Psychotropic medication for people with autism spectrum disorders ucsd child psychiatry 032211 1 0 r

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UCSD Child Psychiatry March 22, 2011

Redacted for Posting personal and case material has been removed to respect the privacy of families ď‚ž If you notice something missing that was there during the actual talk and have a question, please contact Dr Feder at ď‚ž

Assistant Clinical Professor, Dept of Psychiatry, University of California at San Diego School of Medicine Director of Research, Graduate School, Interdisciplinary Council on Developmental and Learning Disorders

ICDL Graduate School –teaching, review of clinical write ups, travel and room for meetings, co-writing and running Southern California Institute NIMH/ Duke University – minimal – administrative time for pharmacogenetic research NIH R21 grant/ San Diego BRIDGE Collaborative – minimal – token honorarium for ongoing consultation and participation

DIR Broad – whole child, supports family  Welcoming – all about building love  Enriching – closeness can bring progress 

DIR in a nutshell Developmental levels – from regulation, to warm trust, and then a flow of enriching interactions  Individual Differences – sensory, motor, communication, visual-spatial, cognitive, etc.  Relationship Based – all about connecting, and making time with others for support and help 

    

1989 Magda Campbell: haloperidol helps social learning; others: methylphenidate causes side effects without benefit. 1990’s - 2006: treating target symptoms, based on responses in other conditions to medications; lots of use of neuroleptics for aggression, etc. 2004 Black Box warning for SSRIs in kids 2006 – Risperdal Early 2009 – Celexa ‘not working’ for OCD in ASD Late 2009 – Abilify Cochrane 2010 – SSRI’s not so good?

Evidenced Based Medicine Sackett, et. al. British Medical Journal 1996;312:71-72 (13 January)  “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.” 

EBM is a tricky combination: We need current best evidence, otherwise medical practice is out of date. ď‚ž We need good clinical expertise and judgment, for even excellent external evidence may be inapplicable to or inappropriate for an individual patient. ď‚ž

• • • • • • • • •

Diagnosis Target Symptoms Treatment Protocol Alternative Treatments Results of No Treatment Side Effects FDA Labeling: ‘experimental’ Consent & Assent Comments, Questions & Concerns: ‘track closely’


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Find a doctor you like and can work with Keep the doctor in the loop – doctor must have data Don’t overwhelm the doctor with data Doctors can be confused with terms like “biomedical” Respectfully offer resources – don’t expect your doctor to read a book for you, but do expect your doctor is interested in other opinions from other doctors

Most people consider meds because they feel stuck, maybe desperate  Emergencies: aggression, depression, others?  Lack of progress 

• •

What do we want for our children? The usual wish: a meaningful life (socially, emotionally, maybe cognitively)

Requires a plan, and medication alone is not a plan.

The Central Question ď‚ž

Are you trying to improve an appropriate situation or make up for a bad one?

Will they change my child’s brain and fix it?  Could they injure my child?  What should I expect? 

To avoid ‘losing time’ while pulling the program together  To ‘do as much as possible’  Awakenings – are we trying for a miracle? 

The Bottom Line: ď‚ž

medication probably does not treat core symptoms, but might make some target symptoms or co-occurring conditions better, creating more affective availability so that we can make progress, if you can avoid significant side effects.

Gridding Target Symptoms

Target symptoms  Prioritizing Symptoms  Core Symptoms 

Support regulation and co-regulation by treating, e.g., impulsivity, inattention, anxiety, rigid thinking, perseveration.  Widen tolerance of emotions so the person is less likely to become overwhelmed.  Treat co-occurring conditions, e.g., depression.  Might promote abstract reasoning and thinking. 

Specific Psychotropic Medications The following list and the information provided is not comprehensive  Start low, go slow  Expect worse side effects  Need adequate time for trials to succeed. 

Stimulants    

  

Methylphenidate: Ritalin, Concerta, Metadate, Methylin, Focalin Dextroamphetamine: Adderall, ‘mixed salts’, Vyvanse Slightly different mechanisms. Similar possible side effects: appetite, sleep, withdrawal, depressed mood, unstable mood, tics, obsessiveness, etc. Drug diversion vs. drug abuse risk ‘ADHD’ and ASD Often makes a good plan workable.

SSRIs   

One of many classes of ‘antidepressants’ Cochrane 2010 Can really help depressed mood, maybe anxiety, less likely obsessiveness (although works well for that for ‘neurotypicals’) Prozac (fluoxteine), Zoloft (sertraline), Paxil (paroxetine), Luvox (fluvoxamine), Celexa & Lexapro (citalopram). Similar possible side effects: ‘behavioral activation’, weight gain (and loss), mood instability, lower seizure threshold, etc. Black box warning about suicidal thinking vs. lower rates of actual suicide in people treated with SSRIs

Neuroleptics 

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Zyprexa (olanzapine), Risperdal (risperidone), Abilify (aripiprizole), Seroquel (quetiapine), Geodan (ziprasidone), Haldol (haloperidol), Mellaril (thioridizine), Thorazine (chlorpromazine) and others. Discovered while looking for cold pills, developed for symptoms of psychosis. Helping aggression, mood stability, and miracles? As well as tics, and adjunct for depression, perseveration, etc.? Side effects can include weight, lipid, and sugar issues, as well as seizures, fevers (NMS) and new abnormal movements (TD), stroke (elderly), cardiac Should we always consider neuroleptics?

