Microsoft powerpoint - psychotropics made simple 090705.ppt

PSYCHOTROPICS
OVERVIEW
• Introductory Concepts
MADE SIMPLE
• Medication Education
• Drug Class Reviews
Roger W. Sommi, Pharm.D., FCCP, BCPP
– Antipsychotics
Professor of Pharmacy Practice and Psychiatry
– Antidepressants
UMKC Schools of Pharmacy and Medicine
– Mood Stablizers
– Antianxiety Agents
Research Director, Psychopharmacy Research
and Education Program
– Hypnotics
Western Missouri Mental Health Center
– Alcohol Abuse
– Nicotine Dependence
Therapeutic Effects of
Therapeutic Effects of
Psychotropic Medication
Psychotropic Medication
3) Curative versus preventative effects
1) Target symptoms
a. psychotropic medications relieve symptoms
b. help prevent the return of symptoms
2) Monitoring Therapeutic Effects of
- longer symptom free intervals between episodes
- fewer symptoms during future episodes
Medication/Progress Notes
- relief of symptoms between episodes.
c. adjunctive therapy in the treatment of mental
disorders
d. not to be relied upon as sole treatment
Therapeutic Effects of
Psychotherapy
Psychotropic Medication
Useful in nearly every Psychiatric
4) Onset of Effect
disorder
Early - generally due to side effects
Different changes in brain function
May be imperative for response in
Specific Effects - weeks to months
patients with trauma history
Generally synergistic with meds
CBT most studied
Long-term Maintenance
Treatment
Determining Need for
1. Not necessary for all patients
Medication
2. Not predictable which patients require long-
Based on:
term therapy
- treatment responsive symptoms
3. Long-term therapy is used for those patients
who respond and have recurrent episodes
- dangerousness
4. First episode - 6 months
- patient preference
5. Consider long-term side effects in decision
6. Taper the dose to the minimal therapeutic
7. Consolidate of doses to improve compliance
8. Routine follow up is imperative
Determining Need for
Determining Need for
Medication
Medication
Based on:
Based on:
- treatment responsive symptoms
- treatment responsive symptoms
- dangerousness
- dangerousness
- patient preference
- patient preference
Symptom Quality
Symptom Severity
Symptom Quality
Symptom Severity
Expected?
Intensity
on Function
Patient Education
1. 70-80% of patients readmitted stopped
PATIENT EDUCATION
taking their medication
2. Medication adherence is generally poor in
• NONADHERENCE LEADS TO:
psychiatric patients
3. Low levels of knowledge, side effects,
- HIGH RATE OF RECIDIVISM
cultural influences, high levels of
- HIGHER COST OF TREATMENT
knowledge, and false beliefs are some of
- MAY POTENTIALLY LEAD TO POOR
the most popular hypotheses for
nonadherence
PROGNOSIS
- OVERALL LOSS OF FUNCTIONING
4. Inform rather than give information
5. Include the family/caregiver
HEALTH BEHAVIOR
HEALTH BELIEFS
• PRIMARY MOTIVATION FOR HEALTH
• HEALTH SEEKING PROCESS
BEHAVIOR
- past behaviors and experiences
• BASED ON PERCEIVED:
- acute versus chronic illness
- probably and severity of threat
and vulnerability
• SYMPTOM RECOGNITION
- benefits
- barriers
- danger
- disability
• INFLUENCES ON BELIEFS
TREATMENT ADHERENCE
• NOT INFLUENCED BY GENDER,
Treatment
RACE, MARITAL STATUS,
SOCIOECONOMIC STATUS, OR
Nonadherence
LEVEL OF EDUCATION
• UNCONTROLLABLE FACTORS
• CONTROLLABLE FACTORS
IMPLICATIONS FOR
COMMON QUESTIONS
MEDICATION EDUCATION
FROM PATIENTS
• NEED TO ADDRESS ISSUES OF
NONADHERENCE
• How was the drug selected?
• How did the physician arrive at the
• NEED TO ADDRESS INFORMATION
dose I am receiving?
• How was the regimen decided?
• BELIEFS ABOUT ILLNESS AND
• What are the expected effects from
TREATMENT ALSO NEED TO BE
medication?
ASSESSED AND ADDRESSED
• When will changes be made in my
medication?
COMMON QUESTIONS
COMMON QUESTIONS
FROM PATIENTS
FROM PATIENTS
• What would happen if I took an
• When and how will the decision be
overdose of medication?
made to discontinue treatment?
• How long will I be treated?
• How will the medication be stopped?
• How will progress be assessed?
• What will happen after the medication
• What will happen if medications fail
is discontinued?
or progress is slow?
• Are there any things I can do other
• How will I be followed for my
than medications to improve the
medications? (how often, by whom,
outcome of treatment?
• Can I learn not to get sick again?
