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Transcript
Psychotropic drugs
Prof elham aljammas
Sept 2015
objectives
Identify general pharmacologic strategies
 Discuss antidepressants including
indications for use and side effects
 Describe mood stabilizers including
indications for use and side effects
 Review antipsychotics including how to
choose an antipsychotic and side effects
 Identify anxiolytic classes and indications
for use

Management strategies
-Adjust dosage for optimum benefit,
safety and compliance.
-Use adjunctive and combination
therapies if needed however always
strive for the simplest regimen.
-Keep your therapeutic endpoint in
mind.
Psychotropic drugs
 Treat
mood, cognition, and behavioral
disturbances associated with
psychological disorders
 Most are not used recreationally or
abused
 Benzodiazepines are the exception
General classes of disorders
Mood
 Anxiety
 Psychotic
 Other Disorders
 Attention Deficit Disorder

Depression

Depression is a serious disorder that
afflicts approximately 14 million adults in
the United States each year. The lifetime
prevalence rate of depression in the
United States has been estimated to
include 16 percent of adults (21 percent
of women, 13 percent of men), or more
than 32 million people
Antidepressants
Indications:
 Unipolar and bipolar depression,
 organic mood disorders,
 schizoaffective disorder,
 anxiety disorders including OCD, panic,
social phobia, PTSD,
 premenstrual dysphoric disorder
 and impulsivity associated with
personality disorders.

General guidelines



Antidepressant efficacy is similar so selection
is based on past history of a response, side
effect profile and coexisting medical
conditions.
There is a delay typically of 3-6 weeks after a
therapeutic dose is achieved before
symptoms improve.
If no improvement is seen after a trial of
adequate length (at least 2 months) and
adequate dose, either switch to another
antidepressant or augment with another
agent.
Mood disorders/Antidepressants
MAO Inhibitors
 Tricyclics
 Selective Serotonin
Reuptake Inhibitors
 Dual Action
Antidepressants
 Selective Norepinephrine
Reuptake Inhibitors
 Atypical antidepressant

Mood Stabilizers
(Antimanic
Agents)
LithiumCarbonate
Valproic Acid
Carbamazepine
Lamotragine
Topirimate
MAOI








Use in late 1950s & ended in early 1960s
use ended due to side effect (death)
MAO breaks down many chemicals including
tyramine
Tyramine is present in cheeses, red wines, alcohol,
smoked fish
MAO in liver breaks down tyramine
Causes a hypertensive crisis "cheese syndrome"
increased blood pressure ➔ stroke ➔ death
increased heart rate ➔ heart attack ➔ death
MAOI
Bind irreversibly to monoamine oxidase
thereby preventing inactivation of biogenic
amines such as norepinephrine, dopamine
and serotonin leading to increased synaptic
levels.
 Are very effective for depression
 Side effects include orthostatic hypotension,
weight gain, dry mouth, sedation, sexual
dysfunction and sleep disturbance
 Hypertensive crisis can develop when
MAOI’s are taken with tyramine-rich foods
or sympathomimetics.

MAOI


Serotonin Syndrome can develop if take
MAOI with meds that increase serotonin or
have sympathomimetic actions. Serotonin
syndrome sx include abdominal pain,
diarrhea, sweats, tachycardia, HTN,
myoclonus, irritability, delirium. Can lead to
hyperpyrexia, cardiovascular shock and
death.
To avoid need to wait 2 weeks before
switching from an SSRI to an MAOI. The
exception of fluoxetine where need to wait
5 weeks because of long half-life.
SSRI
s
Tricyclic antidepressants
Act as agonists to catecholamines
 No "cheese syndrome"
 Side effects are the major problem
 Cardiotoxic
 Sedative action
 Block acetylcholine system, especially
muscarinic receptors
 blurred vision, dry mouth, urinary retention,
constipation, mental confusion
 Block histamine receptors - sedation

prescaution
Very effective but potentially unacceptable
side effect profile i.e. antihistaminic,
anticholinergic, antiadrenergic
 Lethal in overdose (even a one week
supply can be lethal!)
 Can cause QT lengthening even at a
therapeutic serum level

TCA
Have tertiary amine side chains
Side chains are prone to cross react with
other types of receptors which leads to
more side effects including antihistaminic
(sedation and weight gain), anticholinergic
(dry mouth, dry eyes, constipation, memory
deficits and potentially delirium),
antiadrenergic (orthostatic hypotension,
sedation, sexual dysfunction)
 Act predominantly on serotonin receptors
 Examples:Imipramine, amitriptyline, doxepin,
clomipramine


SSRI












Selectively block re-uptake of 5-HT
Work on DA and NE as well but very little
Eliminate ACh and antihistamine effects
No more effective than MAOIs or tricyclics
Better because there are fewer side effects
On market since late 1980s & early 1990s
Fluoxetine – Prozac
Sertraline - Zoloft
Paroxetine - Paxil
Fluvoxamine - Luvo
Citalopram - Celexa
Escitalopram - Lexapro
SSRI












Selectively block re-uptake of 5-HT
Work on DA and NE as well but very little
Eliminate ACh and antihistamine effects
No more effective than MAOIs or tricyclics
Better because there are fewer side effects
On market since late 1980s & early 1990s
Fluoxetine – Prozac
Sertraline - Zoloft
Paroxetine - Paxil
Fluvoxamine - Luvo
Citalopram - Celexa
Escitalopram - Lexapro
Selective serotonin reuptake
inhibitors





Block the presynaptic serotonin reuptake
Treat both anxiety and depressive
Most common side effects include GI upset,
sexual dysfunction (30%+!), anxiety,
restlessness, nervousness, insomnia, fatigue
or sedation, dizziness
Very little risk of cardiotoxicity in overdose
Can develop a discontinuation syndrome
with agitation, nausea, disequilibrium and
dysphoria
SNRI
Selectively inhibits NE transporter.

