2010_Pease_Treatment_of_Adults_with_Psychotic_disorders

advertisement
Meds, Medical Monitoring and More:
Treatment of Adults with Psychotic Disorders
Julie Keller Pease, M.D.
MAPP 2010 Educational Session
April 30, 2010
Meds
DSM – IV lists 9 disorders under the category of
schizophrenia and other psychotic disorders
 Schizophrenia
 Schizophreniform disorder
 Schizoaffective disorder
 Delusional disorder
 Brief psychotic disorder
 Shared psychotic disorder
 Psychotic disorder due to a general medical condition
 Substance-induced psychotic disorder
 Psychotic disorder not otherwise specificed
FDA Approved Indications
for Antipsychotic Medications




Schizophrenia
Bipolar disorder
Adjunct treatment of depression
Irritability associated with autistic disorder
Additional conditions treated with
antipsychotics








Psychotic disorders, including schizoaffective disorder, brief psychotic
disorder, etc
Mood disorders with psychotic symptoms, e.g. major depression with
psychotic features
Other psychiatric disorders: e.g. PTSD, OCD, personality disorders
Aggression and irritability associated with
 Pervasive developmental disorders
 Disruptive behavior disorders
 Other psychiatric disorders, including personality disorders
Behavioral and psychological symptoms associated with dementia,
intellectual disability
Agitation associated with delirium, drug withdrawal
Tourette’s
Miscellaneous
 Anti-emetic, anti-pruritic, intractable hiccups, insomnia, anxiety
Most common uses of atypical
antipsychotics
Off label use accounts for ~ 1/3 of prescriptions
Atypical Antipsychotic Use by Age
Real and Projected Global Sales of
Antipsychotics 1990-2009 ($ millions)
Projected vs. Actual Sales of
Antipsychotics (US$ Billions) 2005-2009
25
20
Projected Global
Sales
15
Actual US Sales
10
Actual Global
Sales
5
0
2005
2006
2007
2008
2009
Antipsychotics were the top therapeutic
class in US Sales in 2008 and 2009
Timeline of Major
Antipsychotic Therapies
Paliperidone
ECT, etc.
Olanzapine
Aripiprazole
Quetiapine
Chlorpromazine
Fluphenazine
Thioridazine
Haloperidol
Risperidone
Clozapine (released in USA in
Consta
Ziprasidone
1990)
1950
1960
1970
1980
1990
2001
2003
2007
2009 – Paliperidone palmitate,asenapine,iloperidone
The First “Modern” Antipsychotic
Chlorpromazine (Thorazine®)
 Antipsychotic properties discovered in
1952
 Studied originally for usefulness as a
sedative
 Found to be useful in controlling
agitation in patients with schizophrenia
 Introduced in U.S. in 1953
Typical antipsychotic medications
 High Potency (2-20 mg/day)
(haloperidol,fluphenazine, thiothixene)
 Mid Potency (10-100 mg/day)
(perphenazine, loxapine)
 Low Potency (300-800+ mg/day)
(chlorpromazine, thioridizine)
Dopamine blockade effects
 Limbic and frontal cortical regions:
antipsychotic effect
 Basal ganglia: Extrapyramidal side
effects (EPS)
 Hypothalamic-pituitary axis:
hyperprolactinemia
Typical Antipsychotics:
Extrapyramidal side effects
(EPS, EPSE) are common




