Olanzapine (Zyprexa and Zydis)

Olanzapine is at least as good as other atypical anti-psychotics for relieving the symptoms of schizophrenia and a few studies claim that it is better.  However, it is more expensive and causes much more weight gain than ziprasidone (Geodon).  The weight gain results in a fair number of cases of diabetes.  Blood sugars should be monitored.  Also, since much of the research may be biased by drug industry funding, the claims that olanzapine is better than other atypical anti-psychotics are not trustworthy.  Another alternative with the weight gain side-effect is Abilify.

Side-effects in 532 olanzapine patients in short-term industry-funded DB PC trials by the amount they exceeded placebo side-effects were: sleepiness 26%, dizziness 7%, abnormal gait 5%, weight gain 5%, constipation 5%, fever 4%, dry mouth 4%, back pain 3%, cough 3%, and all of the following at 2% each: chest pain, postural hypotension, rapid heart beat, upset stomach, bruising, joint pain, and arm or leg pain.  Many other symptoms were reported less often.  While most symptoms get better with time, weight gain tends to get worse with a fair percentage of patients gaining considerable weight.

Zydis is a tablet form of olanzapine which dissolves instantly on contact with the tongue.  This has an advantage for patients in the hospital who pretend to take their medication, but then later spit it out.  I have seen Zyprexa and Zydis used as sleep remedies.  This makes a very expensive sleeping pill, but I have seen it used that way, even for teenagers in the hospital.  

Zydis 5 mg. costs $8.30 per pill and Zydis 10 mg. $12 per pill when purchased as bottles of 30 from drugstore.com and Zyprexa 10 mg. tabs are $9.50 per pill.  Other pills used in hospital as "an needed" medications for anxiety or agitation cost much less.  Hydroxyzine pamoate (generic Vistaril) costs only 38 cents for two 50 mg. capsules, haloperidol 5 mg. 22 cents, and chlorpromazine 100 mg. costs 32 cents.  Even Geodon is less by Zyprexa at $5 per capsule of any strength.

Clozapine Equal to Olanzapine (Zyprexa) for Schizophrenia: In a DB randomized study of 114 patients with schizophrenia, there was no significant difference favoring olanzapine or clozapine. The lack of a marked correlation between PANSS and the subjective well-being measure SWN improvements indicates that patients and psychiatrists perceive treatment differently. Naber D, Riedel M, et al. Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia. Acta Psychiatr Scand 2005: 111: 106-115. 

Chlorpromazine Helped Fewer Haldol Resistant than Olanzapine: In a poor study, 103 schizophrenic patients considered treatment-resistant were treated with haldol 10-40 for 6 week. 84 who did not improve were put in a DB study of chlorpromazine 1200 with benztropine 4mg/d vs. olanzapine (a congener of clozapine) 25mg/d. 15% improved on olanzapine and none of chlorpromazine. Conley, U Maryland, Am J Psychiatry ’98;155:914-20. Ed: This was a poor study because very few patients on chlorpromazine will require so much benztropine and most will not require any, but benztropine worsens confusion and would tend to increase BPRS scores.  As an aside, olanzapine occupies 70-80% D2 receptors at 10-20 mg/day but over 80% with 30 mg/day. Atypicals usually occupy under 60%. Kapur, Am J Psychiatry ’98;155:921-8. Clozapine occupies 24%-66%. Risperidone occupies 66%-80%. Both had over 80% occupation of 5-HTs receptors. Typicals occupy 70-90% D2s.

Clozapine-to-Olanzepine Switch 42% Success: At patient request, often to avoid weekly blood testing, 19 patients were switched but only 42% were responders and 37% decompensated badly enough to be hospitalized. Responders had been on clozapine a briefer time and lower dosage. David Henderson J Clin Psychiatry 11/98 59:585-8. Olanzapine blocks dopamine D2 and serotonin 5-HT2 receptors.