Blocks re-uptake.
 Atomoxetine (Strattera)
 Reboxetine (Edronax,Vestra)
 Dual action AD
 Affinity for both 5-HT and NE.
 Block re-uptake for both
 In this sense, like TCAs
 Duloxetine - Cymbalta

Atypical Antidepressants
The atypical antidepressants are a mixed
group of agents that have actions at
several different sites. This group includes
bupropion
, mirtazapine
,nefazodone], and
trazodone

atypical antidepressants
Bupropion (Wellbutrin)
 No effect on either 5-HT or NE
 Effective at blocking DA reuptake
 May be similar action to cocaine
 Lowers seizure threshold
 Venlafaxine (Effexor)
 5-HT, DA and NE reuptake blocker

Drugs for bipolar


Treat the manic phases of Bipolar Disorder
Lithium




Valproic Acid
Carbamazepine/Oxcarbazepine
Lamotragine
Topirimate

Symbyax – Combo of olanzepine and
fluoxetine (Zyprexa & Prozac)
Mood Stabilizers
Indications: Bipolar, cyclothymia,
schizoaffective, impulse control and
intermittent explosive disorders.
 Classes: Lithium, anticonvulsants,
antipsychotics
 Which you select depends on what you
are treating and again the side effect
profile.

lithium
Only medication to reduce suicide rate.
Rate of completed suicide in BAD ~15%
Effective in long-term prophylaxis of both
mania and depressive episodes in 70+% of
BAD I pts
 Factors predicting positive response to
lithium
 Prior long-term response or family member
with good response
 Classic pure mania
 Mania is followed by depression



LITHIUM



Before starting :Get baseline creatinine, TSH
and CBC. In women check a pregnancy testduring the first trimester is associated with
Ebstein’s anomaly 1/1000 (20X greater risk
than the general population)
Monitoring: Steady state achieved after 5
days- check 12 hours after last dose. Once
stable check q 3 months and TSH and
creatinine q 6 months.
Goal: blood level between 0.6-1.2mmol /lit
Lithium side effects
Most common are GI distress including
reduced appetite, nausea/vomiting, diarrhea
 Thyroid abnormalities
 Non significant leukocytosis
 Polyuria/polydypsia secondary to ADH
antagonism. In a small number of patients
can cause interstitial renal fibrosis.
 Hair loss, acne
 Reduces seizure threshold, cognitive slowing,
intention tremor

Lithium toxicity
Mild- levels 1.5-2.0 see vomiting, diarrhea,
ataxia, dizziness, slurred speech,
nystagmus.
 Moderate-2.0-2.5 nausea, vomiting,
anorexia, blurred vision, clonic limb
movements, convulsions, delirium,
syncope
 Severe- >2.5 generalized convulsions,
oliguria and renal failure

Study Questions







Choose the ONE best answer.
12.1 A 55-year-old teacher began to experience changes in mood.
He was losing interest in his work and lacked the desire to play his
daily tennis match. He was preoccupied with feelings of guilt,
worthlessness, and hopelessness. In addition to the psychiatric
symptoms, the patient complained of muscle aches throughout his
body. Physical and laboratory tests were unremarkable. After 6
weeks of therapy with fluoxetine, the patient's symptoms resolved.
However, the patient complains of sexual dysfunction.Which of the
following drugs might be useful in this patient?
A. Fluvoxamine.
B. Sertraline.
C. Citalopram.
D. Mirtazapine.
E. Lithium.

Correct answer = D. Sexual
dysfunction commonly occurs with
TCAs, SSRIs, and SNRIs. Mirtazapine is
largely free from sexual side effects.
A 25-year-old woman has a long history of
depressive symptoms accompanied by body
aches. Physical and laboratory tests are
unremarkable. Which of the following drugs
might be useful in this patient?
 A. Fluoxetine.
 B. Sertraline.
 C. Phenelzine.
 D. Mirtazapine.
 E. Duloxetine.

Correct answer = E. Duloxetine is an
SNRI that can be used for depression
accompanied by neuropathic pain.
MAOs and SSRIs have little activity
against neuropathic pain
A 51-year-old woman with symptoms of
major depression also has narrow-angle
glaucoma. Which of the following
antidepressants should be avoided in this
patient?
 A. Amitriptyline.
 B. Sertraline.
 C. Bupropion.
 D. Mirtazepine.
 E. Fluvoxamine.


Correct answer = A. Because of its
potent antimuscarinic activity,
amitriptyline should not be given to
patients with glaucoma because of the
risk of acute increases in ocular
pressure. The other antidepressants all
lack antagonist activity at the
muscarinic receptor.
A 36-year-old man presents with symptoms of
compulsive behavior. If anything is out of order,
he feels that “work will not be
accomplished effectively or efficiently.―
He
realizes that his behavior is interfering with his
ability to accomplish his daily tasks but cannot
seem to stop himself. Which of the following
drugs would be most helpful to this patient?
 A. Imipramine.
 B. Fluvoxamine.
 C. Amitriptyline.
 D. Tranylcypromine.
 E. Lithium.

Correct answer = B. Selective serotonin
reuptake inhibitors are particularly
effective in treating obsessivecompulsive disorder; flu vox amine is
approved for this condition. The other
drugs are ineffective in the treatment
of obsessive-compulsive disorder.