Parkinsonism
Akathisia
Dystonia
Tardive dyskinesia (TD)
Parkinsonian side effects
 Rigidity, tremor, bradykinesia, masklike
facies
 Management:
 Lower antipsychotic dose if feasible
 Change to different drug (i.e., to an atypical
antipsychotic)
 Anticholinergic medicines:
 benztropine (Cogentin)
 trihexyphenidyl (Artane)
Akathisia
 Restlessness, pacing, fidgeting; subjective
jitteriness; associated with suicide
 Resembles psychotic agitation, agitated
depression
 Management:
 lower antipsychotic dose if feasible
 Change to different drug (i.e., to an atypical
antipsychotic)
 Adjunctive medicines:
 propranolol (or another beta-blocker)
 benztropine (Cogentin), trihexyphenidyl (Artane)
 benzodiazepines
Acute dystonia
 Muscle spasm: oculogyric crisis,
torticollis, opisthotonis, tongue protrusion
 Dramatic and painful
 Treat with intramuscular (or IV)
diphenhydramine (Benadryl) or
benztropine (Cogentin)
Tardive Dyskinesia (TD)
 Involuntary movements, often
choreoathetoid
 Often begins with tongue or digits,
progresses to face, limbs, trunk
 Etiologic mechanism unclear
 Incidence about 3% per year with
typical antipsychotics
 Higher incidence in elderly
Tardive Dyskinesia (TD) continued
 Major risk factors:
 high doses, long duration, increased age,
women, history of Parkinsonian side
effects, mood disorder
 Prevention:
 minimum effective dose, atypical meds,
monitor with AIMS test
 Treatment:
 lower dose, switch to atypical, Vitamin E
(?)
Neuroleptic Malignant
Syndrome (NMS)
 Fever, muscle rigidity, autonomic instability,
delirium
 Muscle breakdown indicated by increased CK
 Rare, but life threatening – medical emergency
 Risk factors include:
 High doses, high potency drugs, parenteral
administration
 Management:
 stop antipsychotic, supportive measures (IV fluids,
cooling blankets, bromocriptine, dantrolene)
Other common side effects of
Typical Antipsychotics:
 Anticholinergic side effects: dry mouth,
constipation, blurry vision, tachycardia
 Orthostatic hypotension (adrenergic)
 Sedation (antihistamine effect)
 Weight gain
Limitations of Typical
Antipsychotics
 Poor adherence due to side effects
 Poor treatment response in 30% of
treated patients
 Incomplete treatment response in
an additional 30% or more
The First “Atypical”
Antipsychotic: Clozapine




Available in Europe, 1970
FDA approved 1990
For treatment-resistant schizophrenia
30% response rate in severely ill, treatmentresistant patients (vs. 4% with
chlorpromazine/Thorazine)
 Receptor differences: Less D2 affinity, more
5-HT
10
Clozapine Helps
Treatment-Resistant Patients
Double Blind, Randomized Trial of Clozapine vs
Chlorpromazine in Treatment Resistant Patients
BPRS Schizophrenia
Factor
16
14
12
10
clozapine
chlorpromazine
8
6
4
2
0
0
1
2
3
Weeks in Trial
4
5
6
11
Clozapine: pros and cons





Superior efficacy for positive symptoms
Possible advantages for negative symptoms
Virtually no EPS or TD
Advantages in reducing hostility, suicidality
Associated with agranulocytosis (1-2%)
 WBC count monitoring required
 Seizure risk (3-5%)
 Warning for myocarditis
 Significant weight gain, sedation, orthostasis,
tachycardia, sialorrhea, constipation
 Costly
 Fair acceptability by patients
Atypical antipsychotics
(aka second-generation, novel)
FDA approval
 1990
 1994
 1996
 1997
 2001
 2002
 2003
 2007
Generic Name
clozapine
risperidone
olanzapine
quetiapine
ziprasidone
aripiprazole
risperidone MS
paliperidone
(Brand Name)
(Clozaril) *
(Risperdal) *
(Zyprexa)
(Seroquel)
(Geodon)
(Abilify)
(Consta)
(Invega)
New Atypical Antipsychotics
 Paliperidone (Invega®) - Risperdal metabolite
 Very similar side effect profile to Risperdal
 Very similar effectiveness to Risperdal
 Asenapine (Saphris®) - another atypical antipsychotic
 Similar efficacy - similar safety Profile
 Iloperidone (Fanapt®) - another atypical antipsychotic
 No major efficacy benefits, QTc = ziprasidone
 Long-Acting Injectables
 Olanzapine (Zyprexa Relprevv®): 2-4 wks, safety concerns (PDSS)
 Paliperidone Palmitate (Sustenna®): monthly
 Sertindole (Serlect®)
 Bifeprunox
 Development discontinued
Defining “atypical”
antipsychotic
Relative to conventional drugs:
 Lower ratio of D2 to 5-HT2A receptor
affinity
 Lower propensity to cause EPSE
(extrapyramidal side effects) due to
weaker D2 binding/antagonism
Atypical Antipsychotics:
Side Effects
• Atypical antipsychotics tend to have
better subjective tolerability (except
clozapine)
• Atypical antipsychotics much less likely
to cause EPSE and TD, but may cause
more:
• Weight gain
• Metabolic problems (lipids, glucose)
Summary: ADA/APA Consensus Conference on
Antipsychotic Drugs and Obesity and Diabetes
Drug
Weight Gain
Risk for
Diabetes
Worsening
Lipid Profile
Clozapine (Clozaril)
+++
+
+
Olanzapine (Zyprexa)
+++
+
+
Risperidone (Risperdal)
Paliperidone (Invega)
++
D
D
Quetiapine (Seroquel)
++
D
D
Aripiprazole* (Abilify)
+/-
--
--
Ziprasidone* (Geodon)
+/-
--
--
+ = increase effect; -- = no effect; D = discrepant results
*newer drugs with limited long-term data
Source Diabetes Care; Volume 27, Number 2, Feb 2004
Weight gain at 10 weeks
6
5
4
Kg
3
2
1
Allison et al 1999
CLOZ
CPZ
OLZ
RISP
ZIP
HAL
-1
PLB
0
Mean change in weight (kg)
Change in Body Weight Following
Switch to Aripiprazole-8 Wk Study
1
0
†
-1
-2
*
-3
n=
Olanzapine
Risperidone
Haloperidol
169
106
14
Prior antipsychotic
*p<0.001; †p=0.077
LOCF analysis.
Casey, et al. Int J Neuropsychopharmacol. 2002;5(suppl 1):S187.
Estimated Weight Change (lb)
After Switch to Ziprasidone†
Weeks
10 14
6
19 23 27 32 36 40 45
49 53 58
0
*
-5
***
**
-10
***
-15
-20
**
Improvement
LS Mean Change, lb
5
*P<0.05
**P<0.001
***P<0.0001
***
-25
†Repeated
Switched from
Conventionals
Olanzapine
measures analysis
Risperidone
Presented at APA 2004, New York, NY
QTc Prolongation
 Drugs with Risk of
Torsades de Pointes