Clozapine as Good as Olanzapine in DB: A Hungarian 147-patient, 18-week DB study of schizophrenic patients who had not improved on or tolerated another anti-psychotic found that 58% improved ("responded") while on olanzapine vs. 61% while on clozapine. Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia. Bitter I, Dossenbach MR, Brook S, Feldman PD, Metcalfe S, Gagiano CA, Furedi J, Bartko G, Janka Z, Banki CM, Kovacs G, Breier A. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jan;28(1):173-80

Cost: Olanzapine Supposedly Cheaper Than Risperidone: Patients taking olanzapine instead of risperidone stayed on therapy longer (P < .0001) and were prescribed anti-Parkinsonian medications less frequently (P < .005). Compared with risperidone, olanzapine treatment resulted in lower direct mental health care costs ($1,827 less, P < .03) and lower direct total health care costs ($1,834 less, P < .05). Manag Care Interface 2002 Feb;15(2):75-81

Fluphenazine (Prolixin) Not as Good as Olanzapine (Zyprexa) in 6 Month Trial: A small DB PC study of just 60 patients from Vienna but lasting 6 months found patients on olanzapine had a significantly better improvement in psychotic symptoms. Side-effects were weight gain with olanzapine and EPS with fluphenazine. Double-blind, randomized comparison of olanzapine versus fluphenazine in the long-term treatment of schizophrenia. Dossenbach MR, Folnegovic-Smalc V, Hotujac L, Uglesic B, Tollefson GD, Grundy SL, Friedel P, Jakovljevic MM. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Mar;28(2):311-8. Ed: This industry funded study continues to show atypicals better.  However, I favor other atypicals to avoid the weight gain and diabetes caused by olanzapine. For more, see Olanzapine.

Haldol did as Well as Olanzapine in Large DB: A 309-patient 1-year VA study of schizophrenic patients with serious symptoms and dysfunction for the previous two years randomized to  haloperidol 5-20 mg/d and prophylactic benztropine mesylate 1-4 mg daily, olanzapine 5-20 mg/d and benztropine placebo. 59% completed the study, while 39% partially completed the year-long assessment period. There were no significant differences between the olanzapine group and the haloperidol group in completion rates (45.9% vs. 39.3%; P = .25), nor in reasons for discontinuation. Comparable scores on the Positive and Negative Syndrome Scale (PANSS) over 12 months, both on total score (P = .35), and positive and negative subscales (P = .64 and P = 0.31, respectively). The haloperidol cohort did achieve higher scores on the Heinrichs-Carpenter Quality of Life Scale (QOLS), but only at six weeks (P = .04), and overall there were no significant differences between the groups (P = .71). Olanzapine had lower scores for akathesia, but not for tardive dyskinesia or other extrapyramidal symptoms. Weight gain was much more frequently reported with olanzapine group. Although no significant differences in costs for VA service, olanzapine medication costs were four to five times higher, resulting in a $3,000 to $9,000 increase in total annual health costs. Robert Rosenheck, JAMA. 11/26/2003;290:2693-2702

Haldol IM Equals Olanzapine IM: Olanzapine 10mg IM up to 3 times on the 1^st day did as well as haldol 7.5 mg IM up to 3 times. J Clin Psychiatry 01;62:22. Lilly

Haldol Not as Good as Olanzapine 1^st Episode: When compared to haloperidol in 83 patients as part of the 1997 patient international study, 67% v 30% responded (40% decrease in symptoms). The main side-effect to olanzapine was somnolence with very little EPS but more weight gain. TM Sanger, Eli Lilly, Am J Psychiatry 1/99 156:79-87. Same study, those with depressive symptoms did better with olanzapine. Arch Gen Psychiatry 3/98 55:250-8. Funded by Lilly. Haldol was unusually ineffective in this study.

