1. Practical Psychotropic Drug Management in Developmental Disabilities
Craig A. Erickson, M.D.
Director, Developmental Disability Research and Treatment in Psychiatry
Director, Fragile X Research & Treatment Center
Medical Director, P3 Southwest Neurodevelopmental Disorders Inpatient Unit
Director of Research, The Kelly O’Leary Center for Autism Spectrum Disorders
Associate Professor of Psychiatry
Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine- Affiliated

2. Conflicts of Interest Source Consultant (past* or present^)
Stock or Equity Interest
Speakers Bureau
Research Support (past* or present^)
Honorarium/
Support for this Talk
Bristol-Myers Squibb X*
Roche/Genentech
Seaside Therapeutics
Novartis
Confluence Pharmaceuticals X^ X
US Dept of Defense
AACAP
FRAXA Research Foundation
Alcobra
Neuren
Simons Research Foundation
Autism Speaks
Cincinnati Children’s Hospital Research Foundation
John Merck Fund
National Fragile X Foundation

3. Roadmap Target symptom approach to treatment PRN medications
Polypharmacy
Medication Discontinuation
Vignette Examples

4. Target Symptoms for Medication
Motor hyperactivity and inattention
Interfering ritualistic behavior
Aggression, self-injury, property destruction

5. Target Symptoms Continued:
Mood disturbances: depression, bipolar
Anxiety: panic attacks, agoraphobia, general anxiety, phobia, PTSD
Others: sleep disturbances, pica, inappropriate sexual behavior

6. Motor Hyperactivity and Inattention
Psychostimulants: methylphenidate, dextroamphetamine, mixed amphetamine salts
Alpha-2 agonists: guanfacine, clonidine
Non-stimulants: atomoxetine, bupropion, tricyclic antidepressants

7. Psychostimulants Work quickly
Side effects: reduced appetite, insomnia, tics, increased pulse/blood pressure
May cause behavioral worsening
May need to be given multiple times per day
Need new prescription each month

8. Alpha-2 Agonists Need to monitor blood pressure and heart rate
Can be sedating
Generally don’t make symptoms worse
Need to be given 2-3 times per day

9. Non-Stimulants
Atomoxetine: effective in ADHD; preliminary studies in developmental disabilities.
May take longer to work than stimulants.
Generally won’t make tics worse.
May help with comorbid mood and/or anxiety.

10. Non-Stimulants (Cont’d)
Bupropion: has been shown to be effective for ADHD.
Not well-studied in developmental disabilities.
Can lower the seizure threshold and should NOT be given to a patient with a history of seizures or active seizure disorder.
Can make tics worse.

11. Non-Stimulants (Cont’d)
Tricyclic antidepressants: not well-studied in developmental disabilities.
Associated with side effects including: dry mouth, blurry vision, constipation.
Can lower the seizure threshold.
Can affect cardiac rhythm.

12. Ritualistic Behavior Selective Serotonin Reuptake Inhibitors (SSRIs)
Fluoxetine
Fluvoxamine
Sertraline
Paroxetine
Citalopram
Escitalopram

13. SSRIs
Data indicate SSRIs may be more effective in post-pubertal vs. pre-pubertal individuals with developmental disabilities
Side effects: insomnia, sedation, stomach upset, sexual dysfunction, weight gain
Can generally be given once a day
Concern about increasing suicidal thinking/behavior

14. Irritability: Aggression, Self-Injury, Severe Tantrums
Typical antipsychotics
Atypical antipsychotics
Mood stabilizers
Alpha-2 agonists
Naltrexone

15. Irritability (Cont’d)
Typical Antipsychotics
Haloperidol
Thioridazine (rare use, sudden death)
Chlorpromazine
Trifluoperazine
Fluphenazine

16. Irritability (Cont’d)
Typical Antipsychotics
Side-Effects
acute extrapyramidal symptoms (EPS), tardive dyskinesia (TD), sedation, weight gain, drooling

17. Irritability (Cont’d)
Atypical Antipsychotics
Clozapine
Risperidone
Olanzapine
Quetiapine
Ziprasidone
Aripiprazole
Paliperidone

18. Clozapine Common side effects include weight gain, sedation, drooling
Can lower the seizure threshold
Agranulocytosis and need for careful blood monitoring

19. Risperidone
Well-studied in autism (FDA approval) and mental retardation associated with behavioral dyscontrol
Common side effects: weight gain, sedation (transient), drooling, elevated prolactin

20. Olanzapine Only small controlled studies in developmental disabilities
Common side effects: weight gain (at times significant), has been associated with glucose and lipid dysregulation, sedation

21. Quetiapine No controlled studies in developmental disabilities
Common side effects: weight gain (may be less prominent than with clozapine and olanzapine), sedation, orthostatic hypotension if dose increased too quickly

22. Ziprasidone No controlled studies in developmental disabilities
Common side effects: sedation (transient), occasional insomnia or behavioral activation. Not associated with significant weight gain
Should not be given to patients with cardiac problems

23. Aripiprazole
Positive controlled study in youth with autism spectrum disorders
Common side effects: EPS and nausea/vomiting if given at too high a starting dose. Akathisia. Occasionally transient sedation or activation. Not associated with significant weight gain or prolactin elevation