IMPLICATIONS FOR
MEDICATION EDUCATION
INFORMATION DATA BASE
• BE AWARE OF THE COMMON QUESTIONS
• INFORMATION VERSUS INFORMING
• MAKE THE PATIENT AWARE OF THESE
QUESTIONS
• GROUP VERSUS INDIVIDUAL
• THINK ABOUT WHAT YOUR ANSWERS WILL BE
- general information
• ENCOURAGE THE PATIENT TO FIND THE
- patient specific information
ANSWERS THEMSELVES
• REFER PATIENT TO ANOTHER SOURCE IF YOU
CANNOT ANSWER THE QUESTION
BASIC POINTS
IMPLICATIONS FOR
OF INFORMATION
MEDICATION EDUCATION
• type(s) of psychotropic medication(s)
• name(s) of psychotropic medication(s)
• THE AMOUNT OF INFORMATION IS NOT AS
IMPORTANT AS THE TYPE OF INFORMATION
• dose patient is receiving
PRESENTED
• purpose of medication
• common side effects of medication(s)
• INFORMATION MUST BE PRESENTED IN A
• what to do if side effects should happen
MANNER THAT THE PERSON UNDERSTANDS
• signs of severe toxicity
• PAY ATTENTION TO THE READABILITY,
• drug-drug and drug-food interactions
UNDERSTANDABILITY, ORGANIZATION, AND
• appropriate administration
LOGIC OF THE INFORMATION
AN ANALOGY FOR TEACHING
AN ANALOGY FOR TEACHING
MENTAL ILLNESS
COMMON COLD/FLU
MENTAL ILLNESS
COMMON COLD/FLU
PROBLEM:
PROBLEM:
1) Virus
SYMPTOMS:
SYMPTOMS:
cough, headache, sore
throat, sneezing, etc.
TREATMENT:
TREATMENT:
1) Rest
2) Fluids
3) Medication
MENTAL ILLNESS
COMMON COLD/FLU
USING THE COLD ANALOGY
PROBLEM:
PROBLEM:
1) Environment
SIMILARITIES:
2) Heredity
3) Neurochemical Changes
1) No "cure" for either illness.
SYMPTOMS:
SYMPTOMS:
2) Symptoms of either illness are dysfunctional.
anxiety, insomnia, mood
cough, headache, sore
3) Medications used in both illnesses only relieve
swings, agitation, delusions,
throat, sneezing, etc.
symptoms.
hallucinations, etc.
4) If the medication is stopped during treatment, the
TREATMENT:
TREATMENT:
symptoms will recur because the problem is still present.
2) Therapy
2) Fluids
5) Just as no two persons have the same cold/flu
symptoms, no two have similar symptoms with mental
3) Medication
3) Medication
illness.
USING THE COLD ANALOGY
USING THE COLD ANALOGY
SIMILARITIES:
DIFFERENCES:
6) Medications for both illnesses have side effects.
1) Medications used for mental illness
7) Both illnesses require rest; bed rest for a cold/flu,
need to be continued for a longer
and a rest from the stressful environment for
mental illness.
period of time to prevent the recurrence
of symptoms.
8) There are many different medications for
treatment of either illness.
CAUTION - acknowledge the differences
in severity and importance of colds vs.
9) Sometimes, even with treatment there is a
mental illness
recurrence of the illness.
RESPONSE TO
Response Model
MEDICATION
2-4 Weeks
• Relief of Depressed
• DISCUSS REALISTIC
• Less Hopeless/
EXPECTATIONS
1-3 Weeks
Helpless
• Thoughts of Suicide
• Increased Activity,
Sex Drive, Self-care,
• RELATE TO THE PATIENT'S
and Memory
• Thinking and Movements
EXPERIENCE
First Week
Normalize
• Sleeping and Eating
• Decreased Anxiety
Patterns Normalize
• Improvement in Sleep
• Improvement in Appetite
ADVANTAGES OF MODEL
SIDE EFFECTS
FRAMEWORK
• LIMIT DISCUSSION TO COMMON SIDE
• BASED IN THE EXPERIENCES OF
THE PATIENT
• DISCUSS PATIENTS' EXPERIENCE
• EASY TO UNDERSTAND
• DISCUSS SEEKING HELP FOR SIDE
• GIVES THE PERTINENT
INFORMATION - STIMULUS FOR
FURTHER DISCUSSION
• SUGGESTIONS FOR MINIMIZING SIDE
• BUILDS SELF-CONFIDENCE
DISADVANTAGES
Consent for Treatment
• COLD ANALOGY MAY BE PERCEIVED
AS DOWN PLAYING THE IMPORTANCE
• Patient, family, guardian
OF MENTAL ILLNESS
• Should occur with any changes in
• DIFFERENCES BETWEEN COLDS AND
medication
MENTAL ILLNESS ie. prognosis, need
for continued treatment
• Unusual uses of medication
• ADDRESS THESE ISSUES UPFRONT
Presenting
Symptomatology/
"What a waste it is to lose
Diagnosis
one's mind. Or not to have
Potential Drug
Interactions
a mind is being very
Factors in
wasteful. How true that is.”
