Quetiapine, sold under the trade name Seroquel among others, is an atypical antipsychotic used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder.[6][7] Although not recommended, it is also used as a sleep aid due to its sedating effect.[8] It is taken by mouth.[6]
Common side effects include sleepiness, constipation, weight gain, and dry mouth.[6] Other side effects include low blood pressure with standing, seizures, a prolonged erection, high blood sugar, tardive dyskinesia, and neuroleptic malignant syndrome.[6] In older people with dementia, its use increases the risk of death.[6] Use in the third trimester of pregnancy may result in a movement disorder in the baby for some time after birth.[6] Quetiapine is believed to work by blocking a number of receptors including serotonin and dopamine.[6]
Quetiapine was developed in 1985 and approved for medical use in the United States in 1997.[6][9] It is available as a generic medication.[10] In the United States, the wholesale cost is about US$12 per month as of 2017.[11] In the United Kingdom, a month's supply costs the NHS about £60 as of 2017.[10] In 2016, it was the 86th most prescribed medication in the United States, with more than 8 million prescriptions.[12]
Medical uses
Quetiapine is primarily used to treat schizophrenia or bipolar disorder.[13] Quitapine targets both positive and negative symptoms of schizophrenia.[14]
Schizophrenia
A 2013 Cochrane review compared quetiapine to typical antipsychotics:
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 haloperidoland aripiprazole.[16]
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.[17]
It is debatable whether, as a class, typical or atypical antipsychotics are more effective.[18]Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages.[19] While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.[17]
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. They concluded that it produces suicide attempt, suicide; death; QTc prolongation, low blood pressure; tachycardia; sedation; gynaecomastia; galactorrhoea, menstrual irregularity and white blood cell count at a rate similar to first generation antipsychotics.[20]
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); and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).
Major depressive disorder
Quetiapine is effective when used by itself[7] and when used along with other medications in major depressive disorder (MDD).[7][21] However, sedation is often an undesirable side effect.[7]
In the United States,[4] the United Kingdom[22] 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.[23]
Alzheimer's disease
Quetiapine does not decrease agitation among people with Alzheimer's. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended.[24]
Others
The use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects.[25][26]
It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome,[27] musical hallucinations[28] and anxiety disorders.[29]
Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their very 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.[30][31]
Adverse effects
Sources for incidence lists:[2][4][22][23][31][32]
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)[16]
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[22][31][16]
§ 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.[16] As with many other atypical antipsychotics, this action is likely due to its actions at the H1 histamine receptor and 5-HT2C receptor.[1]
Rare (<1% incidence) adverse effects
§ Prolonged QT interval (had an odds ratio for prolonging the QT interval over placebo of 0.17)[16]
§ 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.
§ 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.
§ Tardive Dyskinesia. A rare and often irreversible neurological condition characterised by involuntary movements of the face, tongue, lips and rest of the body. Most commonly occurs after prolonged treatment with antipsychotics. It is believed to be particularly uncommon with atypical antipsychotics, especially quetiapine and clozapine[23][33]
Both typical and atypical antipsychotics can cause tardive dyskinesia.[34] According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%.[34] Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.[35]
Weight gain can be a problem for some, with quetiapine causing more weight gain than fluphenazine, haloperidol, loxapine, molindone, olanzapine, pimozide, risperidone, thioridazine, thiothixene, trifluoperazine, and ziprasidone, but less than chlorpromazine, clozapine, perphenazine, and sertindole.[36]
Studies conducted on beagles have resulted in the formation of cataracts. While there are reports of cataracts occurring in humans, controlled studies including thousands of patients have not demonstrated a clear causal association between quetiapine therapy and this side-effect.[citation needed] However, the Seroquel website[37] still recommends users have eye examinations every six months.
As with some other anti-psychotics, quetiapine may lower the seizure threshold,[38] and should be taken with caution in combination with drugs such as bupropion.
Overdose
Most instances of acute overdosage result in only sedation, hypotension and tachycardia, but cardiac arrhythmia, coma and death have occurred in adults. Serum or plasma quetiapine concentrations are usually in the 1–10 mg/L range in overdose survivors, while postmortem blood levels of 10–25 mg/L are generally observed in fatal cases.[44] Non-toxic levels in postmortem blood extend to around 0.8 mg/kg, but toxic levels in postmortem blood can begin at 0.35 mg/kg.[45][46]
