Psychotropic Medication Use During Inpatient Rehabilitation for Traumatic Brain Injury

By Flora M. Hammond, M.D., Rehabilitation Hospital of Indiana, and Jennifer Bogner, Ph.D., Ohio State University

A range of behavioral, emotional, arousal, cognitive, and physical problems usually occur soon after a traumatic brain injury (TBI). What medications are commonly used to treat these problems during TBI rehabilitation? The answer has been largely unknown until recently.

In the absence of scientific studies, medication management during acute rehabilitation has been driven largely by a person’s clinical presentation and the physician’s subjective experiences and preferences, resulting in highly variable prescribing practices. Physicians often evaluate the benefit and safety of medications for people with TBI based on studies in other patient populations. For example, antipsychotic medications are commonly prescribed based on studies of how well they work for people in psychiatric populations and in settings other than acute inpatient rehabilitation.

Medications are typically adjusted throughout the rehabilitation stay to best meet the needs of the person being treated. Medications that may cause adverse effects and no longer appear needed are often discontinued, while others are added as necessary. Some of the medications commonly used may potentially have adverse effects on health, function, and treatment efficiency. For example, neuroleptics used for people with moderate-to-severe TBI have been associated with longer durations of post-traumatic amnesia (PTA). Additionally, falls have been found to be associated with some medications in the residential TBI treatment setting.

The TBI Practice-Based Evidence (TBI-PBE) multisite project has provided a unique opportunity to describe patterns of psychotropic medication administration at specialized inpatient brain injury rehabilitation units (nine in the United States and one in Canada). We examined:

• medications administered;
• how many medications per patient;
• when initiated;
• when discontinued; and
• the relationship between medication prescription and patient demographic, injury, medical, and function.

We also conducted a second study examining the relationship between medication use and changes in agitated behavior, which can often be a barrier to engaging a person with TBI in rehabilitation. While neither of these studies can determine which medications are most effective, they can help identify which medication regimens represent the standard of care, which regimens are more specific to the site or physician, and which regimens are associated with certain patient and injury characteristics or changes in agitation.

Study 1: Description of medications used in inpatient rehabilitation

How was the study conducted?

We looked at the type and frequency of psychotropic medications prescribed to 2,130 patients who received acute inpatient rehabilitation and were at least 14 years of age. To compare medication administration across different functional levels, we divided the sample into five groups based on functional independence measure (FIM) cognitive scores at admission.

How many patients received psychotropic medication?

Only 5 percent of the patients in our study received no psychotropic medication during their rehabilitation stay; 8.5 percent received only one psychotropic medication, while 31.8 percent received at least six of these agents at some point during rehabilitation. The number of agents per patient increased during the rehabilitation stay with 6 percent receiving at least six psychotropic medications during the first two days of rehabilitation, compared to 14 percent receiving at least six of these medications during the last two days. Those with worse cognitive function at admission received a greater number of psychotropic medications (3-8 agents) than those with higher cognitive categories (most received 0-5 agents).

What medications were administered?

Narcotic pain medications were the most frequently administered (received by 72 percent of the patients), followed in frequency by antidepressants (67 percent), anticonvulsants (47 percent), antianxiety agents (33 percent), hypnotics (30 percent), stimulants (28 percent), antiparkinson agents (25 percent), antipsychotics (25 percent), and miscellaneous psychotropics (18 percent). Miscellaneous psychotropics included acetylcholinesterase inhibitors (AChE-I; i.e., donepezil, physostigmine, rivastigmine), glatiramer acetate, interferon beta-1a, nicotine and varenicline.

Did the medications used change across the rehabilitation stay?

In order to learn about how medications were changed during the rehabilitation stay, we looked at medications received during the first and last two days of rehabilitation. Figure 1 shows that the only class to show decreased use across the stay was narcotics. Antipsychotics, anticonvulsants, and anti-anxiety agents were used as frequently during the first two days of the stay as they were during the last two days. Stimulants, hypnotics, antiparkinsonian agents, and antidepressants were used more during the last two days than during the first two days ofthe stay.

Were there differences in how medications were administered across the study sites?

Medication administration patterns varied greatly across treatment sites. Sites with higher antipsychotic use had lower use of antianxiety agents, and vice versa. Sites with high antiparkinson administration had lower antipsychotic use, and vice versa. For anticonvulsant use, most sites were similar except in one case where 80 percent of patients received an anticonvulsant agent during their rehabilitation stay. With a range of 7 to 31 percent, miscellaneous psychotropic agents were used relatively infrequently. Antidepressant use was uncommon at one site (27 percent), with use ranging from 46 to 91 percent across the other sites. The site with the highest use of antidepressants had a practice pattern of using the antidepressants SARI and tertiary amine TCAs as its first line treatment of insomnia. Across sites, antiparkinson agent use ranged from 1 to 57 percent and stimulants use 5 to 50 percent.

