Treatment Resistant Depression in Collabora2ve Care. An overview for Care Managers. April 25th, 2016 Gina Perez, MD

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Treatment Resistant Depression in Collabora2ve Care An overview for Care Managers April 25th, 2016 Gina Perez, MD

Gina Perez, MD Dr. Perez joined The Institute for Family Health in 2010, where she provides care within a multidisciplinary team, treating adult patients with various psychiatric disorders and developmental disabilities. In 2014 she became Upstate Regional Medical Director for Psychiatry. Dr. Perez remains active in medical education through the Mid-Hudson Family Practice Residency Program, serving as Chair of the Clinical Curriculum Committee and working closely with the residency training program to build innovative approaches to family practice resident education. Dr. Perez is a Psychiatric Consultant for the Depression Collaborative Care Program at Institute for Family Health.

Case: Mrs. Smith 52 year old female with current depression episode x 1 year Depression collabora2ve care model x 5 months Ini2al PHQ- 9 was 24 five months ago Current PHQ- 9 is 20 Mul2ple medical issues: Diabetes, Hypertension, Hypothyroidism, weight gain of 30 pounds in past year Work stress, increasing financial burden with 2 children in college Past trauma in teens, experiencing nightmares x 2 months Increased irritability at work x 2 months Alcohol use 2 drinks nightly to help with sleep Lexapro 10mg daily x 1 year Past failed trials with fluoxe2ne, paroxe2ne Cogni2ve behavioral therapy, misses 40% of the 2me

Is this pa2ent Treatment Resistant?

Depression & Treatment Response Life2me prevalence 13% Second most costly disease in the US 1/3 of pa2ents with depression fully respond to an2depressants 30-40% of pa2ents with depression do not respond adequately Remission = no symptoms (Hamilton Depression Ra2ng Scale Score less than 7) Case Challenge: A 35- Year Old Man with Depressed Mood, Insomnia, and Suicidal IdeaBon. Hashmi, A; Khawaja, I; Shah, A. Psychiatric Annals, Vol 46 (4), 2016 Novel Approaches for Managing treatment- Resistant depression. Shah, A. Psychiatric Annals, Vol 46 (4), 2016

Treatment Resistant Depression 2 or more failed an2depressant treatments (from different pharmacologic classes) of adequate dose and dura2on CogniBve behavioural therapy as an adjunct to pharmacotherapy for primary care based pabents with treatment resistant depression: results of the CoBalT randomised controlled trial. Wiles, Nicola et al. The Lancet, Volume 381, Issue 9864, 375 384 RepeBBve Transcranial MagneBc SBmulaBon for Treatment- Resistant Depression: A SystemaBc Review and Meta- Analysis. Gaynes, B et al. J Clin Psychiatry 2014;75(5):477-489

Who Is At Risk?

Case: Mrs. Smith More complicated than just depression Many factors Possibly meets criteria for treatment resistant depression if her med trials were adequate dose and dura2on Where do we go from here?

Iden2fy the problems Map them out Psychiatric symptoms/diagnoses Other medical issues Stressors that may be impac2ng symptoms

Case: Mrs. Smith Depression Alcohol use Hypothyroidism Financial stress Hypertension Anger Job Stress PTSD Diabetes

Correct Diagnosis?

Case: Mrs. Smith Depression Alcohol use Hypothyroidism Financial stress Hypertension Anger Job Stress PTSD Diabetes

Depression Start of this depression episode? Dura2on of this episode? # of life2me episodes Typical presenta2on for depression? Rescreen for bipolar Rescreen for psycho2c symptoms Rescreen for substance misuse Check urine drug screen Consider repeat physical and labs

DSM- V Criteria for Major Depression Episode (MDE) 5/9 symptoms *1 of which must be Depressed mood or Anhedonia *Anhedonia *Depressed Mood Recurrent Thoughts of Death or Suicide Poor ConcentraBon Psychomotor RetardaBon or AgitaBon Sleep Disturbance App or Weight Changes Feelings of Worthlessness or Excessive Guilt

Major Depressive Episode Symptoms Gina Perez, MD

Big Picture Concept In order to make a diagnosis of a mood disorder, take into account all of the mood episodes a person has experienced in his/her life Mood Episode + Mood Episode + =Mood Disorder

Mood Episodes Manic Hypomanic Euthymic Persistent Dep d/o Major depressive

Adding up Mood Episodes Mood Episode Major Depressive Disorder Persistent Dep D/o (2 years) Bipolar Disorder Type I Bipolar Disorder Type II Cyclothymia (2 years) Manic (1 week+) Hypomanic (4 days+) Euthymic Per dep d/o (2yrs) Depressive symptoms Major Depressive (2wks)

