Description

Quetiapine, sold under brand names such as Seroquel®, is an atypical antipsychotic medication. It belongs to the class of second-generation antipsychotics and is distinguished by its unique receptor binding profile. Unlike many other antipsychotics, it has a relatively low affinity for dopamine D2 receptors and a higher affinity for serotonin receptors, which is thought to contribute to its lower risk of certain side effects, particularly extrapyramidal symptoms (EPS). It is available in both immediate-release (IR) and extended-release (XR) formulations.

Indications

Quetiapine has a broad range of approved indications for both psychotic and mood disorders, often used at different doses for each condition. Its main indications include:

• Schizophrenia: Treatment of acute and chronic schizophrenia.

• Bipolar Disorder:
  • Treatment of depressive episodes associated with bipolar disorder (bipolar depression).

• • Acute treatment of manic or mixed episodes associated with bipolar disorder.

• • Maintenance treatment of bipolar I disorder, often as an add-on therapy.

• Major Depressive Disorder (MDD): As an adjunctive therapy (add-on to an antidepressant) for patients with MDD who have not responded adequately to antidepressant monotherapy.

Due to its sedative effects, it is also sometimes used off-label for insomnia, though this is not a recommended long-term use.

Mechanism of Action

Quetiapine’s therapeutic effects are attributed to its complex and varied interactions with multiple neurotransmitter receptors, particularly dopamine and serotonin.

1. Dopamine Antagonism: Quetiapine is an antagonist at dopamine D2 receptors. It blocks dopamine from binding to these receptors, which helps to alleviate the positive symptoms of psychosis, such as hallucinations and delusions. Unlike first-generation antipsychotics, quetiapine has a “fast-on, fast-off” binding to the D2 receptor, meaning it rapidly binds to and then dissociates from the receptor. This temporary blockade is believed to be the reason for its lower risk of causing extrapyramidal side effects.
2. Serotonin Antagonism: Quetiapine is a potent antagonist at serotonin 5-HT2A receptors. This antagonism is thought to be a key part of its atypical profile, as it contributes to its efficacy against both positive and negative symptoms of schizophrenia and may also play a role in its antidepressant effects.
3. Other Receptor Actions: Quetiapine also has significant activity at several other receptors, which contribute to its overall effects and side-effect profile:

• • Histamine H1 Receptor Antagonist: Its strong antagonism of H1 receptors is responsible for its marked sedative effects.

• • Alpha1-Adrenergic Receptor Antagonist: Its antagonism of alpha1-adrenergic receptors can lead to orthostatic hypotension (a drop in blood pressure when standing).

• • Partial Serotonin 5-HT1A Receptor Agonism: This action may contribute to its antidepressant effects.

In summary, quetiapine’s unique balance of receptor antagonism—particularly its high affinity for serotonin 5-HT2A receptors and its transient binding to dopamine D2 receptors—distinguishes it from other antipsychotics and contributes to its efficacy in treating a range of both psychotic and mood-related conditions with a lower risk of motor side effects.