Update in
Clinical Psychopharmacology
Peter A. DeMaria, Jr., M.D., FASAM, DFAPA
Tuttleman Counseling Services
Temple University
Clinical Professor of Psychiatry & Behavioral Sciences
Temple University School of Medicine
Philadelphia, PA
Disclosures
• I am a treatment advocate for Reckitt-Benkiser
Pharmaceutical Co..
• Use of trade versus generic drug names
• Off-label use of drugs.
• Role of counseling/psychotherapy
Website:
https://sites.google.com/site/achapsychopharmacology/
Case A - Alisha
Alisha is a 19 y/o sophomore student who
presents for follow-up. A month ago she was
diagnosed with major depression and started
on citalopram 20 mg daily. She reports that she
is tolerating the medication without side effects
and has started to feel better but still has crying
spells, difficulty with sleep low energy and is
increasingly worried about completing her
academically demanding schedule.
Evaluating a Response
to Antidepressant Medication
• Is the patient taking it?
– Ambivalence/stigma towards medication
– Parental pressure to avoid medication
– Availability (insurance, cost)
• Is it the right:
– Drug?
– Dose?
– Length of time?
• Are there co-morbid conditions?
Case A – Alisha (Part 2)
Alisha reports that she got the medication
and assures you that she has been compliant.
You review the time course of response and
recommend that she increase the dose to 40
mg to optimize her response to treatment.
Additionally, you ask if she has been able to
connect with the counseling center. She tells
you that she has an intake appointment in
the next week.
Case A – Alisha (Part 3)
(One month later; 2 months on citalopram)
Alisha returns for her follow-up visit. She has
been taking citalopram 40 mg daily and thinks it
might be making her tired. She connected with
a therapist at the counseling center and likes
her. Alisha still reports decreased energy and
feeling down. Her relationship with her partner
has deteriorated and she is having thoughts of
cutting herself. She denies SI.
STAR*D
• Largest (n=4041, age 18-75 y/o) study of
treatment of non-psychotic MDD
• Multiple real-world psychiatric and primary care
settings
• Conducted between July 2001 and April 2004
• Funded by National Institute of Mental Health
(NIMH)
• Goal was remission (< 5 on the QIDS-C16)
• Treatment involved 6 levels with patient ability to
choose options
• Available at www.star-d.org
STAR*D
• MDD is a chronic and recurrent illness.
• Using objective measurements of symptoms and side
effects can help with treatment decisions.
• Remission can take time (at least 8, but up to 14
weeks).
• Many steps may be needed to reach remission.
– Level 1 (citalopram @ 8 wks.): Remission = 37%,
Response = 49%
– Remission rate of 50% was reached after 2 steps.
– Remission rate of 70% was reached after 4 steps
• Remission results in better log-term outcomes.
• Participant attrition is high.
(Warden D et al. The STAR*D project results: a comprehensive review
of findings. Current Psychiatry Reports 9:449-459, 2007.)
Treatment Options for Non-Responsive MDD
• Optimize dose and treatment time
• Add psychotherapy
• In-class switch
(e.g. SSRI → SSRI)
• Between class switch
(e.g. SSRI → SNRI/other agent)
• Augment
• Brain stimulation
Augmentation Strategies
in Treating Major Depression
•
•
•
•
•
Add a second AD with a different MOA
L-Methylfolate (7.5 - 15 mg/day)
T3 (5 - 50 mcg)
Lithium
Atypical antipsychotic
– Aripiprazole (2 – 15 mg/day)
– Quetiapine XR (50 – 300 mg/day)
• Supplements (?)
– Omega-3-fatty acids
– SAMe (1600 mg/day)
– Creatine (5 gm/day)
Vilazodone (Viibryd)
•
•
•
•
•
•
•
•
MOA: SSRI and partial5-HT1A agonist
Metabolism: P450 CYP 3A4
FDA Approval: Major depression
Efficacy demonstrated compared to placebo; no
head-to-head trial with other AD. Separates from
placebo at one week (?).
