Practical Psychopharmacology for More Complex Mental Health Presentations

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MINISTRY OF CHILDREN AND YOUTH SERVICES Practical Psychopharmacology for More Complex Mental Health Presentations Part 2: Antipsychotics & Mood Stabilizers Dr. Ajit Ninan & Joel Lamoure 1

: Who are we? Our Mission is to provide specialized, traumaresponsive mental health and developmental services to achieve the best possible outcomes for Ontario s children and youth. Services Assessment Consultation Treatment Research Education Our services are: Accessible Inclusive Individualized Evidence-Informed

Conflict of Interest Disclosures Ajit Ninan and Joel Lamoure I have not had in the past 3 years, a financial interest, arrangement or affiliation with one or more organizations that could be perceived as a direct or indirect conflict of interest in the content of this presentation.

Disclaimer The content in this presentation is for personal study and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. 4

Practical Psychopharmacology for More Complex Mental Health Presentations: A 3 part series Part 1: Stimulants (view http://www.cpri.ca/index.php/workshop/26/) Part 2: Antipsychotics and Mood Stabilizers (Jan 31, 2018) Today Part 3: Anti-Depressants/Anti-Anxiety Medications (April 11, 2018) 5

Objectives By the end of this presentation, participants will be able to Identify why an Antipsychotic/mood stabilizer is prescribed (including off label prescriptions), and how they work List commonly prescribed antipsychotics/mood stabilizers, factors associated with dosing Describe the safety profile of antipsychotics/mood stabilizers, including side effects, interactions, risk factors, and monitoring Describe the process of selecting an antipsychotic/mood stabilizer for a young person with a complex presentation (Learning through Case Study) 6

BRIEF OVERVIEW: ANTIPSYCHOTICS & MOOD STABILIZERS 7

Diagnosis vs. Symptoms

Overview: Standard Definitions Mood Stabilizers Medicines used in the treatment of Bipolar disorder Antipsychotics Medicines used to relieve symptoms of psychosis (delusions, hallucinations) Second generation: atypical First generation: typical Sources: https://www.camh.ca/en/education/about/camh_publications/documents/flat_pdfs/upm_mood_stabilizers.pdf http://www.camh.ca/en/hospital/health_information/a_z_mental_health_and_addiction_information/antipsychotic_medicati on/pages/antipsychotic_medication.aspx 9

Medications: Mood Stabilizers Divalproex Lamotrigine Lithium Carbamazepine Topiramate Pregabalin Gabapentin https://commons.wikimedia.org/wiki/file:lamictal_25mg.jpg

Medications: Antipsychotics (atypical) Olanzapine Quetiapine Risperidone Paliperidone Lurasidone Ziprasidone Asenapine Clozapine Aripiprazole https://c1.staticflickr.com/9/8382/8579826302_6bd84aa54 0.jpg https://commons.wikimedia.org/wiki/file:ri sperdal_tablets.jpg

Basics of Therapeutics Goals of therapy: Minimizing signs and symptoms Maximizing quality of life and ability to function within society (functionality) Achieving remission Preventing relapse Pharmacotherapy should be individualized as response to antipsychotics and mood stabilizers is highly client variable Individuals will have different symptom control at different doses depending on a variety of individualized factors Gray J. Therapeutic Choices (5 th edition). Toronto, ON: Canadian Pharmacists Association; 2008; Addington D et al. Can J Psychiatry 2005; 50(Suppl 1):1S-56S.

https://commons.wikimedia.org/wiki/file:neuronal_signal_transmission.gif HOW DO ANTIPSYCHOTICS AND MOOD STABILIZERS WORK? 13

Neurotransmitters Involved in Regulating Mood Norepinephrine Serotonin Energy Interest Motivation Anxiety Irritability Mood, emotion, cognitive function Sex Appetite Aggression Impulsivity Drive Dopamine Others Adapted from Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. Cambridge, UK: Cambridge University Press; 2000:152.

