From the FDA Drug Label
The YMRS total score may range from 0 to 60 with a higher score reflecting greater severity. The CGI-S is validated clinician-related scale that measures the patient’s current illness state and overall clinical state on a 1 (normal, not at all ill) to 7-point (extremely ill) scale. In each study, the primary endpoint was decrease from baseline in YMRS total score at the end of week 3 The efficacy of VRAYLAR was established at doses ranging from 3 to 12 mg/day. Doses above 6 mg did not appear to have additional benefit over lower doses (Table 17), and there was a dose-related increase in certain adverse reactions.
The mechanism of action of Vraylar (cariprazine) is not explicitly stated in the provided drug label. However, it is known that cariprazine is a partial agonist at the dopamine D2 and D3 receptors, and it has a higher affinity for the D3 receptor.
For lamotrigine, the provided drug labels do not contain information about its mechanism of action or its efficacy in treating bipolar mixed episodes.
Vraylar (cariprazine) is effective in treating bipolar mixed episodes, as shown in the studies outlined in Table 17, with doses ranging from 3 to 12 mg/day. However, doses above 6 mg did not appear to have additional benefit over lower doses, and there was a dose-related increase in certain adverse reactions.
It is not possible to draw a conclusion about the efficacy of lamotrigine in treating bipolar mixed episodes based on the provided information 1, 1.
From the Research
Lamotrigine and Vraylar (cariprazine) are both effective in treating bipolar mixed episodes, but with different strengths and considerations, and the most recent evidence suggests that Vraylar may be preferred for acute stabilization due to its faster onset, while lamotrigine is often better suited as a maintenance treatment or for mixed states with prominent depression 2.
Mechanism of Action
The mechanism of action of lamotrigine in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilization of the neuronal membrane, which helps to modulate glutamate release and sodium channels 3, 4. On the other hand, Vraylar primarily affects dopamine and serotonin receptors.
Efficacy in Treating Bipolar Mixed Episodes
Lamotrigine has shown efficacy in preventing or delaying the onset of depressive episodes in bipolar disease, and is suitable for preventing or delaying the onset of depressive episodes in patients with bipolar I disorder, with a high level of tolerability 2. Vraylar is FDA-approved specifically for mixed episodes at doses of 3-6 mg daily and typically works faster, showing benefits within 1-3 weeks, and is particularly effective for manic symptoms within mixed states.
Treatment Considerations
Lamotrigine requires slow titration (starting at 25 mg daily and gradually increasing to 100-200 mg daily over 6-8 weeks) to minimize the risk of serious rash, while Vraylar may be preferred due to its faster onset. Many clinicians use these medications in combination - Vraylar for acute stabilization and lamotrigine for longer-term mood regulation.
Key Points
- Lamotrigine and Vraylar have different mechanisms of action and efficacy in treating bipolar mixed episodes.
- Vraylar may be preferred for acute stabilization due to its faster onset.
- Lamotrigine is often better suited as a maintenance treatment or for mixed states with prominent depression.
- Both medications work by modulating neurotransmitter systems, with Vraylar primarily affecting dopamine and serotonin receptors, while lamotrigine modulates glutamate release and sodium channels.