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Quetiapine

Brands and Forms

  • Seroquel
    • Tablet: 25mg, 50mg, 100mg, 200mg, 300mg, 400,mg
  • Seroquel XR
    • extended-release tablet: 50mg; 200mg, 300mg, 400mg
  • Ketipinor

Uses of Quetiapine

Quetiapine is used in the treatment of Psychotic Disorders, Bipolar Disorder, Depressive Disorders, PTSD, OCD, and Generalized Anxiety Disorder.

Quetiapine can also be used in the management of behavioral disturbances, such as agitation and impulsivity, that can occur in various conditions like Impulse-Control Disorders, Disruptive Behavior Disorders, and Borderline Personality Disorder.

How Quetiapine Works

Quetiapine is an Atypical Antipsychotic. It is an antagonist at the dopamine D2 receptor and the serotonin 1a and 2a receptors, but also has interactions with a myriad of other receptors.

Cautions when Using Quetiapine

In elderly individuals with Dementia, use of Antipsychotics has been associated with increased rates of sudden death. It is unclear whether the antipsychotic use is a cause, or simply a marker, of deteriorating health in these individuals.

Weight gain and metabolic side-effects (elevated glucose, lipids and cholesterol) can be pronounced in some individuals.

Orthostatic hypotension can occur, especially during the initial dose titration. Use caution in people with known cardiovascular or cerebrovascular disease or who are otherwise at risk for hypotension.

Use caution in people at risk for seizures or aspiration pneumonia.

People using Quetiapine should become familiar with its effects before driving or operating heavy machinery.

Dosing of Quetiapine

The immediate-release form of Quetiapine is intended for use twice daily, usually before sleep and again in the morning. However, because Quetiapine can cause sedation, prescribing it in the morning can lead to daytime drowsiness. For this reason, in clinical practice the full daily dose of immediate-release Quetiapine is often given all at night, before sleep. The issue with this method is that the effects of this medication tend to wear-off towards the afternoon of the next day.

As a result, an increasingly common practice is to use Seroquel XR, the extended-release form, which avoids this problem because it lasts 24 hours while being reasonably well-tolerated in the daytime. It is usually taken once a day in the evening, about 4-6 hours before bedtime, because the dose tends to peak within 4-6 hours, which is when it is most sedating.

Another common occurrence with Quetiapine is that within the first 7-10 days of starting this medication, individuals usually experience quite pronounced sedation, as well as some postural hypotension (drops in blood pressure while standing, which can lead to faintness, dizziness, heart racing, and nausea). After these 10 days, these side-effects will disappear almost completely in about 80% of individuals who try this medication. For this reason, it is best that individuals wait a full 10 days after starting Quetiapine before deciding whether or not to continue it. It is also common that these side-effects actually become less pronounced at doses above 400mg daily.

Quetiapine doses differ depending on the condition for which it is being used:

Major Depression and Generalized Anxiety Disorder

When used as monotherapy for Major Depression or Generalized Anxiety Disorder (GAD), the usual target dose is Seroquel XR 150mg daily. It should be started at 50mg on the first two days (preferably in the evening, about 4-6 hours before bedtime), and then increaed on the third day to 150mg daily.

For Major Depression, the dose can be increased to 300mg daily if needed. It is advised to wait at least 2 weeks at 150mg daily before deciding to increase the dose further.

Bipolar Depression

When used as monotherapy for an episode of Major Depression in Bipolar Disorder, the target dose is 300mg per day of Seroquel XR. It should be started at 50mg on the first day in the evening, then 100mg on the second day, then 200mg on the third day, and then 300mg on the fourth day. After 2 weeks, the dose may be further increased, if needed, to 600mg daily.

Bipolar Mania and Mixed States, and Schizophrenia

When used for Manic and Mixed Episodes in Bipolar Disorder, or for Schizophrenia, the target dose range is 400-800 per day. Doses in the higher range tend to more effective. In clinical practice, some psychiatrists will use doses above 1000mg daily, though the safety of use of doses above 800mg per day has not been fully studied. Either immediate-release Quetiapine or Seroquel XR can be used.

Insomnia

Because Quetiapine tends to be sedating, it is often used as a sleep aid. In these cases, the immediate-release form should be taken before bedtime, at a starting dose of 25mg. Depending on the response and tolerability, the dose can be further increased in increments of 25mg every few days. If at doses as high as 150mg at bedtime it is still not helping adequately for the insomnia, then there is usually no point in increasing the dose further.