Major Depressive Episodes can be a part of! Major Depressive Disorder! Bipolar Disorder (Types I & II)! Schizoaffec2ve D/O (BP & Dep type)

Manic Episode DSM- V Criteria At Least 1 Week Dura2on Elevated mood (+3 other sx) or Irritable mood (+4 other sx) Addi2onal Symptoms: Decreased NEED for sleep Grandiosity Pressured speech Increased goal directed ac2vity Flight of Ideas/Racing thoughts Distrac2bility Risky Behavior

Gina Perez, MD Manic Episode Symptoms

When you see a depressed pa2ent, Always screen for past episodes of Mania

Bipolar Depression V. Major Depressive Disorder (Unipolar Depression) Bipolar Depression is a DIFFERENT than Major Depressive Disorder Treatment for Bipolar Depression is NOT the same Bipolar Depression treatment: Que2apine, Zyprexa/Prozac combo pill, Lurasidone (Latuda), Lithium, Lamotrigine, Depakote Do not give an5depressants for Bipolar Depression An2depressants are harmful to pa2ents with Bipolar Depression

Sample screening ques2ons for past episodes of mania In the past, has there ever been a period of 2me in which you did not NEED to sleep for a few days? had excessive energy x several days for no clear reason? felt elated or overly irritable for several days, for no clear reason? people thought your were using drugs when you weren t? If they answer yes, clarify 2ming, dura2on Then screen for other symptoms of mania within that same 5me period Always make sure that you and the pa2ent are talking about the same 2me period & dura2on for symptoms

Rescreen for psychosis Psychosis in general means a loss with reality in some way Specific psycho2c symptoms can include: hallucina2ons (sensory percep2on that isn t there) delusion (false fixed belief) disorganized thoughts (tangen2al, FOI, loose associa2ons) disorganized behavior

When someone has an episode at the top or bopom of the mood scale (i.e., Mania or MDE), the person can experience psycho2c features along with the mood episode This does not mean that the primary problem is a psycho2c disorder It does mean that this is a more serious mood episode ~16-54% of pa2ents with MDE may get psycho2c features

Schizoaffec2ve Disorder Bipolar Type & Depressed Type Presence of mood episodes Presence of psychosis, that extends beyond the mood episodes by at least 2 weeks

Is there Substance Misuse? Rule out substance abuse causing symptoms Rule out substance withdrawal Rule out designer drugs that may be missed on urine drug screens Rule out misuse of supplements

Is this really Major Depressive Disorder? Or is it another medial problem/ medica2on side effect presen2ng like depression?

Differen2al Diagnosis of Mood Symptoms Hypo/hyperthyroidism Diabetes mellitus Cushing s disease Addison s disease Parathyroid dysfunc2on Parkinson s Disease Hun2ngton s Disease Trauma2c Brain Injury Demen2a Mul2ple Sclerosis Stroke Electrolyte disturbance Renal failure Vitamin deficiencies/excesses Wilson s Environmental toxins Heavy metal exposure Irritable bowel Chronic pancrea22s Crohn s disease Cirrhosis Hepa2c encephalopathy Myocardial infarc2on CABG Cardiomyopathies COPD Sleep apnea Chronic Pain Pancrea2c carcinomas Brain tumors Toxoplasmosis Anemia Paraneoplas2c effects lung cancer Lupus Rheumatoid arthri2s Fibromyalgia HIV Lyme s Disease Mononucleosis

Differen2al Diagnosis of Mood Symptoms Steroids Chan2x Seizure medica2ons An2depressants can destabilize mood in bipolar disorder Interferon B- blockers Accutane Calcium channel blockers Alcohol Barbiturates Sta2ns Zovirax Some an2convulsants Some an2- parkinson s drugs Benzodiazepines Hormone altering drugs S2mulants Proton pump inhibitors and h- 2 blockers An2cholinergic drugs for GI

Differen2al Diagnosis of Mood Symptoms Depression Care Managers can help Pay apen2on to the 2ming and dura2on of symptoms Does the 2ming of depression episode coincide with medica2ons? Over the counter supplements? Stopping a certain medica2on?

Think about the pa2ent s presenta2on Is this how major depression typically presents? Review epidemiology of depression

Depression Epidemiology: Age of Onset

Aser a single major depressive episode the risk of a second episode is around 50% Aser a third episode, the risk of a fourth is about 90% Each new episode occurs sooner and more abruptly with new and more severe symptoms

The longer depression has been present, the worse the prognosis 50% chance of remission of depression that has been present for 3-6 months Only a 5% likelihood of remission within the next 6 months of a depression that has been present for 2 years 12% of pa2ents with acute major depression do not recover aser 5 years

Are there Confounding Diagnoses?

