NEW ORLEANS – Low-dose cariprazine (Vraylar) has been associated with reduced anxiety in patients with major depressive disorder (MDD), and potential adjunct therapy for this population has also demonstrated improvements in most individual symptoms of depression, according to two post hoc analyzes of a phase III trial.
When combined with an antidepressant for patients with MDD who had an inadequate response to monotherapy, a daily dose of cariprazine 1.5 mg showed a significantly greater reduction in anxiety compared to placebo on Hamilton Anxiety Rating Scale (HAM-A) total score, as measured by least squares mean difference (LSMD) from baseline.
At week 6, patients receiving the 1.5 mg dose had a reduction of 9.1 compared to a reduction of 7.8 in the placebo group (LSMD -1.30, 95% CI -2.47 at -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 the Psych Congress. No significant difference from placebo was observed among trial participants who received a daily dose of 3 mg.
The second analysis, also presented by Maletic, showed significant improvements with cariprazine on eight of the 10 components of the Montgomery-Åsberg Depression Rating Scale (MADRS) when data for the two doses were pooled.
“In people who have not responded to their previous antidepressant treatments, if they receive cariprazine [the] the indication is that it will not only provide assistance with their depressive symptomatology, but will clearly produce a reduction in anxiety in patients who have mild and moderate disturbances. [anxiety],” he said MedPage today.
The first results of the phase III trial – study 3111-301-001 – were reported earlier this year at the annual meeting of the American Psychiatric Association. The trial met its primary endpoint, demonstrating that adjuvant cariprazine at the lowest dose resulted in a significant reduction in the MADRS total score in these patients with MDD.
Effect on anxiety
When the study population data were divided into groups based on baseline anxiety severity, participants with at least mild anxiety (HAM-A score >7) or anxiety at least moderate (> 14) had better results with the lower dose of cariprazine compared to 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 from either dose of cariprazine in addition to a background antidepressant, but results were not significant, due to small sample size, according to Maletic.
“We cannot speak of serious [anxiety] because it is not statistically significant, but at least numerical indicators [show] that all categories of anxiety patients are likely to benefit from this combination,” he said. 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 antidepressant treatment. At baseline, almost all participants (98.8%) had at least mild anxiety. Of these, 82.6% suffered from at least moderate anxiety and 34.9% suffered from severe anxiety.
Effect on MADRS Components
Maletic reported that adjuvant cariprazine also produced significantly greater improvement on multiple MADRS scores for individual depressive symptoms compared to placebo.
Significant improvements were observed compared to placebo with the 1.5 mg daily dose for seven of the 10 MADRS symptoms, and pooled data for both doses of cariprazine 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)
- Tiredness: 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)
- Thoughts of suicide: 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 results of the current study, developer AbbVie has submitted a supplemental new drug application for an additional indication as an add-on treatment for MDD in patients receiving ongoing antidepressant therapy.
The study was sponsored by AbbVie.
Maletic reported financial relationships with AbbVie/Allergan, Acadia, Alfasigma, Alkermes, Axsome, Eisai-Purdue, Intra-Cellular, Ironshore, Janssen, Lundbeck A/S, Jazz Pharmaceuticals, Noven, Otsuka, Sage, Sunovion, Supernus and Takeda ; the co-authors also stated that they are employees of or hold stock/options of AbbVie.