Haldol as Good as Olanzapine in 1^st Episode, but Slightly Better Retention: In a 12-week DB trial with 2 years total follow-up under open conditions, there were greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. EPS and akathesia were higher with Haldol, but wt gain was higher with olanzapine with a 67% vs. 54% 2-year retention favoring olanzapine. UNC. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Lieberman JA, Tollefson G, Tohen M, Green AI, Gur RE, Kahn R, McEvoy J, Perkins D, Sharma T, Zipursky R, Wei H, Hamer RM; HGDH Study Group. Am J Psychiatry. 2003 Aug;160(8):1396-404

Haldol Not as Good as Olanzapine for Women: Women on olanzapine had a significantly better treatment response than men, regardless of chronicity. Finally, premenopausal women had a significantly better treatment response than postmenopausal women, regardless of treatment and chronicity in a 6 week DB 1995 study of women and men. Harvard, JM Goldstein, Psychiatry Res 2002 May 15;110(1):27-37

Haldol Not as Good as Olanzapine: In a large Eli Lilly study of 526 drug-resistant schizophrenics in a DB for 6 weeks, 47% of olanzapine patients vs. 35% of haldol patients improved for both positive and negative symptoms. Biol Psychiatry 2/99;45:403; Lilly's study also reported that olanzapine was better for mood symptoms than haldol. Patients were not as severely ill as other studies. Haldol also was only given at 10 mg/day after it was started at 5 mg/day. Biol Psychiatry ’98;43:803. Also Biol Psychiatry 99;45:403

Haldol Not as Good as Olanzapine Negative Symptoms: Two other large Eli Lilly studies: the first one of 335 schizophrenics for 6 week in a DB PC trial of olanzapine 5, 10, or 15 mg/day vs. haldol 10-20 mg/day. High-dose olanzapine was superior to haldol, especially with negative symptoms with reduced affective flattening, alogia, attention problems, avolition-apathy, but no change anhedonia-asociality. Tollefson G, Sanger T: Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine. Amer J Psychiatry 97;154:466-74. In another report, side-effects were dry mouth 22% with olanzapine; parkinsonism 14% vs. 38% with haldol; akathisia 12% vs. 40% with haldol. Patients gained an average of 4 pounds in just six weeks on olanzapine. Open trial 2000 patients U.S. and Europe. Tollefson, Amer J Psychiatry 97;154:457-65.

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

Risperidone as Good as Olanzapine: In a 377-patient DB trial of 2-6 mg/day of risperidone or 5-20 olanzapine = equal side-effects and both did well although more weight gain with olanzapine and risperidone better with affective and positive symptoms. EPS similar: 24% vs. 20%. Am J Psychiatry 158:765-774, May 2001.

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.

Risperidone Not Quite as Good as Olanzapine: An industry-funded study of 336 patients in a DB trial found both improved although olanzapine helped more with negative symptoms and had fewer side-effects. J Clin Psychopharm ’97;1:407

Traditional Antipsychotics Higher Readmission Rates than Olanzapine and Risperidone: In Israel all schizophrenic patients discharged in 1998 were followed for two years. Risperidone and olanzapine was allowed only for those unresponsive or intolerant to typicals. After 2 years of follow-up, there were 25% less likely of rehospitalization on olanzapine or risperiodone. Rabinowitz, Am J Psychiatry 01;158:266

Ziprasidone Not as Good in Study by Zyprexa Manufacturer: In a 28-week DB study of of 548 patients with schizophrenia financed and directed by the manufacturer of olanzapine, 10-20 mg/day of olanzapine did better than 80-160 mg/day of ziprasidone on remaining on the medication (60% vs. 42%) and on the Positive and Negative Syndrome Scale overall scale and Clinical Global Impression ratings. Weight change was greater with olanzapine (7 pounds gain vs. 2.5 pound loss). Fasting lipid profiles were better in the ziprasidone group. Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia. Breier A, et al. Lilly Pharmaceuticals. . Am J Psychiatry. 2005 Oct;162(10):1879-87. Ed: This study obviously can't be trusted in view of extensive evidence that manufacturer studies inflate evidence in favor of their own drugs.

