olanzapine and fluoxetine hydrochloride
Dosage Form: capsule
FULL PRESCRIBING INFORMATION
Suicidality and Antidepressant Drugs — Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Symbyax or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and 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. Symbyax is not approved for use in pediatric patients. [See Warnings and Precautions (5.1), Use in Specific Populations (8.4), and Patient Counseling Information (17.2)].
Increased Mortality in Elderly Patients with Dementia-Related Psychosis — Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Symbyax (olanzapine and fluoxetine HCl) is not approved for the treatment of patients with dementia-related psychosis[see Warnings and Precautions (5.2, 5.19) and Patient Counseling Information (17.3)].
Indications and Usage for Symbyax
Depressive Episodes Associated with Bipolar I Disorder
Symbyax® is indicated for the acute treatment of depressive episodes associated with Bipolar I Disorder in adults [see Clinical Studies (14.1)].
Treatment Resistant Depression
Symbyax is indicated for the acute treatment of treatment resistant depression (Major Depressive Disorder in adults who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) [see Clinical Studies (14.2)].
Symbyax Dosage and Administration
Depressive Episodes Associated with Bipolar I Disorder
Symbyax should be administered once daily in the evening, generally beginning with the 6 mg/25 mg capsule. While food has no appreciable effect on the absorption of olanzapine and fluoxetine given individually, the effect of food on the absorption of Symbyax has not been studied. Dosage adjustments, if indicated, can be made according to efficacy and tolerability. Antidepressant efficacy was demonstrated with Symbyax in a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg [see Clinical Studies (14.1)]. The safety of doses above 18 mg per 75 mg has not been evaluated in clinical studies.
While there is no body of evidence to answer the question of how long a patient treated with Symbyax should remain on it, it is generally accepted that Bipolar I Disorder, including the depressive episodes associated with Bipolar I Disorder, is a chronic illness requiring chronic treatment. The physician should periodically reexamine the need for continued pharmacotherapy.
Treatment Resistant Depression
Symbyax should be administered once daily in the evening, generally beginning with the 6 mg/25 mg capsule. While food has no appreciable effect on the absorption of olanzapine and fluoxetine given individually, the effect of food on the absorption of Symbyax has not been studied. Dosage adjustments, if indicated, can be made according to efficacy and tolerability. Antidepressant efficacy was demonstrated with Symbyax in a dose range of olanzapine 6 to 18 mg and fluoxetine 25 to 50 mg [see Clinical Studies (14.2)]. The safety of doses above 18 mg per 75 mg has not been evaluated in clinical studies.
While there is no body of evidence to answer the question of how long a patient treated with Symbyax should remain on it, it is generally accepted that treatment resistant depression (Major Depressive Disorder in adult patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) is a chronic illness requiring chronic treatment. The physician should periodically reexamine the need for continued pharmacotherapy.
Specific Populations
The starting dose of Symbyax 3 mg/25 mg to 6 mg/25 mg should be used for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of Symbyax (female gender, geriatric age, nonsmoking status) or those patients who may be pharmacodynamically sensitive to olanzapine. Dosing modification may be necessary in patients who exhibit a combination of factors that may slow metabolism. When indicated, dose escalation should be performed with caution in these patients. Symbyax has not been systematically studied in patients >65 years of age or in patients <18 years of age [see Warnings and Precautions (5.19), Use in Specific Populations (8.5), and Clinical Pharmacology (12.3, 12.4)].
Treatment of Pregnant Women During the Third Trimester — When treating pregnant women with fluoxetine, a component of Symbyax, during the third trimester, the physician should carefully consider the potential risks and potential benefits of treatment. Neonates exposed to SNRIs or SSRIs late in the third trimester have developed complications requiring prolonged hospitalizations, respiratory support, and tube feeding. The physician may consider tapering the dose of fluoxetine in the third trimester [see Use in Specific Populations (8.1)].
Discontinuation of Treatment with Symbyax
Symptoms associated with discontinuation of fluoxetine, a component of Symbyax, SNRIs, and SSRIs, have been reported [see Warnings and Precautions (5.23)].
