PRACTICAL GUIDELINES ON THE USE OF CARIPRAZINE IN BIPOLAR 1 DISORDER: EXPERT CONSENSUS FROM SOUTHEAST ASIA
Authors: Sulaiman *Ahmad Hatim , Amin Mustafa M , Ang Jin Kiat , Ho Roger , Jaafar Nik Ruzyanei Nik , Ng Chong Guan , Nurhidayat Adhi Wibowo , Paholpak Pongsatorn , Pariwatcharakul Pornjira , Sanguanvichaikul Thitima , Ung Eng Khean , Wardani Natalia Dewi , Yeo Brian , Correll Christoph U 
Published: February 2025

Abstract

Background
Cariprazine, a D3/D2 partial agonist with preferential binding to D3 receptors, is one of the few treatment options for acute manic, mixed, and depressive episodes associated with bipolar 1 disorder (BP1D) that is approved by regulatory authorities in some countries including those from Southeast Asia.

Aims and Objectives
An expert panel from Southeast Asia convened to consolidate practical recommendations and real-world application of cariprazine in managing adults with BP1D.

Methodology
The modified RAND-UCLA Appropriateness Method was employed in consensus development. Clinical scenarios were created based on a thematic literature search. Fourteen expert psychiatrists were invited to participate in the expert panel meeting. Two rounds of ratings were conducted to rate the appropriateness of clinical scenarios (on a 9-point Likert Scale) and a face-to-face discussion among the experts took place before the second round of rating. Results were presented as descriptive statistics.
Disagreement was defined as more than one-third of participants voting at the lowest 3 scales (1 to 3) and more than one-third of the participants voting at the highest 3 scales (7 to 9). In the absence of disagreement, a clinical scenario is “appropriate” if the median score is within 7 to 9, “equivocal” if the median score is 4 to 6, and “inappropriate” if the median score is within 1 to 3. Clinical scenarios were then converted to consensus statements.

Results
The thematic literature search identified 41 published manuscripts that were used to facilitate creation of clinical scenarios for acute mania or mixed episodes and depression associated with BP1D. For bipolar depression, the majority of the expert panel (85%) recommended that the minimum duration of cariprazine treatment to consider an effective trial is 4-8 weeks for bipolar depression; for acute mania/mixed episodes, the majority of the expert panel (71%) recommended 3-4 weeks duration.
Conversely, recommendations on the duration of cariprazine use in the maintenance phase varied among the experts, with the majority recommending &gt;1 year of treatment (62%). The panel agreed that cariprazine for BP1D is appropriate as monotherapy in most cases (bipolar depression - median [Mdn]: 8, interquartile range [IQR]: 8;9; acute mania/mixed – Mdn:8; IQR: 8;9) and as combination therapy for certain scenarios in bipolar depression (Mdn:8; IQR: 8;9) and acute mania or mixed episodes (Mdn:8; IQR: 8;9). Likewise, the panel had similar views on cariprazine’ s suitability as first-line treatment in bipolar depression (Mdn:8; IQR: 8;9) and acute mania/mixed episodes (Mdn:8; IQR: 8;9). Furthermore, the panel was in agreement that cariprazine may be appropriate for first episode bipolar depression (Mdn:8; IQR: 8;9) and acute mania/mixed episodes (Mdn:8; IQR:8;9). The panel also recommended suitability of higher or lower dose of cariprazine in various clinical scenarios in BP1D.

Conclusion
These consensus recommendations on the use of cariprazine in BP1D may serve as practical guidance to support the clinical decision making of psychiatrists on the management of their adult patients with BP1D.