Selecting Appropriate
Pharmacotherapy
Response and
ADR History
Available Agents
-- Vice President Dan Quayle
Side Effect
Effect on
ADME & Pdynamic
Changes w/age
Disorder
Choosing the Appropriate
Risk: Benefit for Drug
1. No difference in efficacy between agents in the same
2. Cannot choose an agent based on efficacy
3. Chosen based on which would be least toxic
Benefits
4. Factors
• Adverse Effects
• Improved Functioning
- target symptoms present
• Toxicity
• Improved Quality of Life
- past history of medication response of family
• Exacerbation of other
• Reduced Symptoms
- past history of adverse effects from medication
problems
• Decreased Mortality
- medical problems of the patient, esp. cardiac and neurological problems
- side effect profiles of the available agents
- available dosage forms
- chemical structure/neurotansmitter effect
- cost
5. Rule of thumb
6. "Therapeutic Trial"
Generic vs. Trade Name
Antipsychotic Medications
• Generally not a problem
Atypical Antipsychotics
• Most newer agents not yet available
Typical/Conventional Antipsychotics
as generics
Low potency (Thorazine, Mellaril)
• Problems come when patient is
High potency (Haldol, Prolixin)
switched from one to another
Long-acting Antipsychotics
• Watch for loss of therapeutic effect
Prolixin-D®
or emergence of side effects
Haldol-D®
Risperdal Consta ®
Trade Name
GENERIC NAME
Antipsychotic Agents and
Low Potency
Thorazine
Chlorpromazine
200-1600 mg/day
Mellaril
Thioridazine
200-800 mg/day
Formulations
Serentil
Mesoridazine
100-400 mg/day
High Potency
Molindone
40-250 mg/day
Loxitane
Loxapine
40-225 mg/day
Trilafon
Perphenazine
12-64 mg/day
Stelazine
Trifluoperazine
10-60 mg/day
Thiothixene
10-120 mg/day
High Potency
Haloperidol
4-100 mg/day
Prolixin
Fluphenazine
2-60 mg/day
Antipsychotic
Haldol-D
Haloperidol
100-300 mg/month
Decanoate
Prolixin-D
Fluphenazine
6.25 - 75 mg/2
Decanoate
Risperdal
Risperidone
25-50 mg/2 weeks
Atypical
Antipsychotic
Clozaril
Clozapine
200-800 mg/day
Risperdal
Risperidone
4-12 mg/day
Olanzapine
5-20 mg/day
Seroquel
Quetiapine
250-750 mg/day
Ziprasidone
80-240 mg/day
Aripriprazole
10-30 mg/day
** in development - not FDA Approved
New and “off label” uses
Atypical Antipsychotic Agents
Mania
Mixed
“Atypical” because:
Maintainence
• lower potential for extrapyramidal
depression
Resistant Depression
• greater efficacy in negative symptoms
Refractory OCD
Borderline
• greater efficacy in refractory illness
Autism Spectrum
• lower potential to cause prolactin
Agitation/ Psychosis of Dementia
elevations
• greater 5HT-2/D2 receptor effects
Schizophrenia: Core Symptom
Atypical Antipsychotic Agents
Clusters
Positive Symptoms
Negative Symptoms
• delusions
• blunted affect
Dosing Range
• hallucinations
• alogia
Clozapine (Clozaril)
200 - 900 mg/day
• disorganized speech
• avolition
• catatonia
• anhedonia
Risperidone (Risperdal)
1 - 8 mg/day
• withdrawal
Olanzapine (Zyprexa)
7.5 - 30 mg/day
Social and Occupational Dysfunction
Quetiapine (Seroquel)
150-800 mg/day
• employment
• interpersonal relationships
Ziprasidone (Geodon)
40-160 mg/day
• self-care
Aripiprazole (Abilify)
10-30 mg/day
Cognitive Symptoms
Mood Symptoms
• attention
• dysphoria
• memory
• suicidality
• executive functions
• hopelessness
Antipsychotic Response
B. Target symptoms for
Degree of improvement (percentages of patients)
Total marked or moderate benefit
antipsychotic treatment
Judgment
Orientation
Realistic planning
-hostility
-social withdrawal
Compulsiveness
Self-mutilation
-agitation/anxiety
-loose associations
Participation in adjunctive therapy
Sociability
Appropriateness of conversation
-insomnia
-inappropriate affect
Delusions
-suspiciousness
-delusions
Appetite
Amicability
Accessability
-poor self-care habits -hallucinations
Mannerisms
-preoccupations
Negativism
Hallucinations
Hostility
Hyperactivity
Combativeness
Time Course of Response to Antipsychotic Medications
p e rs is t e n t s y m p t o m s
| im p a ire d
| in s ig h t / ju d g m e n t
| in a p p ro p ria t e a f f e c t
| f ix e d d e lu s io n s /
3 - 6 w e e k s | h a llu c in a t io n s
Some people talk in their
| im p ro v e m e n t in
| t h o u g h t d is o rd e r
| d e c re a s e in d e lu s io n s /
| h a llu c in a t io n s
sleep. Lecturers talk
| a p p ro p ria t e
1 - 2 w e e k s
| c o n v e rs a t io n s
| im p ro v e m e n t in
| s o c ia liz a t io n
while other people
| s e lf - c a re h a b it s
| im p ro v e
| im p ro v e m e n t in
d e c re a s e d :
a g it a t io n /
h o s t ilit y /
a g g re s s io n /
c o m b a t iv e n e s s /
Albert Camus
n o rm a liz a t io n o f s le e p
a n d e a t in g p a t t e rn s
Adverse Effects of
Monitoring for Tardive
Antipsychotics
Dyskinesia
1. Drowsiness
1. Patients should have baseline and q
usually resolves within 2 weeks
6 month evaluations
2. Extrapyramidal Side Effects (EPS)
Dystonias
2. If symptoms noted - then q 3
Pseuoparkinsonism
Akathisia
Tardive Dyskinesia
3. DISCUS vs AIMS
- need routine evaluation using AIMS
or DISCUS
Adverse Effects of Antipsychotics
Adverse Effects of
3. Anticholinergic side effects: tolerance
usually develops to these side effects
Antipsychotics
over 1-2 months.