Haloperidol
Mesoridazine
Thioridazine
Pimozide
Chlorpromazine
Erythromycin
Methadone
Quinidine
 Drugs with Possible
Risk of Torsades








Paliperidone
Quetiapine
Risperidone
Ziprasidone
Iloperidone
Asenapine
Sertindole
Lithium
Source: www.azcert.org: QTdrugs.org Advisory Board of Arizona CERT
Side Effects of Atypical Antipsychotics
CLOZAPINE
PALIPERIDONE
RISPERIDONE
OLANZAPINE
QUETIAPINE
ZIPRASIDONE
ARIPIPRAZOLE
Low Blood
Pressure
+++
+
+/0
++
0/+
0/+
Dry Mouth,
constipation
+++
0
+/++
0
0
0
EPSE,
↑ prolactin
0
+/++
0/+
0
+/0
0
Sedation
+++
+/-
++
+++
0
0
Weight
Gain
++++
+
++++
++
+/-
+/-
Lipids
+++
+
+++
++
0
0
↑ Blood
Sugar
+++
+
+++
++
0
0
Summary of Antipsychotic Side
Effects
Side Effect
Higher Liability
Lower Liability
EPS
Conventional
antipsychotics
Conventional
antipsychotics
CLZ, OLZ, QTP
TD
CLZ, OLZ, QTP
Hyperprolactinemia Conventional
CLZ, OLZ, QTP
antipsychotics, RIS
Sedation
CPZ, CLZ, QTP, OLZ
RIS, ARIP, ZIP
Anticholinergic
CPZ, CLZ
RIS
effects
thioridazine, pimozide, CPZ,
QTc prolongation
mesoridazine, haloperidol
Weight gain
CPZ, CLZ, OLZ
Hyperglycemia, DM
Atypical antipsychotics
HAL, ZIP
Long-acting injectable (depot)
antipsychotics
 Until late 2003, only haloperidol and
fluphenazine available in the U.S.
 Long-acting risperidone introduced late 2003,
long-acting paliperidone, olanzapine in 2009
 Injections every 2 weeks (fluphenazine,
risperidone, olanzapine) or 4 weeks
(haloperidol, paliperidone, olanzapine)
 Goal is to decrease non-adherence and thus
reduce relapse
 Used more commonly in other countries, and in
states with outpatient commitment
Are second-generation
antipsychotics more effective than
first-generation antipsychotics in the
treatment of schizophrenia?






