What commonly used medication for behavior and psychiatric symptoms in dementia is not approved for the purpose, is often used inappropriately, has no evidence that it is better than placebo for dementia-related agitation, causes significant side effects, and has resulted in a huge fine against its manufacturer for inappropriate promotion of its off-label use?
The answer, of course, is valproic acid. But you are not alone if you thought that the answer was “antipsychotics.” After all, the concern of the past several decades about antipsychotics has become a shrill cry to vilify them and inhibit their use by every possible means. Advocates may prefer banning them outright, which the Centers for Medicare & Medicaid Services cannot do by law.
A September 11, 2021, New York Times
article entitled “Phony Diagnoses Hide High Rates of Drugging at Nursing Homes” (https://nyti.ms/3miySfH
) asserted the following:
Diagnoses are often fabricated to support the use of psychopharmacologic medications.
Antipsychotics are still being used too often and for the wrong reasons.
Nursing homes must report the number of residents that are on antipsychotics unless the residents have schizophrenia or two other conditions.
Other medications such as valproic acid are being substituted due to the pressure to reduce antipsychotics.
One out of nine nursing home residents has a schizophrenia diagnosis versus one out of 150 in the general population.
Is Any of This New?
Using medications to try to manage mood and behavior goes back over 150 years but has accelerated dramatically since the 1950s. In the 1950s, chlorpromazine — the first widely available antipsychotic — began a revolution in the treatment of mental illness (Neuropsychopharmacology 1993;8:291–303). By the 1970s, both rational and haphazard use of medications to treat behavior and psychiatric issues (BPIs) was becoming widespread.
As a medical resident in the mid-1970s, I remember seeing many hospital admissions from nursing homes who were suffering major complications from massive doses of first-generation antipsychotics as well as early sedatives and hypnotics including benzodiazepines and barbiturates. Unfortunately, the vast increase in psychopharmacological medications since then has expanded the opportunities to cause harm as well as to do good. These issues are universal and definitely not limited to nursing homes.
How Has the Regulatory Process Tried to Influence Prescribing, and Has It Worked?
Over a decade ago, CMS launched a national initiative to “improve dementia care” in nursing homes and reduce the use of antipsychotic medications. Pressured primarily by advocates and by Congress, CMS has tried to inhibit antipsychotic use by discrediting the medications, creating more documentation hurdles, and using the threat of citations and lower quality measures scores to inhibit the off-label use of antipsychotics for anything other than major mental illness and several neurological conditions.
Although the data have indicated a significant reduction in antipsychotic prescribing, it is unclear whether there has been a meaningful improvement in the overall use of medications and management of BPIs in nursing homes (J Am Med Dir Assoc 2019;20:1074–1079). Legitimate concerns about the whole initiative have been largely ignored if not ridiculed.
How Have Nursing Homes Responded?
To some extent, nursing homes have tried to improve the way they manage BPIs and use medications more appropriately and safely. Truthfully, many nursing homes try to reach out for help from medical practitioners and psychiatric consultants, but the results are very mixed if not highly problematic (Caring for the Ages 2021;22:10).
As patients have gotten more complex and the treatment options have proliferated, the misunderstandings and problematic care persist. Furthermore, confusion about “allowable” indications and widespread fear of putting people on the “wrong” medications have unquestionably denied necessary and appropriate medications to patients who need them (e.g., those with bipolar disorder with major psychosis) and have led to substituting “allowed” medications in situations where they are ineffective, not indicated, or problematic. Irrational dose reductions not infrequently result in harmful relapses of major psychiatric symptoms (N Engl J Med 2012;3367:1497–1507).
There has also been diagnostic fabrication. I have seen firsthand actual cases of abuse through deliberate diagnostic manipulation and inappropriate prescribing. Amazingly, I also have seen surveyors, managers, medical practitioners, and consultants misunderstand and overlook such situations.
Ultimately, the entire situation involves a modicum of truth and some very significant distortion. The pressure from consumers and Congress to simply crack down has failed to address the real root causes. Clinically complex issues do not lend themselves to simplistic solutions (see the Caring columns OBRA Regulations Revisited and Dear Dr. Steve throughout 2020 and 2021).
Is the Relentless Focus on Antipsychotics Warranted?
Years of relentless antipsychotic bashing have made “antipsychotics” a pejorative term. Any evidence or opinion that has challenged the conventional wisdom about antipsychotics (J Am Med Dir Assoc 2015;16:817–824) has been largely dismissed
However, despite their risks (JAMA 2005;294:1934–1943), antipsychotics overall are not inherently better or worse than any other category of psychopharmacologic medication. All these medications affect various chemicals in the brain as well as other organs (e.g., liver and bone marrow damage from antiepileptics, anorexia related to antidepressants, or renal failure due to lithium). The inappropriate and ineffective use of any psychopharmacological medication can be dangerous if not destructive.
