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Identifying and Reducing Professional Liability When Treating Older Adults, by Jacqueline M. Melonas, RN, MS, JD and Charles D. Cash, JD, LLM, ARM
Since the “advice” by the British Medicines and Healthcare products Regulatory Agency (MHRA) presented in late 2003 and the subsequent FDA reanalysis of antidepressant trials in children and adolescents in 2004- with the resultant addition of “black box” warnings in October 2004- psychiatrists who treat children and adolescents have labored under a cloud of doubt regarding the safety and efficacy of antidepressants, particularly SSRIs.1,2 The British reportsuggested that SSRIs not only increased the risk of suicidal behavior but also were of minimal benefit in children and adolescents. The reportconcluded that the risk to benefit ratio militated against prescription of these medications for patients 18 years and younger. Although the FDA report did not address SSRI efficacy, it did find a modest 2-fold (4% vs 2%) increase in “suicidal behaviors or suicidal ideation” in 24 placebo-controlled trials of more than 4400 children and adolescents treated with antidepressants. There were no completed suicides among these patients.
During the past 4 years, a veritable blizzard of reviews and re-analyses of the original data as well as new data on the relationship between antidepressant use and suicidality have provided significant reassurance to the psychiatrist charged with treating children and adolescents. To cite only a representative sample of these papers, Bridge and colleagues,3 for example, conclude from a re-analysis of 27 studies of antidepressant treatment in pediatric major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders that efficacy has been shown for all conditions; SSRIs showed greater efficacy in anxiety and OCD than in MDD. The authors note that adolescents appear to respond better to antidepressant treatment of both depression and anxiety than do children under 12 years. In addition, the investigators found that the overall pooled risk for suicidal ideation and attempts across these studies was less than 1%.
Posner and colleagues4 have cogently shown that the original data sets used by the FDA did not systematically and prospectively gather detailed information about suicidality; as a result, conclusions were based on vague descriptions.
To provide a definitive answer in this debate, the FDA has instituted prospective use of the Columbia- Suicide Severity Rating Scale (CSSRS),5 a clinician-administered instrument that identifies both suicidal behavior and ideation, in all behavioral clinical trials.
From another perspective, epidemiological studies of the relationship between prescription rates of SSRIs in youth and adults have repeatedly found an inverse relationship between prescription rates and suicides.6 Leon and associates7 found that among 36 persons younger than 18 years who committed suicide in New York City over a 3-year period for whom toxicology was available, only 1 had detectable levels of antidepressant medication. Furthermore, Simon and Savarino8 demonstrated that in children and adolescents of all ages, the risk of suicide attempts was greatest in the month before treatment with antidepressants. Subsequent risks were fairly constant throughout the first 6 months of treatment.
Despite these multiple sources of reassurance, the practitioner must grapple with a skeptical public and fears of litigation. An unfortunate side effect of these fears has been a decrease in SSRI prescriptions for children and adolescents in the United States, accompanied by an increase in suicides in both age groups during the same period.9 The formula for navigating the choppy seas created by this controversy is a combined understanding of the legal issues in prescribing medication and the development of a comprehensive risk management strategy throughout treatment.
The first legal issue encountered is that of so-called off-label prescribing, defined by the FDA as the “use for indication, dosage form, dose regimen, population, or other use parameter not mentioned in the approved labeling.” 10 Because fluoxetine is the only currently approved medication for treatment of depression in children (the other SSRI indications in children are for OCD), the majority of prescriptions for children and adolescents will be off-label.
The Physicians Desk Reference (PDR) states, “Once a product is approved for marketing, a physician may choose to prescribe it for uses or in treatment regimens or patient populations that are not included in approved drug labeling. The FDA also observes that accepted medical practice includes drug use that is not reflected in approved drug labeling.”11 Current estimates suggest that 40% to 60% of all prescriptions by physicians are off-label.12
Despite the widespread use of medications for nonapproved uses, when embarking on off-label treatment, the practitioner should consider whether the treatment will benefit the patient and whether its use is consistent with “standard of care.” The latter is best defined as the care rendered by peers within the practitioner’s community and informed by the current medical literature. In some areas there is little literature to guide therapeutic choices, but, as noted, there is an ample body of research and review papers to draw on when using medication to treat children and adolescents.
