The role of pharmacological interventions has been central to the treatment of brain injuries. Medications can help to alleviate pain and physical problems that interfere with daily functioning, as well as help with brain recovery and problems related to social behavior and other performing other complex activities. In combination with Applied Behavior Analysis, pharmacology can be a powerful and effective approach to treating brain injuries.

The use of medications, however, is not without drawbacks and risks.

The following presentation provides relevant information specifically related to the use of medications to treat brain injuries and the complications associated with reducing these medications over time.

Considerations in Psychotropic Medication Reduction After Traumatic Brain Injury

Randall D. Buzan, MD
Associate Professor of Psychiatry
University of Colorado School of Medicine
Consulting Psychiatrist – Learning Services Colorado

Outline of Talk


Good intentions are not enough

Why Reduce Meds?


  • Sometimes “less is more” and patients may feel and function better, or at least no worse, OFF their meds
  • Side effects
  • Save the hassle and expense
  • It’s required in facility settings: Omnibus Reconciliation Act of 1987 mandates an attempt to find the “minimum effective dose”

Anna’s Story

Anna is a 40 y.o. DD woman admitted 4-1-09 for “extreme aggression” after beating people up in previous placement. At age 6 she suffered a brain injury and frontal lobe injury and mild MR due to spinal meningitis. She had delayed development and multiple placements due to challenging behavior that included: manipulation, confabulation, perseveration, threats to run away, and severe aggression against self, others, and property.

Previous med trials included Seroquel 1050 mg, Risperidone 11 mg, Klonopin 1.5 mg, haldol 5 mg, Lithium 300 mg, Abilify 10 mg, Depakote 2500 mg, Amantidine 100 mg, Topamax 50 mg, Meridia 5 mg, Paxil 40 mg, Trazodone 100 mg, Geodon and Xanax

Behavioral Intervention

  • Functional Assessment indicated that aggression was maintained by attention
  • Reinforce socially-appropriate competing attention-gathering behaviors and extinguish aggression behaviors
    • DRA – Differential Reinforcement of Alternative Behavior
    • Teaching Social Skills, Requesting, Cooperation, Planning, Budgeting, etc.
    • Rehabilitation & Therapy
  • Medication tapering

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Conceivably all patients when:

  • Clinically stable with an established baseline
  • Clinically unchanged on the drug
  • No history of dangerous decompensation with similar taper in the past 4 months
  • Have received an adequate course for the index episode of a known psychiatric illness (e.g. 6-9 months with Major Depression)
  • Ideally, receiving Applied Behavior Analysis Treatment and collecting data

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What to Taper First?

  • Med deemed least effective
  • Med deemed most dangerous/toxic
  • A drug whose elimination time frame requirements are realistic for the patient

When to Taper?

  • When decompensation will not seriously compromise a treasured event: job interview; trip to Europe
  • No new environmental factors expected that could confound assessment of response to taper
  • When the team and milieu are stable and able to handle a decompensation
  • No acute medical/psychosocial problems that make a taper unsafe
  • When the data reveal stabilization of behavior


In a setting that can handle a possible decompensation:

  • Client mix that is not too vulnerable
  • Stable and adequately experienced staff
  • Sufficient family support

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This depends on the drug!

Medications for Depression

  • Tricyclic antidepressants (TCA’s)
  • Selective serotonin reuptake inhibitors (SSRI’s)
  • SNRI’s: Cymbalta, Effexor, Pristiq
  • Monoamine oxidase inhibitors (MAOI’s)
  • Trazodone
  • Mirtazapine
  • Bupropion
  • Viibryd
  • Lamictal
  • Mood stabilizers
  • Herbs/hormones
  • Stimulants
  • Atypical antipsychotics

Medications for Bipolar Patients

Cognitive Enhancing Agents

Meds for Anxiety Disorders

Tapering drugs for aggression

Not without Risk!

TBI and Aggression

  • 35-96% of brain injured patients are agitated acutely
  • 34% of patients demonstrate aggression acutely, and 31-71% of severe TBI patients followed for 15 years have subsequent aggression
  • Aggression is associated with Major Depression, frontal lesions, poor premorbid social function, and Etoh/drug use.
  • 56% of patients who got depressed in the first year after TBI demonstrated aggression

Silver et al APA Textbook of TBI 2005 pp. 259-277

Frontal Inhibition of Aggression

Phineas Gage

A blasting charge sent a 1.5” wide and 3’ long metal spike through his face and frontal lobe

Mr. Gage after his injury

Phineas Gage lost orbitofrontal Cx

  • Lost his social judgment, and became impulsive, irresponsible, and profane.
  • Traveled as far as S. America and drifted from job-to-job, including in PT Barnem’s museum in NY

Tapering Antipsychotics

Drug side effects include:

  • Tardive dyskinesia, wt gain, sedation, cognitive impairment

Rate of taper ideally 10%/month – minimum over 1 month

Withdrawal symptoms can include:

  • Increased movement disorders (withdrawal dyskinesias)
  • insomnia
  • anticholinergic withdrawal
  • agitation

How successful are AP tapers?

