PSYCHOPHARMACOLOGY: Part II

BIO 301
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 Drugs for Major Depression
Antidepressants have many therapeutic uses
Primary approval: treat major Depression as
defined by the DSM IV- TR
Other indications
Anxiety/panic disorder, OCD, PTSD, Social phobia
Bulimia, anorexia nervosa
Bipolar depression
IBS, enuresis
Neuropathic pain
ADHD
Smoking cessation
Autism
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 Major Classes of Antidepressants
Selective Serotonin Reuptake Inhibitors
[SSRIs]
Monoamine Oxidase Inhibitors [MAO]
Tricyclic Antidepressants [TCA]
Miscellaneous

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SSRIs

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 SSRIs
1st line of drug therapy for
depression
Action: selective inhibition of
5-HT reuptake
OD does not cause
cardiotoxicity
Can interact adversely
w/MAOs & other serotonergic
drugs: must avoid combo
Used late in pregnancy: lead to
withdrawal syndrome &
persistent HTN in the infant
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 SSRIs
Serotonin Syndrome
Patient at risk when used in combo w/other
meds
Symptoms present as:
Confusion, hypomania,
Restlessness, myoclonus,
Hyperreflexia, diaphoresis,
Shivering, tremor, diarrhea
Mydriasis, autonomic instability
[hypertensive], tachycardia, agitation
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 SSRIs
Serotonin Syndrome:
Treatment
D/C medication
Supportive measures:
Cooling blanket
Benzos [myoclonus]
Anticonvulsants
Antihypertensives
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 SSRIs
Side Effects
GI upset: nausea
Insomnia
Restlessness, agitation
Irritability
Headache
Sexual dysfunction: priaprism, anorgasmia
Discontinuation of therapy
Withdrawal syndrome, HA, GI distress, dizziness,
impaired concentration, flu-like symptoms, insomnia,
anxiety

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 SSRIs
Fluoxetine [Prozac]
Neonatal effects: use in pregnancy
Teratogenesis: low. 2 SSRIs: heart defects possible: fluoxetine
[Prozac], paroxetine [Paxil]
Suicide risk: may increase risk in depressed pt [early phase];
greatest: children/adoles./young adult.
EPS: less frequent
Bruxism: clenching and grinding teeth [during sleep]
Bleeding disorders: {Prozac]can increase risk. How? Impede
platelet aggregation.
Hyponatremia: [fluoxetine:Prozac]: older patient on
thiazides: Na <135 mEq/L. Monitor serum Na baseline and
thereafter.
Skin rash, dizziness/fatigue
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 SSRIs
Drug interactions: Prozac
MAOIs & other serotonergic agents
Coumadin: Monitor PT/INR closely
TCA & Lithium: Prozac increases drug levels of
these agents. Exercise caution.

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 Serotonin/Norepinephrine Reuptake
Inhibitors [SNRI]
Venlafaxime [Effexor, Effexor SR]: 1st SSNRI
Powerful block of NE & 5-HT uptake and weak
blockade of dopamine
Use: major depression, gen. anxiety disorder, social
anxiety [social phobia]
Used when pt does not respond to SSRIs
Can cause dose-related systolic HTN [uncontrolled
pt], GI upset
Desvenlafaxine [Pristiq] [2008]
Same action as Effexor
Both have same effects as SSRIs and SE 13
 Serotonin/Norepinephrine Reuptake
Inhibitors [SNRI]
Duloxetine [Cymbalta]
2nd SSNRI approved for major depression
Powerful inhibitor of 5-HT & NE reuptake
Also approved for fibromyalgia, generalized anxiety disorder, pain of
diabetic peripheral neuropathy
Can cause small increase in BP [monitor BP], sexual dysfunction, nausea,
dry mouth, insomnia, constipation, reduced appetite, fatigue,
diaphoresis, blurred vision
Promotes mydriasis: NOT for use by patients with uncontrolled narrow-
angle glaucoma
Liver toxicity: CONCERN. Monitor LFTs [serum transaminase is elevated].
DO not give to pre-existing liver disease or drinkers.
Withdrawal syndrome with abrupt discontinuation
Serotonin syndrome if combine with MAOI
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 Tricyclic Antidepressants [TCAs]
1st widely used
antidepressants to treat
depression.
Unfavorable side effect profile
2nd line of defense after
development of SSRIs
Most dangerous effect:
Cardiac toxicity
1st TCA: imipramine [Tofranil]
[1950s]