The Texas Children’s Medication Algorithm Project: Update for Texas Consensus Panel on Medication Treatment of Childhood Major Depressive Disorder is an excellent starting point for treatment planning in this area.13 Although guidelines routinely indicate latitude among recommended treatments (owing to the obvious legal liability created by rigid formulas), the practitioner should anchor his or her off-label choices in practices endorsed by experts in the field when they are available. In addition, a body of case law indicates that the choices must be respectful of product labeling: warnings should be heeded and dosing should be within ranges that are consistent with the PDR and general practice in the area.14,15 If there is deviation, the practitioner should explain his reasoning in the patient’s chart and also explain the risks and benefits fully to the patient and family.
Liability on the part of the pharmaceutical manufacturer comes into play only when it can be shown that there was incomplete product testing, that information provided was misleading or fraudulent, or that advertising and labeling of the drug were inaccurate. Put another way, the manufacturer’s liability greatly diminishes once the FDA has approved the safety and efficacy of a drug and documenaccompanying labeling. Under the “learned intermediary” doctrine, manufacturers fulfill their legal duty by providing adequate warnings to physicians of known risks and contraindications for their products.16 The physician then assumes the duty to inform patients of the risks and benefits of the treatment as part of the informed consent process.
Although the weight of available data suggests that SSRIs pose little or perhaps no risk for increased suicidal behavior, how should the psychiatrist confronted with a depressed child or adolescent proceed? The simple answer is the practice of good medicine including a comprehensive evaluation, collaborative treatment planning, informed consent, and ongoing monitoring of adverse effects and progress. Table 1 summarizes these elements.
The evaluation. The heart of good practice-and one of the strongest bulwarks in managing risk-is the evaluation. For the child and adolescent, this should involve information gathered from at least 3 sources: parents or guardians, the child’s school, and the child himself. In addition to detailing the current symptoms and stressors, a complete evaluation should include developmental history, family history, and substance abuse, each of which represents potential risk factors for suicide. The suicide evaluation itself should not only assess behaviors intended to cause self-harm or death but also suicidal ideation and hopelessness. The latter is a particularly important risk factor for future suicidal behavior.
The format of the C-SSRS allows it to be administered in approximately 5 minutes. It directs inquiry to suicide attempts, suicidal actions that were aborted or interrupted, and preparatory actions. The C-SSRS breaks down suicidal ideation into a spectrum that runs from wishes to be dead, through suicidal wishes with nonspecific plans, all the way to suicidal intent with specific plans. The psychiatrist should develop a monitoring plan and/or institute a higher level of care commensurate with the level of suicidality. Documentation of the evaluation and all interventions is essential.
Collaborative treatment planning. Assuming the child/adolescent is not acutely suicidal and can be treated as an outpatient, the psychiatrist develops a treatment plan in a multi-step process with the child and his parent or guardian. First, the practitioner needs to develop a shared consensus with the child and family regarding the problem and its manifestations. Although the child’s acceptance of this formulation may vary greatly (particularly with adolescents), the parents and child must be “on board” with the formulation to participate in the informed consent process.
Informed consent. This begins with educating the parents and child about the condition and discussing the risks and benefits of available treatments, as well as the risks and benefits of foregoing treatments. Alliance with the family (and as much as possible with the child) is thestrongest risk management strategy when treating children and adolescents (and in any treatment). Furthermore, the informed consent process continues throughout the treatment as choices are made and progress is assessed.
