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Off-label prescribing: 7 steps for safer, more effective treatment
Have you noticed two curious patterns in off-label prescribing? Psychiatrists avoid agents approved for treating insomnia but prescribe anticonvulsants for a variety of unapproved uses.
Most of us prescribe medications for therapeutic uses not found in FDA-approved labeling. Among 200 psychiatrists surveyed, 65% said they had prescribed off label in the previous month, and only 4% had ever received a patient complaint about the practice.Malpractice Verdicts).
Box
Private insurance. Psychotropic costs are rising 20% a year, contributing to the nation’s annual 13% overall prescription drug cost increase.15 To control rising costs, some medical insurance plans consider off-label use as “unapproved and experimental” and deny coverage. Pharmacy benefit and self-insured employer plans may act similarly, although some states require insurers to cover off-label use of all approved edications.
Government programs. Medicaid does not exclude coverage of off-label prescriptions. How the new Medicare prescription drug plan (Part D) handles off-label prescribing remains unclear.
Why psychiatrists prescribe off-label
| Therapeutic reasons |
| Patient has a disorder for which no drug is labeled |
| Patient falls outside of labeled age or demographic group, such as children, older patients, and pregnant women |
| Patient fails to respond to labeled products |
| Off-label product may potentiate response to a labeled agent or minimize its adverse effects |
| Preferences |
| Manufacturers and respected peers promote use of off-label products as first- or second-line agents18 |
| Practitioner wishes to foster innovative treatments |
| Patients or families request an off-label drug instead of labeled alternatives |
| Practitioner avoids using a particular labeled drug or drug class |
Most state medical practice laws spell out the information required in the patient chart to demonstrate informed consent, defined variously as:
- what a reasonable provider would tell a patient
- what a reasonable patient would expect to hear from the provider
- what a patient would need to hear before deciding on a treatment course.
What the law says
Off-label prescribing is legal, common, necessary, and recognized in some states by statute and by U.S. Supreme Court review.
Court decisions. In a class action suit before the top court (Buckman Company vs. Plaintiff’s Legal Commission, 2001), 5,000 plaintiffs claimed damages from orthopedic screws and plates that were FDA-approved for use in long bones but not for use in the spine. A unanimous court held that such off-label use is an accepted and necessary offshoot of FDA regulatory function and does not interfere with the practice of medicine.
The courts also have determined that off-label use does not mean “experimental” and itself is not a risk. Off-label use may be consistent with the standard of care and does not categorically indicate negligence (though a practitioner who prescribes negligently—such as prescribing a drug to which a patient is known to be allergic—may be found liable).
Drug manufacturers’ risk. The courts recognize that patients receive prescription drugs from doctors, not directly from the manufacturers. The law thus provides some immunity to manufacturers if your patient is injured by a drug you prescribe off-label. The learned-intermediary rule says anufacturers must warn you adequately of a drug’s foreseeable risks, and you then assume the responsibility to warn the patient.
The courts recognize exceptions, though, and have required manufacturers to warn patients directly about vaccines given in mass immunizations, drugs withdrawn from the market, drugs advertised directly to consumers, and other risks.
- BMJ Publishing Group. Clinical evidence. Summary of what is known—and not known—about more than 200 medical disorders and 2,000 treatments. www.clinicalevidence.com.
- Cochrane Library of evidence-based clinical reviews. www.cochrane.org.
- Agency for Health Care Research and Quality. Draft comparative effectiveness review of off-label use of atypical antipsychotic drugs. http://effectivehealthcare.ahrq.gov/synthesize/reports/draft.cfm.
- Amitriptyline • Elavil, others
- Carbamazepine • Carbetrol; Epitol; Equetro; Tegretol
- Gabapentin • Gabarone; Neurontin
- Lamotrigine • Lamictal
- Trazodone • Desyrel; Trialodine
- Valproate • Depakote; Depakene
Dr. Kramer reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. McCall receives research support from GlaxoSmithKline, Sanofi-Aventis, Sepracor, Takeda, and Wyeth, is an advisor to King Pharmaceuticals and Sepracor, and is a speaker for GlaxoSmtihKline, Sepracor, and Wyeth.
1. Lowe-Ponsford FL, Baldwin DS. Off-label prescribing by psychiatrists. Psychiatr Bull 2000;24(11):415-17.
2. Zito JM, Safer DJ, dosReis S, et al. Trends in the prescribing of psychotropic medications to preschoolers. JAMA 2000;283(8):1025-30.
