Quetiapine (Seroquel)

Quetiapine is an atypical anti-psychotic and probably works as well as the others.  However, different patients will have differing side-effects and benefits from each of the atypicals.  Who will do best on which medication is very difficult to judge ahead of time.  At present, it seems to be a process of trial and error and working with your psychiatrist to find the right medication so as to minimize side-effects.  I much prefer ziprasidone (Geodon) because of cost and side-effect issues.

In controlled studies, the manufacturer reports an unusually low level of side-effects causing discontinuation, i.e., only 4% of patients discontinued quetiapine because of side-effects vs. 3% with placebo.  Side-effects occurring more often with quetiapine than placebo (2% or more difference), with quetiapine had a higher percentage by: excessive sleepiness 7%, dizziness 6%, dizziness on standing 5%, constipation 4%, dry mouth 4%, dyspepsia 4%, abdominal pain 2%, rapid heart beat 2%, weight gain 2%, and nasal inflammation 2%.  Ones occurring 1% more often with quetiapine were: headache, asthenia, back pain, fever, rash, and ear pain. 

Seizures occur in 0.8%. Cholesterol is increased by an average of 11% and triglycerides by 17%.  Do not drive if quetiapine is making you sleepy.

In research with dogs, but not other animals, quetiapine caused an increase in cataracts.  How often this occurs in humans is unknown, but at least one case has been reported which have led to bilateral cataract surgery (not my patient, but I reported the case to the FDA).  The manufacturer recommends every six month eye exams for cataracts, an absurdly expensive recommendation that no psychiatrist whom I know of actually follows.  Early symptoms of cataracts include deteriorating day or night vision.  A more advanced symptom is the patient seeing a film over the eye while looking in the mirror. 

The dry mouth side-effect of quetiapine appears to be an anti-cholinergic side-effect which I have successfully treated with bethanechol.  Unfortunately, the 3-cent per pill generic bethanechol has been yanked off the market and only the $1.67 per pill brandname is available.

Quetiapine can cause small increases in liver enzyme blood tests which usually return to normal levels in a few weeks as well as increases in cholesterol (11% increase at 6 weeks) and triglycerides (17%).  It also causes a small increase in the rate of diabetes reported at 0.83% more than the average anti-psychotic.

Phenytoin increases the clearance of quetiapine 5-fold, requiring a considerable increase in quetiapine dosage.  The same may occur with carbamazepine, rifampin, and glucocorticoids. Cimetidine (Tagamet) slightly (20%) increased quetiapine blood levels but P450 3A inhibitor ketoconazole increased the blood level by 335%.  Erythromycin is such an inhibitor.  Fluoxetine, imipramine, lithium, risperidone, haloperidol all have no effect on blood levels.  Alcoholic beverages should be avoided on quetiapine.  Elderly patients should have their doses reduced by an average of 40%.  Some research below suggests that quetiapine should not be used with the elderly.

Avoid overheating while on quetiapine and drink enough to avoid dehydration.  Seroquel is extremely expensive.  A good initial anti-psychotic dose (800 mg/day) costs $760/month with half that for a good maintenance dose.  By contrast, Geodon is $280/month initially and only $140/month maintenance so long as the 80 mg. maintenance dose is given as a once a night, single capsule treatment.  Traditional anti-psychotics, e.g. perphenazine, chlorpromazine, or haloperidol, are still much less expensive.

Seroquel Patients Usually Undermedicated, But High Cost Eats Up Savings: Using a health plan database of patients with bipolar disorder or schizophrenia treated with quetiapine monotherapy for at least four consecutive months, commercially insured patients with schizophrenia (n = 581) or bipolar disorder (n = 2421) received quetiapine monotherapy at average daily doses of 237 mg and 147 mg, respectively. For schizophrenia, mental health charges decreased by $1.28 for each additional milligram of quetiapine (P = 0.1097). For bipolars, they decreased by $1.31 per additional milligram (P = 0.0484). For schizophrenia, hospitalizations were reduced by 0.4% for each additional milligram of quetiapine (P = 0.0189). Relationship between initial quetiapine dose and effectiveness as reflected in subsequent mental health service use among patients with schizophrenia or bipolar disorder. Gianfrancesco F, et al. Montgomery Village, MD. . Value Health. 2005 Jul-Aug;8(4):471-8. Ed: Unfortunately, Seroquel is so expensive at $.99 per mg per month, that increasing the dose is not cost-effective. Geodon is much more cost-effective and the preferred first-line choice.  