The CATIE Schizophrenia Trial
CUTLASS
Rosenheck et al, AJP cost-effectiveness
Luecht el al, Lancet 2009 meta-analysis
NICE Guidelines
Updated APA Practice Guidelines
Proportion of Patients
Continuing Treatment
CATIE Study Phase 1:
Time to Discontinuation for Any Cause
Olanzapine (N=330)
Perphenazine (N=257)
1.0
0.9
Risperidone (N=333)
Quetiapine (N=329)
Ziprasidone (N=183)
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
3
6
9
12
15
Time to Discontinuation for Any Cause (months)
Lieberman JA et al. N Engl J Med. 2005;353:1209-1223.
18
Proportion of Patients
Continuing Treatment
CATIE Study Phase 2T:
Time to Discontinuation for Any Cause
1.0
0.8
0.6
0.4
0.2
0
3
6
9
12
15
18
Time to Phase 2 Discontinuation (months)
Olanzapine (N=66)
Quetiapine (N=63)
Stroup TS et al. Am J Psychiatry. 2006; 163:611-622.
Risperidone (N=69)
Ziprasidone (N=135)
Cost Utility of the Latest Antipsychotic
Drugs in Schizophrenia Study (CUTLASS)
 227 patients with schizophrenia who were judged by
their treating clinician to potentially benefit from a new
antipsychotic medication trial "because of inadequate
response or adverse effects" were randomized to
receive either a first- or a second-generation
antipsychotic (excluding clozapine). The specific
antipsychotic was chosen by the treating clinician. The
primary outcome measure, assessed by blind raters at
12, 26, and 56 weeks, was "quality of life" reflecting
social and vocational function. Symptom changes were
secondary outcomes.
 There was no difference in any outcome measures
between groups.
Average Monthly Symptom Scores
Rosenheck R et al. Cost Effectiveness of Second-Generation Antipsychotics and Perphenazine in a
Randomized Trial of Treatment for Chronic Schizophrenia Am J Psychiatry 2006; 163:2080-89
Comparison of second-generation vs firstgeneration drugs for schizophrenia: a
meta-analysis (Leucht, et al, Lancet 2009)



Clozapine, olanzapine and risperidone were better than firstgeneration drugs for overall efficacy, with small to medium effect
sizes
Other second generation drugs were NOT more efficacious, even
for negative symptoms
Second-generation drugs induced fewer EPSE than haloperidol,
but only a few have fewer EPSE than low potency first-generation
drugs
 BUT:




Second-generation drugs induced more weight gain (except
ziprasidone and aripiprazole)
Only clozapine demonstrated improved quality of life compared to
older drugs
Atypicals are very expensive – cost effectiveness not proven
Need more rigorous studies to accurately define older firstgeneration drugs
Antipsychotic medication
reduces relapse rates:
but……not all SGA > FGA
Risk of relapse in one year:
Consistently taking medications:
20-30%
Not taking medications consistently: 65-80%
Leucht, et al; Lancet 2009: olanzapine and risperidone significantly
better than first-generation antipsychotics in preventing relapse.
Aripiprazole and clozapine: no significant difference. No studies
available for other second-generation antipsychotics
Updated APA Practice Guidelines
for Treatment of Schizophrenia
Guideline Watch (November 2009):
The 2004 guideline recommends that selection of an antipsychotic
agent be guided by the patient's past medication history, current
symptoms and co-occurring conditions, other concurrent
treatments, and preferences. The guideline states that secondgeneration agents should be considered first-line options for
patients in the acute phase, mainly because of the decreased risk
of extrapyramidal side effects and tardive dyskinesia, but
acknowledges debate over the relative advantages,
disadvantages, and cost-effectiveness of first- and secondgeneration agents. The guideline also states that for some
patients, a first-generation agent may be an appropriate first-line
option. This latter recommendation has been strengthened by the
results of several recently published effectiveness studies that
suggest that the first-generation antipsychotics perphenazine and
molindone may be equally effective as second-generation agents.
In fact, the distinction between first- and second-generation
antipsychotics appears to have limited clinical utility.
Updated NICE Guidelines for
Treatment of Schizophrenia (UK)
Pharmacological interventions
For people with newly diagnosed schizophrenia, offer oral
antipsychotic medication. Provide information and discuss the
benefits and side-effect profile of each drug with the service user.
The choice of drug should be made by the service user and
healthcare professional together, considering:
− the relative potential of individual antipsychotic drugs to cause
extrapyramidal side effects (including akathisia), metabolic side
effects (including weight gain) and other side effects (including
unpleasant subjective experiences)
− the views of the carer where the service user agrees.
Do not initiate regular combined antipsychotic medication, except for
short periods (for example, when changing medication).
Medical Monitoring
Medical Issues in Schizophrenia
and Bipolar Disorder
Factor
Prevalence in
Schizophrenia
Prevalence in Bipolar
Prevalence in
General Population
Smoking
75%
43-75%
25%
Obesity
50%
58%
33%
13-14%
9.9-26%
7%
HIV
3%
?
0.3%
Hepatitis C
20%
?
1.8%
Diabetes Mellitus
Other:
-inactivity, poor nutrition
-substance use
Meyer JM and Nasrallah H eds. Medical Illness and Schizophrenia. APPI 2003
Regenold WT, et al. Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and
schizoaffective disorders independent of psychotropic drug use. Journal of Affective Disorders. 2002 Jun;70(1):19-26
Health Risk
Maine DIG Surveys
(Age 18-64 Years)
Health Risk
Age
Group
2007 DIG
Survey
(n=731)
2008 DIG
Survey
(n=1190)
2007 Maine
BRFSS
Smoking
18-44
45-64
46.1%
49.5%
50.5%
45.7%
26.3%
18.8%
Obesity
18-44
45-64
49.4%
49.6%
45.9%
47.1%
26.0%
27.6%
High Cholesterol
18-44
45-64
40.5%
38.6%
29.2%
48.0%
23.2%
46.0%
High Blood Pressure
18-44
45-64
34.0%
34.7%
24.3%
45.6%
13.5%
34.0%
Chronic Health Conditions
Maine DIG Surveys
(Age 18-64 Years)
Health Risk
Age
Group
2007 DIG
Survey
(n=731)
2008 DIG
Survey
(n=1190)
2007
Maine
BRFSS
Chronic Disease*
18-44
45-64
29.6%
31.5%
19.2%
36.8%
3.8%
14.8%
Cardiovascular
Disease**
18-44
45-64
11.3%
9.7%
5.3%
14.3%
1.3%
7.7%
Diabetes
18-44
45-64
23.0%
25.5%
15.1%
29.2%
2.7%
9.4%
* Chronic Disease = reported CVD or diabetes
** Cardiovascular Disease (CVD) = reported angina or heart attack
Multi-State Study Mortality Data:
Years of Potential Life Lost
Year
AZ
MO
OK
1997
26.3
25.1
28.5
1998
27.3
25.1
28.8
29.3
26.3
29.3
26.9
1999
32.2
26.8
2000
31.8
27.9
RI
TX
UT
OH
24.9
1998 2002
32.0
Compared with the general population, persons with major mental illness
typically lose more than 25 years of normal life span
Colton CW, Manderscheid RW. Preventing Chronic Disease. Apr 2006;3:1-14
Miller BJ, et al. Psych Services Oct 2006; 57: 1482-87
Shift in Risk Perception
of Antipsychotics
Past Areas of
Concern
Current Medical Realities
Diabetes
Weight Gain
Weight
Gain
Sedation
Tardive
Dyskinesia
Insulin
Resistance
CHD
Prolactin
Hyperlipidemia
Prolactin
TD
Hyperlipidemia
Insulin
Resistance
Sedation
Coronary Heart
Disease
Undertreatment of Common Disorders in the