-dry mouth
-blurred vision
5. Neuroleptic Malignant Syndrome
-constipation
-urinary retention
6. Miscellaneous side effects:
-nasal congestion
-increase in heart rate
-decreased sweating
-skin rash
-photosensitivity
4. Cardiovascular side effects
-postural hypotension
7. Rare side effects
-arrhythmias/palpitations
Medications Used to Treat
ANTIPSYCHOTIC SIDE EFFECT PROFILE
EPS and Dosage Ranges
SEDATION
ANTICHOL.
CARDIOV.
Thorazine
Moderate
TRADE NAME GENERIC NAME T1/2 DYSTONIA PSEUDO AKATHISIA
PARKINSON
Mellaril
Moderate
Akineton®
biperiden
Serentil
Moderate
Artane®
trihexyphenidyl 3-4
Prolixin
Very High
Ativan®
lorazepam*
10-20 0.5-10
Clozaril
High initially
Benadryl®
diphenhydramine* 2-8
25-50 IM 50-200
Risperdal
Moderate
Low-Moderate Very Low
Cogentin®
benztropine*
6-48 1-2 IM 4-10
High Initially
Inderal®
propranolol
Seroquel
Moderate
Symmetrel® amantadine
Moderate
* - available in intramuscular dosage form
Clozapine
Clozapine
Dibenzodiazepine
Beneficial in positive and negative
symptoms, good evidence in
treatment resistant patients
t1/2 - approximately 12 hrs
May need 6 month trial in treatment
Doses initiated at 12.5-25 mg/day,
resistance
titrated by 25-50 per day x 2 weeks to
target dose
Should check drug level
Clozapine - Adverse Effects
Clozapine - Adverse Effects
Weight Gain- DM, Dyslipidemia
Agranulocytosis (ANC < 500/mm3)
Sedation
risk is 0.38% vs. 1-2% overall
Hypersalivation
can happen anytime and with any dose
Constipation
most common early in therapy <6m
Tachycardia
leukopenia is predictive
Cardiomyopathy
don’t initiate if WBC is < 3500/mm3
Orthostasis
WBC 3000-3500, or drops by 3000 in 1-3 wks -
Seizures
increase monitoring to 2x/wk
< 300 mg/day - 1%
WBC 2000-3000 or ANC 1000-1500 - stop
300 - 599 mg/day - 2.7%
clozapine, resume if WBC > 3500
≥ 600 mg/day - 4.4%
WBC <2000 or ANC <1000 - d/c clozapine - no
rechallenge
Risperidone
Risperidone - Adverse Effects
Dose-related extrapyramidal effects
t1/2 - approximately 20 hrs including
Akathisia
metabolite
Sedation/insomnia/anxiety
Orthostasis
Lower doses and slower titration in
Nausea/vomiting
young and old
Prolactin increases
Wt- 18% gained 7% of baseline in short term
Average dose is 4-6 mg/day
trials vs. 9% on placebo
Tardive Dyskinesia - <1%
Olanzapine
Olanzapine - Adverse Effects
Somnolence
Orthostasis/dizziness
1/2 - approximately 27-38 hrs
Akathisia
Weight gain 29% gained 7% of
Doses initiated at 10-20 mg/day,
baseline in short term trials vs. 3%
titrated in 5 mg increments
on placebo
DM, lipids
Average dose is 10-30 mg/day
Dose-related increases in EPS and
prolactin
IM available 10mg
Elevated hepatic transaminase
Quetiapine
Quetiapine - Adverse Effects
Drowsiness
Agitation
t1/2 - approximately 7 hrs
Weight Gain- 23% gained 7% of baseline in
short term trials vs. 6% on placebo
Doses initially titrated to 300-400
May be dose related
DM, Lipids
Constipation
Average dose is 400-800 mg/day for
Dry Mouth
schizophrenia
Orthostasis
Mild increase in hepatic transaminase
Ziprasidone- Adverse Events
Ziprasidone
QTC prolongation
Rarely clinically significant
t1/2 - 6-8 hrs
Stop if over 500ms
Greater risk with low potassium or
magnesium
Doses 40-160mg/day
Sedation- 14%
EPS- 5%
50% less absorption without food
Weight gain- 10% gained 7% of baseline
in short term trials vs. 4% on placebo
Long-term wt “neutral”
IM available 20mg/dose
Minimal effect on lipids
NTE 40mg in 24hrs
Aripiprazole- Adverse
Aripiprazole
High affinity
90+% D2 occupancy at clinical
Headache
Insomnia
WT- 8% gained 7% of baselline in short
Partial agonist
term vs. 3% on placebo
25-30% of Dopamine activity
Long term wt “neutral”
Minimal effect on lipids
t1/2 - 3-5 days
A Primary Treatment
Long acting injectables
Challenge:
The Compliance Continuum
Known compliance or noncompliance
Lower peak levels of drug
Satisfactory
Noncompliance
Partial Compliance
Compliance
Loading strategies for Decanoates
Some meds taken —
meds taken
often erratically
2-3 wk lag for Risperdal Consta
Lower rehospitalization rates
Adherence to Prescribed Regimen
Impact on Clinical Decisions
Compliance Challenges
Affect Almost ALL Patients
Oral antipsychotics
Continuous Medication
Mean Number of Days
Unknown compliance may prevent evaluation of
ANY Days Without Medication
Without Medication
medication effectiveness
Change medication?
