Ziprasidone

Pronunciation

Class: Atypical Antipsychotics
VA Class: CN709
Chemical Name: 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one monohydrochloride monohydrate
Molecular Formula: C21H21ClN4OS•HCl•H2OC21H21ClN4OS•CH4O3S•3H2O
CAS Number: 138982-67-9
Brands: Geodon

Warning(s)

Special Alerts:

[Posted 02/22/2011] ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.

BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.

RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment. For more information visit the FDA website at: and .

Warning(s)

  • Increased Mortality in Geriatric Patients
  • Substantially higher mortality rate (4.5%) in geriatric patients with dementia-related psychosis receiving atypical antipsychotic agents (e.g., aripiprazole, olanzapine, quetiapine, risperidone) compared with those receiving placebo (2.6%).1 68

  • Most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).1 68

  • Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.1 68 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Introduction

Atypical or second-generation antipsychotic agent.1 4 10 11 29

Uses for Ziprasidone

Schizophrenia

Symptomatic management of schizophrenia.1

Should be reserved for patients whose disease fails to respond adequately to appropriate courses of other antipsychotic agents because of a greater capacity to prolong the QT/QTc-interval compared with that of several other antipsychotic agents.1 (See Prolongation of QT Interval under Cautions)

Slideshow: Can Prescription Drugs Lead to Weight Gain?

IM injection used for rapid control of behaviors that interfere with diagnosis and care (e.g., threatening behaviors, escalating or urgently distressing behavior, self-exhausting behavior).1

Bipolar Disorder

Treatment of acute manic and mixed epsiodes (with or without psychotic features) associated with bipolar 1 disorder.1 73 74

Ziprasidone Dosage and Administration

Administration

Administer orally or by IM injection.1

Concomitant use of oral and IM ziprasidone not recommended by manufacturer.1

Oral Administration

Administer orally twice daily with food.1

IM Administration

Vials are for single use only.1

Reconstitution

Reconstitute vial containing 20 mg with 1.2 mL of sterile water for injection to provide a solution containing 20 mg/mL.1 Do not use other solutions to reconstitute the injection, and do not admix with other drugs.1 Shake vigorously to ensure complete dissolution.1

Observe strict aseptic technique since the drug contains no preservative.1 Discard unused portions.1

Dosage

Available as ziprasidone hydrochloride or ziprasidone mesylate; oral dosage expressed in terms of hydrochloride monohydrate and IM dosage expressed in terms of ziprasidone.1 12

Adults

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Schizophrenia
Oral

Initially, 20 mg twice daily.1

Dosage may be increased after a minimum of 2 days.1 12 Observe patients for several weeks prior to upward titrations of dosage to ensure use of the lowest effective dosage.1

In patients responding to ziprasidone therapy, continue the drug as long as clinically necessary and tolerated, but at lowest possible effective dosage;12 periodically reassess need for continued therapy.1 Efficacy maintained for up to 52 weeks in clinical trials, but optimum duration of therapy currently is not known.1

Acute Agitation in Schizophrenia
IM

Initially, 10–20 mg given as a single dose.1

Repeat doses of 10 mg every 2 hours or 20 mg every 4 hours, up to a maximum cumulative dosage of 40 mg daily.1

Oral therapy should replace IM therapy as soon as possible; safety and efficacy of administering ziprasidone IM injection for longer than 3 consecutive days not evaluated.1

Bipolar Disorder
Oral

Initially, 40 mg twice daily on day 1.1 Increase dosage to 60 or 80 mg twice daily on the second day.1

Subsequent dosage adjustments based on efficacy and tolerability may be made within a dosage range of 40–80 mg twice daily.1

Efficacy for long-term use (i.e., >3 weeks) or for prophylactic use in patients with bipolar disorder not systematically evaluated.1 If used for extended periods, periodically reevaluate the long-term risks and benefits for the individual patient.1

Prescribing Limits

Adults

Schizophrenia
Oral

Maximum 80 mg twice daily.1 12

Acute Agitation
IM

Maximum cumulative dosage of 40 mg daily.

Bipolar Disorder
Oral

Maximum 80 mg twice daily.1

Cautions for Ziprasidone

Contraindications

  • Known history of QT interval prolongation (including congenital long QT syndrome), recent AMI, or uncompensated heart failure.1 (See Prolongation of QT Interval under Cautions.)