Ziprasidone as Good as Olanzapine (Zyprexa): In a DB multi-center study for 6-weeks for acute schizophrenic exacerbations, patients improved equally on both medications on all measures except for verbal fluency with favored olanzapine. Mt. Sinai Med School. Randomized, controlled, double-blind, multicenter comparison of the cognitive effects of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Harvey PD, Siu CO, Romano S. Psychopharmacology (Berl). 2003 Nov 13

Ziprasidone (Geodon) Did as Well as Olanzapine (Zyprexa): In a 6-month DB flexible dosage continuation study of schizophrenic or schizoaffective patients who had responded, comparable improvements in BPRS and CGI severity scores were seen with both olanzapine and ziprasidone. Olanzapine increased weight, total cholesterol, low-density lipoprotein cholesterol, and fasting insulin. Mean QTc values at endpoint were 407.1 msec (baseline mean=406.0 msec) and 394.4 msec (baseline mean=399.7 msec) for ziprasidone and olanzapine, respectively. No patient had a QTc interval >/=500 msec. Six-month, blinded, multicenter continuation study of ziprasidone versus olanzapine in schizophrenia. Simpson GM, et al. University of Southern California. . Am J Psychiatry. 2005 Aug;162(8):1535-8.

Side Effects

Agitation, Aggression, Mania from Olanzapine: Two cases were reported of chronic schizophrenic patients getting agitated after switched to olanzapine. Canad J Psychiatry ’98;43:1054

Agranulocytosis: 1 Case from Olanzapine: Lancet 99;354:566. Improved with discontinuation and GCSF

Breast Milk: Olanzapine Levels Only 1% of Mother's: Infants’ blood levels were not detectable and breast milk levels only 1% of mothers’ blood levels. Transfer of Olanzapine Into Breast Milk, Calculation of Infant Drug Dose, and Effect on Breast-Fed Infants. Gardiner SJ, Kristensen JH, Begg EJ, et al. The American Journal of Psychiatry. 2003;160(8):1428-1431

Carbamazepine Decreases Olanzapine Blood Levels: Carbamazepine induces CYP enzymes reducing levels some anti-psychotics, lowering olanzapine an average of 36%. Watch for increase olanzapine effect when stopping carbamazepine. Lickt, Denmark, J Clin Psychoph 00;20:110.

Cholesterol and Hyperlipemia Caused by Olanzapine: Tripling of hyperlipidemias v conventionals or risperidone. Koro Arch Gen Psychiatry 10/02 59:1021

Diabetes Induced by Olanzapine: Case of 32 yo Afro obese male becoming hyperglycemic and insulin ineffective. Normal with discontinuation, although recurred on restarting even at low level. J Clin Psychiatry 98;59:687

Diabetes Risk Increased 42% by Olanzapine: Study of over 9000 patients on risperidone, olanzapine, quetiapine, or traditional anti-psychotics and 10,000 controls. Only Olanzapine increased risk of diabetes. Antipsychotic-Induced Type 2 Diabetes: Evidence From a Large Health Plan Database, Gianfrancesco F, White R, Wang RH, Nasrallah HA. The Journal of Clinical Psychopharmacology. 2003;23(4):328-335

Diabetes: Glucose Levels Low, Hyperglycemic Coma, Seizures: At least 15 cases of clozapine and olanzapine causing diabetes have been reported (Bio Psychiatry 98;44:778). Transient asymptomatic decreases in glucose have been reported. Am J Psychiatry 01;158:500. Seizures less than 1%, similar to other neuroleptics.

