Chlorpromazine Haloperidol Quetiapine Risperidone Perphenazine Olanzapine
Incident users 9,740 24,900 83,402 129,046 14,427 151,646
Prescriptions 36,283 123,494 591,804 1,051,896 68,436 1,196,400
Person-years (p-y) 2,079 7,908 37,759 70,934 5,064 81,484
Principal inpatient or first-listed emergency department SD/VAs 14 53 86 271 11 276
Incidence rate per 1,000 p-y
(95 % confidence interval)
6.7
(3.7-11.3)
6.7
(5.0-8.8)
2.3
(1.8-2.8)
3.8
(3.4-4.3)
2.2
(1.1-3.9)
3.4
(3.0-3.8)
Unadjusted incidence rate ratio
(95% confidence interval)
2.0
(1.1-3.4)
2.0
(1.5-2.7)
0.7
(0.5-0.9)
1.1
(1.0-1.3)
0.6
(0.3-1.2)
reference
USER-LEVEL VARIABLES
Female sex 36.3% 51.7% 64.8% 60.1% 72.3% 57.7%
Age, in years
< 35 11.0% 11.1% 14.0% 12.7% 10.4% 12.8%
35-44 29.6% 28.2% 35.1% 30.0% 28.6% 32.1%
45-54 24.7% 24.0% 27.7% 25.4% 26.0% 26.3%
55-64 16.9% 16.6% 13.3% 15.7% 18.2% 14.9%
65-74 17.8% 20.0% 9.9% 16.2% 16.8% 13.9%
Race
White 45.8% 44.8% 54.3% 47.0% 35.6% 48.2%
Non-White 54.2% 55.2% 45.7% 53.0% 64.4% 51.8%
PRESCRIPTION-LEVEL VARIABLES
Nursing home residence 10.6% 16.9% 11.5% 21.0% 3.2% 15.3%
Diagnoses ever in past
Agranulocytosis (Neutropenia) 3.8% 2.2% 1.9% 1.8% 1.1% 2.1%
Alcohol abuse 19.5% 16.5% 21.1% 16.3% 9.1% 19.1%
Anemia 35.2% 31.8% 30.8% 33.3% 29.9% 32.7%
Arrhythmia / Conduction Disorders 19.7% 17.4% 18.2% 19.4% 15.7% 18.7%
Asthma / COPD 35.4% 32.0% 37.8% 32.8% 37.9% 36.1%
Bulimia 0.4% 0.2% 0.7% 0.3% 0.3% 0.4%
Cancer 21.9% 16.4% 20.2% 18.6% 16.7% 19.2%
Cerebral Palsy 2.6% 1.8% 1.8% 2.9% 0.9% 2.0%
Cerebrovascular Disease 15.4% 18.8% 16.7% 20.4% 14.3% 18.5%
Coronary Artery Disease 22.6% 20.7% 22.7% 24.2% 23.1% 23.4%
Diabetes 27.2% 28.2% 27.7% 30.0% 31.0% 25.6%
Emesis / Nausea 22.8% 15.3% 21.5% 15.9% 14.9% 16.8%
Enuresis 9.9% 11.0% 11.9% 12.3% 9.6% 11.2%
Epilepsy / Convulsions 22.8% 20.6% 19.4% 21.4% 9.9% 18.6%
HIV / AIDS 9.1% 5.0% 7.5% 6.9% 3.1% 10.3%
Headache 27.4% 22.9% 35.8% 26.8% 32.8% 30.1%
Heart Failure / Cardiomyopathy 16.4% 15.6% 13.7% 16.2% 13.4% 14.6%
Hereditary and Degenerative Diseases of the Central Nervous System 11.1% 17.2% 14.8% 15.0% 6.1% 13.7%
Hiccough (Non-psychogenic) 7.9% 0.2% 0.1% 0.1% 0.1% 0.2%
Hypercholesterolemia 33.6% 30.0% 37.1% 34.4% 38.2% 34.8%
Hypertension 47.9% 48.0% 48.3% 49.9% 52.4% 48.2%
Hyperthyroidism / Thyrotoxicosis 4.5% 3.6% 4.9% 4.2% 4.2% 4.5%
Hypothyroidism 16.4% 16.5% 20.2% 18.6% 17.7% 17.7%
Kidney Disease 20.8% 16.3% 17.1% 16.8% 14.5% 16.8%
Liver Disease 25.2% 19.4% 24.0% 20.4% 17.7% 23.7%
Neuropathic Pain 22.8% 17.0% 27.8% 20.9% 25.8% 23.2%
Obesity 11.4% 10.8% 16.8% 13.5% 12.1% 10.2%
Organic Psychotic Conditions 19.8% 27.3% 24.9% 28.2% 8.7% 25.4%
Dementias 4.0% 10.4% 8.0% 13.2% 2.8% 9.7%
Alcohol-induced mental disorders 4.1% 4.6% 5.0% 4.5% 1.9% 5.4%
Drug-induced mental disorders 6.2% 4.3% 7.2% 4.5% 2.7% 6.5%
Transient mental disorders 6.4% 10.8% 9.0% 10.3% 3.9% 9.6%