AEDs        

Anti-Epileptic Drugs (aka anti-seizure medications) So many and all so different in character For seizures, and for mood stabilization Bimodal seizure risk in ASDs ‘Subclinical Seizures’ – 24 hr EEGs Might help other medications work better (stimulants, antidepressants) Combined pharmacology vs. polypharmacy Sudden stopping might make seizures more likely

Specific AEDs 

Depakote (valproic acid, valproate) – pretty reliable, easy to load, watch levels, platelets, bruising, liver, pancreas, carnitine, menstrual irregularities, weight, sedation. Problems when using with Lamictal Tegretol (carbemazepine) - ?reliable, watch levels, blood counts, EKG, lots of drug interactions, weight gain, sedation, rash Trileptal (oxycarbezine) – ‘Tegretol light’?; motor problems, electrolyte issues, rash?

More AEDs   

  

Keppra (levetiricetum) – easy to use, but does it work? Lamictal (lamotragine) – mood stability, ?better mood. Must go slow, and watch for rash Topamax (topiramate) – adjunct, may cause weight loss, loss of expressive language, usually need to go slow. Neurontin (gabapentin) – Does it work at all? Does it harm at all? Does help pain syndromes. Lyrica (pregabalin) – for pain in fibromyalgia, partial seizures Zarontin (ethosuccimide) – for partial/ absence seizures; liver issues

Steroids    

LKS variant theory – epileptic aphasia – 24 hr EEGs Regression at a young age Cell membrane stabilization in inflammation So many side effects: cushinoid, moon face, hump, central obesity, peripheral wasting, immune compromise, skin striations, mood instability including depression and hypomania Pulsed dosing regimens

Central Alpha Agonists Tenex & Intuniv (guanfacine), Catapres (clonidine)  Reducing ‘fight – flight’ sympathetic tone, which can help in many ways  Vigilance theory  Side effects can include sedation, dizziness, early tolerance  Mild medicine 

Other Commonly Considered Medications… 

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 

Straterra (atamoxetine) – for ADHD; may be as good as placebo, may act like an antidepressant (+/-) Wellbutrin (bupropion, etc.) Rozerem (ramelteon) – melatonin agonist SNRIs – Effexor (venlafaxine), Cymbalta (duloxetine), Remeron (mirtazepine), Serzone (nefazedone) Deseryl (trazodone) – antidepressant often used for sleep; cognitive side effects, priapism Buspar (an azaspirone) – mild, serotonergic cross reactions

More Others… 

Lithium – great mood stabilizer; antisuicidal; bipolar-ASD connection; levels, thyroid, kidney function Namenda (memantine) – Alzheimer’s med – ‘antagonist of the N-methylD-aspartic acid (NMDA) glutamate receptor, this drug was hypothesized to potentially modulate learning, block excessive glutamate effects that can include neuroinflammatory activity, and influence neuroglial activity in autism’

And the latest ideas:  

Oxytocin? Social connectedness in praries voles and mice, now tried in ASDs Medical marijuana? Can lead to poorer memory with hippocampal cell loss, poor initiative/ motivation, impaired motor control, and psychosis Any open label trial is likely to have some responders and lead to a new stream of people trying it out.

Meds that I often avoid…     

Paxil (paroxetine) - withdrawal Effexor (venlafaxine) - withdrawal Tegretol (carbemazepine) – hard to make it work Combo Depakote and Lamictal Tricyclics – Tofranil (imipramine), Norpramin (desipramine), Pamelor (nortriptyline); and, esp. good for typical OCD, Anafranil (clomipramine). Cardiac and blood pressure issues. Monoamine Oxidase Inhibitors – Nardil (phenelzine) , Parnate (tranylcypromine), Marplan (isocarboxazide), Emsam (selegiline) – can be useful although dietary, blood pressure drop and hypertensive crisis must be considered; lots of drug-drug interactions

Special Caution on Benzodiazepines! 

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Benzodiazepines – Valium (diazapam), Ativan (lorazepam), Xanax (alprazolam), Klonopin (clonazepam), and others Used so freely by many doctors and families Problems nearly always outweigh risks Addicting Destabilizing mood Interfere with learning Interfere with motor function Interfere with memory

Abnormal Involuntary Movement Scale (AIMS)

Look at the whole picture  Be careful with meds  Engage the Child 

Your Experiences?

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