3. Kelly DL, Love RC, Mackowick M, et al. Atypical antipsychotic use in a state hospital inpatient adolescent population. J Child Adolesc Psychopharmacol 2004;14(1):75-85.
4. Rosenheck R, Leslie D, Sernyak M. From clinical trials to real-world practice: use of atypical antipsychotic medication nationally in the Department of Veterans Affairs. Med Care 2001;39(3):302-8.
5. Fountoulakis KN, Nimatoudis I, Iacovides A, Kaprinis G. Off-label indications for atypical antipsychotics: A systematic review. Ann Gen Hosp Psychiatry 2004;3(1):4.-
6. Pomerantz JM, Finkelstein SN, Berndt ER, et al. Prescriber intent, off-label usage, and early discontinuation of antidepressants: a retrospective physician survey and data analysis. J Clin Psychiatry 2004;65(3):395-404.
1. Beck JM, Azari ED. FDA, off-label use, and informed consent. Food Drug Law J 1998;53:71-104.
8. Hepper F, Fellow-Smith E. Off-label prescribing in a community child and adolescent mental health service: Implications for information giving and informed consent. Clin Manag 2005;13(1):29-33.
9. O’Reilly JD, Dalal A. Off-label or out of bounds? Prescriber and marketer liability for unapproved uses of FDA-approved drugs. Ann Health Law 2003;12:295-324.
10. Ware JC, Pittard JT. Increased deep sleep after trazodone use: a double-blind placebo-controlled study in healthy young adults. J Clin Psychiatry 1990;51:18-22.
11. McCall WV. Use of off-label medications in the treatment of chronic insomnia. J Clin Sleep Med 2005;1(4):e494-5.
12. Chen H, Deshpande AD, Jiang R, Martin BC. An epidemiological investigation of off-label anticonvulsant drug use in the Georgia Medicaid population. Pharmacoepidemiol Drug Saf 2005;14(9):629-38.
13. Mack A. Examination of the evidence for off-label use of gabapentin. J Manag Care Pharm 2003;9(6):559-68.
14. Citrome L, Levine J, Allingham B. Utilization of valproate: extent of inpatient use in the New York State Office of Mental Health. Psychiatr Q 1998;69(4):283-300.
15. De Leon O. Antiepileptic drugs for the acute and maintenance treatment of bipolar disorder. Harv Rev Psychiatry 2001;9(5):209-22.
16. Le Bon O, Murphy JR, Staner L, et al. Double-blind, placebocontrolled study of the efficacy of trazodone in alcohol postwithdrawal syndrome: polysomnographic and clinical evaluations. J Clin Psychopharmacol 2003;23(4):377-83.
17. Zuvekas SH. Prescription drugs and the changing patterns of treatment for mental disorders, 1996-2001. Health Aff (Millwood) 2005;24(1):195-205.
18. Glick ID, Murray SR, Vasudevan P, et al. Treatment with atypical antipsychotics: new indications and new populations. J Psychiatr Res 2001;35(3):187-91.
Have you noticed two curious patterns in off-label prescribing? Psychiatrists avoid agents approved for treating insomnia but prescribe anticonvulsants for a variety of unapproved uses.
Most of us prescribe medications for therapeutic uses not found in FDA-approved labeling. Among 200 psychiatrists surveyed, 65% said they had prescribed off label in the previous month, and only 4% had ever received a patient complaint about the practice.Malpractice Verdicts).
Box
Private insurance. Psychotropic costs are rising 20% a year, contributing to the nation’s annual 13% overall prescription drug cost increase.15 To control rising costs, some medical insurance plans consider off-label use as “unapproved and experimental” and deny coverage. Pharmacy benefit and self-insured employer plans may act similarly, although some states require insurers to cover off-label use of all approved edications.
Government programs. Medicaid does not exclude coverage of off-label prescriptions. How the new Medicare prescription drug plan (Part D) handles off-label prescribing remains unclear.
Why psychiatrists prescribe off-label
| Therapeutic reasons |
| Patient has a disorder for which no drug is labeled |
| Patient falls outside of labeled age or demographic group, such as children, older patients, and pregnant women |
| Patient fails to respond to labeled products |
| Off-label product may potentiate response to a labeled agent or minimize its adverse effects |
| Preferences |
| Manufacturers and respected peers promote use of off-label products as first- or second-line agents18 |
| Practitioner wishes to foster innovative treatments |
| Patients or families request an off-label drug instead of labeled alternatives |
| Practitioner avoids using a particular labeled drug or drug class |
Most state medical practice laws spell out the information required in the patient chart to demonstrate informed consent, defined variously as:
- what a reasonable provider would tell a patient
- what a reasonable patient would expect to hear from the provider
- what a patient would need to hear before deciding on a treatment course.
