Sedation quetiapine

Quetiapine Sedation, mild weight gain, orthostatic hypotension 100 50-100 mg/day increments 600... 

What Is a Side Effect This chapter picks up where Chapters 1 and 2 left off. As we discussed in the earlier chapters, all medications, psychiatric and otherwise, have multiple effects. One takes a medication to achieve a therapeutic effect. Occasionally, a single medication may have more than one therapeutic effect. All other effects are side effects. Different medications may have differing therapeutic and side effects depending on the intended use. For example, trazodone and quetiapine are often prescribed to aid in sleep, and in this instance sedation is the desired effect, yet when used as an antidepressant and antipsychotic, respectively, the sedation is often an unwanted effect. Psychotropic medications typically have multiple effects. First, they usually interact with more than one nerve cell protein, be it a transporter or a receptor. Quite often, one of the medication s receptor or transporter interactions produces the therapeutic effect. The other interactions tend to not be involved in the therapeutic effect and only serve to produce side effects. Sometimes a neurotransmitter will have multiple different receptor types, but the medication interacts with... 

Quetiapine (3) has the lowest affinity for the D2 and 5-HT2a receptors among the atypicals therefore, relatively high doses are required for maximal efficacy. Quetiapine causes significant weight gain, but less than that of olanzapine. Other side-effects include sedation, dizziness and hypotension. 

Recreational drug users note the same effects. Several comment on similarities between olanzapine and quetiapine and the benzodiazepine drugs, such as diazepam (Valium), because of the intense sedation. However none report the euphoria that characterises benzodiazepine effects. One correspondent reported protracted insomnia after stopping olanzapine, comparing it to benzodiazepine withdrawal (Sixseal.com 2007). 

Clozapine, olanzapine, and quetiapine display significant affinity to histamine Hj receptors, and it is widely accepted that some side effects of these agents (e.g., weight gain liability, sedation) are attributed to their histamine antagonism... 

Two patients developed resistant auditory hallucinations when taking quetiapine (11). One of these patients, a 39-year-old woman who took 600 mg/day, developed mild sedation, which resolved spontaneously by week 4. 

I Sedation and Cognition. Sedation must be recognized as an antipsychotic side effect and not as an indication of therapeutic effect. It occurs more frequently with antipsychotics with antihistaminic properties. Chlorpromazine, thioridazine, mesoridazine, clozapine, olanzapine, and quetiapine are most frequently implicated. Administration of most or all of the daily dosage at bedtime (depending on the drug half-life) can decrease daytime sedation and in some patients eliminate the need for hypnotic agents. Sedation occurs early in treatment... 

After single-dose administration, the mean bioavailability of quetiapine is 9% with significant interindividual variation. If a CYP 3A4 inhibitor (e.g., cimetidine, ketoconazole, nefazodone, grapefruit juice, or erythromycin) is added to quetiapine, increased side effects (e.g., sedation or orthostasis) may occur. Fluoxetine may also decrease clearance of a medication such as quetiapine metabolized through CYP 3A4. However, with fluoxetine, it is the long-acting metabolite norfluoxetine, and not fluoxetine, that is the primary inhibitor of 3 A4 metabolism. If an enzyme inducer such as carbamazepine or St. lohn s wort is added to quetiapine, then decreased antipsychotic effects may occur. ... 

Placebo-coutroHed studies Quetiapine has been compared with placebo in the avoidance of relapses in patients in remission in a randomized, double-blind clinical trial [119 ]. Patients who had taken antipsychotic drugs for at least 1 year for first episode of psychosis took either maintenance quetiapine 400mg/day ( =89) or placebo (n = 89) and were followed for 12 months or until a relapse occurred. The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% with quetiapine (95% CI=29%, 53%) and 79% (95% CI=68%, 90%) with placebo. The rate of withdrawal because of adverse or serious adverse events was greater with quetiapine (18% versus 8%) patients taking quetiapine reported more adverse reactions sleepiness or sedation, reduced salvation, and constipation). 

Observational studies In 477 patients with schizophrenia (mean age 38 years), who were switched from their medication to quetiapine (mean median dose 575 mg/ day) because of insufficient efficacy (66%) or insufficient tolerability (34%) in a 12-week, multicenter, open-label study supported by AstraZeneca, the marketing authorization holder of quetiapine common adverse events included somnolence (18%), sedation (15%), and dizziness and dry mouth (14% each), and extrapyramidal symptoms (8.0%) [108 ]. There were higher glucose concentrations both at baseline (n = 8) and end-point (n = 12). The mean body weight change was 1.0 kg. 

In a 12-week, open, fiexible-dose study of quetiapine in 40 out-patients with generalized anxiety disorder who had not achieved remission after at least 8 weeks of adequate doses of standard therapy, the most common adverse reactions were sedation (n — 29), dry mouth (n = 12), and sexual dysfunction (n = 10) [109 j. Mean total weight gain from pre-treatment to week 12 was about 0.5 kg and 14% of patients had a 7% weight gain. Seven patients withdrew because of adverse events sedation (n = 5), panic attacks (n = 1), and bilateral iritis (n = 1). 

A case of excessive and persistent sedation on clozapine even down to a dose of 1 mg per day is reported in a 29-year-old male who was also sedated on quetiapine [113 ]. 

A 3-week, double-blind, placebo-controlled trial of quetiapine monotherapy in children and adolescents with mania was reported [202 ]. The most common adverse events associated with quetiapine were somnolence, sedation, dizziness and headache most events were mild to moderate in intensity. Potentially clinically relevant increases in total cholesterol, LDL-cholesterol and triglyceride concentrations were more frequent and numericdly larger with quetiapine mean weight gain at end point (observed cases) was 1.7kg for both quetiapine doses and 0.4kg for placebo. 

Observational Studies A naturalistic study of first-episode psychosis outpatients treated with quetiapine reported fatigue, sedation, dizziness, followed by gastrointestinal disorders and nausea and orthostatic hypotension as the most frequent adverse events [203 ]. 

A study of 30 mood disorder patients switched from quetiapine IR to XR reported the switch was tolerated by most patients with discontinuation in only two patients [204 ]. Early side effects included early/central insomnia wi day drowsiness (16.7%), increased appetite and weight (8.4%), mild asthenia (4.2%) and constipation (4.2%). A series of studies were conducted to characterise the pharmacokinetics of quetiapine ER which was foxmd to be generally well tolerated with a safety profile comparable to quetiapine IR, though with less initial sedation [205 ]. 

A study of quetiapine and venlafaxine vs. venlafaxine for the treatment of depression foxmd more sedation and weight gain for the combination [208 ]. 

Reviews A review of quetiapine for the treatment of acute bipolar mania, mixed episodes and maintenance therapy reported the most common adverse events in acute trials were somnolence, sedation, dry mouth, weight gain, dizziness, asthenia, pharyngitis and postural hypotension [210 ]. In the maintenance trials, the most common adverse events were somnolence, upper respiratory tract infection, nasopharyngitis and headache. 

A review of quetiapine XR in the treatment of schizophrenia and bipolar disorder is reported to possess similar side effects to quetiapine IR, with the most common being sedation, dry mouth, somnolence, dizziness and headache [21V],... 

Drug overdose Quetiapine overdose is associated with sedation and cardiovascular symptoms such as hypotension, tachycardia and QTc prolongation. A case of a 40-year-old female with profound cardiovas ar depression requiring extracorporeal life support in an ICU is reported [233 ]. In another case, a 42-year-old woman found unconscious experienced cardiovascular collapse and was treated with intravenous lipid emulsion in an ICU [234 ]. 

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