Recommendations for documentation of this process run the gamut from having parents sign a statement that they have reviewed the diagnosis and the risks and benefits of treatment (a process that may alienate some) to the less intrusive process of documenting in the medical record that the relevant issues were discussed and understood.
Treatment planning should include a comprehensive approach: medication alone is not a sufficient treatment of depression in a child or adolescent. When indicated and available, an evidenced-based psychotherapy, such as the cognitive-behavioral treatment used in the Treatment of Adolescents With Depression Study, is highly recommended.17 In addition to attention to the presenting symptoms, the psychiatrist should develop plans to address each of the areas that may exacerbate symptoms and increase the risk of suicide-including treatment of substance abuse, family meetings to address psychosocial stressors, intervention in the child’s school to support academic and social functioning.
If the symptoms of depression are severe and/or psychotherapy is not producing a desired result, then starting medication is indicated. The Texas Consensus guidelines recommend fluoxetine, sertraline, and citalopram as first-line agents, particularly because there are relatively good data for efficacy and safety of these agents in this population.13 Venlafaxine as a second- or third-line agent, should be used with caution given its adverse-effect profile. FDA analysis suggests that the use of venlafaxine is associated with a more than 8-fold increase in suicidal behavior and ideation, although a subsequent study found no difference in suicidality between SSRIs and venlafaxine in adolescents.2,18
Ongoing monitoring. With the initiation of medication, the psychiatrist needs to educate the family about potential adverse effects. The literature review and findings of Gaultieri and Johnson19 are particularly instructive. These investigators found that adverse behavioral effects developed in 36 of 128 children and adolescents taking the full range of SSRIs as well as venlafaxine and bupropion. In descending order of frequency, these effects were hyperactivity and disinhibition, dysphoria and emotional reactivity, self-injurious behavior, and suicide ideation, threats, or attempts (Table 2). These effects may represent manifestations of akathesia, an occasional sequela of SSRI therapy that can create a sense of desperation and panic, at times leading to suicidal ideation. None of these adverse effects resulted in serious injury, emergency department visits, or hospitalizations, and were handled on the phone or with an additional visit. Of the 36 patients, 34 continued on the initial drug at a lower dosage or were switched to another medication. In the 11 patients who were suicidal or self-injurious while taking medication, 10 had similar behaviors before treatment.
These findings are reassuring regarding the toxicity of the medications and emphasize that the primary condition and the patient’s prior behaviors require careful attention in assessing and managing risk.
In guiding parents and guardians, the practitioner should consider using the FDA Medication Guide dated January 26, 2005.20 This succinct summary for families of the risks and adverse effects of medications emphasizes the need to be in touch with the treating psychiatrist if problems arise. Because it does not reflect current re-analyses and may appear alarming, the psychiatrist should review it directly with the parent or guardian. The FDA guide recommends weekly contact with the psychiatrist during the first month of treatment. When this is not feasible, a reasonable substitute could be visits every 2 weeks during the first 4 to 6 weeks of treatment with intervening phone contact. When the child is in psychotherapy with another professional, it is essential that the therapist be enlisted in monitoring the warning signs presented in the FDA guide. Documentation of this coordination of care is another important risk management strategy.
Finally, good practice dictates regular assessment of progress in reducing the presenting symptoms and monitoring adverse effects. Use of a structured instrument, such as the Children’s Depression Inventory, to track progress is desirable, but careful documentation in the record of signs, symptoms, and adverse effects also fulfills this goal.21 When problems arise, immediate consultation with the family and child followed by appropriate adjustments and/or changes in the medication are essential. A frequent complaint in professional liability litigation is the practitioner’s failure to respond to complaints of adverse effects and/or lack of effectiveness.
Since the initial warnings from the British MHRA and our own FDA, a substantial number of subsequent reanalyses and reviews provide comforting reassurance that if there are risks of increased suicidality during the antidepressant treatment of children and adolescents, they are generally small. The benefits of treatment appear to outweigh the risks.
