Quetiapine ( ), sold under the brand name Seroquel among others, is a medication of the atypical antipsychotic class. It is used in the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Quetiapine is also widely prescribed off-label as a sleep aid for its tranquillizing effects. Some have raised concerns that the undesirable side effects from off-label use may outweigh its benefits, though this remains an active area of research. It is taken orally.
Common side effects include sedation, fatigue, weight gain, constipation, and dry mouth. Other side effects include low blood pressure with standing, seizures, high blood sugar, tardive dyskinesia, and neuroleptic malignant syndrome. In older people with dementia, its use increases the risk of death. Use in the third trimester of pregnancy may result in a movement disorder in the baby for some time after birth. Quetiapine is believed to work by blocking a number of receptors, including those for serotonin and dopamine.
Quetiapine was developed in 1985 and was approved for medical use in the United States in 1997. It is available as a generic medication. In 2023, it was the most prescribed antipsychotic and 60th most commonly prescribed medication in the United States, with more than 10million prescriptions. It is on the World Health Organization's List of Essential Medicines.
The drug is typically among two antipsychotics (the other being olanzapine) to have superior efficacy for the treatment of bipolar disorder. Quetiapine is one of only two antipsychotics (the other is cariprazine) that produce equal efficacy as standalone therapies for mixed manic-depressive mood swings as they do in combination with an SSRI antidepressant. However, it is less potent than clozapine, amisulpride, olanzapine, risperidone, and paliperidone in alleviating psychotic symptoms or treating schizophrenia.
Medical uses
Quetiapine is primarily used to treat schizophrenia and bipolar disorder. It targets both positive and negative symptoms of schizophrenia.
Schizophrenia A 2013 Cochrane review compared quetiapine to typical antipsychotics: + Quetiapine compared to typical antipsychotics for schizophrenia SummaryQuetiapine may not differ from typical antipsychotics in the treatment of positive symptoms, general psychopathology, and negative symptoms. However, it causes fewer adverse effects in terms of abnormal ECG, extrapyramidal effects, abnormal prolactin levels and weight gain. Outcome Findings in words Findings in numbers Quality of evidence Global state No clinical significant response There is no clear difference between people given quetiapine and those receiving typical antipsychotic drugs. These findings are based on data of moderate quality. RR 0.96 (0.75 to 1.23) ModerateMental state Average positive symptom score (PANSS) On average, people receiving quetiapine scored higher (worse) than people treated with typical antipsychotic drugs. There was, however, no clear difference between the groups. This finding is based on data of moderate quality. MD 0.02 higher (0.39 lower to 0.43 higher)* Moderate Average negative symptom score (PANSS) On average, people receiving quetiapine scored lower (better) than people treated with typical antipsychotic drugs. This finding is based on data of moderate quality. MD 0.82 lower (1.59 to 0.04 lower)* Moderate Cognitive function Average score On average, people receiving quetiapine scored higher (better) than people treated with typical antipsychotic drugs. There was no clear difference between the groups. This finding is based on data of very limited quality. MD 1.55 higher (0.62 lower to 3.72 higher)* Very low Leaving the study early For any reason Quetiapine is not clearly more acceptable than typical antipsychotic drugs. These findings are based on data of moderate quality. RR 0.91 (0.81 to 1.01) Moderate Adverse effects Extrapyramidal effects Quetiapine may reduce the chance of experiencing these movement disorders. This finding is based on data of moderate quality. RR 0.17 (0.09 to 0.32) Moderate Prolactin levelAverage level (ng/mL) On average, people receiving quetiapine scored lower (better) than people treated with typical antipsychotic drugs. There was a clear difference between the groups. This finding is based on data of moderate quality. MD 16.20 lower (23.34 to 9.07 lower)* Moderate *The meaning of these findings for day-to-day care is not clear
In a 2013 comparison of 15 antipsychotics in effectiveness in treating schizophrenia, quetiapine demonstrated standard effectiveness. It was 13–16% more effective than ziprasidone, chlorpromazine, and asenapine and approximately as effective as haloperidol and aripiprazole.
There is tentative evidence of the benefit of quetiapine versus placebo in schizophrenia; however, definitive conclusions are not possible due to the high rate of attrition in trials (greater than 50%) and the lack of data on economic outcomes, social functioning, or quality of life.
It is debatable whether, as a class, typical or atypical antipsychotics are more effective. Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages. While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.
A Cochrane review comparing quetiapine to other atypical antipsychotic agents tentatively concluded that it may be less efficacious than olanzapine and risperidone; produce fewer movement related side effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine; and produce weight gain similar to risperidone, clozapine and aripiprazole. It found that quetiapine produces suicide attempts; death; QTc prolongation, low blood pressure; tachycardia; sedation; gynaecomastia; galactorrhoea, menstrual irregularity, and decline in white blood cell count at a rate similar to first-generation antipsychotics.