CATIE Schizophrenia Trial at Enrollment
Treated
Untreated
100
75
88.0
69.8
62.4
50
37.6
30.2
25
12.0
0
Diabetes
Mellitus
Hypertension
Nasrallah HA, Meyer JM et al. Schiz Res 2006.
Dyslipidemia
Clinical Issues:
barriers to medical monitoring
 Lack of access to medical care for patients with
severe mental illnesses
 Lack of access to support/consultation for PCP
 Lack of coordination/collaboration between
mental health, primary care, laboratory
 Switching to more metabolically neutral
medications may reverse many problems, but
requires careful attention by the psychiatrist
and motivation by the client
Physical and Laboratory
Assessment at Diagnosis:
APA Practice Guidelines
 Vital Signs
 BMI
 CBC, CMP, Thyroid, FBG, Lipids, other infection, βHCG, toxicology screen, EKG, Prolactin
 imaging
 Neurological exam (EPS, TD)
 Eye exam (Cataracts)
Monitoring Equipment
Medical Monitoring:
What We Should Be Doing
Inquiry
 Personal or family
history:
 Diabetes
 Hypertension
 CHD (MI or Stroke)
 Cigarette smoking
 Diet
 Physical Activity
 Substance use
Measure
 Height
 Weight
 BMI
 Waist circumference
 Blood Pressure
Lab
 Fasting Glucose
 Fasting Lipids
ADA Screening Guidelines for Patients on
Second-generation Antipsychotics
Baseline
Personal Family History
X
Weight (BMI)
X
Overweight (25.0 – 29.9)
Obese (≥30.0)
Waist circumference
(<40” in males, <35” in females)
4 weeks
8 weeks
12 weeks
Annually
X
X
X
X
X
quarterly
X
Blood Pressure
X
X
X
Fasting Plasma Glucose
X
X
X
(HbA1c)
(HbA1c)
X
X
IFG (100 – 125 mg/dL)
Diabetes (>125 mg/dL)
Fasting Lipid Profile
5 yrs
Total cholesterol (<200)
HDL (>40), LDL (<100), TG (<150)
Normal Values (in parentheses) based on 2007 ADA Guidelines and National Cholesterol Education Program (NCEP) Guidelines. More frequent
assessments may be warranted based on patient results and the monitoring recommendations in package inserts for individual medications used.
The 5 A’s for obesity mgmt
 ASK (history, risk factors, correlations between
medications and weight change)
 ADVISE and educate
 ASSESS motivation, barriers, wt. goals
 ASSIST (nutrition education, referrals)
 BMI > 30 consider weight loss agent
 BMI >40 explore bariatric surgery
 ARRANGE follow-up, review goals and
intervention options, congratulate successes
Weight Control Strategy Worksheet
 Try to keep your appetite tamed 
- Eat small portions frequently instead of full meals or large portions infrequently
to keep your appetite from building and overeating when you do eat.
- Eat more slowly to give the “I ate” signals time to get to your brain from your
stomach
- Keep your mind occupied with other activities. Delay eating by choosing to do
another activity before you eat or snack.
- Learn relaxation or mindfulness, and practice it daily
↓↓↓ Try to keep your intake down ↓↓↓
- Keep a journal or log to make yourself aware of your food intake
- Use smaller sized plates & glasses to make a “full” portion with less food.
- Keep a calorie count
- Beware “hidden” calories, especially in soda etc.
- Make sure you have plenty of low calorie and high fiber (makes you feel full)
food around to do your eating with, especially the food you use to eat small
portions often
- Swap vegetables for sweets, swap pretzels for chips
- Drink plenty of water
- Avoid fruit juices and sodas – drink water or seltzer instead of other cold drinks
- Drink your coffee or tea “black” – without sugar, creamer, milk or sweeteners
-
↑↑↑ Try to keep your energy output up ↑↑↑
- Exercise daily – brisk walks (striding fast enough so you could converse but it
would be “breathy”) are thought to be a “best” exercise – 30 minutes to an hour
daily. Two 15 minute walks equals one 30 minute walk if time is a problem.
- Seek active rather than sedentary activities
- Take stairs rather than elevators.
- Plan your errands and activities to include walking
- Keep a journal or log to make yourself aware of your activity level
-
Pharmacologic Interventions
for weight loss
 FDA- approved
 use only if BMI >30 or >27 if metabolic syndrome is present
 Initiate only after a 6-month period with weight loss <1 lb/week
despite adherence to “healthy lifestyle regimen”
 Sibutramine, Orlistat, Phentermine
 Off-label
 Glucophage (Metformin)
 Topiramate
 Bupropion + naltrexone, phentermine + topiramate, bupropion
+ zonisamide
 New/investigational
 Lorcaserin (selective serotonin 2C receptor agonist)
 Betahistine (H1 agonist/H3antagonist)
Managing Side Effects of Your Medication
The most common side effects of antipsychotic medications are:
Dry mouth, constipation, lack of energy, drowsiness, upset stomach, dizziness,
feeling hungrier than usual, gaining weight, insomnia, tremors, and restlessness.
These side effects generally do not bother people enough to stop taking their
medications. Here are some suggestions for managing side effects:
If you
experience
this…
Sleep disturbance
Try this:


Feeling hungrier
than usual

Gaining weight





Dizziness

Dry mouth

Constipation

Upset stomach



Restlessness
Talk with your doctor about adjusting the doses
or timing of your medication schedule
Drink plenty of water or other sugar-free drinks
– 6 to 8 glasses a day.
Drink a glass of water before meals to help you
feel fuller.
When you want a snack, try eating a half-cup of
fruit or raw vegetables or a rice cake.
Chew sugar-free gum.
Instead of snacking, try taking a walk.
Get some extra exercise each day. Talk with
your doctor before making any major changes in
your exercise routine.
Stand up slowly if you have been sitting or lying
down.
If you become anxious, try diaphragmatic
breathing or relaxation.
Enjoy sugar-free mints or sugar-free hard candy.
Let them melt in your mouth.
Eat foods that are high in fiber, such as bran
cereals and raw vegetables.
Try taking your medication with a meal
Talk to your doctor about a dosage change.
Talk to your doctor about medication options for
managing this side effect.
**Contents of this handout courtesy of Eli Lilly and Co. – modified by Julie Pease, M.D.
Informed Consent
PATIENT MEDICATION CONSENT, AGREEMENT TO REPORT ADVERSE SYMPTOMS, and ASSUMPTION OF RISK AGREEMENT
Note: No medication is absolutely positively 100% risk free. Even taking over-the-counter medicines, like Aspirin and Tylenol for example, can result in serious side effects
or even death. However, all prescribed medicines are approved as safe and effective by the Food and Drug Administration (FDA), and most of the time they cause little or
no harm. Nevertheless, there are some specific concerns that you should be aware of with certain medicines that are commonly prescribed, and that is the purpose of this
medication consent.
1. Atypical Antipsychotics (ABILIFY, CLOZARIL, GEODON, RISPERIDAL, SEROQUEL, SYMBYAX, and ZYPREXA): These may cause or result in certain adverse
medical problems:
a.
Elevated blood sugar, diabetes, and weight gain: elevated blood sugars, in some cases extreme and associated with coma or death, have been reported in patients
treated with these medications. These changes may occur with or without weight gain. I agree to report any significant weight gain and/or symptoms of elevated blood
sugar (including increased thirst, increased urination, increased eating, and weakness) to my doctor. Patients who develop any of these symptoms should have a test for
elevated blood sugar and cholesterol.
b.
Increased risk of stroke and a higher death rate in elderly patients with dementia. These medications are not indicated for the treatment of agitation except in
patients with schizophrenia or bipolar disorder.
a.
Neuroleptic Malignant Syndrome (NMS): this is a rare but potentially life-threatening condition with symptoms of unstable blood pressure, confusion, coma,
delirium, fever, and/or muscle stiffness.
b.
Elevated prolactin levels: this may be associated with enlarged breasts, breast discharge, sexual dysfunction, osteoporosis, and very rarely pituitary (brain) tumors.
2. Tardive Dyskinesia (TD): All antipsychotic medications, including haloperidol (HALDOL) and fluphenazine (PROLIXIN), those listed in #1 above, and others such as
_______________________ may result in a condition called tardive dyskinesia (TD). The symptoms of TD, which are primarily abnormal movements or muscle cramps
and which may be irreversible, have been explained to me and I accept the risk and agree to report any muscle cramps or abnormal movements to my doctor immediately.
6.Pregnancy: Taking medication during pregnancy exposes the fetus to medication and can present a risk to the unborn child. Some psychiatric medications are known to
have a higher risk of birth defects (e.g. Depakote); others may be continued during pregnancy with minimal risk depending upon the medication and the circumstances.
This needs to be considered carefully in the decision making process for medication use by women of childbearing ages. If planning to become pregnant, I agree to discuss
my medications with my doctor before trying to conceive. If I do become pregnant while taking medication, I agree to call my doctor immediately so that we can discuss
the risks/benefits of continuing medication or the need/process by which to stop the medication if the situation and risks of continuing warrant that. All medications are
passed into breast milk in differing amounts. Some may be used with relative safety during breastfeeding and others are not recommended for use during lactation.
10. Off-label Use: One or more of the medications I have been prescribed is or are prescribed “off-label.” This means that the medication is prescribed for a use not
approved by the Food and Drug Administration (FDA), use at doses above those recommended, or use for periods of time longer than approved.
11. Driving a Car or Use of Machinery OR Use With Alcohol: One or more of the medications prescribed to me may adversely affect my ability to drive a motor vehicle or
operate machinery. I agree not to drive or operate machinery if I feel even slightly impaired, and I take full responsibility for this liability. MEDICATIONS SHOULD
NOT BE TAKEN OR USED WITH ALCOHOL.
13. Potential risks and benefits of taking this or these medications, as well as alternative treatments, have been discussed with me and I accept these risks. I was given an
opportunity to discuss my medications, all of my questions have been satisfactorily answered, and I was given a copy of this form to take home with me.
____________________________________________
PATIENT SIGNATURE
Date
____________________________________________
Parent/Guardian Signature
Date
_______________________________________
Prescriber’s Signature
Date
Copyright © safePrescribing.com 2007 -
Internet Resources







www.psych.org (Practice Guidelines)
www.mainepsych.org *new website coming soon
www.tobaccofreemaine.org
www.mayoclinic.com (Metabolic syndrome, wt loss)
www.nami.org (Diagnosis, medication, support info.)
www.cdc.gov/HealthyLiving/
www.mainecarepdl.org/index.pl/home/ps
ych-work-group-pwg (Monitoring recommendations)
 www.azcert.org (QT Drug Lists and DDI Lists)
Conclusions
• Except for clozapine, most of the currently available
agents, including the newest atypicals, are more alike
than different in terms of effectiveness
• Safety and avoidance of metabolic side effects are
major reasons to choose certain medications
• Providers have a duty to monitor weight, blood
pressure, blood sugar and lipids, and to support healthy
lifestyle choices
• Consider long-acting injectable medications for
treatment of psychosis in cases of relapse due to nonadherence
• Providers should consider alternatives to antipsychotics
when treating non-psychotic disorders
More
Treatment-Resistant
Psychotic Disorders