Atypical Antipsychotics and Affinities Gray J. Therapeutic Choices (5 th edition). Toronto, ON: Canadian Pharmacists Association; 2008; Addington D et al. Can J Psychiatry 2005; 50(Suppl 1):1S-56S.

Atypical Antipsychotics and Cognition 16

A Note About Mood Stabilizers neurotransmitters vs gene expression vs intracellular transmission 17

Learning Through. HOW IS AN ANTIPSYCHOTIC / MOOD STABILIZER CHOSEN? 18

CASE STUDY 1 19

Case Study Time 1 10 y/o African Canadian boy, Trevor Extensive history of disruptive behaviours, physical aggression, frequent states of agitation and irritability School suspensions due to outbursts Previously diagnosed with ADHD Recent tele-psychiatry consult suggested a diagnosis of Disruptive Mood Dysregulation Disorder ADHD was well treated with a long acting stimulant medicine Previously prescribed fluoxetine 20 mg to treat anxiety His pediatrician started risperidone 0.25 mg twice daily. 20

Case Study Time 2 After one week, risperidone titrated to 0.5 mg twice daily ; eventually to 1 mg twice daily At this dose, his mother expressed concern that he appeared to have some strange movements of his fingers and toes that he didn't appear aware of The pediatrician feels perplexed on how to manage this. 21

CAMESA Guideline A practical tool for metabolic monitoring of children and youth treated with second-generation antipsychotics 22

CASE STUDY 2 23

Case Study Time 1 16 y/o Caucasian male, Dale One year history of regular THC use (several times per week) Develops symptoms of bizarre delusions, auditory hallucinations, disorganized thinking and behaviours Withdrawing from family and peer interactions and his grades have deteriorated significantly Demonstrated paranoia and is highly reluctant to leave the home Father had been diagnosed with schizophrenia at the age of 25 and subsequently became divorced from his mother Dale was hospitalized and placed on olanzapine, titrated up to 10 mg once daily with a good response and tolerated well He was discharged with follow up care with his family physician until a psychiatrist was available One week after discharge he began to deteriorate and was brought into the family physician with florid psychosis. 24

Case Study Time 2 After interventions were made, a positive response was observed In one month's time, noted to have gained 8 kg (17 lbs) His mother described extensive carbohydrate craving that had now become a power struggle The physician reviewed what options to consider. 25

Comparison of Side Effects EPS Metabolic/ Weight Gain Sexual side effects Sedation Insomnia Cardiac risk Clozapine - ++++ - ++++ - ++ Olanzapine +- ++++ - ++ - - Risperidone + +- ++ ++ +- - Quetiapine - + - ++ +- - Ziprasidone +- - - +- ++ +- Bezchlibnyk-Butler KZ, Jeffries JJ (eds.). Clinical Handbook of Psychotropic Drugs (17 th edition). Toronto, ON: Hogrefe & Huber Publishing; 2007.

Antipsychotic Issues: Cardiovascular complications Neuromuscular concerns Endocrine changes Weight gain Elevated risk of developing diabetes mellitus Diabetic ketoacidosis Metabolic syndrome

The ADA-APA Consensus Guidelines for Monitoring Physical Health Parameters in patients on atypical antipsychotic agents. 9-11 Baseline 4 Weeks 8 Weeks 12 Weeks Annually Personal family history 9 X X Weight (BMI) 9 Overweight (25.0-29.9) 9 Obese (>30.0) 9 X X X X Morbidly Obese (>= 40.0) Waist circumference 9 (<40 in males, <35 in females) 10 X X Blood pressure 9 X X X Fasting plasma glucose 11 X X X Fasting lipid profile 9 Targets: Total cholesterol (<5. 2 mmol/l) 10 HDL (>1.04 mmol/l ) 10 LDL (<2.59 mmol/l) 10 TG (<3.89 mmol/l) 10 9. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601. 10. Adult Treatment Panel. JAMA. 2001;285(19):2486-97. 11. American Diabetes Association. Standards of medical care in diabetes 2007. Diabetes Care. 2007; 30(suppl 1):S4-S41. X X 28