Dosage Forms and Strengths
Capsules (mg equivalent olanzapine/mg equivalent fluoxetine):
- 3 mg/25 mg
- 6 mg/25 mg
- 6 mg/50 mg
- 12 mg/25 mg
- 12 mg/50 mg
Contraindications
The use of Symbyax is contraindicated with the following:
- Monoamine Oxidase Inhibitors (MAOI) — [see Drug Interactions (7.1)]
- Pimozide — [see Drug Interactions (7.9)]
- Thioridazine — [see Drug Interactions (7.9)]
Warnings and Precautions
Clinical Worsening and Suicide Risk
Patients with Major Depressive Disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with Major Depressive Disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, Obsessive Compulsive Disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug versus placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.
| Age Range | Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated |
| Increases Compared to Placebo | |
| <18 | 14 additional cases |
| 18-24 | 5 additional cases |
| Decreases Compared to Placebo | |
| 25-64 | 1 fewer case |
| ≥65 | 6 fewer cases |
No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for Major Depressive Disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms [see Warnings and Precautions (5.23)].
Families and caregivers of patients being treated with antidepressants for Major Depressive Disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for Symbyax should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.
It should be noted that Symbyax is not approved for use in treating any indications in the pediatric population [see Use in Specific Populations (8.4)].
Elderly Patients with Dementia-Related Psychosis
Increased Mortality — Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Symbyax is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning, Warnings and Precautions (5.19), and Patient Counseling Information (17.3)].
In olanzapine placebo-controlled clinical trials of elderly patients with dementia-related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than placebo-treated patients (3.5% vs 1.5%, respectively).
Cerebrovascular Adverse Events (CVAE), Including Stroke — Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with olanzapine compared to patients treated with placebo. Olanzapine and Symbyax are not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning and Patient Counseling Information (17.3)].
Neuroleptic Malignant Syndrome (NMS)
A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs, including olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.
If after recovering from NMS, a patient requires treatment with an antipsychotic, the patient should be carefully monitored, since recurrences of NMS have been reported [see Warnings and Precautions (5.7) and Patient Counseling Information (17.4, 17.8)].
Hyperglycemia
Physicians should consider the risks and benefits when prescribing Symbyax to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level (fasting 100-126 mg/dL, nonfasting 140-200 mg/dL). Patients taking Symbyax should be monitored regularly for worsening of glucose control. Patients starting treatment with Symbyax should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug [see Patient Counseling Information (17.5)].
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including olanzapine alone, as well as olanzapine taken concomitantly with fluoxetine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics.
Mean increases in blood glucose have been observed in patients treated (median exposure of 9.2 months) with olanzapine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). The mean increase of serum glucose (fasting and nonfasting samples) from baseline to the average of the 2 highest serum concentrations was 15.0 mg/dL.
In a study of healthy volunteers, subjects who received olanzapine (N=22) for 3 weeks had a mean increase compared to baseline in fasting blood glucose of 2.3 mg/dL. Placebo-treated subjects (N=19) had a mean increase in fasting blood glucose compared to baseline of 0.34 mg/dL.
In an analysis of 7 controlled clinical studies, 2 of which were placebo-controlled, with treatment duration up to 12 weeks, Symbyax was associated with a greater mean change in random glucose compared to placebo (8.65 mg/dL vs -3.86 mg/dL). The difference in mean changes between Symbyax and placebo was greater in patients with evidence of glucose dysregulation at baseline (including those patients diagnosed with diabetes mellitus or related adverse reactions, patients treated with anti-diabetic agents, patients with a baseline random glucose level ≥200 mg/dL, or a baseline fasting glucose level ≥126 mg/dL). Symbyax-treated patients had a greater mean HbA1c increase from baseline of 0.15% (median exposure 63 days), compared to a mean HbA1c decrease of 0.04% in fluoxetine-treated subjects (median exposure 57 days) and a mean HbA1c increase of 0.12% in olanzapine-treated patients (median exposure 56 days).
In an analysis of 6 controlled clinical studies, a larger proportion of Symbyax-treated subjects had glycosuria (4.4%) compared to placebo-treated subjects (1.4%).
The mean change in nonfasting glucose in patients exposed at least 48 weeks was 5.9 mg/dL (N=425).