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 Chemistry
Imipramine [Tofranil]
3-rings in nucleus of drug,
hence classification:
Tricyclic antidepressants
Similar in structure to
Phenothiazines:
share some common actions:
sedation, orthostatic hypotension, anticholinergic
effects

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 Examples of TCAs
Amitriptyline [Elavil]
Clomipramine [Anafril]
Desipramine [Norpramine]
Doxepin [Sinequan]
Imipramine [Tofranil]: prototype
Nortiptyline [Aventyl]
Amozpine [Ascendin]

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 TCAs
Action
Block neuronal reuptake of
2 monoamine
transmitters:
norepinephrine [NE] &
serotonin [5-
hydroxytryptamine or 5-
HT].
Some block reuptake of NE
and 5-HT & others only
block reuptake of NE

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 TCAs
Anticholinergic effects: BLOCKADE OF
MUSCARINIC RECEPTORS
CNS: Sedation [usually taken at hs]: BLOCKADE
OF HISTAMINE RECEPTORS IN CNS
CARDIOTOXIC: dysrhythmias
EKG: recommended: baseline
Orthostatic hypotension: BLOCKADE OF
ALPHA-1 ADRENERGIC RECEPTORS

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 TCAs
Diaphoresis
Seizures: lower seizure threshold
Hypomania: on occasion may produce too
much of a good thing.
Suicide risk: may increase risk of
Yawngasm: WHAT? Spontaneous
_____________while yawning. Honest!

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 TCAs
Drug interactions
MAOI: severe HTN
Direct-acting sympathomimetics: potentiate
responses to these agents [Epi, dopamine]
Indirect-acting sympathomimetics: decrease
responses to these agents [ephedrine,
amphetamine
Anticholinergic agents
CNS depressants
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 TCAs
Toxicity
One of the easiest psychiatric drugs to kill self with
OD can be life-threatening: RISK OF FATALITY WITH OD
Minimize risk: acutely depressed are given no more than
1 week supply on discharge
Clinical manifestations: primarily from anticholinergic and
cardiotoxic actions
Treatment: gastric lavage followed Activated charcoal
Physostigmine [cholinesterase inhibitor]: counteract
anticholinergic actions.
Propanolol [Inderal], lidocaine or phenytoin [Dilantin]:
control dysrhythmias
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 TCAs
Take approximately 2-4 weeks for patient to
experience therapeutic effects
Week 1: decreased anxiety, improved sleep,
pt. unaware of changes
Week 1-3: increased activity & self-care,
improved concentration, memory,
psychomotor retardation resolves
Week 2-4: relief of depressed mood, less
hopelessness, suicidal ideation subsides
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 TCAs
Therapeutic blood drug levels monitoring:
useful to maintain therapeutic levels within
appropriate range
AVOID in elderly: anticholinergic SE, ortho
hypotension, sedation, CARDIAC
DYSRHYTHMIAS
Discontinue therapy: Should be TAPERED,
ABRUPT withdrawal lead to withdrawal
syndrome w/GI complaints, dizziness,
insomnia, irritability
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 Monoamine Oxidase Inhibitors
[MAOIs]
Originally used to treat TB
2nd or 3rd choice antidepressants
Particular concern: HYPERTENSIVE CRISIS: eating
TYRAMINE rich foods
DOC: treatment of atypical depression, major
depression w/out melancholia, or depressive disorders
resistant to TCAs
Atypical depression: hypersomnia, anxiety, absence of
vegetative symptoms
Contraindications: CV defects, major cardiovascular
disease and tumor of the adrenal medulla
NOT tolerated well in older patients 25
 MAOIs
Phenelzine [Nardil]
Tranylcypromine [Parnate]
Isocarboxazid [Marplan]
Selegiline [Emsam]
Transdermal patch

