Schizophrenia in Teenagers and Young
Adults
From the Johns Hopkins Clinical Schizophrenia Program:
Russell L. Margolis, M.D.
Krista Baker, LCPC
Tom Sedlak, M.D., Ph.D.
For information about clinical services, contact Krista
Baker, 410-550-0137
NAMI Maryland Conference October 18, 2013F
Pharmacological strategies for early
stages of schizophrenia
Russell L. Margolis, M.D.
Johns Hopkins Clinical Schizophrenia Program
NAMI Maryland Conference October 18, 2013
Disclosures
Drs. Margolis and Sedlak are salaried employee of Johns Hopkins
University; Ms. Baker of Johns Hopkins Bayview Medical Center:
We are beholden to many who influence us:
Dr Ray DePaulo
Dr. Rothman
Our Boss; chair of The Dean
Psychiatry at JHU
Johns Hopkins
(watching over us
from above)
Michael Bloomberg
(watching over us from NY)
Also, for Dr. Margolis, and of no obvious direct relevance:
• cells licensed to Merck
• Huntington’s disease clinical trials funded by Pfizer/Forest/Medivation/Prana/Neurocrine
• Funding from the NIH, Cure Huntington’s Disease Initiative, Hereditary Disease Foundation
Our talks, or may not, discuss off-label use of pharmaceutical agents. It is not
possible to predict ahead of time.
The situation:
1. Person recently diagnosed with schizophrenia
2. Returning to outpatient care after hospitalization
3. Doing much better on medicines; not necessarily
fully recovered symptomatically or functionally
Need for continued medicine: little doubt
104 patients who responded to treatment after first episode of illness (Robinson et
al, 1999): Total relapse rate by the end of 5 years: 82%
Predictors of relapse
Social or academic difficulties prior to illness onset: 1.5 x higher
Not taking medicines: ~5x higher
Non-predictors: sex, scz vs scz-aff, obstetrical complications, duration of psychotic
symptoms, type of symptoms at baseline, psychotic response to methylphenidate, EPS,
growth hormone, homovanillic acid levels, brain volume measures, neuropsychological
measures, time until treatment response, extent of residual symptoms
Nearly identical findings in a recent study of 140 patients (Caseiro et al, 2012)
Studies in which patients deliberately taken off medicines after first episode: 8094% relapse rate within 2-3 years (e.g., Emsley et al, 2012; Zipursky et al, 2013).
Choice of medicines: Currently available
antipsychotics in U.S.
Typical (first generation)
antipsychotics
Atypical (second generation)
antipsychotics (
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haloperidol (Haldol)*
fluphenazine (Prolixin)*
chlorpromazine (Thorazine)
droperidol (Inapsine)
loxapine (Loxitane)
mesoridazine (Serentil)
molindone (Moban)
pimozide (Orap) (off-label)
perphenazine (Trilafon)
thioridazine (Mellaril)
thiothixene (Navane)
trifluoperazine (Stelazine)
aripiprazole (Abilify)*
clozapine (Clozaril)
olanzapine (Zyprexa)*
quetiapine (Seroquel)
risperidone (Resperidal)*
ziprasidone (Geodon)
paliperidone (Invega)*
iloperidone (Fanapt)
asenapine (Saphris)
lorasidone (Latuda)
* Long acting injectable forms also available
Which to choose?
1. Efficacy: Conflicting evidence. Olanzapine a little better?
2. Minimize side effects
Movement disorders: older agents, but also newer agents
Metabolic syndrome: marked variation among meds
Newcomer, 2005
3. Cost: 1 month haloperidol $4, lurasidone $165-379 on-line
Clozapine as third line agent
Clozapine most effective agent for patients who fail other antipsychotics
Current conventional wisdom: Use after two good trials of another agent
Example: Agid et al, 2011
244 individuals with first episode psychosis (average age ~22)
1st trial : up to three months of increasing doses of risperidone or olanzapine
75% responded (olanzapine a little better)
2nd trial: Nonresponders to first trial put on the other medicine
17% responded
3rd trial: nonresponders to 2nd trial put on clozapine:
75% responded
Should clozapine be a first or second line treatment option?
Problem is logistics (weekly blood draw) and side effects: agranulocytosis,
myocarditis, sialorrhea, tachycardia, myoclonus, seizures, constipation, etc
Non-adherence to antipsychotics treatment in
schizophrenia : Common!!!
sampling of the literature
Cramer & Rosenheck, 1998
Nose et al, 2003
Lacro et al, 2002
rate
60%
30%
41-50%
comment
Review, old studies
Review
Review
Ascher-Svanum et at, 2006
Tiihonen et al, 2011
19%
54%
Large single study
Finnish, rate one month
after discharge from
first hospitalization
Best predictor of nonadherence: Nonadherence!
