Quentiapin: spelling variant of the atypical neuroleptic quetiapine

Quentiapin is a common spelling variant of the correct active ingredient name quetiapine (brand names Seroquel, Seroquel Prolong, many generics). Confusion arises because in the English original quetiapine the letters t and n sit close together and pronunciation often blurs them. Pharmacologically the same substance from the class of atypical neuroleptics (second generation antipsychotics) is meant.

Quetiapine (often written quentiapin) was approved in the EU in 1997 and is among the most prescribed atypical neuroleptics. Characteristic are the marked dose-dependent effects: at low doses sedating and sleep-inducing properties dominate, at higher doses antipsychotic and mood-stabilising effects are added.

Mechanism of action

Quetiapine acts on a broad receptor profile with different affinities:

• High-affinity binding at H1 histamine receptors explains the sedation
• Moderate affinity at 5-HT2A serotonin receptors and at alpha 1 adrenoceptors
• Low to moderate affinity at D2 dopamine receptors with rapid dissociation, which makes extrapyramidal side effects rarer than with classic neuroleptics
• The active metabolite norquetiapine additionally inhibits the noradrenaline reuptake transporter and acts as a partial 5-HT1A agonist, which explains the antidepressant effect

This polypharmacology makes quetiapine effective in schizophrenia, bipolar depression and acute mania. At low doses for sleep, the antihistaminergic component dominates.

Indications

• Schizophrenia: acute and maintenance therapy
• Bipolar disorder: manic, mixed and depressive episodes, maintenance therapy
• Major depression: augmentation in case of insufficient response to antidepressants (Quetiapine Prolong)
• Off-label uses: low-dose for sleep disorders, generalised anxiety disorder, borderline personality disorder, behavioural symptoms in dementia (with caution due to increased mortality)

Important: in many countries quetiapine carries a black box warning for dementia-associated behavioural symptoms because studies showed increased mortality.

Dosing and administration

Schizophrenia: titration from 50 mg up to 300 to 750 mg per day, divided into two single doses.

Bipolar mania: titration up to 400 to 800 mg per day.

Bipolar depression: 300 mg once in the evening.

Add-on in major depression (Quetiapine Prolong): 150 to 300 mg once in the evening.

Off-label sleep: 12.5 to 50 mg in the evening, in the low dose range.

Dosing is independent of meals; Quetiapine Prolong should be taken either fasting or with a light meal. Prolong tablets must not be split or chewed. Titration is slow over several days to avoid orthostatic reactions and excessive daytime sedation.

Side effects

Very common: sedation, dry mouth, headache, dizziness, weight gain, hyperlipidaemia, hyperglycaemia.

Common: tachycardia, orthostatic hypotension, constipation, dyspepsia, mildly raised liver values, rhinitis, nightmares, hyperprolactinaemia (less than with risperidone).

Uncommon: extrapyramidal symptoms (rare and usually mild), restless legs syndrome, peripheral oedema, syncope, myalgia.

Rare and very rare: neuroleptic malignant syndrome, tardive dyskinesia, QT prolongation with torsade de pointes, diabetic ketoacidosis, pancreatitis, hepatitis, agranulocytosis, priapism, Stevens Johnson syndrome, severe skin reactions.

Metabolic profile: quetiapine is among the atypicals with a high metabolic risk. Weight gain, insulin resistance, diabetes onset and dyslipidaemia are real risks, especially at higher doses and with long-term therapy. Regular checks of weight, waist circumference, fasting glucose, HbA1c and lipid panel are essential.

Interactions

• Strong CYP3A4 inhibitors (itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin): increased levels, reduce dose or avoid combination
• Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John's wort): reduced levels, dose may need to be increased or alternative chosen
• Other QT prolonging substances (methadone, class Ia or III antiarrhythmics, some antipsychotics): additive prolongation, caution and ECG monitoring
• Alcohol and other CNS depressants: additive sedation, caution when driving
• Antihypertensives: additive blood pressure lowering
• L-dopa: antagonistic effect, usually tolerable in low doses

Special considerations

Pregnancy: data limited. In late pregnancy risk of extrapyramidal symptoms and withdrawal in the newborn. If clinically necessary, lowest effective dose.

Breastfeeding: small amounts pass into milk; individual evaluation; usually acceptable at low doses.

Older patients and dementia: increased mortality with dementia-related behavioural symptoms; use only on strict indication and for as short a time as possible.

Children and adolescents: only under specialist indication, careful counselling on metabolic risks.

Driving: markedly impaired reaction, especially at the start and with dose increases. Patients should only return to driving after individual stabilisation.

Misuse potential: quetiapine has no classical addiction potential, but in recent years misuse cases have been reported in correctional facilities and substance use disorders, mainly because of its sedating effect.

Related substances

• Quetiapin, correct spelling of the substance
• Aripiprazol, atypical neuroleptic with partial D2 agonism
• Agomelatin, melatoninergic antidepressant
• Zolpidem, short-acting hypnotic for sleep disorders
• Chlorprothixen, classic neuroleptic with sedating note

Frequently asked questions

Sources

• EMA European Medicines Agency
• BfArM Federal Institute for Drugs and Medical Devices
• AWMF guidelines schizophrenia and bipolar disorder
• Gelbe Liste quetiapine monograph