Side effects: diarrhea. Insomnia, dizziness
Dosing: Start with 10 mg increase weekly to 20 mg
then 40 mg.
Take with food
Benefits(?): low sexual dysfunction, no weight gain
Focal Brain Stimulation
• Vagal Nerve Stimulation
(VNS)
– Pulse generator implanted
in the left chest wall
– Electrode wrapped around
the left vagus nerve
– Pulse on for 30 seconds and
off for 5 minutes
– Efficacy = ?
• Transcranial magnetic
stimulation (TMS)
– Uses an electromagnetic
coil placed against the
scalp to create a rapidly
changing magnetic field
that depolarizes neurons.
– Outpatient procedure
– Safe and well tolerated
– Efficacy =?
On the Horizon
• Starting 2 versus 1agent at treatment
initiation
• NMDA receptor antagonists (ketamine)
• Corticotropin releasing factor-1 (CRF1)
antagonists
• Glucocorticoid receptor antagonists
• Substance P receptor antagonists
• Melanocyte inhibiting factor (nemifitide)
• Melatonin receptor antagonists
• Focal and deep brain stimulation therapies
Case B - Nicole
Nicole is a 21 y/o junior who presents
complaining of panic attacks and anxiety. In
talking with her, she states that she feels no one
likes her and she is just a failure. She worries
about her family and her dying grandmother.
Her sleep is poor and she has lost interest in
food. She isn’t interested in her school work
and wonders if she would just be better off
dead.
Differential Diagnosis of “Anxiety”
•
•
•
•
•
•
•
Secondary to a medical condition
Substance induced
Major depression
Mania/hypomania
Psychotic disorder
Personality disorder
Anxiety disorder
Anxiety is a non-specific symptom;
Need to determine the cause
DSM-IV vs. DSM-5
DSM-!V
• Anxiety Disorders
–
–
–
–
–
–
–
Specific phobia
Panic disorder
Social phobia
OCD
PTSD
Acute stress
Generalized anxiety disorder
• Adjustment disorders
DSM-5
• Anxiety Disorders
–
–
–
–
Specific phobia
Social anxiety disorder
Panic disorder
Generalized anxiety disorder
• O-C & Related Disorders
– OCD
• Trauma & Stressor Related
Disorders
– PTSD
– Acute stress disorder
– Adjustment disorder
Pharmacologic Treatments
•
•
•
•
Benzodiazepines
SSRI/SNRI
Tricyclic antidepressants
Other agents
J of Clin. Psychiatry, 60(5), 252, May 1999
FDA Approved Indications MDD PD OCD SP PTSD GAD PMDD BN ND FM
SSRI
Citalopram (Celexa)
X
Escitalopram (Lexapro)
X
X
Fluoxetine (Prozac)
X
X
X
X
X
Fluvoxamine (Luvox)
X
Paroxetine (Paxil/CR)
X
X
X
X
X
X
X
Sertraline (Zoloft)
X
X
X
X
X
X
SNRI
Desvenlafaxine (Pristiq)
X
Duloxetine (Cymbalta)
X
X
X
Mirtazapine (Remeron)
X
Venlafaxine (Effexor/XL)
X
X
X
X
Tricyclic Antidepressant
Clomipramine (Anafranil)
X
Other
Bupropion (Wellbutrin)
X
X
Buspirone (BuSpar)
X
Vilazodone (Viibryd)
X
SSRI/SNRIs in Anxiety Disorders
Advantages
• High efficacy
• Non-addicting
• Effective for a number
of conditions
Disadvantages
• Can take 2-8 weeks or
longer to be effective
• Side effects
• Drug interactions
• Discontinuation
syndrome
Other Options for Anxiety Disorders
•
•
•
•
•
Buspirone
Beta blockers (e.g. propranolol)
Tricyclic antidepressants
Vilazodone (SSRI/5-HT1A Partial agonist)
Antipsychotics
• Typical (e.g. Trifluoperazine)
• Atypical (e.g. Quetiapine)
• Antihistamines
• Hydroxyzine
• Anticonvulsants
• Gabapentin/Pregabalin
• Combinations
Psychotropic Choice for Specific Conditions
Condition
Pharmacotherapy Options
Obsessive compulsive disorder SSRI
Clomipramine
Social anxiety disorder
SSRI/SNRI
Panic disorder
SSRI
TCA
Benzodiazepine
SSRI
PTSD
Generalized anxiety disorder
SSRI/SNRI
Benzodiazepine
Buspirone
Case C - Marc
Marc is a 22 y/o junior who presents
requesting a refill of his medication. He tells
you he was diagnosed with bipolar disorder
and ADHD and is currently prescribed:
lamotrigine 200 mg daily, escitalopram 10 mg
daily, clonazepam 1 mg BID, zolpidem 5 mg
HS, and Adderall-XR 20 mg qAM.
