Quetiapine side effects, benefit by Ray Sahelian, M.D.
February 10 2016

Quetiapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions). It is also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen together) in patients with bipolar I disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Quetiapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain. The antipsychotic drug quetiapine ( Seroquel ) is of limited use in treating agitation or psychosis in patients with dementia with parkinson-like movement disorder.

Quetiapine for Schizophrenia
Quetiapine, a dibenzothiazepine derivative, is an atypical prescription medication antipsychotic, multireceptor antagonist that has a preclinical profile similar to clozapine. Randomized studies have demonstrated the efficacy of quetiapine relative to placebo in the treatment of acute relapse and the long-term management of schizophrenia. Quetiapine is generally well tolerated relative to other antipsychotic medications, although side effects include sedation, orthostatic hypotension, anticholinergic and metabolic side effects.

Quetiapine for bipolar disorder
AstraZeneca Pharmaceuticals LP has announced that SEROQUEL (quetiapine fumarate) tablets are now indicated for the treatment of patients with depressive episodes associated with bipolar disorder. Quetiapine tablets are also indicated for the treatment of acute manic episodes associated with bipolar I disorder as either monotherapy or adjunct therapy to lithium or divalproex and for the treatment of schizophrenia. Quetiapine is available as 25-mg, 50-mg, 100-mg, 200-mg, 300-mg, and 400-mg tablets.

Depressive disorder
Neuropsychiatr Dis Treat. Jan 30 2014. A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder. In this study, neither quetiapine XR (150/300 mg/day) nor escitalopram (10/20 mg/day) showed significant separation from placebo.

Quetiapine dosage
The usual dosage of quetiapine for the treatment of patients with depressive episodes associated with bipolar disorder is 300 mg/day administered once daily at bedtime. The recommended initial dosing schedule is 50 mg, 100 mg, 200 mg, and 300 mg per day for Days 1-4, respectively. Antidepressant efficacy was demonstrated with quetiapine at both 300 mg and 600 mg; however, no additional benefit was seen with 600 mg.

Quetiapine side effects and danger
The most commonly observed quetiapine side effects in clinical trials for schizophrenia and bipolar disorder were dry mouth, sedation, somnolence, dizziness, constipation, SGPT increase, dyspepsia, lethargy, and weight gain. The most commonly observed adverse effect in clinical trials as adjunct therapy with lithium or divalproex in bipolar mania were somnolence, dry mouth, asthenia, constipation, abdominal pain, postural hypotension, pharyngitis, and weight gain. In the elderly and in patients with hepatic impairment, consideration should be given to a lower starting dose, a slower rate of dose titration, careful monitoring during the initial dosing period, and a lower target dose.

J Clin Pharm Ther. 2016. Quetiapine safety in older adults: a systematic literature review. The most commonly reported adverse events were somnolence (25-39%), dizziness (15-27%), headache (10-23%), postural hypotension (6-18%) and weight gain (11-30%). Comparing quetiapine with placebo, quetiapine resulted in significantly greater cognitive impairment, higher rates of falls and injury and increased mortality in patients with parkinsonism, but not in patients with dementia. Compared with risperidone and olanzapine, quetiapine had significantly lower risk of mortality, reduced rate of cerebrovascular events, increased rate of falls and injury and less metabolic disorders compared with olanzapine, but higher metabolic disorders compared with risperidone.

Prescrire Int. 2015. Atypical neuroleptics in elderly patients: acute kidney injury. Using data from health insurance databases, a Canadian team showed that patients aged 65 years or older had a statistically significant increased risk of hospitalisation with acute kidney injury within the 90 days after they were newly prescribed the oral "atypical" neuroleptics risperidone, quetiapine or olanzapine. Adverse effects that can lead to kidney injury were identified: hypotension, acute urinary retention, pneumonia, myocardial infarction and ventricular arrhythmia. All-cause mortality also increased.

Late-onset seizures associated with quetiapine poisoning.
J Med Toxicol. 2009 Mar; Young A, Kleinschmidt K, Wax P. Division of Emergency Medicine, UT Southwestern Medical Center, Dallas, TX.
Quetiapine, a second-generation antipsychotic, acts at multiple brain neurotransmitter receptors and has the potential for serious complications. Although seizures have been described in the literature, delayed seizure onset has not been reported. We report the first case of delayed seizures after a significant quetiapine overdose. Case Report: A 27-year-old female presented to the emergency department following an overdose of approximately 30 g of quetiapine. Twenty-four hours after arrival, the patient had 2 seizures. The patient was then intubated and remained in the ICU for four days. EEG was negative for epileptiform activity. The serum quetiapine levels were 8.6 mg/L on hospital day one and 3.2 mg/L on hospital day three. Quetiapine poisoning, with serum levels, associated with seizures has been reported in one prior case. Our case report represents late-onset seizures with serum levels above therapeutic range (>1 mg/L). The serum concentrations of quetiapine in this case were consistent with those in postmortem case reports.

Quetiapine and suicides
Suicidality in children and adolescents–antidepressants increased the risk of suicidal thinking and behavior in short-term studies of 9 antidepressant drugs in children and adolescents with major depressive disorder and other psychiatric disorders. Patients started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.

Quetiapine for GI disorder
Atypical Antipsychotic Quetiapine in the Management of Severe Refractory Functional Gastrointestinal Disorders.
Dig Dis Sci. 2009. Grover M, Dorn SD, Weinland SR, Dalton CB, Gaynes BN, Drossman DA. Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Management of severe refractory functional gastrointestinal disorders is difficult. Quetiapine, an atypical antipsychotic, may benefit patients by mitigating associated anxiety and sleep disturbances, augmenting the effect of antidepressants, and providing an independent analgesic effect. Outpatient records from a university-based functional gastrointestinal disorders clinic were reviewed, and 21 patients with refractory symptoms who received quetiapine were identified and interviewed. Outcomes included global relief of symptoms, treatment efficacy questionnaire, and change in gastrointestinal (GI) and psychological symptoms. Eleven of 21 patients continued therapy at the time of interview. Six of 11 demonstrated global relief of symptoms, and 9 were satisfied with treatment. The remaining 10 of 21 discontinued therapy because of somnolence and lack of GI benefits. Quetiapine in low doses appeared beneficial in more than half of the adults with severe functional gastrointestinal disorders who stayed on treatment. This response in otherwise refractory patients suggests quetiapine might augment the effectiveness of antidepressants in severe functional gastrointestinal disorders.

Questions
My mother has suffered from unipolar clinical depression for almost 30 years and it has been treated variously. Two years ago she was put on quetipaine along with two antidepressants. Eight months ago she slid into a depression from which she has not emerged, she is very, very low, flat, joyless. In the past she has always bounced back within a few weeks. Could her compromised return to health be due to the quetiapine? This episode is not typical of any previous one. She is not bipolar or psychotic. She has been on 300 mg daily for two years. She would like to ask her doctor to consider withdrawing. Do you have any evidence of increased depression or lethargy in users of quetiapine?
   I don't have any specific information regarding this medication, but it is not uncommon for this to occur with other antidepressants when used for prolonged periods.