Reconsider diagnosis
Evaluate adequacy of medication trials
Consider a trial of clozapine
Consider augmenting medication
Consider ECT
Consider Cognitive Behavior Therapy
On The Horizon
 Some features of schizophrenia may be due to
decreased levels of activity at NMDA glutamate
receptors
 Glycine and related compounds can stimulate those
receptors and might prove useful as a treatment for
schizophrenia
 Glycine Transport Inhibitors (GlyT1 Blockers)
 The GlyT1 transporter is localized to important
areas of the brain
 Sarcosine: enhances NDMA receptor function by
inhibiting glycine uptake
How A Reuptake Inhibitor Works
Presynaptic
Nerve Ending
Glycine Reuptake Pump
Synaptic
vesicles with
Glycine
Glycine
Postsynaptic
Neuron
NMDA Receptors
Schizophrenia is a
heterogeneous illness
 Defined by a constellation of symptoms,
including psychosis
 Multifactorial etiology, variable course
 Social/occupational dysfunction a
required diagnostic criterion
 Good treatment must address all aspects
of dysfunction
Features of Schizophrenia
Positive symptoms
Delusions
Hallucinations
Functional Impairments
Work/school
Interpersonal relationships
Self-care
Cognitive deficits
Attention
Memory
Verbal fluency
Executive
function
(e.g.,
abstraction)
Disorganization
Speech
Behavior
Negative symptoms
Anhedonia
Affective flattening
Avolition
Social withdrawal
Alogia
Mood symptoms
Depression/Anxiety
Aggression/Hostility
Suicidality
Treatments for schizophrenia:
Strong evidence for effectiveness
 Antipsychotic medications
 Family psychoeducation
 Assertive Community Treatment
(ACT teams)
Family Psychoeducation
 Provides information about
schizophrenia: course, symptoms,
treatments, coping strategies
 Supportive
 One aim is to decrease expressed
emotion (hostility, criticism, etc.)
 Not blaming
Assertive Community
Treatment (ACT)
 ACT is effective evidence-based treatment





Supported by 25 randomized controlled trials
Reduces hospitalization rates
No more expensive than traditional care
More satisfactory to patients
Individualized, multidisciplinary treatment
 ACT is also called





Training in community living
PACT (Program for Assertive Community Treatment)
Continuous treatment teams
Intensive psychiatric community care (in VA system)
Riverview: Progressive Treatment Program
Other interventions for
schizophrenia:
Some evidence for effectiveness





Some types of psychotherapy
Case management
Vocational rehabilitation
Outpatient commitment
ECT (for catatonia)
CBT for Schizophrenia
 CBT is helpful for refractory or breakthrough
psychotic symptoms
 Requires high insight (“I can’t trust my
perceptions because I am sick”.)
 CBT for delusions
 Direct confrontation should be avoided
 Focus not on the belief but on the evidence for it
 Encourage development of arguments against
beliefs by patients
CBT for Schizophrenia
 CBT for hallucinations
 Distraction method (Extinguishing)
 Wearing headphones to focus attention away so the
hallucinations are extinguished with decreased reactivity
 Focusing method (Desensitization)
 Describe, record and recognize the connection between
stressors and hallucinations
 Explore what the voices mean to them
 Use self-talk to cope with hallucinations
 Negative symptoms
 Activity scheduling
 Skills training
Schizophrenia Treatment:
Case management
• Case manager helps coordinate treatments,
provides support
• Help navigating life, such as managing every
day activities, transportation, etc.
• Helps broker access to available services
• Benefits:
improves compliance, reduces stressors, helps
identify and treat problems with substance use
Schizophrenia Treatment
Psychosocial Remedial
Therapies
• To improve social and vocational skills
• Clubhouse model offers opportunities to
socialize, transitional employment
• Vocational rehabilitation—especially
supported employment
DSM-IV Schizophrenia
 2 or more of the following for most of 1 month:





Delusions
Hallucinations
Disorganized speech
Grossly disorganized or catatonic behavior
Negative symptoms
 Social/occupational dysfunction
 Duration of at least 6 months
 Not schizoaffective disorder or a mood disorder
with psychotic features
 Not due to substance abuse or a general
medical disorder
Schizophrenia
 Lifetime prevalence rates range from .5% to
1%
 Low incidence rate – 1 per 10,000 per year, but
very debilitating disorder
 Onset from adolescence to age 45
 Affects men and women equally - men have
earlier onset (18-25) than women (25-35)
Download