  • Concomitant therapy with other drugs that prolong the QT interval (e.g., class Ia and III antiarrhythmics, arsenic trioxide, chlorpromazine, dofetilide, dolasetron mesylate, droperidol, gatifloxacin, halofantrine, levomethadyl acetate, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, probucol, quinidine, sotalol, sparfloxacin, tacrolimus, thioridazine).1 Ziprasidone also is contraindicated in patients receiving drugs shown to cause QT prolongation as an effect and for which this effect is described in the full prescribing information as a contraindication or a boxed or bolded warning.1

  • Known hypersensitivity to ziprasidone.1

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Possible increased risk of death with use of atypical antipsychotics in geriatric patients with dementia-related psychosis.1 68 (See Boxed Warning and see Geriatric Use under Cautions.)

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.1 68

Prolongation of QT Interval

Greater capacity to prolong the QT/QTc interval compared with that of several other antipsychotic agents.1

Experience is too limited to rule out the possibility that ziprasidone may be associated with a greater risk of ventricular arrhythmias (e.g., torsades de pointes) and/or sudden death than other antipsychotic agents.1

Patients at particular risk of torsades de pointes include those with bradycardia, hypokalemia, or hypomagnesemia, those receiving concomitant therapy with other drugs that prolong the QTc interval, and those with congenital prolongation of QTc interval.1 (See Contraindications under Cautions.) Avoid ziprasidone therapy in patients with history of cardiac arrhythmias.1

Determine baseline serum potassium and magnesium concentrations in patients at risk for substantial electrolyte disturbances, particularly those receiving concomitant diuretic therapy.1 Correct hypokalemia or hypomagnesemia prior to initiating ziprasidone.1

Clinical and ECG monitoring of cardiac function, including appropriate ambulatory ECG monitoring (e.g., Holter monitoring), is recommended during ziprasidone therapy in patients with symptoms that could indicate torsades de pointes (e.g., dizziness, palpitations, syncope).1

Discontinue ziprasidone if the QTc interval exceeds 500 msec.1

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, may occur in patients receiving antipsychotic agents.1 12

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, has been reported.1 Consider discontinuance of ziprasidone.1

Hyperglycemia and Diabetes Mellitus

Severe hyperglycemia, sometimes associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents.1 13 14 15 16 17 18 19 20 21 22 23 24 25 26 40 41 42 43 47 Closely monitor patients with preexisting diabetes mellitus for worsening of glucose control, and perform fasting glucose tests at baseline and periodically for patients with risk factors for diabetes (e.g., obesity, family history of diabetes).1 13 14 16 17 18 19 20 21 22 23 24 25 If manifestations of hyperglycemia occur, test for diabetes mellitus.1 13 14 16 17 18 19 20 21 22 23 24 25

Sensitivity Reactions

Rash

Rash and/or urticaria, possibly related to dose and/or duration of therapy, reported.1 Adjunctive treatment with antihistamines or steroids and/or drug discontinuance may be required.1 Discontinue ziprasidone if alternative etiology of rash cannot be identified.1

General Precautions

Cardiovascular Effects

Orthostatic hypotension reported, particularly during initial dosage titration period.1 Use with caution in patients with known cardiovascular or cerebrovascular disease and/or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy).1

Nervous System Effects

Possible risk of seizures;1 use with caution in patients with a history of seizures or with conditions known to lower the seizure threshold (e.g., dementia of the Alzheimer’s type, geriatric patients).1

Disruption of ability to reduce core body temperature possible; use caution in patients exposed to conditions that may contribute to an elevation in core body temperature (e.g., dehydration, extreme heat, strenuous exercise, concomitant use of anticholinergic agents).1

Somnolence reported.1 Potential impairment of judgment, thinking, or motor skills.1

GI Effects

Esophageal dysmotility and aspiration possible; use with caution in patients at risk for aspiration pneumonia (e.g., geriatric patients, those with advanced Alzheimer’s dementia).1 (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Suicide

Attendant risk with psychotic illnesses; closely supervise high-risk patients.1 Prescribe in the smallest quantity consistent with good patient management to reduce the risk of overdosage.1

Sexual Dysfunction

Priapism possible.1

Endocrine Effects

Elevated prolactin concentrations possible.7

Metabolic Effects

Weight gain possible.1 7 May cause less weight gain than clozapine, olanzapine, quetiapine, or risperidone.4 10 11 12

Specific Populations

Pregnancy

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category C.1

Lactation

Not known whether ziprasidone is distributed into milk.1 Women receiving ziprasidone should not breast-feed.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