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 MAOs

Action
MAO Inhibitors (also called MAOI's) work by
interfering with the enzyme responsible for
metabolizing seratonin, epinephrine, dopamine and
norepinephrine.
inhibiting the activity of monoamine oxidase,
thus preventing the breakdown of monoamine
neurotransmitters and thereby increasing their
availability.
There are two isoforms of monoamine oxidase,
MAO-A and MAO-B

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 MAOIs
Side Effects
HYPERTENSIVE CRISIS FROM TYRAMINE
FOODS
Headache, stiff neck [nuchal rigidity],
sweating, n/v
MEDICAL EMERGENCY
Patient must adhere to the diet and
medication restriction for about 2 weeks
after discontinuing MAOIs.
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 MAOIs
Other S/E
Orthostatic hypotension
Edema
Sexual dysfunction
Weight gain
Abrupt discontinuation may produce monoamine
oxidase inhibitor withdrawal syndrome: nausea,
sweating, palpitation, nightmares, hallucinations,
delirium and paranoid psychosis
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 MAOIs
Drug-Food Interactions
Must AVOID
AGED CHEESES
AVOCADOS, FIGS, FERMENTED BEAN CURD,
SOYBEANS
ANCHOVIES, FAVA BEANS, YEAST , LIVER,
PROCESSED MEATS,
CHIANTI, SHERRY
SMOKED, PICKLED MEATS/FISH
BANANAS [LARGE AMOUNTS]
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 Drug-Drug Interactions
Antiasthmatics: theophylline inhalers
Antihypertensives: Aldomet
Anesthetics w/epinephrine
Allergy, hay fever, cough and cold preps
BuSpar
Meperidine [Demerol]: no longer used in practice
SSRIs
Yohimbine [Yocon]
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 Miscellaneous Antidepressants
Trazadone [Desyrel]
Treat insomnia due to sedating qualities, postural
hypotension, syncope
SE: Priaprism [men], prolonged clitoral erection [women]
Bupriopion [Wellbutrin]: short-half-life, taken TID
SE: nervousness, headache, insomnia, seizure [high dose]
Other therapeutic effects: helpful in reducing cigarette, ETOH
and drug cravings [aka Zyban]
Suppresses appetite
Does not cause weight gain or sexual dysfunction [known to
increase sexual desire and pleasure]
Mirtazapine [Remeron]: usually prescribed at hs
SE: sedation and weight gain, hypercholesteremia,
reversible agranulocytosis/neutropenia [rare]
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 Miscellaneous Antidepressants
Nefazodone [Serzone]
Amoxapine [Asendin]
Reboxetine [Vestra]

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 Mood Stabilizers
Relieve acute manic or depressive episodes
Agents
Lithium [Mood Stabilizer] only
Anticonvulsants used to stabilize mood
Valproate acid [Depakote]
Cabamazepine [Tegretol]

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 Mood Stabilizers
Lithium [Lithobid]
Low therapeutic index: so toxicity can occur at
low levels only slightly greater than therapeutic
levels. Monitoring levels: mandatory
Uses: Treatment of BIPOLAR disease
Patients usually start in low divided doses to
minimize effect
Dose is titrated according to pt. response & side
effect
MUST MONITOR FOR THERAPEUTIC RANGES

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 CHEMISTRY
Simple organic ion
Carries single positive charge
Shares same group as K and Na [Periodic
table]
Has properties in common with both elements

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 MOOD STABILIZERS
Lithium should reach a steady state after 5
days
Must check Lithium levels
Usually q 3days until stabilized then periodically
Must draw serum levels at least 12 hours
AFTER LAST DOSE.

