Background

Akathisia is a neuropsychiatric syndrome that is commonly related to the use of dopamine antagonist/partial agonists. The characteristics of cariprazine-related akathisia, restlessness, and extrapyramidal symptoms (EPS) were investigated in patients with bipolar I depression.

Methods

Akathisia-related data from 3 fixed-dose clinical studies of cariprazine 1.5 mg/d and 3 mg/d in bipolar depression were evaluated in pooled post hoc analyses. Outcomes related to treatment-emergent adverse events (TEAEs) included incidence, time to onset, time to resolution, severity, discontinuations, and rescue medication use.

Results

The incidence of akathisia was 7.6% for overall cariprazine (1.5 mg/d=5.5%; 3 mg/d=9.6%) and 2.1% for placebo; acute EPS occurred in 4.5% of cariprazine-treated (1.5 mg/d=3.8%; 3 mg/d=5.1%) and 2.1% of placebo-treated patients. Findings were similar for restlessness. Most TEAEs were mild/moderate (>95%), occurred during the first 3 weeks of cariprazine initiation or dose increase, and resulted in few discontinuations (<3%); median time to resolution of an akathisia or EPS TEAE after the last dose of cariprazine was ∼1 week. Rescue medication was used by <3% of patients to manage akathisia/EPS events.

Limitations

Post hoc analyses; no active comparator.

Conclusions

In patients with bipolar depression, the incidence of cariprazine-related akathisia was higher than acute EPS or restlessness, with lower cariprazine doses associated with lower incidences of events. Akathisia and EPS TEAEs occurred early in treatment and were mild/moderate in severity. Few patients with akathisia or acute EPS discontinued treatment, suggesting that TEAEs were well tolerated. Cariprazine-related akathisia and EPS can be minimized with conservative dosing and titration strategies.

Trial Registration

ClinicalTrials.gov Identifiers: NCT01396447, NCT02670538, NCT02670551

中文翻译：

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双相抑郁症患者的卡吡嗪和运动障碍，躁动不安和锥体外系症状

背景

静坐症是一种神经精神综合症，通常与使用多巴胺拮抗剂/部分激动剂有关。对患有双相性I型抑郁症的患者进行了卡比拉嗪相关的静息，躁动不安和锥体外系症状（EPS）的特征调查。

方法

在合并的事后分析中评估了来自3例固定剂量卡比拉嗪1.5 mg / d和3 mg / d在双相抑郁症中与静坐相关的数据。与治疗紧急不良事件（TEAE）相关的结果包括发生率，发病时间，解决时间，严重程度，停药和抢救药物。

结果

总体cariprazine的静坐不全发生率为7.6％（1.5 mg / d = 5.5％； 3 mg / d = 9.6％）和安慰剂2.1％；在接受卡哌拉嗪治疗的患者中有4.5％（1.5 mg / d = 3.8％; 3 mg / d = 5.1％）和安慰剂治疗的患者2.1％出现了急性EPS。对于躁动不安的发现相似。大多数TEAE属于轻度/中度（> 95％），发生在卡比拉嗪起始或剂量增加的前3周内，几乎没有中断（<3％）；最后一次卡比拉嗪注射后，静坐或EPS TEAE消退的中位时间约为1周。少于3％的患者使用抢救药物来管理静坐/ EPS事件。

局限性

事后分析；没有活动的比较器。

结论

在患有双相抑郁症的患者中，卡比拉嗪相关的静坐症的发生率高于急性EPS或躁动不安，而卡比拉嗪剂量的降低与事件发生率的降低相关。静坐症和EPS TEAEs发生在治疗初期，严重程度为轻度/中度。很少有静坐不全或急性EPS患者停止治疗，这表明TEAE耐受性良好。保守的剂量和滴定策略可以使卡比拉嗪相关的静坐症和EPS降至最低。

试用注册

ClinicalTrials.gov标识符：NCT01396447，NCT02670538，NCT02670551