No substantial differences in safety of oral ziprasidone relative to younger adults.1

Lower initial dosages, slower titration, and careful monitoring during the initial dosing period may be advisable in some geriatric patients.1

IM ziprasidone mesylate not systematically evaluated in geriatric patients.1

Possible increased risk of death in geriatric patients with dementia-related psychosis.1 68 Substantial (1.6- to 1.7-fold) increase in mortality rate reported in geriatric patients with dementia who received atypical antipsychotic agents (e.g., aripiprazole, olanzapine, quetiapine, risperidone) for treatment of behavioral disorders; most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).1 68

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.1 68 (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Renal Impairment

Commercially available ziprasidone mesylate injections contain sulfobutylether β-cyclodextrin sodium, an excipient that is cleared by renal filtration; use with caution.1

Common Adverse Effects

Oral therapy for schizophrenia: somnolence, respiratory tract infection.1

Oral therapy for bipolar mania: somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting.1 73 74

IM therapy for acute agitation in schizophrenia: somnolence, headache, nausea.1

Interactions for Ziprasidone

Ziprasidone is metabolized by the CYP3A4 isoenzyme; CYP1A2 also may contribute but to a much lesser extent.1 Little inhibitory effect on CYP isoenzymes 1A2, 2C9, 2C19, 2D6, or 3A4; pharmacokinetic interaction unlikely with drugs metabolized by these isoenzymes.1

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interactions (altered metabolism) with inhibitors or inducers of CYP3A4.1

Pharmacokinetic interaction with inhibitors or inducers of CYP1A2, CYP2C9, CYP2C19, or CYP2D6 are unlikely.1

Drugs That Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation; concomitant use contraindicated) when used with drugs that prolong the QTc interval.1 Ziprasidone also is contraindicated in patients receiving drugs shown to cause QT prolongation as an effect and for which this effect is described in the full prescribing information as a contraindication or a boxed or bolded warning.1 (See Contraindications and Prolongation of QT Interval under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Antacids

No effects on ziprasidone pharmacokinetics1

Antiarrhythmics (class Ia and III)

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Arsenic trioxide

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Benztropine

Pharmacokinetic interaction unlikely1

Carbamazepine

Increased ziprasidone metabolism1

Chlorpromazine

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Cimetidine

No change observed in ziprasidone pharmacokinetics1

CNS agents

Additive sedative effects12

Dextromethorphan

No change observed in dextromethorphan metabolism1

Dofetilide

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Dolasetron mesylate

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Dopamine agonists

Antagonistic effects1

Droperidol

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Gatifloxacin

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Halofantrine

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Hypotensive agents

Additive hypotensive effects1

Use with caution1

Ketoconazole

Increased plasma ziprasidone concentrations1

Levodopa

Antagonistic effects1

Levomethadyl acetate

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Lithium

No change observed in lithium clearance1

Lorazepam

Pharmacokinetic interaction unlikely1

Mefloquine

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Mesoridazine

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Moxifloxacin

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Oral contraceptives

No change observed in estradiol or levonorgestrel pharmacokinetics1

Pentamidine

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Pimozide

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Probucol

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Protein-bound drugs (e.g., propranolol, warfarin)

Pharmacokinetic interaction unlikely1

Quinidine

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Sotalol

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Sparfloxacin

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Tacrolimus

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Thioridazine

Increased risk of QT interval prolongation1

Concomitant use contraindicated1

Ziprasidone Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 60% following a 20 mg oral dose under fed conditions.1

Peak plasma concentrations occur 6–8 hours after oral administration or about 1 hour after IM injection.1

Food

Food increases the absorption up to twofold.1

Distribution

Extent

Not known whether the drug is distributed into milk in humans.1

Plasma Protein Binding

>99% bound to plasma proteins, principally to albumin and α1-acid glycoprotein.1

Elimination

Metabolism

Extensively metabolized in the liver principally via reduction by aldehyde oxidase; about one-third of metabolic clearance is mediated by CYP isoenzymes, principally CYP3A4.1

Elimination Route

Approximately 20% of a dose is excreted in the urine and about 66% in feces, principally as metabolites.1 Not removed by hemodialysis.1

Half-life

Mean terminal half-life following oral administration is about 7 hours;1 following IM administration, the half-life is 2–5 hours.1

Special Populations

In patients with clinically important (Child-Pugh class A or B) cirrhosis, half-life increased by 2.3 hours compared with that of patients in the control group.1