Ascher-Svanum et al, 2006
1579 patients in 3 year prospective naturalistic study taking oral antipsychotics
Prior to enrollment
Odds ratio (Confidence Interval)
Non-adherence in past 6 months
4.1 (3.1-5.6)
Illicit drug use
1.8 (1.1-3.0)
Alcohol use
1.6 (1.1-2.2)
Antidepressant use
1.4 (1.1-1.9)
Medicine-related cognitive concerns 1.3 (1.1-1.5)
Prior adherence had a 79% level of accuracy in predicting future adherence
Other factors: depressive symptoms, violence/arrests, victimization, subjective
medicine related adverse events , cognitive impairment
Multiple other studies confirm that past nonadherence predicts future nonadherence
Conceptualization of non-adherence
Patient-centered factors
Passive:
forgetfulness/confusion
apathy
Active:
avoidance of side effects
belief that medicines are not helpful
general mistrust of treatment
belief that can stop meds once doing better
fear of stigma
Environmental factors
Cost
Access
From Beck et al 2011, others
General Psychotherapeutic Strategies
1. Explore prior experiences with antipsychotics:
avoid agents with objective or perceived negatives
2. Persuasion about both perceived concerns and perceived benefits
3. A focus on illness insight may not be necessary or useful
4. Improving general attitude toward pharmacotherapy
Other conditions require chronic treatment: e.g, asthma, etc
Antipsychotics used for many purposes
5. Therapeutic relationship—requires stability of treatment team
Specific adherence strategies
1. Medicine supervision
Caregiver supervision
Mobile treatment
Assisted living environment
Capitation programs
2. Medicine strategies
Specific adherence rating scales
Pill counts
Electronic monitoring
Automated reminder systems
Choose medicine with once daily dosing
Avoid excessively high doses
Davis and Chen, 2004
Treat metabolic side effects
Wu et al, JAMA, 2008
128 first-episode patients with weight gain on an antipsychotic
Randomized to 750 mg/day metformin, life style intervention ( education, diet,
exercise), both, or neither and followed for 12 weeks;
Similar results for other metabolic measures
Use long-acting injectables:
Haloperidol and fluphenazine decanoate
Risperidone (Consta)
Olanzapine pamoate (Relprevv)
Paliperidone palmitate (Sustenna)
Aripiprazole (Abilify Maintena)
Increase adherence to 60-80%, 2-3x better than pills
Dosing every 2-4 weeks depending on the medicine
Summary
Medicines needed for treating first episode psychosis
Multiple choices of medicines
olanzapine may be best of newer agents
clozapine is valuable as 3rd line, earlier?
Side effects problematic: can be managed
Adherence can be increased: therapeutic alliance, new
home, once daily dosing, treat side effects, avoid
overly high doses
Krista Baker, LCPC
Clinical Supervisor
Early Psychosis Intervention Clinic
Johns Hopkins Bayview Medical Center
No relevant disclosures
Where do I start?
 The importance of finding the right OP TEAM-need
this for referrals to higher levels of care/continuity and
coordination of care. Where can I get information?
 Getting an accurate diagnosis is so important to guide
medication decisions
 Determine the appropriate level of care
 How does insurance or lack of insurance affect my
decisions?
ALPHABET SOUP
Typical First Sessions in OP
 Complete Diagnostic and Psychosocial
Evaluation
 Meet psychiatrist and discuss medication and
current side effects
 Elicit concerns from patients and families (ex:
recent dangerous behavior, substance abuse,
acute symptoms, self-care deficit)
 Assess current level of functioning and need for
referrals for additional services
Psycho-Social
Psychosocial
Interventions
Interventions
 Support & Psycho-education
 Creating a Comfortable
Environment
 Social Skills/Social Contact
 Relationship Building
 Short and Long Term Goal
Setting
 Relaxation Techniques
 Nutritional Information/Referral
 Discussing Medication
Adherence
Social
Skills
Training
 Discuss skills and identify where
to start (most impairing)
 Discuss steps in achieving goals
 Model and review
 Provide positive and corrective
feedback when necessary
 Find ways to have patient practice
skill (PRP, home, hospital setting,
online game)
 Provide behavioral reinforcement
for successes
 Establishing and maintaining
social contact is a necessity
 Client centered goals are the key
Cognitive
Behavior
Therapy
Rationale
to this treatment
 Can not proceed until the client
identifies goals
 CBT for SZ is not a tx to
eliminate symptoms but rather
to deal with psychosis as a block
to their goals (ex: I want a job in
Hawaii but can’t get out of bed)match the goal with specific
interventions-this will more
likely improve adherence
 Goals need to be revisited at
every session
 Continued focus on recognizing and

Cognitive
Behavioral
Therapy
Interventions
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reducing negative symptoms
Reality or hypothesis testing-what
evidence do you have to substantiate
that? Pie charts….etc…
“Floating an idea”
Cognitive Restructuring
Help patient to develop coping
strategies for difficult symptoms (look/
point/name, graded task assignment,
bring on sx’s to reinforce you get
through them
Normalizing symptoms and behaviors
(a lot of people going through what
your going through would not be able
to sleep or feel nervous)
Psychiatric Rehabilitation Programs
(PRP)
 Provide daily structure through intensive onsite
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services
Supported housing services
Supported employment services vs. competitive
employment
Rehabilitation coordination (bring together all
services and supports-family, medical, psychiatric,
residential and vocational)
Provides offsite services when necessary
Other treatments to consider…
 Cognitive Remediation
 Multi-Family Groups
 Participation in NAMI peer to peer or family to family
 Referral to a wellness program for exercise
 Occupational Therapy
 Referral for a nutritionist
 Residential Treatment Facilities
Summary
 There is no right or wrong combination-IT’S
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INDIVIDUAL SPECIFIC!