What the law says
Off-label prescribing is legal, common, necessary, and recognized in some states by statute and by U.S. Supreme Court review.
Court decisions. In a class action suit before the top court (Buckman Company vs. Plaintiff’s Legal Commission, 2001), 5,000 plaintiffs claimed damages from orthopedic screws and plates that were FDA-approved for use in long bones but not for use in the spine. A unanimous court held that such off-label use is an accepted and necessary offshoot of FDA regulatory function and does not interfere with the practice of medicine.
The courts also have determined that off-label use does not mean “experimental” and itself is not a risk. Off-label use may be consistent with the standard of care and does not categorically indicate negligence (though a practitioner who prescribes negligently—such as prescribing a drug to which a patient is known to be allergic—may be found liable).
Drug manufacturers’ risk. The courts recognize that patients receive prescription drugs from doctors, not directly from the manufacturers. The law thus provides some immunity to manufacturers if your patient is injured by a drug you prescribe off-label. The learned-intermediary rule says anufacturers must warn you adequately of a drug’s foreseeable risks, and you then assume the responsibility to warn the patient.
The courts recognize exceptions, though, and have required manufacturers to warn patients directly about vaccines given in mass immunizations, drugs withdrawn from the market, drugs advertised directly to consumers, and other risks.
- BMJ Publishing Group. Clinical evidence. Summary of what is known—and not known—about more than 200 medical disorders and 2,000 treatments. www.clinicalevidence.com.
- Cochrane Library of evidence-based clinical reviews. www.cochrane.org.
- Agency for Health Care Research and Quality. Draft comparative effectiveness review of off-label use of atypical antipsychotic drugs. http://effectivehealthcare.ahrq.gov/synthesize/reports/draft.cfm.
- Amitriptyline • Elavil, others
- Carbamazepine • Carbetrol; Epitol; Equetro; Tegretol
- Gabapentin • Gabarone; Neurontin
- Lamotrigine • Lamictal
- Trazodone • Desyrel; Trialodine
- Valproate • Depakote; Depakene
Dr. Kramer reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. McCall receives research support from GlaxoSmithKline, Sanofi-Aventis, Sepracor, Takeda, and Wyeth, is an advisor to King Pharmaceuticals and Sepracor, and is a speaker for GlaxoSmtihKline, Sepracor, and Wyeth.
Have you noticed two curious patterns in off-label prescribing? Psychiatrists avoid agents approved for treating insomnia but prescribe anticonvulsants for a variety of unapproved uses.
Most of us prescribe medications for therapeutic uses not found in FDA-approved labeling. Among 200 psychiatrists surveyed, 65% said they had prescribed off label in the previous month, and only 4% had ever received a patient complaint about the practice.Malpractice Verdicts).
Box
Private insurance. Psychotropic costs are rising 20% a year, contributing to the nation’s annual 13% overall prescription drug cost increase.15 To control rising costs, some medical insurance plans consider off-label use as “unapproved and experimental” and deny coverage. Pharmacy benefit and self-insured employer plans may act similarly, although some states require insurers to cover off-label use of all approved edications.
Government programs. Medicaid does not exclude coverage of off-label prescriptions. How the new Medicare prescription drug plan (Part D) handles off-label prescribing remains unclear.
Why psychiatrists prescribe off-label
| Therapeutic reasons |
| Patient has a disorder for which no drug is labeled |
| Patient falls outside of labeled age or demographic group, such as children, older patients, and pregnant women |
| Patient fails to respond to labeled products |
| Off-label product may potentiate response to a labeled agent or minimize its adverse effects |
| Preferences |
| Manufacturers and respected peers promote use of off-label products as first- or second-line agents18 |
| Practitioner wishes to foster innovative treatments |
| Patients or families request an off-label drug instead of labeled alternatives |
| Practitioner avoids using a particular labeled drug or drug class |
Most state medical practice laws spell out the information required in the patient chart to demonstrate informed consent, defined variously as:
- what a reasonable provider would tell a patient
- what a reasonable patient would expect to hear from the provider
- what a patient would need to hear before deciding on a treatment course.