Choosing the right approach does not mean simply focusing on categories of medications or “right” diagnoses. It requires systematically applying the entire care delivery process and substantial diagnostic skill, as explained in the attending curriculum (modules 2-1 and 4-2) of AMDA – The Society for Post-Acute and Long-Term Care Medicine. Although nonpharmacological interventions should be tried as well, they are inconsistently helpful, and the benefits are often short-lived.
What Is the Relevant Evidence About Using Antiepileptics?
Recent regulatory revisions since 2017 have expanded the requirements to cover other categories of psychopharmacologic medication. Ironically, the list does not include (and previously had not included) antiepileptics. Simply stated, CMS, the professional associations, and most clinical practitioners have yet to recognize and disseminate the evidence regarding the limited indications, limited effectiveness, and major risks of antiepileptics. Therefore, antiepileptics have frequently become the medications of choice — often a very bad choice.
There are some valid but limited indications (e.g., mania) for using antiepileptics such as valproic acid. Accumulated evidence has confirmed the lack of evidence to support the efficacy of antiepileptics for dementia-related behavior and has demonstrated the risk of major complications. According to the UK National Institute for Health and Care Guidance (NICE), valproate preparations “are no more effective than placebo for treating agitation or behavioural disturbances in people with dementia. Adverse effects such as falls, sedation, gait disturbances, tremor, muscular weakness, thrombocytopenia, gastrointestinal disorders and urinary tract infections were more common in people taking valproate preparations than placebo” (NICE Evidence Summary, Mar. 10, 2015; https://bit.ly/3rn4zsK
Valproate has been found to “not delay the emergence of agitation or psychosis or slow cognitive or functional decline in patients with moderate Alzheimer’s disease and was associated with significant toxic effects” (Arch Gen Psychiatry 2011;68:853–861). In addition to neurological (e.g., ataxia) and other (e.g., bone marrow and liver toxicity) medical complications, the documented psychiatric side effects of antiepileptics include agitation, confusion, delirium, euphoria, depression, psychosis, aggression, mania, toxic encephalopathy, nightmares, and suicidality (Med Lett 2008;50:102).
Furthermore, antiepileptics are often prescribed for multiple reasons (seizures, pain, behavior) by the same or by multiple different practitioners. Regardless of the alleged indications, the brain and body will experience the aggregate effects of all antiepileptics given simultaneously. Therefore, we must always consider that antiepileptics may be causing rather than improving substantial behavior and psychiatric symptoms.
What Should I Do as an Individual Practitioner or Medical Director?
Practitioners should always base their decisions when prescribing medications for BPIs primarily on clinical considerations. Although regulatory considerations are definitely relevant, concerns such as quality measures should never predominate.
Ultimately, we must strive to promote competent clinical reasoning and problem solving as the only way to rationalize the use and numbers of various psychopharmacological medications. Appropriately informed medical practitioners must become more involved in detailed patient-specific discussions (J Am Med Dir Assoc
2021;22:2212–2215). Gradual dose reduction meetings rarely if ever offer an adequate approach to systematic clinical reasoning and problem solving. Here are suggestions for a more valid approach:
Identify and utilize some of the many reliable and helpful references on diagnosing and treating BPIs (J Am Med Dir Assoc 2017;18:284–289).
Reinforce essential first steps in addressing behavior issues, including medical considerations (Michael B. First, DSM-5 Handbook of Differential Diagnosis, American Psychiatric Publishing, 2014).
Remind everyone that behavior is not automatically a “psychiatric” issue requiring a consultation.
Discuss with your facility the importance of not trying to game the system.
Focus everyone on clinically valid diagnoses, not on “allowable” diagnoses.
Vigorously help create an environment that limits the panic and prescriptive urgency of staff and practitioners in cases of aggressive and disruptive behavior.
Help your facility reassess and limit its use of consultants.
Inform psychiatric consultants that they are not expected to load up on allowable medications; rather they should identify what they know and how they intend to help provide clinically appropriate care.
Furthermore, it is imperative to read and understand the regulations and surveyor guidance related to the use of psychotropic medications. Most medical practitioners and facilities have not done so or do not understand their implications.
The current political, clinical, and regulatory approaches to the situation have led to serious unintended but predictable consequences, including the excessive and inappropriate use of antiepileptics. Telling people how they should or should not treat BPIs is an inadequate substitute for showing them how to think through these problems correctly. Fixing this messy situation to obtain optimal results demands a different approach all around.
Dr. Levenson has spent 42 years working as a PALTC physician and medical director in Maryland. He has helped lead the drive for improved medical direction and nursing home care nationwide through his work in the educational, quality, and regulatory realms.