Psychiatric Comorbidi2es Very common to have more than one psychiatric diagnosis Anxiety disorders Substance misuse disorders Cogni2ve Disorders Impulse control disorders ADHD Ea2ng Disorder PTSD

Psychiatric Comorbidi2es Think about how the team will address each comorbid problem Medica2on Therapy modality Non- medica2on strategies Lifestyle changes Specialized treatment (outpa2ent substance abuse program, ea2ng disorder group, anxiety management group, par2al program) Are there ways that we can tackle more than one problem with a par2cular treatment?

How are the problems connected? Depression Alcohol use hypothyroidism Financial stress Hypertension Anger Job Stress PTSD Diabetes

How does treatment of one problem impact another problem? SSRI & Therapy exercise Naltrexone Synthroid Affordable meds? Metoprolol Exercise/Weight management Therapy Exercise Therapy Prazosin SSRI Therapy Melormin Diet modificabon Exercise/wt mngmt

Systema2cally Track Depression Symptoms PHQ- 9 scale Check this at every visit with pa2ents Allows for beper monitoring of progress

Systema2cally Track Depression Medica2on Trials Make ongoing list of medica2on trials Medica2on Max dose Dura2on on max dose (adequate? 6 weeks?) Was pa2ent adherent to medica2on Side effects Outcome (lowest PHQ- 9 score, recurrent episodes even on medica2on, par2al response) Keep a running list of what has been tried

Example Medica2on Trials Fluoxe2ne (prozac) x 2 years from 2010-2012, adherent, max dose 80mg x 4 months, no side effects, no benefit for depression, helpful for anxiety Paroxe2ne (paxil) x 1 weeks, 2013, too seda2ng/ increased appe2te, stopped on her own, not helpful for depression or anxiety (never took it past 1 week) Venlafaxine (effexor) x 2 weeks, 2009, doesn t recall dose, made me feel like I drank 100 red bulls, stopped on her own, felt awful aser stopping it ( brain zaps )

An2depressant Op2ons Selec2ve Serotonin Reuptake Inhibitors (SSRIs) Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) Mirtazapine Dopamine/Norepinephrine Reuptake Inhibitors (bupropion) Trazodone Tricyclic An2depressants (TCA) Monoamine Oxidase Inhibitors (MAOIs) Other (Vor2oxe2ne, Vilazodone)

An2depressant chart Neurotransmitter (Nt) or receptor (R) MAOI TCA SSRI bupropion venlafaxine duloxetine trazodone mirtazapine Serotonin Nt + + + + + + + 5HT-1 receptor + + + + + + + 5HT-2 receptor + + + + + X X 5HT-3 receptor + + + + + + X alpha-2 R alpha-1 R X X X Dopamine Nt + + Norepinephrine Nt + + + + + + Histamine-1 R X X X X Muscarinic (M-1) R X X X

Par2al response to an2depressant? Assess for adherence Consider switch to new agent Consider augmenta2on with another agent with different mechanism of ac2on (paying apen2on to how they overlap in func2on/ mechanism) Be mindful of drug- drug interac2ons Avoid polypharmacy when possible

Depression Medica2on Augmenta2on SSRI & Bupropion Mirtazapine & Buproprion An2depressant + Lithium An2depressant + Thyroid (low dose) SSRI + S2mulant An2depressant + Atypical An2psycho2c An2depressant + L- Methylfolate An2depressant + Modafinil (novel s2mulant medica2on)? Case Challenge: A 35- Year Old Man with Depressed Mood, Insomnia, and Suicidal IdeaBon. Hashmi, A; Khawaja, I; Shah, A. Psychiatric Annals, Vol 46 (4), 2016

Psychodynamic Cogni2ve Behavioral Therapy Interpersonal Behavioral Ac2va2on EMDR Solu2on- focused Mo2va2onal Problem Solving Therapy

Psychotherapies Is the pa2ent engaged in therapy? Barriers to therapy Help psychiatric provider decipher when there is an underlying emo2onal conflict/ stressor that will be best addressed in therapy, versus medica2on management

General Non- Medica2on Strategies to Promote Recovery Not as sole strategy, but use these techniques to augment therapy & medica2on Track how the pa2ent feels when engaged in these ac2vi2es Physical Exercise, Yoga Medita2on Healthy ea2ng Sleep hygiene Social engagement Management of other medical condi2ons Light Box Therapy Limit alcohol

Other Considera2ons (aser referral to psychiatry) Electroconvulsive Therapy (most effec2ve treatment for severe depression) Transcranial Magne2c S2mula2on Deep Brain S2mula2on Vagus Nerve S2mula2on Ketamine? (N- methyl- D- aspartate R antagonist) An2- inflammatory agents? (celecoxib, inflimab) S- adenosyl methionine Modafinil (novel s2mulant medica2on)

gperez@ins2tute.org