Stability

Storage

Oral

Capsules

15–30°C.1

Parenteral

Powder for Injection

15–30°C.1

Following reconstitution, store at 15–30°C protected from light for up to 24 hours or at 2–8°C for up to 7 days.1

Actions

  • Exact mechanism of antipsychotic action has not been fully elucidated; may involve antagonism of central type 2 serotonergic (5-HT2) receptors and central dopamine D2 receptors.1 8 9

  • Precise mechanism of antimanic action has not been fully elucidated.1

  • Antagonism of other receptors (e.g., histamine H1 receptors, α1-adrenergic receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence).1

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Importance of taking medication exactly as prescribed by the clinician.1

  • Importance of avoiding driving, operating machinery, or performing hazardous tasks until gain experience with the drug’s effects.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or OTC drugs, dietary supplements, and herbal products, as well as any concomitant illnesses (e.g., diabetes mellitus, seizures, dementia).1

  • Importance of avoiding alcohol during ziprasidone therapy.1

  • Importance of avoiding overheating or dehydration.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ziprasidone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

20 mg

Geodon

Pfizer

40 mg

Geodon

Pfizer

60 mg

Geodon

Pfizer

80 mg

Geodon

Pfizer

Ziprasidone Mesylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IM use only

20 mg (of ziprasidone) per mL

Geodon (with sulfobutylether β-cyclodextrin sodium 294 mg/mL)

Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Geodon 20MG Capsules (PFIZER U.S.): 60/$545.97 or 180/$1,599.93

Geodon 40MG Capsules (PFIZER U.S.): 60/$520.97 or 180/$1,518.02

Geodon 60MG Capsules (PFIZER U.S.): 60/$664.97 or 180/$1,953.99

Geodon 80MG Capsules (PFIZER U.S.): 60/$664.97 or 180/$1,954.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 15, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Pfizer Inc. Geodon (ziprasidone) capsules and for injection prescribing information. New York, NY; 2005 May.

2. Daniel DG, Zimbroff DL, Potkin SG et al. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group. Neuropsychopharmacology. 1999; 20:491-505.

3. Keck P, Buffenstein A, Ferguson J et al. Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial. Psychopharmacology1998; 140:173-84.

4. Taylor D. Ziprasidone: an atypical antipsychotic. Pharmaceutical J. 2001; 266:396-401.

5. Bagnall AM, Lewis RA, Leitner ML. Ziprasidone for schizophrenia and severe mental illness. Cochrane Database Syst Rev. 2000; 4:CD001945. [PubMed 11034737]

6. Goff DC, Posever T, Herz L et al. An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol. 1998 Aug; 18:296-304.

7. Pfizer, New York, NY: Personal communication.

8. Lilly. Zyprexa (olanzapine tablets and orally disintegrating tablets) prescribing information. Indianapolis, IN; 2001 Feb.

9. Janssen Pharmaceutica. Risperdal (risperidone tablets and oral solution) prescribing information. Titusville, NJ; 1999 May.

10. Anon. Ziprasidone (Geodon) for schizophrenia. Med Lett Drugs Ther. 2001; 43:51-2. [PubMed 11402259]

11. Carnhan RM, Lund BC, Perry PJ. Ziprasidone, a new atypical antipsychotic drug. Pharmacotherapy. 2001; 21:717-30. [IDIS 465839] [PubMed 11401184]

12. Pfizer, New York, NY: Personal communication.

13. Eli Lilly and company. Zyprexa (olanzapine) tablets and Zyprexa Zydis (olanzapine) orally disintegrating tablets prescribing information. Indianapolis, IN; 2003 Sep 16.

14. Eli Lilly and Company. Lilly announces FDA notification of class labeling for atypical antipsychotics regarding hyperglycemia and diabetes. Indianapolis, IN; 2003 Sep 17. Press release.

15. Cunningham F, Lambert B, Miller DR et al. Antipsychotic induced diabetes in veteran schizophrenic patients. In: Abstracts of the 1st International Conference on Therapeutic Risk Management and 19th International Conference on Parmacoepidemiology, Philadelphia, PA, Aug 21-24. Pharmacoepidemiol Drug Saf. 2003; 12(suppl 1): S154-5.

16. Otsuka America Pharmaceutical, Inc. Abilify (aripiprazole) tablets prescribing information. Rockville, MD; 2004 Sep.

17. Novartis Pharmaceuticals. Clozaril (clozapine) prescribing information. East Hanover, NJ; 2003 Dec.

18. AstraZeneca Pharmaceuticals. Seroquel (quetiapine fumarate) tablets prescribing information. Wilmington, DE; 2004 Jul.