Did medication use vary by cognitive function at the time of admission?

Medication use was less frequent among those with the highest cognitive function at the time of rehabilitation admission for all the medication classes except anticonvulsants. Anticonvulsant use did not substantially vary across the five subgroups.

Were patient-specific factors related to medications administered?

Age was associated with receiving all of the medications studied except hypnotics. Younger patients were more likely to receive antianxiety agents, antidepressants, antiparkinson, stimulants, antipsychotics, and narcotic analgesics. In contrast, older patients were more likely to receive anticonvulsants and miscellaneous psychotropics. Males were more likely to receive antipsychotics. Antianxiety agents, antidepressants, and hypnotics were less likely to be used in minority populations. As expected, prior history of psychosis, bipolar disorder, or schizophrenia was associated with antipsychotic administration. A history of depression or anxiety was associated with use of antianxiety agents, anticonvulsants, antidepressants and narcotic analgesics. Antidepressants, antipsychotics, and psychotropics were more likely when there was a prior history of substance abuse. Multiple indicators of severe impairment (percent of rehabilitation stay agitated, effort given in therapies, severity of brain impairment, severity of comorbidities not related to the brain, length of PTA, percent of days in pain, and percent of days with less than five hours’ sleep) were related to increased drug administration in nearly all categories. Having seizures during rehabilitation increased the likelihood of administration of anticonvulsants as well as narcotic analgesics.

Summary of Study 1

Nearly all patients received at least one psychotropic medication during their rehabilitation, and almost one-third received six or more. Narcotics and antidepressants are the most frequently used. People with more severe injuries received more medications than higher functioning patients. The use of different medication classes varied across sites, reflecting the lack of adequate research on the most effective medications and the resulting absence of a standard of care.

Study 2: Predictors of agitation during inpatient rehabilitation

The second study provided information about medication use associated with increases in agitation. While the first study focused exclusively on psychotropic medications, the second study looked at the association between any medication class that could affect agitation through the central nervous system or through relief of discomfort.

How was this study conducted?

For this study, only people who were agitated at some time during their rehabilitation stay were studied (n=555). We sought to predict the next day’s agitation based on medications that were used in the 24 hours prior. This study also provided information about the person, injury, and recovery factors that predict agitation.

Which medication classes were associated with more agitation during the day after medication use?

Norepinephrine-dopamine 5 hydroxytryptamine agonists (primarily methylphenidate) were associated with less agitation. This medication has been found in other studies to improve cognition and attention. More severe agitation the next day was found when the patient received anticonvulsants that block sodium channels, second generation antipsychotics (first generation antipsychotics were not studied due to low use), or gabba-aminobutyric acid-A antianxiety/hypnotic agents. Many of the medications in the classes associated with more severe agitation can temporarily suppress cognition through sedation and are thought to negatively impact cognitive recovery.

Summary

• This large, multicenter study describes the patterns of psychotropic medication administered during inpatient TBI rehabilitation at specialized brain injury rehabilitation centers. This information may inform other providers.
• Many psychotropic medications were used during inpatient rehabilitation.
  • Overall psychotropic medication use varied from 18 to 72 percent (mean 42 percent), with 31.8 percent of patients exposed to at least six of the psychotropic agents studied.
  • The high use of psychotropic agents in the absence of proven medications to advance recovery, suggests an urgency to control TBI sequelae, and/or a strong desire to stimulate recovery to optimize function and rehabilitation.
• There was considerable across-site variation, which likely reflects the relative lack of high quality research on TBI neuropharmacology.
• The study reveals the type of psychotropic agents used but not the purpose. Caution should be used in presuming the targeted use of the medications in this study.
  • Medications designed and approved for one use are commonly used for other purposes. For instance, antidepressants may be useful for correction of sleep disorders, pain, and anxiety as well as depression. Antianxiety agents may be used for sleep and behavior modification as well as anxiety. Anticonvulsants are commonly used for neuropathic pain and mood stabilization as well as seizure prevention or management. Antipsychotics may be administered for insomnia, anxiety, psychosis and agitation.
• In general, those with lower admission cognitive function received more of the medications under investigation as compared to those with higher cognitive function at admission.
• Medications that have been found in other studies to improve cognition were associated with less subsequent agitation, and medications that can suppress cognition through sedation were associated with more severe agitation. This does not mean that the medications caused the agitation to increase or decrease, but it does suggest that further study is needed.

Where can I find more information?

For a complete report of this work, a supplemental issue of the Archives of Physical Medicine and Rehabilitation was published in August 2015 (Volume 96, No. 8).

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This article originally appeared in Volume 10, Issue 3 of THE Challenge! published in 2016.