Increase dose?
Augment?
Patients
Long-acting injectables
Known adherence allows evaluation of
medication effectiveness
Missed dose can trigger intervention
Patient–clinician interaction
Atypical
Conventional
Atypical
Conventional
Barnes TRE, Curson D. Drug Safety. 1994;10:464-479.
Urquhart J. Clin Pharmacokinet. 1994;27:202-215.
National Association of State Mental Health Program Directors.
Technical Report on Psychiatric Polypharmacy; 2001.
Mahmoud RA et al. Poster. 1997 ACNP Meeting; Kamuela, HI.
Long-Term Medication Compliance:
Mirror Image Studies Comparing Number of Hospital Days - Depot v. PO
Similar for Atypical vs Conventional
Antipsychotics
Duration No. Hosp Days
Patients (yrs)
on depot value
Prescription Refill Rate
Denham & Adamson,1973 103
12-40 mo 8,719
Devito et al, 1978
Adherent
Freeman, 1980
Gottfries and Green, 1974 36
Marriott and Hiep, 1976
Atypical
Conventional
Atypical
Conventional
12 months
Tegeler & Lehmann, 1981 78
Prescription refill rate = (# adherent fills / total # of fills ) x 100.
n=117 for conventional, n= 171 for atypicalDolder CR et al. Am J Psychiatry. 2002;159:103-108. Davis JM, Matalon L, Watanabe MD, Blake L. Drugs 1994;47(5):741-773.
Pharmacologic Treatment of
Initiation of Treatment
Schizophrenia
Consider contraindications to specific medications
Choose based on:
• Stabilze Patient on Drug to be Used
Past response
Side effects
• Assess Adverse Effects
Patient preference
Planned route of administration
• Consider Need forTherapeutic Drug
Clozapine is Gold Standard for treatment
Monitoring
resistance
No evidence for Polypharmacy
• Patient Education/Informed Consent
Negative symptom response is modest even
with Atypicals
Antidepressant uses
PolyTherapy
Major Depression
2 or more concurrent antipsychotics
Dysthymia
Not cross-taper
Panic Disorder
Few case reports
Generalized Anxiety
Very expensive
Similar mechanisms of action
PTSD
Bipolar Depression
Eating Disorders
Premenstrual dysphoric disorder
Treatment Options for
Depression
Antidepressants
Noradrenergic and S2 Antagonists
Specific Serotonin
Antidepressants
Antidepressants
Benzodiazepines
• Alprazolam
Monoamine
Depression
• Fluoxetine
• Amitriptyline
• Phenelzine
• Sertraline
• Desipramine
• Isocarboxazid
• Lithium
Inhibitors
• Thyroid
• Paroxetine
• Doxepin
• Tranycypromine
• Stimulants
• Fluvoxamine
• Imipramine
Selective
• Combination
Selective
• Nortriptyline
Serotonin
Serotonin
• Clomipramine
Reuptake
Norepinephrine
Inhibitorss
Reuptake
Inhibitors
Antidepressants
Antidepressants
SSNRI/SSRI
Bupropion
S2 Antag.
• Venlafaxine
• Trazodone
• Nefazodone
• Mirtazapine
• Amoxapine
• Maprotaline
Target Symptoms for
Phases of Treatment for
Antidepressant Treatment
DepressionRecovery
-mood/feeling -vegetative signs
Remission
slowed movement
“Normalcy”
irritability
slowed thinking
Response
pessimism
poor memory and
Recurrence
Symptoms
self-reproach
concentration
anxiety fatigue
verity
Se
-suicidal thoughts
constipation
Syndrome
-hopelessness
decreased sex drive
Continuation Maintenance
Treatment
anorexia
Treatment
Treatment
(4-9 months)
(≥ 1yr)
(6-12 wks)
-no enjoyment
weight change
insomnia
Adapted from: Depression Guideline Panel, Depression in Primary Care, AHCPR, April 1993.