Table 2 shows short-term and long-term changes in random glucose levels from adult Symbyax studies.
a Not Applicable. | ||||||
| Up to 12 weeks exposure | At least 48 weeks exposure | |||||
| Laboratory Analyte | Category Change (at least once) from Baseline | Treatment Arm | N | Patients | N | Patients |
| Random Glucose | Normal to High (<140 mg/dL to ≥200 mg/dL) | Symbyax | 609 | 2.3% | 382 | 3.1% |
| Placebo | 346 | 0.3% | NAa | NAa | ||
| Borderline to High (≥140 mg/dL and <200 mg/dL to ≥200 mg/dL) | Symbyax | 44 | 34.1% | 27 | 37.0% | |
| Placebo | 28 | 3.6% | NAa | NAa | ||
Controlled fasting glucose data is limited for Symbyax; however, in an analysis of 5 placebo-controlled olanzapine monotherapy studies with treatment duration up to 12 weeks, olanzapine was associated with a greater mean change in fasting glucose levels compared to placebo (2.76 mg/dL vs 0.17 mg/dL).
The mean change in fasting glucose for olanzapine-treated patients exposed at least 48 weeks was 4.2 mg/dL (N=487). In analyses of patients who completed 9-12 months of olanzapine therapy, mean change in fasting and nonfasting glucose levels continued to increase over time.
Olanzapine Monotherapy in Adolescents — The safety and efficacy of olanzapine and fluoxetine in combination have not been established in patients under the age of 18 years. The safety and efficacy of olanzapine have not been established in patients under the age of 13 years. In an analysis of 3 placebo-controlled olanzapine monotherapy studies of adolescent patients, including those with Schizophrenia (6 weeks) or Bipolar I Disorder (manic or mixed episodes) (3 weeks), olanzapine was associated with a greater mean change from baseline in fasting glucose levels compared to placebo (2.68 mg/dL vs -2.59 mg/dL). The mean change in fasting glucose for adolescents exposed at least 24 weeks was 3.1 mg/dL (N=121). Table 3 shows short-term and long-term changes in fasting blood glucose from adolescent olanzapine monotherapy studies.
a Not Applicable. | ||||||
| Up to 12 weeks exposure | At least 24 weeks exposure | |||||
| Laboratory Analyte | Category Change (at least once) from Baseline | Treatment Arm | N | Patients | N | Patients |
| Fasting Glucose | Normal to High (<100 mg/dL to ≥126 mg/dL) | Olanzapine | 124 | 0% | 108 | 0.9% |
| Placebo | 53 | 1.9% | NAa | NAa | ||
| Borderline to High (≥100 mg/dL and <126 mg/dL to ≥126 mg/dL) | Olanzapine | 14 | 14.3% | 13 | 23.1% | |
| Placebo | 13 | 0% | NAa | NAa | ||
Hyperlipidemia
Undesirable alterations in lipids have been observed with Symbyax use. Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using Symbyax, is recommended [see Patient Counseling Information (17.6)].
Clinically meaningful, and sometimes very high (>500 mg/dL), elevations in triglyceride levels have been observed with Symbyax use. Clinically meaningful increases in total cholesterol have also been seen with Symbyax use.
In an analysis of 7 controlled clinical studies, 2 of which were placebo-controlled, with treatment duration up to 12 weeks, Symbyax-treated patients had an increase from baseline in mean random total cholesterol of 12.1 mg/dL compared to an increase from baseline in mean random total cholesterol of 4.8 mg/dL for olanzapine-treated patients and a decrease in mean random total cholesterol of 5.5 mg/dL for placebo-treated patients. Table 4 shows categorical changes in nonfasting lipid values.