24. Paliperidone Major active metabolite of risperidone
Potentially fewer drug-drug interactions
Once daily dosing
Potentially less weight gain and prolactin elevation

25. Irritability (Cont’d)
Mood Stabilizers
Valproic acid
Lithium
Carbamazepine
Gabapentin
Topiramate
Oxcarbazapine

26. Valproic Acid
The only controlled study in autism found no drug vs. placebo difference
Common side effects: sedation, weight gain
Need to monitor blood level for therapeutic range and to follow liver function tests
May be useful in patients with seizures and aggression

27. Lithium No controlled studies in developmental disabilities
Common side effects: tremor, polydipsia, polyuria, weight gain
Need to monitor blood for therapeutic range and to follow kidney and thyroid function

28. Carbamazepine No controlled studies in developmental disabilities
Common side effects: dizziness
Need to monitor blood level for therapeutic range and to follow blood count and sodium level

29. Oxcarbazepine Not well studied in developmental disabilities
Negative study in adolescent bipolar disorder
Need to monitor serum sodium

30. Gabapentin No controlled studies in developmental disabilities
Common side effects: some sedation, some weight gain
No need to monitor blood levels
Not particularly effective on a clinical basis

31. Topiramate No controlled studies in developmental disabilities
Common side effects: sedation, cognitive dulling. Not associated with weight gain
No need to monitor blood levels

32. Irritability (Cont’d)
Alpha-2 Agonists
Guanfacine: not particularly effective for aggression
Clonidine: can be effective for aggression. Need to balance sedation vs. clinical benefit
Need to monitor blood pressure and heart rate

33. Irritability (Cont’d)
Naltrexone
Not effective on a clinical basis
No significant side effects, except:
Need to monitor liver function

34. Irritability: Conclusion
Best evidence based treatments in persons with developmental disabilities:
Risperidone
Aripiprazole

35. Mood - Depression
SSRIs: fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine etc.
Bupropion
SNRIS: Venlafaxine (elevated blood pressure), duloxetine
Mirtazapine (weight gain, sedation)
Tricyclic antidepressants

36. Mood – Bipolar Disorder
Valproic acid
Lithium
Carbamazepine
Gabapentin
Topiramate
Lamotrigine (Steven’s Johnson Syndrome)

37. Anxiety SSRIs/SNRIs generally most effective
Cautious use/avoid benzodiazepines
Lorazepam, alprazolam, clonazepam, diazepam etc.

38. Anxiety Buspirone: few side-effects combined with limited benefit
Consider mirtazapine (dosed at bedtime)
Commonly associated with sedation and increased appetite

39. Sleep Disturbance - Insomnia
Diphenhydramine (paradoxical rxt’n)
Clonidine
Trazodone (priapism)
Chloral hydrate
Benzodiazepines (paradoxical rxt’n)
Melatonin
Mirtazapine

40. Pica SSRIs Antipsychotics Behavioral strategies
All strategies may hinge on framing what drives pica: anxiety/impulsivity/something else/unknown

41. Inappropriate Sexual Behavior
SSRIs
Hormonal strategies
Behavioral strategies

42. PRN Medications “As needed” drugs “Chemical restraints”
Common in mental health outside of MR/DD world
Beta blockers for social anxiety
Benzodiazepines and hydroxyzine for anxiety/panic
Antipsychotics for agitation associated with psychotic and bipolar illness

43. PRN Medications Acute Inpatient Psychiatry Units
About 50% of all inpatients receive at least one PRN medication during course of hospital stay
Most frequently antipsychotics and/or benzodiazepines
Classic PRN combo for agitation: 5mg haloperidol + 2mg lorazepam IM
Usher K, Luck L. Psychotropic PRN: a model for best practice management of acute psychotic behavioural disturbance in inpatient psychiatric settings. J Ment Health Nurs Mar;13(1):18-21

44. PRN Medications Long-term state psychiatric facilities
In one study, 23% of residents received at least one PRN medication in last month
Craig TJ, Bracken J. An epidemiologic study of prn/stat medication use in a state psychiatric hospital. Ann Clin Psychiatry 1995 Jun;7(2):57-64

45. PRN Medications Nursing homes
35% of all psychotropic drugs prescribed for PRN use
Stokes J.A.; Purdie D.M.; Roberts M.S. Factors influencing PRN medication use in nursing homes. Pharmacy World and Science, Volume 26, Number 3, June 2004 , pp (7)

46. PRN Medications Supervised living environments
No systematic studies look at % of patients with PRN orders?
Clinically we see minority of patients with behavioral PRNs

47. PRN Medications Issues:
Chronic, frequent use: If you need it all the time is it really a PRN?
Who makes the call: Who/Whom are the appropriate personnel to decide if PRN needed?

48. PRN Medications Issues Continued: Aren’t you just sedating someone?
Risk of falls/hypotension/dystonic reaction/disinhibition: ie side effects.