Initiation of Therapy
Symptom Remission
• Dosing
2-4 Weeks
- Underdosing is primary problem with TCAs
- Initiate therapy with divided doses to minimize ADRs
• Relief of Depressed
- SRIs can be initiated at therapuetic doses
• Less Hopeless/
1-3 Weeks
- consider age of patient and adjust accordingly
Helpless
• Thoughts of Suicide
• Increased Activity,
Sex Drive, Self-care,
• Dosage Adjustment
and Memory
- Target dose should be achieved as quickly as tolerated
• Thinking and Movements
First Week
Normalize
- Improvement in 3-4 weeks of therapy
• Sleeping and Eating
- Consider increments/decrements/or alternates in
• Decreased Anxiety
Patterns Normalize
• Improvement in Sleep
nonresponsive patients
• Improvement in Appetite
- Maximal response in 8 weeks of therapy
Survival
Medication Maintenance
Recurrence rate of 30% in 3 years at full dose, 70%
at half dose
1. Goal is preventing new episode of depression
50-70% of patients will relapse over 1 year period
2. Potential Candidates:
without maintenance treatment
Three or more episodes of major depressive disorder
Two episodes and:
Risk of relapse continues to increase over time
a. Family history of bipolar disorder in 1st degree relative
Risk of relapse significantly reduced with
b. History of recurrence within 1yr after d/c of effective
maintenance therapy - 80-90% remain well during
pharmacotherapy, or poor symptom control in continuation
first year of maintenance therapy
c. Family history of recurrent major depression in a first degree
relative
Psychotherapy does not improve survival
d. Onset prior to age 20, or after age 60
significantly over medication management
e. Both episodes were severe, sudden or life threatening in the past 3
f. Concurrent depression and dysthymia
Frank, et.al., Arch Gen Psychiatry 1990;47:1093.
Adapted from: Depression Guideline Panel, Depression in Primary Care, AHCPR, April 1993.
Frank, et.al., J Affect Dis 1993;27:139.
Kupfer, et.al., Arch Gen Psychiatry 1992;49:769.
Antidepressant Side Effects
Antidepressant Side Effects
Bupropion
Trazodone
• Nausea
• Drowsiness
• Hypotension
• Nausea
• Insomnia
• Hypotension
• Diarrhea
• Dry Mouth
• Dizziness
• Diarrhea
• Seizures
• Dizziness
• Headache
• Blurred Vision
• Weight Gain
• Headache
• Weight Gain
• Weight Gain
• Nervousness
• Constipation
• Insomnia
• Hypertension
• Cardiac Effects
• Constipation
• Insomnia
• Hypotension
• Cardiac Effects
• Nervousness
• Sexual Dysfunction
• Sexual Dysfunction
• Weight Gain
• Constipation
• Insomnia
• Memory Impairment
• Cardiac Effects
• Sexual Dysfunction
• Sexual Dysfunction
• Urinary Retention
• Palpitations
• Sexual Dysfunction • Hypertensive Crisis
• Memory Impairment
Antidepressant Side Effects
Have you ever noticed?
Anybody going slower
S2 Antag.
than you is an idiot, and
• constipation
• sedation
anyone going faster
• lightheadedness
• nausea
• postural hypotension • weight gain
than you is a maniac.
• headache
• dizziness
• dry mouth
• dry mouth
• nausea
• constipation
George Carlen
• somnolence
• visual changes
• confusion
• pruitis/rash
• visual changes
• sexual dysfunction
• sexual dysfunction
• agranulocytosis
IV. MANIC-DEPRESSIVE
Target Symptoms for Mania
(BIPOLAR) ILLNESS
-mood disorder
-delusions
irritability
expansive
persecutory
manipulative
religious
A. Agents and Actions
grandiose
• Lithium
-hyperactivity
-schizophreniform
sleep disturbance
loose associations
• Valproic acid (Depakene, Depakote)
pressured speech
hallucinations
• Carbamazepine (Tegretol)
increased motor activity
assaultive/threatening
distractibility
hypersexuality
Acute Phase: Mania
Continuation Phase:
Ensure Safety, Rule out life threatening conditions
Eliminate mood elevating substances
Begins with remission of acute symptoms
Implement specific therapies to control acute
Continue successful acute therapies at full
symptoms
•Add agents as required by acuity and treatment response
to maintain effective serum levels
•Carry out each trial to end point
•D/C due to intoleralnce
consistent with ability to tolerate medication
•Fails to repond to maximal dose
Often must reduce Lithium
•Improvement sustained through continuation phase
Often must reduce Divalproex
+ Clonazep
am Antipsychotic + Bilateral ECT
Often must increase Carbamazepine
Choose duration > estimated natural course
≥ Double duration of last mania
Divalproex
≥ 12 weeks - if no reliable history
+ Carbamazepine
Maintenance/Discontinuation
Symptoms
Untreated
Begins with declaration of recovery
Sustained remission > 8 weeks
Gradual Taper of acute treatments
Maintain Prophylactic Therapies
Monitor - Clinical / Laboratory
Adverse effects
Therapeutic range
Clinical pattern of response
Depressive
Symptoms
a. Dosage Forms:
Valproic Acid
• Lithium carbonate capsules or tablets -
Eskalith®, and others (1 capsule or tablet =
a. Dosage forms
300 mg = 8 mEq Lithium)
• 100, 250, 500 mg capsules (Depakene)
• Lithium carbonate time-released tablets -
• 125, 250, 500 tablets (Depakote)
Eskalith SR (1 tablet = 450 mg = 12 mEq Lithium)
• 250mg/5 cc suspension
Lithobid (1 tablet = 300 mg = 8 mEq Lithium)
• Depakote ER - 500 mg tablets
• Lithium citrate syrup - Lithionate® (1
teaspoonful = 5 ml = 560 mg = 8 mEq Lithium)
b. Dosing
• rapid titration - 20 mg/kg
b. Dosing
Options for
Carbamazepine
Refractory Bipolar Patients:
Anticonvulsants
Hormones
a. Dosage forms
Gabapentin
Estorogen/progesterone
• 100 chewable tablets
Lamotrigine
Precursors
Acetazolamide
Tryptophan
• 200 mg tablets
Adrenergic Blocking agents
Clonidine
Atypical
• 100 mg/5cc suspension
Propranolol
Antipsychotics
Guanfacine
Calcium Channel Blockers
Clozapine
Risperidone
b. Dosing
Verapamil
Olanzapine
Nifedipine
Quetiapine
Nimodipine
Ziprasidone
????????