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 Lithium
Therapeutic Range for Acute Mania
1.0-1.5 mEq/L

Therapeutic Range for Stabilization

0.6-1.2 mEq/L

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 Lithium Toxicity
Mild toxicity
Find hand tremor, GI upset, polyuria, polydipsia
[Thirst] , muscle weakness, lethargy
Moderate toxicity
Level > 1.5 mEq/L: coarsening of tremor,
reappearance of GI symptoms, confusion,
sedation, lethargy, ataxia, mental status
deterioration
Severe toxicity: level > 2.5 mEq/L: seizures,
coma, death, cardiovascular collapse
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 Lithium
Can be used with anticonvulsants &
olanzapine [Zyprexia] and aripiprazole [Abilify]
for treatment of bipolar disorder
Patient Education:
Monitor fluid intake according to activity &
exercise levels
Avoid salt restriction diets as lithium acts like a
SALT
Should not be used if pregnant [1st trimester]

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 Anticonvulsants
Valproate, valproic acid [Depakote]
`1st line tx for rapid cycling of bipolar disorder
More effective than lithium in treating bipolar disorder w/prominent
depressive symptoms
SE:
Mild sedation
GI distress
N/V/D
Dyspepsia, anorexia, osteoporosis
Tremor
Mild elevation of liver enzymes

Effects are transient

Relatively safe and more rapid symptom abatement compared to Lithium 41
 Anticonvulsants
Carbamazepine [Tegretol]
Used w/or without Lithium
OD & undetected accumulation of Tegretol=FATAL
Acute toxicity= Stupor and Coma
SE: AGRANULOCYTOSIS
CBC w/differential: recommended q 2 weeks during 1st
2 months of therapy
SE: nausea, sedation, dizziness
Drug levels must be monitored: Plasma target
trough level: 4-12 mcg/mL
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 Anticonvulsants
Lamotrigine [Lamictal] long term
Effective for bipolar disorder & rapid cycling bipolar
disorder
SE: headache, dizziness, GI distress, blurred/double
vision, rash
Topriamate [Topramax]
Treat epilepsy, binge eating, bipolar
SE: caution in pt w/renal impairment, anemia, HTN,
postural hypotension, vasodilation, arryhthmias,
palpitations, Bundle of His block, dizziness, fatigue,
confusion, anxiety, cognitve/language problems
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 Antianxiety/Benzodiazepines
Used in treatment of various anxiety disorders
RISK FOR ADDICTION & TOLERANCE
TOLERANCE: patient requires __________ of
the med to achieve desired effect
Quick onset
SE: cognitive impairment, decreased
coordination [ataxia], potential drug abuse,
withdrawal symptoms
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 BENZOS
Alprazolam [Xanax]
Chlordiazepoxide [Librium]
Clonazepam [Klonopin]
Diazepam [Valium]
Lorazepam [Ativan]
Temazepam [Restoril]

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 Benzos
CANNOT STOP ABRUPTLY- DANGEROUS FOR PT
MAJOR DANGER: SEIZURE
Not recommended for long term use
Shorter-acting:
Clonazepam [Klonopin]
Lorazepam [Ativan]
Alprazolam [Xanax]
More difficult to taper & more problems w/withdrawal
Longer acting:
Diazepam [Valium]
Chlordiazepoxide [Libirum]
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 Buspirone [BuSpar]
Anxiolytic
Not a CNS depressant
Treats anxiety
Does not cause sedation
Has no abuse potential
Does not intensify effects CNS depressants [Benzos,
ETHOH, barbiturates
Labeled for short-term use
Effects are delayed so should be initiated 2-4 weeks
prior to start of benzos
Lacks sedative, muscle relaxant and anticonvulsant
actions
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 Buspirone [BuSpar]
SE: dizziness, headache, nausea, nervousness,
lightheadedness, excitement
Food-drug: increases
erythromycin/keotconazole; grapefruit juice
increases drug level

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