Atypical antipsychotics
ATC code: N05AH04 (Quetiapine)
Brand names
Seroquel, Seroquel XR
Atypical antipsychotic with antagonism at dopamine D2 and serotonin 5-HT2A receptors, histamine H1 (explaining sedation), and α1 adrenergic receptors (orthostatic hypotension). The active metabolite norquetiapine adds noradrenergic activity via NET inhibition, contributing to antidepressant effects. Low doses (12.5–50 mg) primarily produce H1 blockade and sedation; high doses (300–800 mg) deliver antipsychotic effect.
First line
First-line for bipolar disorder per CANMAT 2018 and 2020. Effective in acute mania, bipolar depression, and maintenance. Uniquely -approved for all three phases of bipolar disorder. Dose 300–600 mg in mania; 300 mg in bipolar depression.
First line
One of the first-line atypical antipsychotics in schizophrenia per 2020 and CG178. Start 25 mg twice daily; target 300–800 mg daily. Efficacy on positive symptoms comparable to other atypicals; safer than haloperidol or risperidone for extrapyramidal side effects; less favorable metabolic profile (weight gain, dyslipidemia, dysglycemia).
Second line
In treatment-resistant unipolar depression, quetiapine 150–300 mg is used as SSRI/SNRI augmentation per 2023. Effective, but metabolic side effects limit long-term use.
Quetiapine is used as augmentation in treatment-resistant depression or in bipolar depression. Not first-line for uncomplicated unipolar depression.
Not recommended
— Primary insomnia without psychiatric diagnosis (off-label quetiapine): Off-label low-dose quetiapine (12.5–50 mg at bedtime) for insomnia in non-psychiatric patients is widespread but unjustified by the risk/benefit profile. 2017 and do not recommend antipsychotics for primary insomnia. Sedation does occur (H1 blockade), but even low doses cause weight gain (5–10 kg over 6 months), dysglycemia, dyslipidemia, orthostatic hypotension, and risk of metabolic syndrome and cardiovascular events. Foundation: CBT-I; pharmacotherapy options include melatonin, short-course doxylamine, benzodiazepine receptor agonists, or orexin antagonists where indicated.
Boxed warning
FDA boxed warning: increased mortality in elderly patients with dementia-related psychosis (mainly from cardiovascular events and pneumonia). Quetiapine is not approved for dementia-related psychosis.
FDA categories were retired in 2015 (historically C). Third-trimester exposure is associated with extrapyramidal symptoms and withdrawal in the newborn. In pregnant patients with schizophrenia or bipolar disorder, continuation is individualized with a psychiatrist.
Transfers into milk in small amounts. Per LactMed, use is acceptable with infant sedation monitoring.
quetiapine is evaluated for the following indications with varying evidence strength: Bipolar disorder (evidence tier A), Schizophrenia (evidence tier A), Major depressive disorder (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of quetiapine (≥ 1 in 100): Sedation, drowsiness, Weight gain (5–10 kg over 6 months), Orthostatic hypotension, Dry mouth, Constipation, Dyslipidemia, raised fasting glucose. See the Safety section for uncommon and serious reactions.
FDA categories were retired in 2015 (historically C). Third-trimester exposure is associated with extrapyramidal symptoms and withdrawal in the newborn. In pregnant patients with schizophrenia or bipolar disorder, continuation is individualized with a psychiatrist.
Transfers into milk in small amounts. Per LactMed, use is acceptable with infant sedation monitoring.
quetiapine is contraindicated in: Hypersensitivity; Concomitant strong CYP3A4 inhibitors (ketoconazole, itraconazole, HIV protease inhibitors). Full list in the Safety section.
FDA boxed warning: increased mortality in elderly patients with dementia-related psychosis (mainly from cardiovascular events and pneumonia). Quetiapine is not approved for dementia-related psychosis.
'safe' is relative. Metabolic side effects, orthostatics, QT prolongation, and rare severe events (neuroleptic malignant syndrome, tardive dyskinesia) make this approach justified only with a psychiatric indication.
physical dependence is not described, but abrupt discontinuation after long-term use can cause rebound psychotic or affective symptoms, insomnia, and anxiety. Taper gradually.