Aripiprazole
Primary Mood Stabilizers
Most Common Adverse
Danger/Warnings
CNS: Tremor, Sedation, Cognitive impairment
- Renal insufficency
GI: Abdominal pain, Diarrhea
- Complicated fluid or salt balance
Other: Thirst, Polyuria, weight gain, acne
- Myasthenia Gravis
Divalproex
- Severe psoriasis
CNS: Tremor, Dizziness, Sedation, Headache
- Pregnancy (esp 1st trimester)
GI: Nausea, Abdominal pain/indigestion
Other: Weight gain
Divalproex
Carbamazepine
Carbamazepine
- Impairment of liver function
- Cardiac, renal or liver
CNS: Sedation, Dizziness, Unsteady Gait,
- Blood dyscrasia
Incoordination,
- Pregnancy (esp 1st trimester)
- Blood dyscrasia
- Pregnancy (esp 1st
Blurred vision, diplopia, Cognitive impairment
trimester)
GI: Abdominal pain, Diarrhea
Other: Thirst, Polyuria, weight gain, acne
Most Worrisome Adverse
Advantages of
Lithium Therapy
Acute intoxication: Seizure, Coma, Death
- will control a manic patient without a
Intoxication Sequelae: CNS, Renal, Cardiac
"drugged effect"
Other: Thyroid inhibition, Arrhythmias, Renal dysfunction,
Teratogenicity
- will normalize mood
Divalproex
- very good prophylactically to decrease
Pancreatitis, Hepatic Failure, Throbocytopenia
mood swings
Teratogenicity, Rash, Stevens-Johnsons, SLE
- relapses, when they occur, are less severe
Carbamazepine
and usually shorter in duration
Aplastic Anemia, Agranulocyctosis,
- blood concentration monitoring allows
Arrythmia, Hyponatremia, Teratogenicity
careful titration to therapeutic
Rash- Erythema Multiforme, Toxic Epidermal Necrolysis,
concentration
Stevens-Johnson, SLE
- low drug cost
Advantages of Carbamazepine
and Valproic Acid Treatment
Lamotrigine- Lamictal
- beneficial in rapid cycling persons
Approved for maintenance
- alternative for persons not responsive or
Not effective for acute manic episodes
who do not tolerate lithium
Delayed time to intervention for depression
-will normalize mood
Less delay in time to intervention for mania
-very good prophylactically to decrease
Side effects
mood swings
Headache
Nausea
-relapses, when they occur, are less severe
Insomnia
and usually shorter in duration
Rare 0.1% severe rash
-blood concentration monitoring allows
careful titration to therapeutic
concentration
Gabapentin- Neurontin
Topiramate- Topamax
$430 Million
Mania trial failed- manufacturer
placebo more effective in controlled
stopped development
Side Effects
Sedation
Sedation
Dizziness
Dizziness
No drug interactions
Treatment Options for Panic Disorder
Antianxiety Agents
Tricyclic
Benzodiazepines
Antidepressants
• Alprazolam
• Imipramine
• Clonazepam
A. Agents and Actions
• Desipramine
• Diazepam
• Nortriptyline
Benzodiazepines
Panic Disorder
- long-acting (t1/2 > 40 hours)
Monoamine
- medium-acting (t1/2 10-40 hours)
• Propranolol
Inhibitors
• Combination
• Phenelzine
• Valproate
• Buspirone
Non-benzodiazepine
• Fluoxetine
• Paroxetine
- buspirone (BuSpar)
• Fluvoxamine
- meprobamate (Miltown, Equanil)
BZDP Agent
Dose Range(mg/d)
T1/2 (hrs)/metab Active Metabolite
Target Symptoms for Anxiety
alprazolam
OH-alprazolam
chlordiazepoxide
4-29/28-100
DMD, oxazepam, DMC
clonazepam
• Motor Tension
chlorazepate
diazepam
14-70/30-200
DMD, oxazepam,
- Trembling, twitching
- Muscle Tension, aches
temazepam
or feeling shaky
or soreness
3-OH-diazepam
estazolam
- Restlessness
- Easy fatigability
flurazepam
3/40-250
N-desalkylflurazepam,
OH-ethylflurazepam
halazepam
14/30-96
DMD, 3-OH-halazepam
• Autonomic Hyperactivity
lorazepam
- Shortness of breath
- Dizziness or
oxazepam
prazepam
DMD, oxazepam,
lightheadedness
desalkylprazepam
- Sweating, cold clammy hands
- Frequent urination/
quazepam
15-40/39-120
2-oxoquazepam,
desalkylflurazepam
temazepam
- Palpitations or tachycardia
- Nausea, diarrhea, GI
triazolam
0.125-0.5
metabolite
distress
- Dry mouth
- "Lump in throat"
Target Symptoms in Anxiety (continued)
SIDE EFFECTS
• Vigilance and Scanning
Benzodiazepine agents
- Feeling keyed up or on edge- Insomnia
• long-acting versus short-acting
- Easy to startle
- Difficulty
• common effects
concentrating
drowsiness
sedation
- Irritability
blurred vision
psychomotor impairment
disorientation
• Panic (in addition to above)
aggression
confusion
- Choking
- Fear of going crazy
excitement
- Paresthesias
- Chest pain/discomfort
• discontinuation: rebound, relapse,
- Fear of dying
recurrence and withdrawal
• abuse, dependence, addiction
SIDE EFFECTS
Buspirone
“There is sleep
• common side effects
sedation
insomnia
agitation
headache
in the grave.”
