Quetiapine for Bipolar Depression
Quetiapine (Seroquel) is highly effective as monotherapy for the acute treatment of bipolar depression and should be considered a first-line treatment option. 1, 2
Efficacy and FDA Approval
- Quetiapine is FDA-approved for the acute treatment of depressive episodes associated with bipolar disorder 1
- Efficacy was established in two 8-week monotherapy trials in adult patients with both bipolar I and bipolar II disorder 1
- Quetiapine produces rapid and sustained improvements in depressive and anxiety symptoms in bipolar depression 2
- Standard dosing is 300 mg/day, with no additional benefit demonstrated at higher doses of 600 mg/day 3
Clinical Benefits
- Quetiapine is the only atypical antipsychotic approved for use as monotherapy in both bipolar mania and depression, offering potential compliance advantages 2
- Quetiapine improves health-related quality of life in patients with bipolar depression 2
- Importantly, quetiapine is not associated with an increased risk of treatment-emergent mania, a significant concern with traditional antidepressants in bipolar disorder 2
Mechanism of Action
- The antidepressant effects of quetiapine may be related to:
- Antagonism of 5-HT2A receptors in cortical regions
- Partial agonism of 5-HT1A in the prefrontal cortex
- Reduced synaptic reuptake of noradrenaline via its metabolite norquetiapine 3
Maintenance Treatment
- Quetiapine is also effective for maintenance treatment of bipolar I disorder, though FDA-approved only as an adjunct to lithium or divalproex for this indication 1
- Patients who respond to quetiapine during acute treatment benefit from continuing therapy for up to 52 weeks 3
- Maintenance therapy with quetiapine for up to 104 weeks is more efficacious than placebo in prolonging time to recurrence of any mood event 3
Side Effects and Tolerability
- Most common side effects include:
- Dry mouth
- Sedation/somnolence
- Dizziness
- Constipation
- Increased appetite 3
- Most treatment-emergent adverse events are mild to moderate in severity 3
- Extrapyramidal symptoms are generally not significantly different from placebo 3
- Some patients experience weight gain and may have clinically relevant increases in blood glucose or lipid parameters 3
Cautions
- Treatment with SSRIs should be avoided in patients with bipolar depression due to risk of mania 4
- Quetiapine should be used with caution when combined with other serotonergic agents due to risk of serotonin syndrome 5
Combination Therapy
- For treatment-resistant bipolar depression, combination therapy with lamotrigine plus quetiapine may be effective 6
- In one study, this combination increased euthymia rates from 0% to 46.2% and decreased syndromal depression rates from 79.5% to 30.8% 6
Quetiapine represents an important treatment option for bipolar depression with established efficacy, tolerability, and the advantage of not inducing manic switches that can occur with traditional antidepressants.