Low-Dose Cariprazine for MDD Tied to Anxiety Reduction

NEW ORLEANS — Low-dose cariprazine (Vraylar) was associated with reductions in anxiety for patients with major depressive disorder (MDD), and the potential adjunctive therapy for this population also demonstrated improvements across most individual symptoms of depression, according to two post hoc analyses of a phase III trial.

When combined with an antidepressant for MDD patients who had an inadequate response to monotherapy, a 1.5-mg daily dose of cariprazine showed a significantly greater reduction in anxiety compared with placebo on the Hamilton Anxiety Rating Scale (HAM-A) total score, as measured by the least squares mean difference (LSMD) from baseline.

At week 6, patients on the 1.5-mg dose had a 9.1 reduction compared with a 7.8 reduction in the placebo group (LSMD -1.30, 95% CI -2.47 to -0.08, nominal P=0.037), reported Vladimir Maletic, MD, MS, of the University of South Carolina School of Medicine in Greenville, during a poster presentation at Psych Congress. No significant difference versus placebo was seen among participants in the trial who received a 3-mg daily dose.

The second analysis, also presented by Maletic, showed significant improvements with cariprazine across eight of the 10 components of the Montgomery-Åsberg Depression Rating Scale (MADRS) when data for the two doses were pooled together.

“In people who have not responded to their previous antidepressant treatments, if they receive cariprazine [the] indication is that it will provide not only assistance with their depressive symptomatology but will clearly produce reduction in anxiety in patients who have mild and moderate [anxiety],” he told MedPage Today.

Initial findings from the phase III trial — Study 3111-301-001 — were reported earlier this year at the American Psychiatric Association annual meeting. The trial met its primary endpoint, demonstrating that adjunctive cariprazine at the lower dose led to a significant reduction in MADRS total score in these patients with MDD.

Effect on Anxiety

When the data for the study population was broken into groups based on baseline anxiety severity, participants with at least mild anxiety (HAM-A score >7) or at least moderate anxiety (>14) had better outcomes with the lower dose of cariprazine compared with placebo:

• Mild: LSMD -1.3 (95% CI -2.52 to -0.10)
• Moderate: LSMD -1.6 (95% CI -2.98 to -0.23)

Participants with severe anxiety (>23) at baseline appeared to potentially derive greater benefit with either dose of cariprazine in addition to a background antidepressant, but the findings were not significant, owing to the smaller sample size, according to Maletic.

“We can’t say about severe [anxiety] because it’s not statistically significant, but at least numerical indicators [show] that all categories of anxious patients are likely to benefit by this combination,” he told MedPage Today.

The analysis included 751 participants divided into three treatment groups — cariprazine 1.5 mg (n=250), cariprazine 3 mg (n=252), and placebo (n=249) — each combined with an antidepressant treatment. At baseline, nearly all of the participants (98.8%) had at least mild anxiety. Of those, 82.6% had at least moderate anxiety, and 34.9% had severe anxiety.

Effect on MADRS Components

Maletic reported that adjunctive cariprazine also produced significantly greater improvement across several MADRS scores for individual depressive symptoms compared with placebo.

Significant improvements were seen versus placebo with the 1.5-mg daily dose for seven of the 10 MADRS symptoms, and pooled data for both cariprazine doses showed significant reductions in eight of the components:

• Apparent sadness: LSMD -0.2 (95% CI -0.44 to -0.03, P=0.0247)

• Reported sadness: LSMD -0.4 (95% CI -0.58 to -0.16, P=0.0006)

• Reduced appetite: LSMD -0.3 (95% CI -0.50 to -0.10, P=0.0036)

• Lassitude: LSMD -0.3 (95% CI -0.56 to -0.12, P=0.0025)

• Inability to feel: LSMD -0.3 (95% CI -0.51 to -0.06, P=0.0126)

• Pessimistic thoughts: LSMD -0.3 (95% CI -0.45 to -0.07, P=0.0088)

• Suicidal thoughts: LSMD -0.1 (95% CI -0.20 to -0.02, P=0.0127)

Cariprazine already carries indications in schizophrenia and bipolar I disorder. Based on the findings of the current study, developer AbbVie has submitted a supplemental new drug application for an additional indication as an adjunctive treatment of MDD in patients who are receiving ongoing antidepressant therapy.