Other conditions

When Quetiapine is used in combinartion with other medication for treating PTSD and OCD, or when it is used for treating impulsivity, the dosing schedule should follow what is described above for Major Depression and GAD.

Onset of action

Symptoms of Mania and Psychosis can improve within 1 week of use, but full therapeutic effect may take several weeks. If there is no significant effect after 4-6 weeks, including a couple of weeks at doses above 600mg/day, then it may not work at all.

For other conditions, 4-6 weeks may be needed to see a therapeutic effect.

Kidney impairment

No dose adjustment necessary.

Liver impairment

Reduced dose may be required.

Side-effects of Quetiapine

Below is a list of most of the reported side-effects of Quetiapine. Most of these side-effects occur in only a minority of individuals, and many also resolve with time while the medication is continued.

Cardiovascular: postural hypotension; tachycardia; palpitations; low blood pressure; fainting; peripheral edema.

Central Nervous System: somnolence; dizziness; headache; slurred speech; lethargy; tremor; weakness; insomnia; abnormal dreams; extrapyramidal symptoms; seizures (rare).

Dermatologic: rash; excessive perspiration.

Endocrine/Metabolic: Weight gain; metabolic syndrome (insulin resistance, elevated blood sugars, hyperlipidemia and hypercholesterolemia).

Eyes, Ears, Nose and Throat: rhinitis; pharyngitis; blurred vision; amblyopia; lens changes.

Gastrointestinal: dry mouth; constipation; dyspepsia; nausea; increased appetite; vomiting; increased salivation; elevated liver enzymes (rare).

Genitourinary: priapism; erectile dysfunction.

Hematologic: leukopenia (rare); neutropenia (rare).

Musculoskeletal: muscle stiffness; muscle pains; muscle spasms; neuroleptic malignant syndrome (rare).

Psychiatric: emotional lability; agitation; anxiety; obsessive-compulsive symptoms; mania (rare).

Respiratory: cough; shortness of breath; aspiration pneumonia (due to esophageal dysmotility; rare).

Common side-effects of Quetiapine

Somnolence (most common during initial dose titration), postural hypotension (can include dizziness, palpitations, nausea; most common during initial dose titration), dry mouth, headache, weight gain, metabolic syndrome (elevated blood sugars, lipids and cholesterol), constipation.

Rare but serious side-effects of note of Quetiapine

Quetiapine overdose

Drowsiness, hypotension, QTc prolongation, tachycardia, coma. Can be fatal.

Quetiapine and pregnancy

Category C: some animal studies show adverse effects at very high doses, but no controlled human studies have been done; should only be used in pregnancy if clearly needed and if benefits outweigh potential risks.

Quetiapine, weight gain and metabolic syndrome

Nearly 20% of people taking Quetiapine will gain about 7% of their total body weight within 8 weeks of starting the medication [ref, ref]. Metabolic side-effects, including elevated glucose and lipids can also occur, which in the long-term increase the risk for heart disease and vascular problem.

See here for further information on these side-effects, and how they can be managed.

Medical Monitoring for Quetiapine

Monitoring for weight gain and a metabolic syndrome requires the following measures to be taken prior to starting the medication, then monthly for the first 3 months of use, and then every 3 months:

  • Body Mass Index (BMI)
  • waistline circumference at umbilicus
  • blood pressure
  • fasting blood glucose
  • fasting blood lipids and cholesterol

The manufacture recommends that eye exams be performed prior to starting the medication, and then at 6 month intervals, to monitor for eye lens changes that could lead to cataracts.

White blood cell (WBC) levels should be measured in people with pre-existing low WBC levels or who have experienced low WBC caused by other medications.

Drug Interactions with Quetiapine

  • Quetiapine can accentuate the hypotensive effects of other antihypertensive medications.
  • Quetiapine blood concentrations can be reduced by barbituated, Carbamazepine, glucocorticoids, Phenytoin, Rifampin, and Thioridazine.
  • Quetiapine blood concentrations can be increased by Valproic Acid, Erythromycin, Fluconazole, Itraconazole, Ketoconazole, protease inhibitors, Vaoriconazole.
  • Quetiapine may enhance the effects of Lorazepam.