Discontinuation for 1 Month or More Increases Suicide in Olanzapine and Risperidone: Of 603 patients, 33% interrupted treatment for at least 30 days. An increased suicide attempt rate was observed when comparing uninterrupted and interrupted drug use (20.0/1000 person years vs. 72.1/1000 person years, respectively). A four-fold increased risk for attempting suicide among patients with drug holidays was found (RR adjusted for age and gender 4.2). Netherlands. Increased suicide attempt rate among patients interrupting use of atypical antipsychotics. Herings RM, Erkens JA. Pharmacoepidemiol Drug Saf. 2003 Jul-Aug;12(5):423-4

Hypomania/Mania, 7 Cases : Treatment refractory patient 31yo female bipolar with psychosis on haldol then risperidone then admitted put on olanzapine with hypomanic in 24 hours. Medline search said to find 6 more olanzapine manias and 16 from risperidone, possibly due to 5-HT2 antagonistic activity which have anti-depressant effects. Int Clin Psychoph 99;14:377

Incontinence from Olanzapine or Clozapine Treated with Ephedrine: Urinary incontinence a side-effect of atypicals due to alpha-1-antagonism. Ephedrine 25mg/day was successful within 24 hours. J Clin Psych 00;61:601; J Clin Psych 96;57:514

Overdose Olanzapine Deaths Reported: 29 deaths were identified where an overdose of olanzapine was either the principal cause of toxicity or a significant contributor in combined toxicity. U Alberta. A review of olanzapine-associated toxicity and fatality in overdose. Chue P, Singer P. J Psychiatry Neurosci. 2003 Jul;28(4):253-61

Priapism: 3 Cases: Due to alpha-adrenergic blockade. Also 6 cases reported with clozapine in the literature. Am J Psychiatry 00;157:659

Sex Difficulty of Risperidone Reversed by Olanzapine: Olanzapine reversed hyperprolactinemia in 24 risperidone-treated female schizophrenic patients with galactorrhea, menstrual irregularity, or sexual dysfunction due to risperidone. This was associated with a decrease in amenorrhea, improved cycle regularity, and a decrease in sexual side effects that the women attributed to antipsychotic medication. J Clin Psychiatry 2002 May;63(5):408-13

Stroke Risk High with Olanzapine, too: Post-hoc analysis by the Eli Lilly drug company of 5 randomized clinical trials using olanzapine in patients with dementia, has shown that patients taking olanzapine have a risk of experiencing a stroke which is 3 times higher than patients taking placebo. van Marum RJ, Jansen PA. Universitair Medisch Centrum Utrecht, Netherlands. Ned Tijdschr Geneeskd. 2005 Jan 22;149(4):165-7. Ed: Strokes in the elderly are doubled by risperidone compared to placebo, but increased only 10% compared to traditional anti-psychotics.

Weight Gain Linked to Olanzapine Improvement: For olanzapine and clozapine, therapeutic response was closely related to an absolute and relative gain in weight and to a gain in BMI. No association between weight gain and therapeutic response was found for risperidone and haloperidol. DB study of 151. J Clin Psychopharmacol 2002 Jun;22(3):244-51

Weight Gain: Fluoxetine Did Not Decrease Olanzapine Weight Gain: 30 patient DB PC 8 week with fluoxetine (Prozac) 20mg/d, olanzapine 10/day. Am J Psychiatry 02;159:1058

Weight Gain: Nizatidine Reduced Olanzapine Weight Gain: 3 cases considerable weight loss in schiz patients on olanzapine treated with H2 antagonist nizatidine. The first two being treated for peptic esophagitis and the third just because olanzapine weight gain a problem. Lost 8# in 8 weeks on nizatidine 150mg BID and maintained 2 months. Cimetidine reported to induce weight loss in obese. Sacchetti, Biol Psyc 00;48:167, Brescia, Italy

