What is the therapeutic dose of Seroquel (quetiapine) for bipolar 2 disorder?

Therapeutic Dose of Quetiapine for Bipolar 2 Disorder

For bipolar 2 disorder, the recommended therapeutic dose of quetiapine is 300 mg/day, administered once daily at bedtime. 1

Dosing Guidelines

According to the FDA-approved drug label, quetiapine for bipolar depression should be administered as follows:

• Day 1: 50 mg once daily at bedtime
• Day 2: 100 mg once daily at bedtime
• Day 3: 200 mg once daily at bedtime
• Day 4: 300 mg once daily at bedtime 1

The maximum recommended dose for bipolar depression is 300 mg/day. This is different from the dosing for other indications such as bipolar mania, where doses may range from 400-800 mg/day.

Evidence Supporting Efficacy

Multiple clinical trials have demonstrated the efficacy of quetiapine for bipolar 2 depression:

• Post-hoc analysis of two randomized, double-blind, placebo-controlled studies showed that both 300 mg/day and 600 mg/day doses were effective for bipolar II depression 2
• The mean change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 8 was -17.1 for 300 mg/day and -17.9 for 600 mg/day, compared to -13.3 for placebo (p=0.005 and p=0.001, respectively) 2
• Importantly, there were no significant differences in efficacy between the 300 mg/day and 600 mg/day dosages 3, supporting the use of the lower dose to minimize side effects

Time to Response

Quetiapine has demonstrated a relatively rapid onset of action:

• Significant improvement in depressive symptoms can be observed as early as week 1 2
• The median time to response (≥50% reduction in MADRS score) and remission (MADRS score ≤12) is significantly shorter with quetiapine 300 mg/day compared to placebo 4

Side Effects and Tolerability

Common side effects of quetiapine in the treatment of bipolar depression include:

• Dry mouth
• Sedation
• Somnolence
• Dizziness
• Constipation
• Increased appetite 3, 2

Most treatment-emergent adverse events are mild to moderate in severity. The 300 mg/day dose is generally better tolerated than higher doses while maintaining equivalent efficacy.

Special Considerations

1. Elderly patients: Start at 50 mg/day and increase in increments of 50 mg/day depending on clinical response and tolerability 1

2. Hepatic impairment: Start at 25 mg/day and increase daily in increments of 25-50 mg/day to an effective dose 1

3. Drug interactions:

   • When co-administered with CYP3A4 inhibitors (e.g., ketoconazole), reduce quetiapine dose to one-sixth of original dose
   • When co-administered with CYP3A4 inducers (e.g., carbamazepine), increase quetiapine dose up to 5-fold 1

Monitoring

While taking quetiapine, patients should be monitored for:

• Weight gain
• Changes in blood glucose
• Changes in lipid parameters
• Extrapyramidal symptoms (though these are relatively uncommon at the recommended dose) 3

In conclusion, while both 300 mg/day and 600 mg/day doses of quetiapine are effective for bipolar 2 depression, the 300 mg/day dose is recommended as it provides equivalent efficacy with potentially fewer side effects. The medication should be titrated gradually over 4 days to reach the target dose of 300 mg/day, administered once daily at bedtime.