49. PRN Medications Maybe best if narrowly defined
PRN use prior to long trips or going to the doctor’s office/other appointments
PRN for sleep if patient still awake after X number of hours/at a certain time

50. PRN Medications Frequency of administration is key
If not needing it for months and months, consider getting rid of it
If need it every other day, look at adjusting scheduled meds/behavioral intervention changes to try and limit need for PRN

51. Polypharmacy A chronic problem in our patient population
“Layers of drugs”
A drug gets added with no plans to remove a preexisting agent

52. Polypharmacy Can end up on drugs with opposite effects
Stimulants and benzodiazepines: “Uppers and downers”

53. Polypharmacy
In our clinic most commonly seen with borderline personality disorder
May be do to fluctuating moods, severity of agitation, anxiety, psychotic-like phenomena
Can almost read a med list and predict the diagnosis
Antipsychotics, plus antidepressants, plus benzodiazepines, plus maybe a stimulant

54. Polypharmacy How To Avoid Target Symptom Approach
Be sure each drug has defined target symptom(s)
If a drug does not adequately treat a target symptom, discontinue it
If adding a drug, always consider what the new drug could replace

55. Polypharmacy Cross-titration
Slowly increasing a new drug while slowly decreasing the drug it replaces
May takes weeks to a few months, but can in some cases be much faster
Goal is to not exacerbate behavior/symptoms in the process

56. Medication Discontinuation
Goal is least number of drugs at lowest doses

57. Medication Discontinuation
Need behavioral/symptom stability before slowly removing effective agents
Like to see at least 6-12 months of good symptom control before removing slowly a effective drug

58. Medication Discontinuation
Good plan to at least try slow med reduction, especially if significant side-effects are at risk/developing
Worst case is behavior worsens and dose need be restored
Do run risk that behavioral control will not be duplicated when dose restored

59. Vignettes 13 year old male with autistic disorder, IQ=50
Reported failures/lack of significant response of/from aripiprazole, risperidone, quetiapine, guanfacine, Adderall
BMI at >99% for age and gender
Gained weight on all antipsychotics
Also on Concerta 54mg, trazodone 50mg for sleep and quetiapine 200mg TID which is viewed as partially effective
Admitted with increased physical aggression- grabs, hits, spits
Sleep OK, no major medical issues

60. Vignettes
4 year old with autism, non verbal, intense hyperactivity, aggression and tantrums in developmental preschool
BMI at 50% for age
No major medical problems, no previous medications

61. Vignettes
14 year old with ASD, IQ 80, intensely fears fire drills, has outbursts going to school, attacks parents on school days, emesis in the morning at school, no medical problems
Recently started aripiprazole 5mg daily, 50% reduction in agitation, but still missing 2 days of school per week

62. Vignettes
7 year with ASD, intermittent agitation controlled on risperidone, admitted due to running away from school in the street, hyperkinetic, cannot sit still, unable to stay in seat at school
Current medication: risperidone .5mg BID, clonidine .2mg HS for sleep, melatonin 3mg QHS for sleep
Previous medication trials: daytime clonidine too sedating, guanfacine non helpful
Unable to swallow pills

63. Vignettes
Age 12, ASD, explosive aggression, history of abnormal EEG, never treated for frank epilepsy
No other medical problems, BMI 50% for age.
Current meds: naltrexone, lithium, risperidone, clonidine .1mg TID and .2mg HS
Past med failures: quetiapine, aripiprazole, guanfacine, olanzapine, haloperidol, fluoxetine, clonazepam

64. Vignettes
Age 16, ASD, severe self-injury, history of retinal detachments, seizure disorder- last seizure 18 months ago, stable on valproic acid
Current meds: haloperidol 10mg TID, trazodone 150mg HS for sleep, Depakote ER 1000mg BID, guanfacine 1mg TID
BMI 50%, no other medical issues other than epilepsy
Previous medication failures: aripiprazole, risperidone, quetiapine, olanzapine, chlorpromazine; was on aripiprazole and risperidone at same time before

65. Vignettes
17 year old developmental disability, no ASD, FAS, history of physical and sexual abuse
Intermittent about 3 times per week major aggression, mainly towards mother
Admitted 4 times in last 12 months
Failed aripiprazole, risperidone, olanzapine, ziprasidone, guanfacine
Current meds: Quetiapine 300mg BID, minimally effective; clondine .2mg HS for sleep, fluoxetine 20mg daily for history of anxiety
BMI 25% for age, no medical problems

66. Vignettes
17 year old developmental disability, no ASD, FAS, history of physical and sexual abuse
Intermittent about 3 times per week major aggression, mainly towards mother
Admitted 4 times in last 12 months
Failed aripiprazole, risperidone, olanzapine, ziprasidone, guanfacine
Current meds: Quetiapine 300mg BID, minimally effective; clondine .2mg HS for sleep, fluoxetine 20mg daily for history of anxiety
BMI 25% for age, no medical problems

67. Vignettes
15 year old with ASD, IQ 125, admitted with self-inflicted chest inflicted chest laceration from knife, bullied at school, suicidal ideation for six months, insomnia, has lost 15 pounds in six months
No medication now or in the past

68. QUESTIONS? Craig.erickson@cchmc.org