Dosing Tips

✽ More may be much more: clinical practice suggests quetiapine often underdosed, then switched prior to adequate trials

• Clinical practice suggests that at low doses it may be a sedative hypnotic, possibly due to potent H1 antihistamine actions, but this can risk numerous antipsychotic-related side effects and there are many other options

✽ Initial target dose of 400–800 mg/day should be reached in most cases to optimize the chances of success in treating acute psychosis and acute mania, but many patients are not adequately dosed in clinical practice

• Many patients do well with immediate-release as a single daily oral dose, usually at bedtime

• Recommended titration to 400 mg/day by the fourth day can often be achieved when necessary to control acute symptoms

• Rapid dose escalation in manic or psychotic patients may lessen sedative side effects

✽ Higher doses generally achieve greater response for manic or psychotic symptoms

• In contrast, some patients with bipolar depression may respond well to doses less than 300 mg/day and as little as 25 mg/day

• Dosing in major depression may be even lower than in bipolar depression, and dosing may be even lower still in generalized anxiety disorder

✽ Occasional patients may require more than 800–1,200 mg/day for psychosis or mania

• Rather than raise the dose above these levels in acutely agitated patients requiring acute antipsychotic actions, consider augmentation with a benzodiazepine or conventional antipsychotic, either orally or intramuscularly

• Rather than raise the dose above these levels in partial responders, consider augmentation with a mood-stabilizing anticonvulsant such as valproate or lamotrigine

• Children and elderly should generally be dosed at the lower end of the dosage spectrum

• Quetiapine XR is controlled-release and therefore should not be chewed or crushed but rather should be swallowed whole

• Quetiapine XL may theoretically generate increased concentrations of active metabolite norquetiapine, with theoretically improved profile for affective and anxiety disorders

• Treatment should be suspended if absolute neutrophil count falls below 1,000/mm³

Overdose

• Rarely lethal in monotherapy overdose; sedation, slurred speech, hypotension

Long-Term Use

• Approved for long-term maintenance in schizophrenia and bipolar disorder, and often used for long-term maintenance in various behavioral disorders

Habit Forming

• No

How to Stop

• See also the Switching section of individual agents for how to stop quetiapine

• Rapid discontinuation may lead to rebound psychosis and worsening of symptoms

Pharmacokinetics

• Parent drug has 6–7 hour half-life

Drug Interactions

• CYP450 3A inhibitors and CYP450 2D6 inhibitors may reduce clearance of quetiapine and thus raise quetiapine plasma levels, but dosage reduction of quetiapine usually not necessary

• May increase effect of anti-hypertensive agents

Other Warnings/Precautions

• In the U.S., manufacturer recommends examination for cataracts before and every 6 months after initiating quetiapine, but this does not seem to be necessary in clinical practice

• Quetiapine should be used cautiously in patients at risk for aspiration pneumonia, as dysphagia has been reported

• Priapism has been reported

• Use with caution in patients with known cardiovascular disease, cerebrovascular disease

• Use with caution in patients with conditions that predispose to hypotension (dehydration, overheating)

• Monitor patients for activation of suicidal ideation, especially children and adolescents

• Avoid use with drugs that increase the QT interval and in patients with risk factors for prolonged QT interval

Do Not Use

• If there is a proven allergy to quetiapine

QUETIAPINE: SPECIAL POPULATIONS

Renal Impairment

• No dose adjustment required

Hepatic Impairment

• Downward dose adjustment may be necessary

Cardiac Impairment

• Drug should be used with caution because of risk of orthostatic hypotension

Elderly

• Lower dose is generally used (e.g., 25–100 mg twice a day), although higher doses may be used if tolerated

• Although atypical antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with dementia-related psychosis

• Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events