In long-term olanzapine and fluoxetine in combination studies (at least 48 weeks), changes (at least once) in nonfasting total cholesterol from normal at baseline to high occurred in 12% (N=150) and changes from borderline to high occurred in 56.6% (N=143) of patients. The mean change in nonfasting total cholesterol was 11.3 mg/dL (N=426).
| Laboratory Analyte | Category Change (at least once) from Baseline | Treatment Arm | N | Patients |
| Nonfasting Triglycerides | Increase by ≥50 mg/dL | OFC | 174 | 67.8% |
| Olanzapine | 172 | 72.7% | ||
| Normal to High (<150 mg/dL to ≥500 mg/dL) | OFC | 57 | 0% | |
| Olanzapine | 58 | 0% | ||
| Borderline to High (≥150 mg/dL and <500 mg/dL to ≥500 mg/dL) | OFC | 106 | 15.1% | |
| Olanzapine | 103 | 8.7% | ||
| Nonfasting Total Cholesterol | Increase by ≥40 mg/dL | OFC | 685 | 35% |
| Olanzapine | 749 | 22.7% | ||
| Placebo | 390 | 9% | ||
| Normal to High (<200 mg/dL to ≥240 mg/dL) | OFC | 256 | 8.2% | |
| Olanzapine | 279 | 2.9% | ||
| Placebo | 175 | 1.7% | ||
| Borderline to High (≥200 mg/dL and <240 mg/dL to ≥240 mg/dL) | OFC | 213 | 36.2% | |
| Olanzapine | 261 | 27.6% | ||
| Placebo | 111 | 9.9% |
Fasting lipid data is limited for Symbyax; however, in an analysis of 5 placebo-controlled olanzapine monotherapy studies with treatment duration up to 12 weeks, olanzapine-treated patients had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.3 mg/dL, 3.0 mg/dL, and 20.8 mg/dL respectively compared to decreases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 6.1 mg/dL, 4.3 mg/dL, and 10.7 mg/dL for placebo-treated patients. For fasting HDL cholesterol, no clinically meaningful differences were observed between olanzapine-treated patients and placebo-treated patients. Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline, where lipid dysregulation was defined as patients diagnosed with dyslipidemia or related adverse reactions, patients treated with lipid lowering agents, patients with high baseline lipid levels.
In long-term olanzapine studies (at least 48 weeks), patients had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.6 mg/dL, 2.5 mg/dL, and 18.7 mg/dL, respectively, and a mean decrease in fasting HDL cholesterol of 0.16 mg/dL. In an analysis of patients who completed 12 months of therapy, the mean nonfasting total cholesterol did not increase further after approximately 4-6 months.
The proportion of olanzapine-treated patients who had changes (at least once) in total cholesterol, LDL cholesterol or triglycerides from normal or borderline to high, or changes in HDL cholesterol from normal or borderline to low, was greater in long-term studies (at least 48 weeks) as compared with short-term studies. Table 5 shows categorical changes in fasting lipids values.
a Not Applicable. | ||||||
| Up to 12 weeks exposure | At least 48 weeks exposure | |||||
| Laboratory Analyte | Category Change (at least once) from Baseline | Treatment Arm | N | Patients | N | Patients |
| Increase by ≥50 mg/dL | Olanzapine | 745 | 39.6% | 487 | 61.4% | |
| Placebo | 402 | 26.1% | NAa | NAa | ||
| Fasting | Normal to High | Olanzapine | 457 | 9.2% | 293 | 32.4% |
| Triglycerides | (<150 mg/dL to ≥200 mg/dL) | Placebo | 251 | 4.4% | NAa | NAa |
| Borderline to High | Olanzapine | 135 | 39.3% | 75 | 70.7% | |
| (≥150 mg/dL and <200 mg/dL to ≥200 mg/dL) | Placebo | 65 | 20.0% | NAa | NAa | |
| Increase by ≥40 mg/dL | Olanzapine | 745 | 21.6% | 489 | 32.9% | |
| Placebo | 402 | 9.5% | NAa | NAa | ||
| Fasting | Normal to High | Olanzapine | 392 | 2.8% | 283 | 14.8% |
| Total Cholesterol | (<200 mg/dL to ≥240 mg/dL) | Placebo | 207 | 2.4% | NAa | NAa |
| Borderline to High | Olanzapine | 222 | 23.0% | 125 | 55.2% | |
| (≥200 mg/dL and <240 mg/dL to ≥240 mg/dL) | Placebo | 112 | 12.5% | NAa | NAa | |
| Increase by ≥30 mg/dL | Olanzapine | 536 | 23.7% | 483 | 39.8% | |
| Placebo | 304 | 14.1% | NAa | NAa | ||
| Fasting | ||||||