19. Janssen Pharmaceutica. Risperdal (risperidone) tablets and oral solution prescribing information. Titusville, NJ; 2003 Oct.

20. Lewis-Hall F. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Princeton, NJ: Bristol-Myers Squibb Company; 2004 Mar 25. From FDA website.

21. Bess AL, Cunningham SR. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2004 Apr 1. From the FDA website.

22. Eisenberg P. Dear health care professional letter regarding safety data on Zyprexa (olanzapine) – hyperglycemia and diabetes. Indianapolis, IN: Eli Lilly and Company; 2004 Mar 1. From the FDA website.

23. Macfadden W. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Wilmington, DE: AstraZeneca Pharmaceuticals; 2004 Apr 22. From the FDA website.

24. Mahmoud RA. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Titusville, NJ: Janssen Pharmaceutica, Inc; 2004. From the FDA website.

25. Clary CM. Dear health care practitioner letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. New York NY: Pfizer Global Pharmaceuticals; 2004 Aug. From the FDA website.

26. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity.. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004; 27:596-601. [PubMed 14747245]

27. Melkersson K, Dahl ML. Adverse metabolic effects associated with atypical antipsychotics. Drugs. 2004; 64:701-23. [PubMed 15025545]

28. Citrome LL, Jaffe AB. Relationship of atypical antipsychotics with development of diabetes mellitus. Ann Pharmacother. 2003; 37:1849-57. [IDIS 510453] [PubMed 14632602]

29. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatr. 2004; 161(Suppl):1-56.

30. Sumiyoshi T, Roy A, Anil AE et al. A comparison of incidence of diabetes mellitus between atypical antipsychotic drugs. J Clin Psychopharmacol. 2004; 24:345-8. [IDIS 515736] [PubMed 15118492]

31. Expert Group. ’Schizophrenia and Diabetes 2003’ expert consensus meeting, Dublin, 3–4 October 2003: consensus summary. Br J Psychiatry. 2004; 47(Suppl):S112-4.

32. Marder SR, Essock SM, Miller AL et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry. 2004; 161:1334-49. [IDIS 520856] [PubMed 15285957]

33. Holt RI. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2086-7. [IDIS 524618] [PubMed 15277449]

34. Citrome L, Volavka J. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2087-8. [IDIS 524619] [PubMed 15277450]

35. Isaac MT, Isaac MB. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2088. [IDIS 524620] [PubMed 15277451]

36. Boehm G, Racoosin JA, Laughren TP et al. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2088-9. [IDIS 524621] [PubMed 15277452]

37. Barrett EJ. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to Holt, Citrome and Volevka, Isaac and Isaac, and Boehm et al. Diabetes Care. 2004; 27:2089-90.

38. Fuller MA, Shermock KM, Secic M et al. Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine. Pharmacotherapy. 2002; 23:1037-43.

39. Koller EA, Cross JT, Doraiswamy PM et al. Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy. 2003; 23:735-44. [IDIS 498493] [PubMed 12820816]

40. Koller EA, Weber J, Doraiswamy PM et al. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry. 2004; 65:857-63. [IDIS 518849] [PubMed 15291665]

41. Ananth J, Johnson KM, Levander EM et al. Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction in a patient taking risperidone and lithium carbonate. J Clin Psychiatry. 2004; 65:724. [IDIS 516345] [PubMed 15163265]

42. Torrey EF, Swalwell CI. Fatal olanzapine-induced ketoacidosis. Am J Psychiatry. 2003; 160:2241. [IDIS 516756] [PubMed 14638601]

43. Wehring HJ, Kelly DL, Love RC et al. Deaths from diabetic ketoacidosis after long-term clozapine treatment. Am J Psychiatry. 2003; 160:2241-2. [IDIS 516757] [PubMed 14638600]

44. Koro CE, Fedder DO, L’Italien GJ et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ. 2002; 325:243. [IDIS 485916] [PubMed 12153919]

45. Citrome LL. Efficacy should drive atypical antipsychotic treatment. BMJ. 2003; 326:283. [IDIS 492968] [PubMed 12561827]

46. Anon. Which atypical antipsychotic for schizophrenia?. Drug Ther Bull. 2004; 42:57-60. [PubMed 15310154]

47. Anon. Atypical antipsychotics and hyperglycaemia. Aust Adv Drug React Bull. 2004; 23:11-2.

48. Sussman N. The implications of weight changes with antipsychotic treatment. J Clin Psychopharmacol. 2003; 23 (Suppl 1):S21-6.