Potential Interventions Consideration of metabolic risk in initial antipsychotic choice Patient, family and caregiver education on metabolic side effects Baseline screening and regular monitoring (more often initially and for patients at high risk) With significant weight gain/metabolic disturbance: review all medications (physical and psychiatric) Stopping or switching medication considered if metabolic problems develop in close temporal relationship to starting a new antipsychotic Lifestyle counselling Referral for structured lifestyle interventions If unsuccessful, consultation and adjunctive pharmacotherapy considered Adapted from: Faulkner G, Cohn T. Can J Psychiatry 2006; 51(8):502-11.

CASE STUDY 3 30

Case Study Time 1 Jill, 14y/o Asian female Diagnosis of bipolar disorder, existing predominantly in the depressed phase impacts her ability to socially engage and function at school History of eczema (flares under stress) Divalproex for six months 4 weeks ago: added lamotrigine Other concurrent medications: daily multivitamins St. John s Wort (as an herbal supplement to help her depressed mood) hydrocortisone cream, moisturizers (for eczema) oral contraceptive Lamotrigine titrated up 25mg every two weeks Started to experience a red, warm, burning rash Started on her torso and has now spread to her mouth and is blistering. Image: https://thumbs.dreamstime.com 31

Case Study Time 2 After stopping the lamotrigine, the rash started to subside over a few weeks The psychiatrist collaborates with the pharmacist to look at next steps therapeutically and how the lamotrigine increase could have caused this reaction, as it was increased very slowly. Image: https://thumbs.dreamstime.com 32

Psychosocial Interventions for Maintenance Therapy Psychoeducation-Individual or Group or Caregiver Collaborative Chronic Care Cognitive Behavioural Therapy Family Focused Therapy Interpersonal and Social Rhythm Therapy 33

Gold Standards- Pharmacotherapy Bipolar Pharmacotherapy Acute Manic Episode Lithium, divalproex, olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, asenapine, brexpiprazole (USA) Appropriately taper antidepressants to off Acute Major Depressive Episode Lithium, lamotrigine (rapid cycling), quetiapine Do not use antidepressants as monotherapy Maintenance treatment Lithium, lamotrigine (limited efficacy in preventing mania), divalproex (mixed states), olanzapine, quetiapine, risperidone LAI, aripiprazole (and LAI), brexpiprazole (USA), asenapine, augmentation Primeau 2013, CANMAT guidelines 2007-2012, Stephen Stahl, Depression and Bipolar Disorders

COMMUNICATING WITH CHILDREN, YOUTH, FAMILIES 35

Premises of Pharmaceutical Care: TAIDCC T Therapeutic A Allergies/ Accurate? I Interactions? D Duplications of therapy? C Compliance/change? C Cost/Coverage? 36

Dis-ease within the Disease 37

Key Takeaways There are many medical and practical considerations that are considered in the selection of interventions Diagnosis and treatment is a bio-psycho-social and family/client centered process that involves getting: The right intervention at the right time to the right person for the right condition with a minimum of side effects. Root cause trauma and history factors into treatment, which may combine therapeutic strategies 38

Side Effects & Monitoring Risk/Benefit Ratio Resources from Improving Safety with Psychotropic Medications (Archived Webinar) http://www.cpri.ca/professionals/education/webinars/2016-2017- webinars/ Resources for Professionals: Psychotropic Medication Monitoring Checklists Publications http://www.cpri.ca/professionals/education/pmm-ed/ Resources for Families: Psychotropic Medication Organizer Podcast http://www.cpri.ca/families/resources/pmm-ed/ 39

Resources CANMAT (Canadian Network for Mood and Anxiety Treatments) http://www.canmat.org/ Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children http://camesaguideline.org/ Kids Help Phone Canada https://kidshelpphone.ca/ 40

QUESTIONS 41