Bipolar disorder vs. Bipolar spectrum disorder
• Definition – Spectrum disorder
• Epidemiology (lifetime prevalence)
– Bipolar I disorder = 1%
– Bipolar spectrum disorders = 2.6 – 6.5%
• Delayed diagnosis/missed diagnosis
– Screen depressed patients for possible bipolar
depression (e.g. MDQ, BSRS)
Mood Disorders – A Spectrum Disease
"Normal"
Mania
Hypomania
Euthymia
Dysthymia
Major depression
Bipolar I Disorder
Bipolar II Disorder
Major depression
Cyclothymia
Dysthymia
Borderline Personality Disorder
The Heterogeneity of Bipolar Disorder
Taken from:
http://www.psychosisbipolar.com/information-aboutpsychoses-57.htmlTaken
Lifetime Comorbidity with Bipolar Disorder
Disorder Class
Anxiety Disorders
Panic disorder
PTSD
GAD
SAD
ADHD
Substance Use Disorders
Alcohol abuse
Alcohol dependence
Drug abuse
Drug dependence
Comorbidity (%)
20.1
24.2
29.6
35.4
31.4
39.1
23.2
28.8
34.0
Treating Bipolar Disorder
• Use mood charting.
• Combination pharmacotherapy is the rule
rather than the exception.
• Mood stabilizers are the cornerstone of
therapy.
• Optimize therapeutic effect and tolerability
while minimizing side effects.
• Antidepressants may worsen the disease
course.
Pharmacotherapy for Mood Disorders
1. Mood stabilizers
Lithium
2. Anticonvulsant Mood Stabilizers
Valproic acid (Depakote)
Carbamazepine (Tegretol)
Lamotrigine (Lamictal)
3. Atypical Antipsychotics
See Chart
4. Combination
Olanzapine/fluoxetine (Symbyax)
FDA Approved Indications for Atypical Antipsychotics
Indication
Schizophrenia
OLA
RIS
ILO
QUE
ZIP
ARI
ASEN
LUR
X
X
X
X
X
X
X
X
X
X
X
X
Schizoaffective
Disorder
X
Bipolar
Mania/Mixed
X
X
Bipolar
Depression
X
X
Adjunct in MDD
X
X
X
X
OLA = Olanzapine, RIS = Risperidone, ILO = Iloperidone, QUE = Quetiapine,
ZIP = Ziprasidone, ARI = Aripiprazole, ASEN = Asenapine, LUR lurasidone
Pharmacotherapy for Bipolar Disorder
Phase
Mania
Depression
Maintenance
Treatment Options
Lithium (Li)
Valproate (VP)
Atypical antipsychotic
Carbamazepine/oxcarbamazepine
Li/VP + atypical antipsychotic
Electroconvulsive therapy (ECT)
Optimize mood stabilizer
Lamotrigine
Quetiapine
Lurasidone
Olanzapine/fluoxetine
Mood stabilizer + antidepressant
In general, continue regimen that is working,
however, simplify as clinically indicated.
Questions?