Weight Gain: Nizatidine (Axid) Reduces Olanzapine Wt Gain in DB: Turkish study DB PC 8 weeks. Nizatidine group showed 10# wt. loss and lowered leptin levels vs 5# further weight gain in placebo plus olanzapine group. Nizatidine treatment and its relationship with leptin levels in patients with olanzapine-induced weight gain. Atmaca M, Kuloglu M, Tezcan E, Ustundag B. Hum Psychopharmacol. 2003 Aug;18(6):457-61; Similar result in 10 pt open Korean study with 3.5% wt loss. Hum Psychopharmacol. 2003 Aug;18(6):453-6

Weight Gain: Ranitidine (Zantac) May Also Help and Cheaper: Randomized open trial found much less weight gain in short trial with ranitidine added to olanzapine. Olanzapine alone 7.5# gain, with 300mg/d ranitidine 2# gain, with 600mg 3# loss. Authors make undocumented olanzapine promotion comment (calling it the drug of choice for schizophrenia) that reviewers and journal editor allowed. Buenos Aires. Lopez-Mato A, Rovner J, Illa G, Vieitez A, Boullosa O. Vertex 2003 Jun-Aug;14(52):85-96; Ranitidine & cimetidine (Tagamet) are generics and would cost about 33 cents/d wholesale at higher dose. Axid would be $6/d!

Weight Gain: Olanzapine Patients Gain Less Weight While on Reboxetine: A DB study in Israel of 26 patients treated with olanzapine found that those on olanzapine alone gained an average of 11 pounds over the four weeks of the study vs. a 5 pound weight gain for those on olanzapine plus reboxetine 8 mg/d. There was a trend toward less depression in the reboxetine group. Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study. Poyurovsky M, Isaacs I, Fuchs C, Schneidman M, Faragian S, Weizman R, Weizman A. Am J Psychiatry 2003 Feb;160(2):297-302

Withdrawal Psychosis, Supersensitivity Psychosis with Olanzapine: 3 male schizophrenics on 10-25 mg/day for at least 8 months had sudden major relapses within 48 hours of abruptly stopping olanzapine with mania, hyperactivity, grandeur, persecution, auditory hallucinations, insomnia. They responded to restarting olanzapine or another antipsychotic. Unlike classic withdrawal symptoms, no cholinergic symptoms and occurs sooner after drug cessation with sudden, often intense symptoms, sometimes with new symptoms. Llorca P-M, Vaiva G, Lancon C: Supersensitivity psychosis in patients with schizophrenia after sudden olanzapine withdrawal. Canad J Psychiatry 01;46:87-8

Dosage Studies

Olanzapine Loading Better for Agitation: In a 148-patient DB Lilly study of agitated schizophrenia. Standard 10 mg/day with lorazepam for up to 4 days than 5-20 mg/day vs. 40 mg/day x2, then 30 mg/day x2, then 5-20 mg/day. Effectiveness of rapid initial dose escalation of up to forty milligrams per day of oral olanzapine in acute agitation. Baker RW, Kinon BJ, Maguire GA, Liu H, Hill AL. J Clin Psychopharmacol. 2003 Aug;23(4):342-8

5-15 mg Better Than 1 mg: DB PC 1 year study with 20% relapse on 5-15 mg/day vs. 45% on 1% vs. 60%+ on placebo. Lilly, Psychiatr Serv ’97;48:1571

High Dose Olanzapine Reported; Retail Cost Very High, Production Cost Very Low: Three cases at 35, 40, and 60mg/d claim high dose help in refractory patients. High-dose olanzapine for treatment-refractory schizophrenia. Lerner V. Clin Neuropharmacol. 2003 Mar-Apr;26(2):58-61, Ben Gurion University. Ed: I would hate to be paying for the olanzapine.  Actually, up to late 2003, olanzapine was available from India via the internet for just 2% of the U.S. cost (e.g. $10 vs. $500 for a typical one month dosage) until the Bush administration successfully pressured the Indian government to stop the low cost exports.  Since the quality of Indian drugs is quite good, often produced by the same multinational giants, this suggests that the extremely high cost of olanzapine not due to its production cost.

Olanzapine Called Safe Up to 40 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.