Persistent mental disorders 5.7% 12.8% 9.2% 14.3% 3.3% 11.1%
Other Non-psychotic Mental Disorders, Mental Retardation 14.4% 11.1% 8.9% 13.9% 3.4% 9.4%
Other Non-psychotic Mental Disorders, Non-Mental Retardation 61.6% 58.2% 75.9% 67.7% 49.1% 69.3%
Anxiety, dissociative, and somatoform disorders 38.4% 32.2% 53.6% 43.3% 41.6% 45.7%
Personality disorders 10.6% 9.8% 15.1% 10.1% 5.7% 10.4%
Adjustment reaction 14.0% 10.5% 22.1% 17.3% 10.7% 18.0%
Depressive disorder 32.7% 29.0% 52.2% 43.0% 31.8% 45.8%
Other 48.8% 44.5% 53.8% 47.7% 34.5% 51.3%
Other Psychoses 62.2% 76.1% 81.1% 77.9% 48.0% 78.0%
Schizophrenic disorders 32.2% 51.9% 30.7% 36.3% 21.2% 38.0%
Episodic mood disorders 42.2% 37.8% 66.8% 55.6% 38.0% 59.1%
Delusional disorders 2.7% 5.1% 3.7% 4.8% 1.8% 4.3%
Other nonorganic psychoses 22.1% 36.3% 25.1% 30.8% 13.2% 28.9%
Pervasive developmental disorders 1.7% 1.2% 0.9% 1.4% 0.5% 0.9%
Porphyrin Metabolic Disorders 0.1% <0.1% 0.1% <0.1% 0.1% 0.1%
Premenstrual Tension Syndrome 0.3% 0.2% 0.7% 0.4% 0.3% 0.4%
Pulmonary Circulation Disorders 3.7% 3.0% 3.3% 3.2% 2.7% 3.1%
Restless Legs Syndrome 0.3% 0.4% 0.7% 0.4% 0.3% 0.4%
Rheumatoid Arthritis and Other Inflammatory Polyarthropathies 15.5% 13.6% 20.0% 17.3% 25.9% 18.9%
Smoking 16.3% 13.6% 17.6% 11.7% 10.9% 14.1%
Substance Abuse 31.7% 26.5% 35.3% 25.0% 19.3% 31.1%
Syndrome of Inappropriate Secretion of Antidiuretic Hormone 0.4% 0.4% 0.3% 0.3% 0.2% 0.3%
Tardive Dyskinesia 0.6% 1.1% 0.9% 0.6% 0.2% 0.8%
Valvular Heart Disease 12.9% 10.2% 12.0% 11.5% 11.3% 11.8%
Drugs used ever in past
ACEI / ATIIRB 25.0% 23.8% 24.0% 24.6% 28.1% 23.1%
Anorexiants / Antiobesity 0.7% 0.3% 1.0% 0.6% 0.6% 0.6%
Antiadrenergic 8.3% 6.1% 6.9% 5.5% 5.2% 6.0%
Antiarrhythmic, Class I, Oral (excluding phenytoin) 0.4% 0.3% 0.3% 0.3% 0.3% 0.3%
Antiarrhythmic, Class III, Oral 0.5% 0.5% 0.3% 0.5% 0.3% 0.5%
Antidiabetic 17.4% 17.7% 16.6% 18.0% 19.8% 13.8%
Beta Blocker, Systemic 21.2% 17.9% 21.4% 18.7% 19.6% 19.0%
Bronchodilator, Adrenergic 29.0% 22.4% 35.0% 26.9% 33.2% 29.9%
CCB, Non-verapamil 17.7% 17.8% 16.1% 17.2% 21.1% 17.3%
CCB, Verapamil 3.2% 2.8% 3.5% 2.9% 3.9% 3.0%
Corticosteroid, Inhaled 12.2% 8.7% 16.8% 12.0% 15.1% 13.6%
Corticosteroid, Oral 19.2% 12.7% 22.1% 15.3% 19.1% 17.0%
Digoxin 4.0% 3.5% 2.3% 3.2% 2.2% 2.7%
Diuretic, Loop 14.2% 13.3% 14.9% 14.1% 14.5% 12.7%
Diuretic, Thiazide 15.1% 13.8% 18.2% 16.1% 20.7% 15.8%
Immunosuppressant for Organ Transplantation 0.7% 0.4% 0.4% 0.4% 0.3% 0.4%
Lipid Lowering Agent 21.0% 18.0% 23.7% 21.6% 26.9% 22.4%
Nitrate 10.5% 9.1% 10.2% 10.1% 12.1% 9.8%
Thyroid Hormone 8.4% 9.1% 11.4% 9.5% 8.8% 8.7%
Vasodilator, Non-nitrate 1.6% 1.0% 0.6% 0.7% 0.4% 0.7%
Warfarin 4.2% 3.8% 3.4% 3.6% 2.0% 3.4%
Xanthine Derivative 4.1% 3.3% 3.9% 3.5% 6.2% 4.0%
Drugs used currently
Antiarrhythmic, Class Ia 0.1% 0.1% <0.1% 0.1% 0.1% <0.1%