What the law says
Off-label prescribing is legal, common, necessary, and recognized in some states by statute and by U.S. Supreme Court review.
Court decisions. In a class action suit before the top court (Buckman Company vs. Plaintiff’s Legal Commission, 2001), 5,000 plaintiffs claimed damages from orthopedic screws and plates that were FDA-approved for use in long bones but not for use in the spine. A unanimous court held that such off-label use is an accepted and necessary offshoot of FDA regulatory function and does not interfere with the practice of medicine.
The courts also have determined that off-label use does not mean “experimental” and itself is not a risk. Off-label use may be consistent with the standard of care and does not categorically indicate negligence (though a practitioner who prescribes negligently—such as prescribing a drug to which a patient is known to be allergic—may be found liable).
Drug manufacturers’ risk. The courts recognize that patients receive prescription drugs from doctors, not directly from the manufacturers. The law thus provides some immunity to manufacturers if your patient is injured by a drug you prescribe off-label. The learned-intermediary rule says anufacturers must warn you adequately of a drug’s foreseeable risks, and you then assume the responsibility to warn the patient.
The courts recognize exceptions, though, and have required manufacturers to warn patients directly about vaccines given in mass immunizations, drugs withdrawn from the market, drugs advertised directly to consumers, and other risks.
- BMJ Publishing Group. Clinical evidence. Summary of what is known—and not known—about more than 200 medical disorders and 2,000 treatments. www.clinicalevidence.com.
- Cochrane Library of evidence-based clinical reviews. www.cochrane.org.
- Agency for Health Care Research and Quality. Draft comparative effectiveness review of off-label use of atypical antipsychotic drugs. http://effectivehealthcare.ahrq.gov/synthesize/reports/draft.cfm.
- Amitriptyline • Elavil, others
- Carbamazepine • Carbetrol; Epitol; Equetro; Tegretol
- Gabapentin • Gabarone; Neurontin
- Lamotrigine • Lamictal
- Trazodone • Desyrel; Trialodine
- Valproate • Depakote; Depakene
Dr. Kramer reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. McCall receives research support from GlaxoSmithKline, Sanofi-Aventis, Sepracor, Takeda, and Wyeth, is an advisor to King Pharmaceuticals and Sepracor, and is a speaker for GlaxoSmtihKline, Sepracor, and Wyeth.
1. Lowe-Ponsford FL, Baldwin DS. Off-label prescribing by psychiatrists. Psychiatr Bull 2000;24(11):415-17.
2. Zito JM, Safer DJ, dosReis S, et al. Trends in the prescribing of psychotropic medications to preschoolers. JAMA 2000;283(8):1025-30.
3. Kelly DL, Love RC, Mackowick M, et al. Atypical antipsychotic use in a state hospital inpatient adolescent population. J Child Adolesc Psychopharmacol 2004;14(1):75-85.
4. Rosenheck R, Leslie D, Sernyak M. From clinical trials to real-world practice: use of atypical antipsychotic medication nationally in the Department of Veterans Affairs. Med Care 2001;39(3):302-8.
5. Fountoulakis KN, Nimatoudis I, Iacovides A, Kaprinis G. Off-label indications for atypical antipsychotics: A systematic review. Ann Gen Hosp Psychiatry 2004;3(1):4.-
6. Pomerantz JM, Finkelstein SN, Berndt ER, et al. Prescriber intent, off-label usage, and early discontinuation of antidepressants: a retrospective physician survey and data analysis. J Clin Psychiatry 2004;65(3):395-404.
1. Beck JM, Azari ED. FDA, off-label use, and informed consent. Food Drug Law J 1998;53:71-104.
8. Hepper F, Fellow-Smith E. Off-label prescribing in a community child and adolescent mental health service: Implications for information giving and informed consent. Clin Manag 2005;13(1):29-33.
9. O’Reilly JD, Dalal A. Off-label or out of bounds? Prescriber and marketer liability for unapproved uses of FDA-approved drugs. Ann Health Law 2003;12:295-324.
10. Ware JC, Pittard JT. Increased deep sleep after trazodone use: a double-blind placebo-controlled study in healthy young adults. J Clin Psychiatry 1990;51:18-22.
11. McCall WV. Use of off-label medications in the treatment of chronic insomnia. J Clin Sleep Med 2005;1(4):e494-5.
12. Chen H, Deshpande AD, Jiang R, Martin BC. An epidemiological investigation of off-label anticonvulsant drug use in the Georgia Medicaid population. Pharmacoepidemiol Drug Saf 2005;14(9):629-38.
