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.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Low-dose quetiapine (12.5–50 mg at bedtime) is widely prescribed off-label for insomnia, but this practice is not justified by the risk/benefit profile. The American Academy of Sleep Medicine (, 2017) and do not recommend antipsychotics for primary insomnia. Quetiapine does cause sedation (via H1-receptor blockade), but even at low doses it leads to weight gain (5–10 kg over six months), impaired glucose and lipid metabolism, orthostatic hypotension, and risk of metabolic syndrome and cardiovascular events. The foundation of insomnia treatment is cognitive-behavioral therapy for insomnia (CBT-I); pharmacotherapy options include melatonin, short-course doxylamine, benzodiazepine receptor agonists, or orexin antagonists when indicated. If quetiapine was prescribed for sleep, consider seeking a second opinion.
18 pairs found. Sorted from critical to minor.
Mechanism
Quetiapine is cleared via hepatic CYP3A4. Ritonavir is the strongest available CYP3A4 inhibitor. Quetiapine plasma levels rise 6- to 10-fold.
Symptoms
Marked sedation, orthostatic hypotension with syncope, tachycardia, QT prolongation on ECG. Hyperglycaemia and metabolic disturbance worsen. Older patients face higher fall and fracture risk.
Management
The combination is not prescribed. Alternative antipsychotics on ritonavir: paliperidone (minimal CYP3A4 metabolism) or aripiprazole with caution and a 50% dose cut.
Mechanism
Amiodarone prolongs QT and weakly blocks CYP3A4 (the main quetiapine metabolic route). Quetiapine is a CYP3A4 substrate with QT effect at high doses. Additive QT prolongation plus moderate quetiapine level rise.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination at high quetiapine doses. At low doses (≤100 mg) and normal potassium and magnesium, the combination is acceptable with ECG monitoring at 2 weeks. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Quetiapine lowers the seizure threshold, especially at doses above 300 mg/day. Bupropion is a potent proconvulsant. Additive seizure risk.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid the combination, especially with quetiapine above 300 mg. Alternative antipsychotics: olanzapine or aripiprazole (minimal seizure threshold effect). Alternative antidepressants: sertraline or escitalopram.
Mechanism
Carbamazepine is a potent CYP3A4 inducer. Quetiapine plasma levels fall by 75–85%, which can cause loss of therapeutic effect (psychosis or mania relapse).
Symptoms
Return of positive symptoms: hallucinations, delusions, agitation. In bipolar disorder: manic episode risk.
Management
During carbamazepine therapy, increase quetiapine 4- to 5-fold with clinical monitoring. Alternative anticonvulsants without induction: sodium valproate, lamotrigine, or levetiracetam.
Mechanism
Quetiapine prolongs QT at high doses. Citalopram does so dose-dependently. Quetiapine depends on CYP3A4, citalopram on CYP2C19 and CYP3A4, so direct pharmacokinetic interaction is absent. The main risk is additive QT.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is acceptable at low doses of both (citalopram ≤20 mg, quetiapine ≤300 mg). ECG before start and at 2 weeks; maintain potassium and magnesium. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Clarithromycin blocks CYP3A4 – the main quetiapine metabolic route. Quetiapine plasma levels rise 6-fold, with stronger sedation, orthostatic hypotension, and QT effect.
Symptoms
Marked sedation, drowsiness, orthostatic hypotension with syncope on standing. Tachycardia, QT prolongation. In older patients: fall and fracture risk.
Management
During clarithromycin therapy, reduce quetiapine 4- to 6-fold and monitor ECG (QT) and blood pressure. Alternative antibiotics: azithromycin or doxycycline (minimal CYP3A4 impact). Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole.
Mechanism
Additive QT prolongation (both prolong QTc). Dronedarone carries an boxed warning for QT risk.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. Alternative antiarrhythmic: a beta-blocker for rate control or catheter ablation.
Mechanism
Additive QT prolongation at high quetiapine doses. Escitalopram prolongs QT dose-dependently ( caps at 20 mg/day).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
The combination is acceptable at low doses: escitalopram ≤10 mg, quetiapine ≤300 mg/day. ECG before start and at 2 weeks; maintain potassium and magnesium. Alternative antipsychotics: olanzapine or aripiprazole.
Mechanism
Dual antipsychotic therapy – additive risk of extrapyramidal symptoms, sedation, QT prolongation, and metabolic side effects. Polypharmacy without therapeutic rationale in most cases.