Helps Attentional Deficit: DB PC 10 patients 2 months. Schizophrenics were initially worse than controls but in end were equal to controls. Sax, University of Cincinnati, Schiz Res 33:151

Twice a Day Just as Good as Three times a Day: DB study of 618 patients for 6 wk on 25mg BID vs. 225 mg BID vs. 150 TID. Higher doses did significantly better but there was no difference between 2 or 3 times a day with twice a day doing even slightly better than three times a day despite 6-7 hr half-life. King, Belfast, Psychopharm (Berl) ’98;137:139

As Good As Risperidone: In an 8-week, DB PC Study of 673 patients with schizophrenia (DSM-IV diagnosis), quetiapine (200-800 mg/day) did just as well as risperidone (2-8 mg/day) with an average dose = 525 mg/day vs. risperidone 5.2 mg/day. Changes in glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001). Comparison of Quetiapine and Risperidone in the Treatment of Schizophrenia: A Randomized, Double-Blind, Flexible-Dose, 8-Week Study. Zhong KX, et al. AstraZeneca Pharmaceuticals, University of North Carolina, and Columbia University. J Clin Psychiatry 2006 Jul;67(7):1093-1103.

As Good As Haldol: DB at 75mg, 150, 300, 600, 750mg/d vs. haldol 12mg/d. At doses of 150 and above equal to haldol. No increase in prolactin. Dose of 300 mg/d necessary to help negative symptoms. Zeneca, Biol Psychiatry ’97;42:233

As Good As Haldol: DB 6-week, 201 patient acute exacerbation found trend favoring quetiapine and less prolactin effect with quetiapine which author says qualifies it for atypical classification. Peuskins, Acta Psych Scand ’97;96:265

Ineffective with Chronic Schizophrenia: Study 23 male outpatient stable on conventional or risperidone but residual symptoms or side-effects. None rx resistant. Switched to quetiapine. At 1 yr, only 30% still on and at 2 yr only 22%. Dosage increased from 260mg/d initially to 470 at 12 weeks to 560mg/d at 2 yr. 74% relapsed on quetiapine. 7/17 after 12 weeks. 79% of patients with TD relapsed. Margolese, J Clin Psychoph 02;22:347

Perphenazine (Trilafon) Does Just as Well as Atypical Anti-Psychotics in Huge Study: In a huge 18-month DB PC study of 1493 patients with schizophrenia at 57 U.S. sites, patients received either olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the FDA. Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. The efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine, while a little more effective, was associated with greater weight gain and increases in measures of glucose and lipid metabolism. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. Lieberman JA, et al. N Engl J Med. 2005 Sep 19

Quetiapine: Med Letter 12/19/98. Seroquel. A dibenzothiazepine. Greater affinity for blocking serotonin 5HTs than dopamine D2, i.e., similar to clozapine, risperidone and olanzapine. Anti-histamine H1 and adrenergic alpha 1 and 2 receptors but not cholinergic, muscarinic or benzodiazepine receptors. Well-absorbed, metabolized by the liver, half-life 6 hr. 750 mg better than 250. (JG Small Arch Gen Psych 54:549, 6/97. As effective as haldol 12 mg. Maximum clinical benefit about 300 mg. Somnolence, dizzy, constipation, postural hypotension, dry mouth, weight gain. EPS and prolactin similar to placebo. TD risk unknown. Some decrease in thyroxine. Cataracts in dogs and slit-lamp recommended Q 6 mo. Dilantin markedly increases clearance. Mellaril less so. Start 25 BID 1^st day to 300-400 total by 4^th day.