weakness
gastrointestinal
dizziness
• abuse potential
Medications Used to Treat Sleep Disorders
Control Drug Sedative
DISORDERS/HYPNOTICS
Sched. t1/2 hr Dose
of Txt. Metab
• Key to treatment is accurate
Ambien®
zolpidem
diagnosis
Ativan®
lorazepam
Benadryl®
diphenhydramine No
• Sleep history is imperative
Dalmane®
flurazepam
• Nonpharmacological interventions
quazepam
7.5-015 n/a
are crucial elements to treatment
Halcion®
triazolam
0.125-0.5 n/a
strategy
Noctec®
chloral hydrate
250-2000 2-3
ProSom®
estazolam
Restoril®
temazepam
Sonata ®
Zaleplon
Non-benzo Sedatives
3 Basic Issues in Diagnosis
(zolpidem)
– Inattention - lack of detail orientation,
Sonata (Zaleplon)
makes mistakes, cannot sustain
Recommended for 7-10 days only
activity, difficulty listening, organizing,
Surprise
forgetful, loses things
Only action at Benzo receptor
– Hyperactivity - fidgets, moves around,
Selective Benzodiazepine
difficulty being quiet, on the go, talks
No amnesia
excessively
No muscle relaxation
– Impulsivity - difficulty waiting turns,
blurts out answers, interrupts/intrudes
Treatment Options for ADHD
Tricyclic
Antidepressants
ISSUES IN TREATMENT
•Tofranil
•Norpramin
Stimulants
– Education - family, child, teacher
– Parent Management Training
– School Training
Selective
– Pharmacotherapy
Serotonin
Reuptake
Inhibitors
•Prozac
Venlafaxine
•Paxil
(Effexor)
•Zoloft
ADHD Medications
Target Symptoms for ADHD
MAX DOSAGE
Catapress Clonidine
0.2-2.4 (mg/day)
Tenex Guanfacine
(mg/day)
• Motor hyperactivity
Adderall
Dextroamphetamine
Amphetamine
2.5 - 40 mg/day
• Attention Span
AdderalXR
1/2 dose of Adderall
Pemoline
0.5-3.0 (mg/kg/day)
• Ability to complete tasks
Dexedrine Dextroamphetamine 0.15-0.3 (mg/kg/day)
BID-TID
(not after
• Impulsivity
Methylphenidate
0.3-0.6 (mg/kg/day)
• Frustration Tolerance
Ritalin LA
(not after
Concerta
• Distractibility
Metadate CD
Dexmethylphenidate 1/2 Ritalin dose
• Socialization-Relationships w/ Peers
Strattera
Atomoxetine
80 mg/day
Tofranil
Imipramine
25-300 (mg/day)
• Ability to accept limit setting
Wellbutrin Bupropion
150-450 (mg/day)
Venlafaxine
75 - 225 (mg/day)
SIDE EFFECTS
Conversion - PO to Depot
Stimulant Medications
Fluphenazine
• Insomnia
• Mood lability (crying)
• Anorexia
• Irritability
• Stabilze on oral fluphenazine prior to
• Weight loss
• Euphoria
conversion
• Nausea
• Sterotypy
• Give injections into the gluteus by “Z
• Tachycardia
• Dizziness
track” method
• Growth suppression
•Tic disorders
• Exacerbation of psychosis / mania
• Give 1.2 - 1.6 times the daily oral
Clonidine/Guanfacine
Atomoxetine
dose each week - two weeks
• dry mouth
• Nausea
• Consider dosage reductions after 3
• Dizziness
• Abdominal pain
• Constipation

Source: http://www.autismconsultingservices.com/inabc/pdf/conference/KettenisPsychotropicsMadeSimple.pdf