Symptoms
Sedation, extrapyramidal symptoms (tremor, rigidity, akathisia), QT prolongation on ECG. Metabolic effects: weight gain, dyslipidaemia (from quetiapine).
Management
Avoid the combination. Choose one antipsychotic: quetiapine for schizophrenia with anxious-depressive component or bipolar disorder; haloperidol for acute psychotic agitation. If dual therapy is needed, restrict to short-term use during acute psychotic episodes.
Mechanism
Ketoconazole is a potent CYP3A4 inhibitor – the main quetiapine metabolic route. Quetiapine plasma levels rise 6- to 7-fold. Marked sedation, orthostatic hypotension, QT prolongation emerge.
Symptoms
Deep sedation, orthostatic hypotension with syncope, tachycardia, QT prolongation on ECG. Older patients: fall risk.
Management
During ketoconazole therapy, reduce quetiapine 4- to 6-fold and monitor ECG and blood pressure. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole.
Mechanism
Additive CNS and respiratory depression. Quetiapine potentiates opioid sedation. Older patients: fall and aspiration risk.
Symptoms
Drowsiness, slowed breathing (rate below 12/min), cyanosis of lips. Severe cases include respiratory arrest. Older patients: fall risk.
Management
The combination is possible in palliative care with careful monitoring. Keep doses minimal. Older patients: cap quetiapine at 25–50 mg at night. Alternative antipsychotic for delirium: dexmedetomidine or low-dose haloperidol.
Mechanism
Rifampicin is the most potent CYP3A4 inducer available. Quetiapine plasma levels fall 5- to 8-fold – clinical inefficacy of the antipsychotic.
Symptoms
Return of positive symptoms: hallucinations, delusions, agitation. In bipolar disorder: manic episode risk.
Management
During anti-TB therapy, increase quetiapine 5-fold with clinical monitoring. Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole. Alternative anti-TB drug: rifabutin (weaker CYP3A4 induction).
Mechanism
Additive CNS depression plus seizure threshold reduction (tramadol lowers it, quetiapine at high doses).
Symptoms
Deep sedation, drowsiness, ataxia. Seizures (especially with prior epilepsy) are possible. Older patients: fall risk.
Management
Avoid the combination with quetiapine above 300 mg. For analgesia on quetiapine, use paracetamol, an NSAID, or morphine/oxycodone (without serotonergic activity).
Mechanism
Additive CNS and respiratory depression. Both are sedating; the combination raises paradoxical respiratory suppression risk in older patients and in COPD.
Symptoms
Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk. In COPD: dyspnoea, hypercapnia. Pronounced morning sedation possible.
Management
Avoid in older patients and in COPD. If unavoidable (anxiety with bipolar depression), cap alprazolam at 0.5 mg at bedtime and use the minimum quetiapine dose. In patients on stable quetiapine for sedation, adding alprazolam is not justified — increase quetiapine alone instead.
Mechanism
Additive anticholinergic and QT effects. Both are sedating and orthostatically active. In older patients, cumulative anticholinergic burden raises delirium risk.
Symptoms
Dry mouth, constipation, urinary retention, accommodation disturbance, tachycardia. In older patients: delirium and confusion risk. Postural dizziness, syncope, fatigue. Older patients: fall and fracture risk. Pronounced morning sedation possible.
Management
Avoid in older patients — delirium and fall risk. In bipolar disorder with chronic pain, alternatives: lamotrigine (a non-sedating mood stabiliser) with gabapentin or pregabalin. If unavoidable (severe insomnia, migraine), begin both at minimum doses and check ECG at 2 weeks.
Mechanism
Additive hypotension. Quetiapine blocks α1-adrenoceptors; amlodipine dilates vessels.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.
Management
The combination is acceptable at low quetiapine doses (≤300 mg/day). Check blood pressure 1–2 weeks after start. In older patients, olanzapine or aripiprazole (less α1-blockade) is preferable.
Mechanism
Additive QT prolongation (quetiapine prolongs QT at high doses).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with quetiapine ≤300 mg, the combination is acceptable. On high quetiapine doses or cardiovascular disease: ECG before start or alternative antibiotics.
Mechanism
Additive hypotension (quetiapine blocks α1-adrenoceptors) and additive bradycardia.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.
Management
The combination is acceptable at low quetiapine doses (≤300 mg/day). Check pulse and blood pressure 1–2 weeks after start. In older patients, olanzapine or aripiprazole (less α1-blockade) is preferable.
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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.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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 category C. 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.