49. Gianfrancesco F, Grogg A, Mahmoud R et al. Differential effects of antipsychotic agents on the risk of development of type 2 diabetes mellitus in patients with mood disorders. Clin Ther. 2003; 25:1150-71. [IDIS 497269] [PubMed 12809963]

50. Bushe C, Leonard B. Association between atypical antipsychotic agents and type 2 diabetes: review of prospective clinical data. Br J Psychiatry Suppl. 2004; 47:S87-93. [PubMed 15056600]

51. Cavazzoni P, Mukhopadhyay N, Carlson C et al. Retrospective analysis of risk factors in patients with treatment-emergent diabetes during clinical trials of antipsychotic medications. Br J Psychiatry Suppl. 2004; 47:s94-101. [PubMed 15056601]

52. Gianfrancesco FD, Grogg AL, Mahmoud RA et al. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002; 63:920-30. [IDIS 488480] [PubMed 12416602]

53. Etminan M, Streiner DL, Rochon PA. Exploring the association between atypical neuroleptic agents and diabetes mellitus in older adults. Pharmacotherapy. 2003; 23:1411-15. [IDIS 510498] [PubMed 14620387]

54. Leslie DL, Rosenheck RA. Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications. Am J Psychiatry. 2004; 161:1709-11. [IDIS 522186] [PubMed 15337666]

55. Sernyak MJ, Leslie DL, Alarcon RD et al. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002; 159:561-6. [IDIS 494206] [PubMed 11925293]

56. Geller WK, MacFadden W. Diabetes and atypical neuroleptics. Am J Psychiatry. 2003; 160:388. [IDIS 513919] [PubMed 12562601]

57. Gianfrancesco FD. Diabetes and atypical neuroleptics. Am J Psychiatry. 2003; 160:388-9; author reply 389. [IDIS 513920] [PubMed 12562599]

58. Lamberti JS, Crilly JF, Maharaj K. Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs. J Clin Psychiatry. 2004; 65:702-6. [IDIS 516341] [PubMed 15163259]

59. Lee DW, Fowler RB. Olanzapine/risperidone and diabetes risk. J Clin Psychiatry. 2003; 64:847-8; author reply 848. [IDIS 500324] [PubMed 12934988]

60. Reviewer Comments (personal observations).

61. Bristol-Myers Squibb., Princeton, NJ: Personal communication.

62. AstraZeneca. Wayne, PA: Personal communication.

63. Eli Lilly and Company. Indianapolis, IN: Personal communication.

64. Novartis Pharmaceuticals Corporation. East Hanover, NJ: Personal communication.

65. Janssen Pharmaceuticals. Titusville, NJ: Personal communication.

66. Citrome LL. The increase in risk of diabetes mellitus from exposure to second generation antipsychotic agents. Drugs Today (Barc). 2004; 40:445-64. [PubMed 15319799]

67. Citrome L, Jaffe A, Levine J et al. Relationship between antipsychotic medication treatment and new cases of diabetes among psychiatric inpatients. Psychiatr Serv. 2004; 55:1006–13.

68. Food and Drug Administration. Public health advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. Rockville, MD; 2005 Apr 11. From the FDA website.

69. American Psychiatric Association. DSM-IV: diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:273-86.

70. Citrome L. New antipsychotic medications: what advantages do they offer? Postgrad Med. 1997; 101:207-210,213,214. (IDIS 380687)

71. Lieberman JA. Atypical antipsychotic drugs as a first-line treatment of schizophrenia: a rationale and hypothesis. J Clin Psychiatry. 1996; 57(Suppl 11):68-71. [IDIS 376650] [PubMed 8941173]

72. Lahti AC, Tamminga CA. Recent developments in the neuropharmacology of schizophrenia. Am J Health-Syst Pharm. 1995; 52(Suppl 1):S5-8. [IDIS 341484] [PubMed 7749964]

73. Keck PE Jr, Versiani M, Potkin S and the Ziprasidone in Mania Study Group. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry. 2003; 160:741-8. [PubMed 12668364]

74. Potkin SG, Keck PE Jr, Segal S et al. Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial. J Clin Psychopharmacol. 2005; 25:301-10. [PubMed 16012271]

75. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002; 159(4 Suppl):1-50.

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