Bipolar disorder In those with bipolar disorder, quetiapine is used to treat depressive episodes; acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium; valproate or lamotrigine); acute mixed episodes; and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).
Major depressive disorder Quetiapine is effective when used by itself and when used along with other medications in major depressive disorder (MDD), but sedation is often an undesirable side effect.
In the United States, the United Kingdom and Australia (while not subsidised by the Australian Pharmaceutical Benefits Scheme for treatment of MDD), quetiapine is licensed for use as an add-on treatment in MDD.
Alzheimer's disease Quetiapine does not decrease agitation among people with Alzheimer's disease. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended.
Insomnia Low doses of quetiapine are commonly prescribed for insomnia. Use for insomnia can present side effects and is an area of concern regarding its off-label use. A 2022 network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine did not demonstrate any short-term benefits in sleep quality. Quetiapine, specifically, had an effect size (standardized mean difference) against placebo for treatment of insomnia of 0.05 (95% –1.21 to 1.11) at 4weeks of treatment, with the certainty of evidence rated as very low. Doses of quetiapine used for insomnia have ranged from 12.5 to 800mg, with low doses of 25 to 200mg being the most typical. Regardless of the dose used, some of the more serious adverse effects may still possibly occur at the lower dosing ranges, such as dyslipidemia and neutropenia. Increases in serum triglycerides, LDL-C, and fasting blood glucose have been observed following quetiapine treatment at doses typically used off-label in the treatment of insomnia. These safety concerns at low doses are corroborated by Danish observational studies that showed use of specifically low-dose quetiapine (prescriptions filled for tablet strengths >50 mg were excluded) was associated with an increased risk of major cardiovascular events as compared to use of Z-drugs, with most of the risk being driven by cardiovascular death. Laboratory data from an unpublished analysis of the same cohort also support the lack of dose-dependency of metabolic side effects, as new use of low-dose quetiapine was associated with a risk of increased fasting triglycerides at 1-year follow-up.
Others
It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome, musical hallucinationsOliver Sacks "Musicophilia" Knopf NY 2007 P.67 and anxiety disorders.
Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their relatively low extrapyramidal side-effect liability. Owing to the risks associated with clozapine (e.g. agranulocytosis, diabetes mellitus, etc.), clinicians often attempt treatment with quetiapine first, although the evidence to support quetiapine's use for this indication is significantly weaker than that of clozapine.
Adverse effects Sources for incidence lists:
Very common (>10% incidence) adverse effects Dry mouth Dizziness Headache Somnolence (drowsiness; of 15 antipsychotics quetiapine causes the 5th most sedation. Extended release (XR) formulations tend to produce less sedation, dose-by-dose, than the immediate release formulations.)
Common (1–10% incidence) adverse effects
High blood pressure Orthostatic hypotension High pulse rate High blood cholesterol Elevated serum triglycerides Abdominal pain Constipation Increased appetite Vomiting Increased liver enzymes Backache Asthenia Insomnia Lethargy Tremor Agitation Nasal congestion Pharyngitis Fatigue Pain Dyspepsia (Indigestion) Peripheral oedema Dysphagia
Extrapyramidal disease: Quetiapine and clozapine are noted for their relative lack of extrapyramidal side effects. Weight gain: SMD 0.43 kg when compared to placebo. Produces roughly as much weight gain as risperidone, less weight gain than clozapine, olanzapine and zotepine and more weight gain than ziprasidone, lurasidone, aripiprazole and asenapine. As with many other atypical antipsychotics, this action is likely due to its actions at the H1 histamine receptor and 5-HT2C receptor.
Rare (<1% incidence) adverse effects
Prolonged QT interval (had an odds ratio for prolonging the QT interval over placebo of 0.17) Sudden cardiac death Syncope Diabetic ketoacidosis Restless legs syndrome Hyponatraemia, low blood sodium. Jaundice, yellowing of the eyes, skin and mucous membranes due to an impaired ability of the body to clear bilirubin, a by product of haem breakdown. Pancreatitis, pancreas swelling. Agranulocytosis, a potentially fatal drop in white blood cell count. Leukopenia, a drop in white blood cell count, not as severe as agranulocytosis. Neutropenia, a drop in neutrophils, the cell of the immune cells that defends the body against bacterial infections. Eosinophilia Anaphylaxis, a potentially fatal allergic reaction. Seizure Hypothyroidism, underactive thyroid gland. Common among bipolar patients; quetiapine increases incidence. Myocarditis, swelling of the myocardium. Cardiomyopathy Hepatitis, swelling of the liver. Suicidal ideation Priapism. A prolonged and painful erection. Stevens–Johnson syndrome. A potentially fatal skin reaction.
Neuroleptic malignant syndrome a rare and potentially fatal complication of antipsychotic drug treatment. It is characterised by the following symptoms: tremor, rigidity, hyperthermia, tachycardia, mental status changes (e.g. confusion), etc.