Antiarrhythmic, Classes Ib & Ic* ** <0.1% 0.1% <0.1% <0.1% <0.1%
Antiarrhythmic, Class III * 0.3% 0.3% 0.2% 0.3% 0.1% 0.2%
Antidepressant, Cyclic and Related 21.5% 16.6% 22.3% 20.0% 76.0% 20.1%
Antiemetic 5-hydroxytryptamine 3 Receptor Antagonist 1.0% 0.2% 0.1% 0.1% 0.2% 0.1%
Anti-infective, Amantadine / Foscarnet 0.5% 1.0% 0.6% 0.5% 0.5% 0.6%
Anti-infective, Azole Antifungal 3.0% 1.5% 1.7% 1.3% 1.6% 1.8%
Anti-infective, Clindamycin 0.6% 0.4% 0.5% 0.4% 0.4% 0.4%
Anti-infective, Macrolide 5.2% 2.8% 4.0% 3.1% 4.3% 3.7%
Anti-infective, Pentamidine <0.1% ** <0.1% <0.1% - <0.1%
Anti-infective, Quinolone 6.2% 4.3% 4.3% 3.9% 4.4% 4.2%
Anti-infective, TMP-SMX 4.0% 2.7% 2.1% 2.1% 2.6% 2.7%
Aspirin 3.8% 4.4% 4.1% 4.6% 5.3% 4.1%
Beta-blocker, Systemic 11.2% 10.0% 10.1% 9.7% 9.6% 9.2%
Bronchodilator, Adrenergic* 10.8% 8.0% 11.1% 9.0% 12.6% 10.5%
CCB* ** <0.1% <0.1% <0.1% <0.1% <0.1%
CCB, Non-verapamil 9.1% 10.1% 7.9% 8.9% 10.7% 8.8%
CCB, Verapamil 1.1% 1.2% 1.3% 1.1% 1.9% 1.1%
Chloral Hydrate 0.5% 0.1% 0.1% 0.1% 0.1% 0.1%
Cyclooxygenase-2 Inhibitor 7.5% 6.2% 10.9% 9.3% 12.6% 10.8%
Diuretic, Loop 6.8% 6.5% 6.4% 6.9% 6.4% 5.9%
Diuretic, Potassium-sparing 3.3% 2.7% 2.7% 2.4% 3.3% 2.2%
Diuretic, Thiazide 5.6% 5.9% 6.9% 6.5% 8.9% 6.2%
Droperidol ** ** <0.1% <0.1% - <0.1%
Ephedrine / PPA / Pseudoephedrine 2.8% 1.9% 2.9% 2.5% 6.7% 2.8%
Epinephrine 0.1% <0.1% 0.1% 0.1% 0.1% 0.1%
Famotidine 4.4% 4.3% 2.5% 3.0% 2.9% 2.8%
Felbamate / Fosphenytoin 0.2% 0.1% <0.1% <0.1% - <0.1%
Galantamine 0.1% 0.1% 0.3% 0.3% <0.1% 0.2%
Hydroxychloroquine / Chloroquine / Mefloquine 0.2% 0.1% 0.3% 0.2% 0.4% 0.2%
Hydroxyzine 5.6% 3.6% 5.0% 4.0% 5.1% 3.9%
Magnesium Supplement 0.4% 0.3% 0.3% 0.2% 0.4% 0.3%
Meperidine 0.2% 0.1% 0.1% 0.1% 0.1% 0.1%
Methadone 0.7% 0.3% 0.6% 0.2% 0.4% 0.4%
NSAID 10.4% 8.2% 12.2% 9.0% 18.9% 10.4%
Octreotide 0.1% <0.1% <0.1% <0.1% ** <0.1%
Phentermine / Sibutramine ** ** <0.1% <0.1% <0.1% <0.1%
Potassium Supplement 4.6% 4.7% 4.1% 4.6% 4.6% 3.9%
Quinine 0.8% 0.5% 0.6% 0.4% 1.3% 0.5%
Sildenafil 1.7% 0.6% 1.2% 1.1% 0.8% 2.9%
Tacrolimus 0.1% 0.1% <0.1% 0.1% ** <0.1%
Tamoxifen 0.3% 0.3% 0.2% 0.2% 0.4% 0.2%
Tizanidine 0.7% 0.2% 0.9% 0.4% 0.9% 0.7%
COPD = chronic obstructive pulmonary disease; HIV = human immunodeficiency virus; AIDS = acquired immune deficiency syndrome; ACEI = angiotensin-converting enzyme inhibitor; ATIIRB = angiotensin-II receptor blocker; CCB = calcium channel blocker; TMP-SMX = trimethoprim-sulfamethoxazole; PPA = phenylpropanolamine; NSAID = nonsteroidal anti-inflammatory drug
*limited to agents considered to prolong the QT interval/induce TdP, per CredibleMeds
** suppression of cell with an N ≤10, in accordance with CMS privacy policies
Table 1: Characteristics of incident antipsychotic users in primary outcome (sudden cardiac death/ventricular arrhythmia) cohort