    • We only have good studies in dementia, not TBI, patients
    • 180 agitated/aggressive Alz Dz patients tx’d with – 1.0 mg risperidone for 16 weeks, then 110 responders randomized to 1/3 groups: 32 weeks of risp or placebo, or 16 weeks risp then 16 weeks placebo
    • 60% of responders switched to placebo relapsed vs. 33% on drug, and in group 3 the relapse was 3-fold higher on placebo (48% on placebo vs 15% on drug)

Devanand et al. N Engl J Med. 2012 Oct 18;367(16):1497-507.

    • Haldol study 0.5-5 mg/d: 80% on placebo relapsed within 6 weeks vs 40% who continued haloperidol
    • DART-AD study: 51 AD patients in “care facilities” continued their AP and 51 were switched to placebo. While the most behaviorally disturbed patients had more decompensation on placebo, no significant deterioration observed in most AND mortality was 70% on placebo but 77% with continued AP

Devanand et al. Int J Geriatr Psychiatry. 2011 Sep;26(9):937-43.
Ballard et al. Lancet Neurol. 2009 Feb;8(2):151-7.

Tapering SSRI’s

  • Drug side effects include: sexual dysfunction, sweating, GI upset, cognitive impairment, weight gain, myoclonic jerks
  • Rate of taper: depends on t-1/2 and duration of treatment(Prozac has 90 hour half life so can taper more rapidly – the others ~ 24 hours so taper over 1 month)
  • Withdrawal symptoms include:
    • serotonin w/d (nausea, electric shock feelings, dizziness/spins)
    • Anticholinergic w/d – esp Paxil – flu-like symptoms
    • Depression and mania
    • Irritability

Half Lives of Psychotropics

Tapering Lithium

    • Drug side effects: (brain and gut): tremor, confusion, anomia and cognitive impairment, diarrhea and GI upset, kidney damage, myoclonic jerks
    • Rate of taper: Baldessarini studies show a 5-fold higher risk of recurrence of mood episodes over 4 years when lithium stopped over 2 weeks or less vs 2-4 weeks or more. In pregnant bipolar women abrupt Li+ d/c increased mood risk 11-fold. Taper over more than 4 weeks or risk large increase in mood episodes!!!
    • Withdrawal symptoms:
      • Mood lability
      • Anticholinergic symptoms – flu-like

Baldessarini et al. J Clin Psychiatry. 1996 Oct;57(10):441-8.
Viguera et al. Am J Psychiatry. 2007 Dec;164(12):1817-24

Tapering anticonvulsants

  • Drug side effects: sedation, tremor, weight gain (Depakote), agranulocytosis, thrombocytopenia, liver irritation, cognitive impairment, gait instability
  • Rate of taper: Slow to avoid withdrawal seizures – over a month if possible
  • Withdrawal symptoms: insomnia, agitation, mood lability and irritability

Tapering Benzodiazepines+
(Ativan, Xanax, Valium, Klonopin)

    • Drug side effects: Sedation, cognitive impairment, gait instability, swallowing problems, abuse/addiction
    • Rate of taper: See Rickels studies: depends on duration of tx and t-1/2 of the drug (Valium 60-100 hours; alprazolam 12 hours; Ambien 2-3 hours). Generally taper over a month or more
    • Withdrawal symptoms: rebound anxiety/panic, insomnia, seizures, hypertension, sweating, tremor

Rickels et al. Arch Gen Psychiatry. 1990 Oct;47(10):899-907
Rickels et al. Am J Psychiatry. 1991 Jun;148(6):757-61
Rickels et al. J Clin Psychopharmacol. 1998 Dec;18(6 Suppl 2):12S-18S

Tapering Cognitive/other agents

  • Cholinesterase inhibitors (aricept/exelon/galantamine)
    • Drug SE’s: agitation/irrit, GI upset, insomnia
    • Rate of taper: can be over a few days or less
    • W/d SE’s: In my experience w/d SE’s are rare
  • Stimulants (Ritalin/dextroamphetamine/Adderall)
    • Drug SE’s: agitation, anxiety, bruxism, sweating, insomnia
    • Rate of taper: over a few days (all have short t-1/2 ~ 4-6 hours)
    • W/D SE’s: sleepiness, fatigue, depression, flushing
  • Withdrawal from B-blockers (propranolol/atenolol) or alpha-agents like clonidine/guanfacine (Intuniv): REBOUND HYPERTERNSION – taper these over a least 2 weeks!

So, taper meds carefully

Keep your eyes on the patient during the process…

And enjoy your clients and all they can teach on the journey!

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