Medications, Disruptive Behavior & Dual Diagnosis Patients

1. Medications, Disruptive Behavior & Dual Diagnosis Patients Jack Rozel, MD, MSL Assistant Professor of Psychiatry, URSMD Medical Director, Child & Adolescent Inpatient Psychiatric Units, Strong Memorial Hospital / URMC

2. Conflict of Interest Disclosure • Research Funding – Alexza (2006-7), Janssen (1997), NIMH (2008-9) • Conference/Travel – Alexza (2006), Eli Lilly (2004), Janssen (2003, 2006), Wyeth Ayerst (2002) • Speakers’ Bureaus – PennsylvaniaACLU (2003-5) • Stock Holdings – Johnson & Johnson (sold 2006), United Health (sold 2006)

3. Additional Disclaimers • Most medications discussed will be off-label • Talk to your doctor before making any medication changes • For professionals: always do your own research (and get and document second opinions!)

6. Today’s Agenda • Strategy • Evidence based medicine • What to do when the evidence isn’t there • Tactics • Medications that can hurt • Medications that can help

7. Evidence based medicine • Assessment and diagnosis should be based in objective, testable, reproducible science • Treatment should be for diseases, not symptoms • Treatment should be proven to be effective and safe for the diagnosis • Research design perils • The plural of “anecdote” is not “data” … and the plural of data is not proof!

8. Making due with limited evidence…

9. Rule out valid diagnoses / other causes • Symptom-targeted pharmacotherapy is inherently risky Investigate and rule out • Medical causes • Psychiatric causes • Psychosocial issues

10. Medicating the kid doesn’t fix bad environment, family dynamics, etc.

11. Clearly define the target behavior • “They were aggressive!” • What actually happened? • Duration, frequency and intensity? • Spontaneous, provoked, predictable? • Verbal, physical, both? • Do not ask: “Show me what happens when you get angry”

13. Start Low & Go Slow

14. Don’t just do something, stand there!

15. The most important step in pharmacotherapy is taking the medication • Right medication, right dose, right time, right route • Cost • Side effects • Complex regimen • Drug interactions

16. The human brain is very complicated

17. Well documented informed consent!

19. Medications One does not discover new lands without consenting to lose sight of the shore for a very long time. Andre Gide

20. Medications & Side Effects • Psychotropic medications = engineered to interfere with our brains • Common, inevitable, difficult to predict • Paradoxical reactions, too!

21. Common Patterns • Antipsychotics • Risperdal, Zyprexa, Abilify, Geodon, Seroquel, Clozapine, Haldol, Trilafon, Mellaril • Akathisia • Dyskinesias, dystonias and parkinsonism • Weight gain, high blood sugar, high cholesterol • Antidepressants • Prozac, Paxil, Effexor, Celexa, Lexapro, Luvox, Pristiq, Cymbalta • Activation/agitation • Withdrawal symptoms • Suicidality

22. Common Problems • Antiepileptic drugs • Keppra, Topamax, Tegretol, Trileptal • Increased irritability • Rash • Stimulants • Concerta, Ritalin, Adderall, Provigil, Dexedrine • Insomnia, activation, agitation • Psychosis

23. Common Patterns • Benzodiazepines • Klonopin, Ativan, Xanax, Valium • Paradoxical activation / agitation • Disinhibition • Dependence / withdrawal • Other medications I worry about • Steroids (e.g., prednisone) • Sleep medications (e.g., Ambien, Lunesta) • Antibiotics (e.g., Cipro, Bactrim, Levaquin)

24. Red Flags • Heavily advertised or marketed • New medication on the market • Herbal or natural medications*

25. What is actually used? Oswald & Sonenklar, J Child Adol Psychopharm 2007 p351 / Table 3

26. Standing or PRN? Good standing medicines Good PRN medicines Sedating antihistamines Adrenergic blockers Some antipsychotics Some benzodiazepines • Antidepressants • Anticonvulsants • Lithium • Antihypertensives • Antipsychotics

27. Risperidone (Risperdal) • Targets: Psychosis, Aggression / agitation, impulsivity, bipolar / mood instability, augment for depression or OCD • Dosing: 0.25-2 mg/dose, up to 6-8mg/day • Pros: FDA approved, strong evidence, PRN or standing, generic, liquid and ODT formulations • Cons: Metabolic side effects, some motor side effects • Why/when? First choice!