Quetiapine Fewer Sexual Side-Effects than Risperidone: In a open label but random assignment study of 49 patients with schizophrenia treated for six week with quetiapine 200-1200 mg/day or risperidone 1-6 mg/day, found four of 25 quetiapine-treated patients (16%) and 12 of 24 risperidone-treated patients (50%) reported sexual dysfunction. While 33% in all had sexual side-effects, only 11% mentioned them spontaneously, emphasizing the need to specifically ask about them. A randomized open-label study of the impact of quetiapine versus risperidone on sexual functioning. Knegtering R, Castelein S, Bous H, Van Der Linde J, Bruggeman R, Kluiter H, Van Den Bosch RJ. J Clin Psychopharmacol. 2004 Feb;24(1):56-61

Best Dose 300 mg: In a DB PC study 286 patients with schizophrenia, the best effects were obtained with over 250 mg/d. Arch Gen Psych’97;54:549. Ed: Quetiapine is very expensive.  I have seen many patients receiving 600-900 mg/day.

Cost Lower with Quetiapine or Ziprasidone vs Olanzapine or Risperidone: Quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of approximately $530 (95% confidence interval [CI] approximately $275, $800), and approximately $485. Univ Hull. Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost. Mortimer A, Williams P, Meddis D. J Int Med Res. 2003 May-Jun;31(3):188-96; Ed: Ziprasidone appears least expensive due to considerable cost savings from once-a-day dosing.

Olanzapine and Quetiapine Changed Less Than Risperidone: In a CATIE randomized, double-blind study of 114 schizophrenic patients comparing olanzapine (7-30 mg/day), quetiapine (200-800), and risperidone (1.5-6) in patients who had just discontinued the older antipsychotic perphenazine, the time to treatment discontinuation was longer for patients treated with quetiapine (9.9 months) and olanzapine (7.1) than with risperidone (3.6). There were no significant differences between treatments on discontinuation due to inefficacy, intolerability, or patient decision. Effectiveness of Olanzapine, Quetiapine, and Risperidone in Patients With Chronic Schizophrenia After Discontinuing Perphenazine: A CATIE Study. Stroup TS, et al. University of North Carolina . [email protected]. Am J Psychiatry 2007 Mar;164(3):415-27.

Quetiapine Called Safe Up to 1600 mg/day: The Physician's Desk Reference (PDR) was established to provide for the practicing of a complete listing of all medications with the FDA-approved labelling, including dosage recommendations. Perhaps in order to maximise individual usage of medications, pharmaceutical companies have frequently targeted lowest possible doses for FDA approval. However, many patients with a variety of illnesses due to resistance and/or multiple illnesses, may need higher than these dose ranges. Only risperidone initially obtained approval for a dose for psychosis (16 mg) higher than that suggested currently (maximum of 8 mg). The dose that was approved for mania was lower: a maximum of 6 mg. The others: respectfully, olanzapine (schizophrenia: 15 mg, mania: 20 mg), quetiapine (schizophrenia: 750 mg; mania: 800 mg), ziprasidone (schizophrenia and mania: 160 mg) and aripiprazole (schizophrenia and mania: 30 mg) obtained approvals for psychosis that may limit adverse events but, at the same time, limit benefits. Other data from various sources (double-blind trials, open-label trials, reviews and case reports) have found safety and/or efficacy for the following maximum doses: olanzapine (40 mg), quetiapine (1600 mg), ziprasidone (320 mg) and aripiprazole (75 mg). In many situations, feared increase in adverse events were not magnified by use of higher doses. Higher than Physician's Desk Reference (US) doses on atypical antipsychotics. Goodnick PJ. UMDNJ Robert Wood Johnson School of Medicine. . Expert Opin Drug Saf 2005 Jul;4(4):653-68.