Communication between providers on a regular basis
is mandatory for effective treatment
If unsure, get a second opinion
Family members should get support
It’s the big picture that counts-don’t let set backs
discourage you
Krista Baker, LCPC
Clinical Supervisor
Early Psychosis Intervention Clinic (EPIC)
Johns Hopkins Bayview Medical Center
kbaker1@jhmi.edu
Marijuana — Its Impact on the Patient with
Psychotic Symptoms
Thomas Sedlak, MD, PhD
Schizophrenia Center
Schizophrenia Consultation Clinic
Johns Hopkins School of Medicine
Disclosures:
• No relevant financial relationships with
commercial interests
Drug Use In The Patient With
Psychotic Symptoms
• Greater severity of symptoms
• Treatment becomes less effective
•Why
Reduced
of full recovery
is this chance
important?
• Increased medical complications
• Increased risk of violence
• Increased risk of suicide
Violence and Schizophrenia
• Substance abuse accounts for the bulk of the risk
Illicit Drug Use Is Highest In Youths
Past Month Illicit Drug Use among Persons Aged 12 or Older, by Age: 2011 and 2012 (source SAMHSA)
Past month
14%
1.2%
0.7%
1920s-40s
1960s
1980s-today
• Prohibition
• Hayes code censorship of Hollywood
• Reefer Madness (1936)
• Tied to counter culture movements
• Organized movement for legalization
• “Medicalization”
Marijuana Effects
• Euphoria, perceptual alterations
• Increased appetite
• Paranoia
• Decreased motivation
• Impaired memory, attention, cognition
• Greater marijuana use = greater impairment
Can There Be Marijuana Withdrawal?
Yes
• Anger, aggression, irritability
• Anxiety, depression
• Loss of appetite
• Restlessness, insomnia, tremor
• Chills, sweats, stomach pain
• Duration up to 7-28 days
Source: Kouri 2000
Association of Marijuana Use
and Schizophrenia
• Marijuana use has long been known to exacerbate
psychotic symptoms
• Marijuana leads to worse outcomes in
Schizophrenia even after controlling for:
• use of other drugs
• medication compliance
[Jablensky 1992, Hides 2006]
Does Cannabis Use Cause Psychotic
disorders?
• Purpose: Was Marijuana (cannabis) use associated with any
risk of later being diagnosed with schizophrenia?
• Longitudinal (retrospective) study of 45,570 Swedish men in
required military service
• Included over 97% of the male population age 18-20
• 3-6 fold increased risk of later developing schizophrenia if
individuals smoked marijuana 50 times or more
• Replicated multiple times in other studies
Synthetic Cannabinoids of Abuse
• 11,406
Often sold
Different
Emergency
brands
as herbal
areRoom
mixtures
“incense”
visitsofpackets
indifferent
2010 in
attributed
synthetics
convenience
to these
stores
• Vomiting,
Smoked often
Packets
or
altered
eaten
do blood
not even
pressure,
containseizures,
the herbshallucinations
they say they do
(chemical analysis not consistent with labeling)
• 11%
Brand
of names
US high
such
school
as “Spice”
seniorsand
tried“K2”
it in received
the past the
yearmost
attention in the media, but there are many varieties
Institute of Environmental Science and Research (7/2011) study found 11 synthetic cannabinoid
ingredients in 41 synthetic cannabis brands sold in New Zealand
Can you buy drugs on the internet?
Other drugs
Use of multiple additional drugs impairs functioning in
psychotic symptoms
• Cocaine
• Amphetamines
• Abuse of prescription drugs (ex. snort Adderall)
• Opioids and Heroin
• Alcohol
• Hallucinogens (LSD, PCP, ketamine)
• Inhalants, sniffing glue
Treating the Patient Using Illicit Drugs
• “Confrontation with a smile”
• Hard to fully treat until they stop using drugs
• Marijuana often dismissed as no risk
• Need for periodic drug testing
• Many facilities have specialized “dual
diagnosis” clinics and providers
• Hospitalization may be required
Many Unknowns Exist:
Your help is needed
• Predicting who is at risk
• Predicting the course of illness
• Predicting the best treatments
• Reducing side effects
• Better treatments for cognition
• Obtaining the highest degree of functioning
• Consider participating in research