Psychopharmacol (2015)

Mean HAM-A total scores by study visit for the OLE study (NCT01152996) and three DB feeder studies (OC). DB, double blind; HAM-A, Hamilton Anxiety Scale; OC, observed case; OLE, open-label extension.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525811&req=5

Figure 4: Mean HAM-A total scores by study visit for the OLE study (NCT01152996) and three DB feeder studies (OC). DB, double blind; HAM-A, Hamilton Anxiety Scale; OC, observed case; OLE, open-label extension.
Mentions: Measures of depression (MADRS), anxiety (HAM-A), global symptoms (CGI-S), and overall functioning (SDS) were assessed at the baseline visit in the short-term DB lead-in study and at the baseline visit in the OLE study. For all the measures of effectiveness, regardless of the study of origin, improvements achieved during the DB period were maintained, and additional improvements were observed during the OLE study. Among the patients in the OLE study, the mean MADRS total score (±SD) decreased from 32.8±4.3 at the start of the initial DB studies to 19.9±10.7 at the OLB, and it was further reduced during the OLE study to 9.0±9.0 by week 52 (OC; Fig. 3). A similar improvement in measures of anxiety was observed during the extension study. The mean HAM-A total score, which decreased from 18.8±5.5 at the start of the initial DB studies to 11.5±6.6 at the start of the OLE study, further decreased to 6.3±5.8 (OC) by week 52 (Fig. 4). The improvements seen in the short-term study for CGI-S were maintained, and improvement continued in the long-term study. The mean CGI-S total score decreased throughout the study from 4.6±0.6 at the start of the DB studies to 3.3±1.2 at the start of the OLE study. At week 52, the mean score was 2.0±1.1 (OC), corresponding to a change from the OLE baseline of −1.2±1.3 (Fig. 5). The mean SDS total score decreased during the OLE study from 11.3±7.7 at OLB to 5.7±6.4 (OC) at week 52 (Fig. 6).

Bottom Line: Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache.In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine were safe and well tolerated.After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period.

View Article: PubMed Central - PubMed

Affiliation: aTakeda Development Center Americas Inc., Deerfield, Illinois bCNS Healthcare, Orlando, Florida, USA.

ABSTRACT
Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery-Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ-4.2), the Clinical Global Impression Scale-Severity of Illness (Δ-1.2), and the Sheehan Disability Scale (Δ-4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine were safe and well tolerated. After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period.

No MeSH data available.


Related in: MedlinePlus