The pursuit of good practice with particular attention to careful informed consent and regular monitoring of specific warning signs in children and adolescents provides the strongest risk management techniqueavailable to the practitioner.
1. MHRA Committee on Safety of Medicines Report of the CSM Expert Working Group on the safety of selective serotonin reuptake inhibitor antidepressants. Published December 2004. http://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf. Accessed August 15, 2005.
2. Hammad T. Review and evaluation of clinical data: Relationship between psychotropic drugs and pediatric suicidality. Food and Drug Administration. Drugs Therapy Perspect. 2008;24.
3. Bridge JA, Iyengar S, Salary BC, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007;297:1683-1696.
4. Posner K, Oquendo MA, Gould M, et al. Columbia Classification Algorithm of Suicide Assessment (CCASA): classification of suicidal events in the FDA’s pediatric suicidal risk analysis of antidepressants.Am J Psychiatry. 2007;164:1035-1043.
5. Posner K, Brent D, Lucas, C, et al. Columbia-Suicide Severity Rating Scale (C-SSRS). New York, NY: Columbia University/New York State Psychiatric Institute; 2006. Accessed October 15, 2008. http://www.fda.gov/ohrms/dockets/ac/07/slides/2007-4306s1-01- CU-Posner.ppt-06-22-2007. Accessed December 5, 2008.
6. Gibbons RD, Hur K, Bhaumik DK, Mann JJ. The relationship between antidepressant prescription rates and rate of early adolescent suicide. Am J Psychiatry. 2006;163:1898-1904.
7. Leon AC, Marzuk P, Tardiff K, et al. Antidepressants and youth suicide in New York City, 1999-2002. J Am Acad Child Adolesc Psychiatry. 2006;45:1054-1058.
8. Simon GE, Savarino J. Suicide attempts among patients starting depression treatment with medication or psychotherapy. Am J Psychiatry. 2007;164:1029-1034.
9. Gibbons RD, Brown CH, Hur K, et al. Early evidence of the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007;164:1356-1363.
10. Woodcock J. A shift in the regulatory approach.Published June 23, 1997.
http://www.fda.gov/cder/present/diamontreal/regappr/sld001.htm. Accessed October 15, 2008.
11. Foreword. Physicians Desk Reference. Montvale, NJ: Thomson PDR;2007.
12. Henry V. Off-label prescribing: legal implications. J Legal Med. 1999;20:365.
13. Hughes CW, Emslie GJ, Crismon ML, et al. Texas Children’s Medication Algorithm Project: update from Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adoles Psychiatry. 2007;46:667-686.
14. Richardson v Miller, 44 SW3d 1 (Tenn App 2000).
15. Mulder v Parke Davis, 181 NW2d 882 (Minn 1970).
16. O’Reilly J, Dalal A. Off-label prescribing or out of bounds? Prescriber and marketer liability for unapproved uses of FDA-approved drugs. Ann Health Law. 2003;12:295-324.
17. Treatment for Adolescents with Depression Study Team. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression. JAMA. 2004;292:807-820.
18. Brent D, Emslie G, Clarke G, et al. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression. JAMA. 2008;299:901-913.
19. Gualtieri CT, Johnson LG. Antidepressant side effects in children and adolescents. J Child Adolesc Psychopharmacol. 2006;16:147-157.
20. Medication guide about using antidepressants in children and teenagers. Revised Jan 26, 2005.
http://www.fda.gov/cder/drug/antidepressants/MG_ template.pdf. Accessed October 15, 2008.
21. Kovacs M. The children’s depression inventory. Psychopharmacology Bull. 1985;21:995-998.
Evidence Bassed References
Gualtieri CT, Johnson LG. Antidepressant side effects in children and adolescents. J Child Adolesc Psychopharmacol. 2006;16:147-157.
Hughes CW, Emslie GJ, Crismon ML, et al.Texas Children’s Medication Algorithm Project: update from Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adoles Psychiatry. 2007;46:667-686.