13. Mack A. Examination of the evidence for off-label use of gabapentin. J Manag Care Pharm 2003;9(6):559-68.
14. Citrome L, Levine J, Allingham B. Utilization of valproate: extent of inpatient use in the New York State Office of Mental Health. Psychiatr Q 1998;69(4):283-300.
15. De Leon O. Antiepileptic drugs for the acute and maintenance treatment of bipolar disorder. Harv Rev Psychiatry 2001;9(5):209-22.
16. Le Bon O, Murphy JR, Staner L, et al. Double-blind, placebocontrolled study of the efficacy of trazodone in alcohol postwithdrawal syndrome: polysomnographic and clinical evaluations. J Clin Psychopharmacol 2003;23(4):377-83.
17. Zuvekas SH. Prescription drugs and the changing patterns of treatment for mental disorders, 1996-2001. Health Aff (Millwood) 2005;24(1):195-205.
18. Glick ID, Murray SR, Vasudevan P, et al. Treatment with atypical antipsychotics: new indications and new populations. J Psychiatr Res 2001;35(3):187-91.
1. Lowe-Ponsford FL, Baldwin DS. Off-label prescribing by psychiatrists. Psychiatr Bull 2000;24(11):415-17.
2. Zito JM, Safer DJ, dosReis S, et al. Trends in the prescribing of psychotropic medications to preschoolers. JAMA 2000;283(8):1025-30.
3. Kelly DL, Love RC, Mackowick M, et al. Atypical antipsychotic use in a state hospital inpatient adolescent population. J Child Adolesc Psychopharmacol 2004;14(1):75-85.
4. Rosenheck R, Leslie D, Sernyak M. From clinical trials to real-world practice: use of atypical antipsychotic medication nationally in the Department of Veterans Affairs. Med Care 2001;39(3):302-8.
5. Fountoulakis KN, Nimatoudis I, Iacovides A, Kaprinis G. Off-label indications for atypical antipsychotics: A systematic review. Ann Gen Hosp Psychiatry 2004;3(1):4.-
6. Pomerantz JM, Finkelstein SN, Berndt ER, et al. Prescriber intent, off-label usage, and early discontinuation of antidepressants: a retrospective physician survey and data analysis. J Clin Psychiatry 2004;65(3):395-404.
1. Beck JM, Azari ED. FDA, off-label use, and informed consent. Food Drug Law J 1998;53:71-104.
8. Hepper F, Fellow-Smith E. Off-label prescribing in a community child and adolescent mental health service: Implications for information giving and informed consent. Clin Manag 2005;13(1):29-33.
9. O’Reilly JD, Dalal A. Off-label or out of bounds? Prescriber and marketer liability for unapproved uses of FDA-approved drugs. Ann Health Law 2003;12:295-324.
10. Ware JC, Pittard JT. Increased deep sleep after trazodone use: a double-blind placebo-controlled study in healthy young adults. J Clin Psychiatry 1990;51:18-22.
11. McCall WV. Use of off-label medications in the treatment of chronic insomnia. J Clin Sleep Med 2005;1(4):e494-5.
12. Chen H, Deshpande AD, Jiang R, Martin BC. An epidemiological investigation of off-label anticonvulsant drug use in the Georgia Medicaid population. Pharmacoepidemiol Drug Saf 2005;14(9):629-38.
13. Mack A. Examination of the evidence for off-label use of gabapentin. J Manag Care Pharm 2003;9(6):559-68.
14. Citrome L, Levine J, Allingham B. Utilization of valproate: extent of inpatient use in the New York State Office of Mental Health. Psychiatr Q 1998;69(4):283-300.
15. De Leon O. Antiepileptic drugs for the acute and maintenance treatment of bipolar disorder. Harv Rev Psychiatry 2001;9(5):209-22.
16. Le Bon O, Murphy JR, Staner L, et al. Double-blind, placebocontrolled study of the efficacy of trazodone in alcohol postwithdrawal syndrome: polysomnographic and clinical evaluations. J Clin Psychopharmacol 2003;23(4):377-83.
17. Zuvekas SH. Prescription drugs and the changing patterns of treatment for mental disorders, 1996-2001. Health Aff (Millwood) 2005;24(1):195-205.
18. Glick ID, Murray SR, Vasudevan P, et al. Treatment with atypical antipsychotics: new indications and new populations. J Psychiatr Res 2001;35(3):187-91.