28. Antihypertensives • Propranolol (Inderal), clonidine (Catapres), guanfacine (Tenex) • Targets: Impulsive aggression, tics, hyperactivity, affective reactivity • Dosing: Varies by agent • Pros: Few major s/e, generic, unlikely to exacerbate behavior, standing or PRN (clonidine) • Cons: Hypotension, drug interactions (Inderal), rebound hypertension • Why/when? Very safe, trauma history, autism

29. Sedating Antihistamines • Hydroxyzine (Atarax, Vistaril), diphenhydramine (Benadryl) • Targets: Anxiety, acute agitation, sleep* • Dosing (PRN): 25-50 mg up to 4x/day • Pros: Rapid onset, good PRN, some evidence from peds emergency medicine • Cons: paradoxical agitation, hangover / anticholinergic fog, rebound insomnia • Why/when? Great PRN … hydroxyzine sometimes standing

30. Lithium (Eskalith, Lithobid) • Targets: Impulsivity, bipolar disorder / mood instability, depression, aggression • Dosing: 300-900 mg 2-3x/day, pill or elixir • Pros: Long safety record, generic, serum level for dosing, few drug interactions • Cons: Tremor, thirst, kidney/thyroid problems, not useful as PRN • Why/when? Major mood disturbance, impulsive/explosive aggression

32. AEDs / Mood Stabilizers • Valproic acid (Depakote), lamotrigine (Lamictal), carbamazepine (Tegretol), oxcarbazepine (Trileptal) • Targets: Impulsivity, impulsive anger, mood instability / bipolar mania • Dosing: varies (some need blood levels) • Pros: Some generic, titrate to blood level • Cons: Therapeutic drug monitoring / blood work, not a PRN, limited efficacy (?), rash / SJS • Why/when? Severe impulsivity / explosivity, bipolar disorder, seizures; favorites = VPA, Lamictal

33. Antidepressants • Prozac, Paxil, Zoloft, Luvox, Effexor, Wellbutrin, Remeron • Targets: Depression, anxiety, irritability, OCD, social anxiety, ADHD, maybe impulsivity • Dosing: Varies by agent (higher for OCD) • Pros: Many are generic, few long term s/e • Cons: activation/agitation, withdrawal, rapidly metabolized in kids, slow onset, no use as a PRN • Why/when? Obvious mood d/o or OCD; favorites = Celexa, Prozac

34. Olanzapine (Zyprexa) • Targets: Bipolar disorder, psychosis, severe impulsivity / agitation, augmentation for depression and maybe OCD • Dosing: 2.5 – 30 mg/day, preferably QHS • Pros: Very effective, rarely causes agitation, available as ODT and IM, great PRN • Cons: weight gain / metabolic side effects, hypotension (esp. with Ativan), expensive • Why/when? Mostly as a PRN, or patient has failed milder anti psychotics

36. Quetiapine (Seroquel) • Targets: Anxiety, bipolar / mood instability, psychosis, agitation • Dosing: 25-200 mg up to 3x/day • Pros: Good for anxiety / affective reactivity, well tolerated, standing or PRN • Cons: metabolic side effects, expensive, no IM dose • Why/when? Often a first choice

37. Ziprasidone (Geodon) • Antipsychotic + Serotonin Blocker • Targets: Agitation, mood instability / bipolar, psychosis • Dosing: 20-120 mg BID; 10-20 mg IM PRN • Pros: Well tolerated, minimal side effects • Cons: Not robustly effective, rare agitation, PO useless as PRN • Why/when? Too much weight gain with other antipsychotic

38. Aripiprazole (Abilify) • Antipsychotic + Serotonin Blocker • Targets: Bipolar, Psychosis, maybe acute agitation • Dosing: 2.5-30 mg, preferably once a day • Pros: FDA approved for kids, minimal metabolic side effects • Cons: expensive, frequent activation/agitation, over-marketted / overhyped • Why/when? Failed everything else, severe weight gain with other medicines, or outpt doctor request (not often)

39. Benzodiazepines • Lorazepam (Ativan), clonazepam (Klonopin) • Targets: agitation, anxiety • Dosing: 0.25-2 mg BID to QID • Pros: generic, mostly safe, good PRN or standing dose • Cons: paradoxical agitation, dependence, • Why/when? Severe anxiety with agitation (test doses before a standing dose)

40. Typical Antipsychotics • Haloperidol (Haldol), perphenazine, (Trilafon), chlorpromazine (Thorazine) • Targets: agitation, psychosis, impulsive aggression / anger, anxiety, bipolar, tics • Dosing: Varies • Pros: Effective, generic, FDA approved for kids (Thorazine and Haldol), good as PRN, PO or IM, long acting Haldol Dec • Cons: Many side effects (akathisia, TD) • Why/when? Probably not often enough…

41. Stimulants • Amphetamine/dextroamphetamine (Adderall), methylphenidate (Concerta, Ritalin) • Targets: Hyperactivity / ADHD, impulsivity • Dosing: Varies by pt and medication • Pros: Immediate onset / wears off by bedtime, long safety record, patch(!) • Cons: over-activation/agitation, insomnia, not for patients with heart disease • Why/when? Obvious ADHD

43. Thank you!Questions?