Quetiapine- A Second Generation Antipsychotic

Quetiapine is a dibenzothiazepine second generation antipsychotic acts as serotonin-dopamine antagonist  (SDA), available in tablet dosage form in the strength of  25, 100 & 200 mg XR. It is developed  by Zeneca and approved by FDA in 1997.

Mode of action

It acts by blocking D2 (Dopamine), 5-HT2 (Serotonin), 5-HT6 (Serotonin), D1 (Dopamine), H1 (Histamine), α1 (Adrenergic) & α2 (Adrenergic). It acts as antipsychotic, sedative, anxiolytic, antimanic, mood stabilizer and antidepressant adjuvants.

Clinical Uses- FDA Approved

• Acute Schizophrenia in adults & ages 13-17 years
• Schizophrenia maintenance
• Acute Mania in adults & ages 10-17 years
• Bipolar maintenance
• Bipolar depression
• Depression (Adjunct)

Clinical Uses- Off Label

• Mixed mania
• Behavioral disturbance in dementias
• Behavioral disturbance in Parkinson’s disease and Lewy body dementia
• Psychosis associated with levodopa treatment in Parkinson’s disease
• Behavioral disturbances in children and adolescents
• Disorders associated with impulse control
• Severe treatment-resistant anxiety

Duration to wait to get actions     

• Psychotic & Manic symptoms may improve in 1week
• Cognition, Behavior change & Affective stabilization- several weeks
• Classically recommended to wait 4-6 weeks
• May take 16-20 weeks
• It is often under-dosed & switched prior to adequate trials
• Efficacy may be underestimated due to under dose

Initiation of medication

The initial dose is 25mg twice daily, with increments of 25-50 mg on the second and third day as tolerated, to a target dose of 300-400 mg by the fourth day depending on clinical response and tolerability, the dose may be adjusted within the range of 300-800 mg/day. Initial gradual upward titration is helpful to reduce side effects. In reality, more aggressive dosing is both tolerated & effective in treating.

Dose in Schizophrenia

Starting with 25 mg twice daily followed by rapid titration 300 mg on the 4^th day and then adjusted according to response, usual range 300–450 mg daily in 2 divided doses with Maximum 800 mg daily.

Dose in Mania

Quetiapine has robust efficacy in all aspects of Bipolar disorder. Dose started with 50 mg twice daily on day 1, 200 mg twice daily on day 4 and then adjusted according to response in steps of up to 200 mg daily to maximum 800 mg daily. The usual range 400–800 mg daily in 2 divided doses.

Bipolar depression & Quetiapine

The 1st choice treatment option is Quetiapine with usual dose is 300 mg/day on day 4 and then can be titrated to 400 mg on Day 5 and up to 600 mg by Day 8. The latest updates on treatment guidelines for bipolar depression give priority to novel treatment approaches, such as quetiapine, over more traditional ones, such as lithium or antidepressants.

Bipolar prophylaxis

Quetiapine is indicated for Bipolar prophylaxis and showed efficacy to it.

Unipolar Resistant Depression

Quetiapine is indicated as an adjunct in a dose of 150mg or 300 mg daily to SSRI/ SNRI.

In doses of 25 to 300 mg at night has been used for insomnia and sometimes Alternatives to clozapine. It is the only antipsychotic approved for all phases and types of bipolar disorder.

Challenge to Stop

To stop Quetiapine slow down titration (over 6-8 wks) in cross-titration as Rapid discontinuation rebound psychosis.