Treatment Modalities for

Mood Disorders
Pharmacogenetics - Genetic differences in
metabolic pathways
Differences in the function of the proteins that
genes code for are actually responsible for the
differing responses to drugs
Of particular importance are genes coding for
liver enzymes. The key liver enzymes
involved in our response to drugs are
cytochrome P450 (CYP) enzymes, whose
main job is to deal with toxins we ingest
1

Nursing Implications
All clients with mood disorders who are
taking meds should be monitored closely
for suicidality and/or changes in behavior
Particularly during initial course of
pharmacotherapy or times of
increases/decreases
Pooled, placebo-controlled studies indicate
an increased risk of suicide for those less
than 24 yrs. who are treated with
psychiatric medications for MDD and other
psychiatric illnesses
2

Antidepressants - Clinical
Use and Efficacy
Approx. 50-60% (some sources state
less) of clients with major depression
will respond to antidepressant therapy
Initial selection for therapy is based on
client history & how the side effects will
affect client physically and mentally
Initial doses are low to allow for
tolerance; common reason for failure
to respond is low dosage and
inadequate period of therapy
3

Antidepressants Mode of
Action
Increase the amounts of DA, NE, 5-HT,
and Ach
Mechanisms include:
Inhibiting neurotransmitter
reuptake
Inhibiting MAO
Blocking receptors
Modulating the effects of
neurotransmitters

(See text for various theories)

4

Monoamine Oxidase
Inhibitors
Iproniazid (antitubercular drug) - Monoamine Oxidase Inhibitor
(MAOI) that caused euphoria - led to use as antidepressant
(1950s)
Mode of Action - Dopamine, norepinephrine & serotonin are
chemically described as monoanimes; inhibit the
degradation of MAOs (making more available) in
presynaptic neuron
Examples phenelzine (Nardil), isocarboxazid (Marplan),
tranylcypromine (Parnate) (text selegiline (EMSAM), but
not often seen in practice)

Rarely used in clinical practice due to S&S

MAOIs- Clinical Use and

Efficacy
Treatment of atypical (novel) depression,
major depression or depressive disorders
resistant to tricyclic antidepressants
Quickly absorbed, liver metabolized
Contraindications include
cerebrovascular defects, major
cardiovascular disease &
pheochromoctyoma (tumor of adrenal
medulla)
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MAOIs Side Effects

MAOIs inhibit the enzyme involved with
the destruction of the monoamine
neurotransmitters

Problematic when ingesting foods or meds

that require breakdown in the liver with this
enzyme

Common Side Effects - orthostatic

hypotension, anticholinergic effects
And
many dietary & drug/drug interactions
7

Anticholinergic Side Effects

Sedation

Constipation

Dry mouth

Impotence

Urinary Retention

Photophobia (light
sensitivity)

Tachycardia

Exacerbation of
glaucoma

Anhydrosis (opposite of
diaphoresis)

Blurred vision

MAOIs Side Effects, cont.

Ingesting foods or drugs that contain
tyramine (a precursor to
norepinephrine) can lead to sharp
increase in norepinephrine causing CNS
stimulation, extreme orthostatic
hypotension, or hypertensive crisis
Process:
Tyramine usually deactivated in GI
tract, but MAOIs block process allowing
large amounts of tyramine to stimulate
PNS = norepinephrine

Client/Family Teaching

Kneisl, 2004

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The Nursing Process:

Antidepressants (cont.)

Interactions (MAOIs)
Hypertensive crisis with amphetamines,
methyldopa, levodopa, dopamine,
epinephrine, norepinephrine, reserpine,
vasoconstrictors, or foods with tyramine
Hypertension, hypotension, coma, convulsions,
and death with narcotic analgesics
Additive hypotension with antihypertensives
Additive hypoglycemia with antihyperglycemic
agents
Potentially fatal reactions with other
antidepressants (avoid use within 2 weeks of each
other)
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Hypertensive Crisis
Medical emergency (different from urgent
hypertension)
Symptoms include increased BP, P, headache,
change in mental status, epistaxis,
nausea/vomiting, chest pain, and diaphoresis
Process: orthostatic hypotension leads to
vasoconstriction, which causes increased
mean arterial blood pressure, which
usually causes increased BP (higher than
180/110 - usually 220/140 or greater), & P

12

Hypertensive Crisis, cont.

Goal = minimize end-organ damage,
e.g., cerebral infarction, cerebral
hemorrhage, acute pulmonary edema,
and hypertensive encephalopathy
Treatment IV or po antihypertensives.
Avoid lowering too much too fast
want to avoid cerebral ischemia

13

Client Family Teaching, cont.

Re: S&S of hypotension and
management of hypotension (MAOIs not
prescribed to those w/ known hx of
hypertension)
OTCs
Food & drug/drug interactions
Management of anticholinergic S&S
Correct use & discontinuation
Report S&S of CNS stimulation
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Cyclic Antidepressants
1st modern antidepressant marketed in 1958 was
imipramine (tricyclic)
Indications treatment resistant depressive
disorders
Mode of Action - partially blocks the re-uptake of
norepinephrine & serotonin
Examples:

amitriptyline (Elavil)
clomipramine (Anafranil)
imipramine (Tofranil)
nortriptyline (Aventyl, Pamelor)

(See your pharmacology text also)

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Cyclics Side Effects

Side effects most commonly occur with
tricyclics and heterocyclics
Sedation, blurred vision, constipation,
urinary retention, orthostatic hypotension,
reduction of seizure threshold,
tachycardia, arrhythmias, prolonged QT
interval, photosensitivity, weight gain
Suicide risk after 2nd week Overdose (narrow
therapeutic index) is often fatal D/T cardiac
complications

16

Cyclics Client Teaching

Re:
Management of anticholinergic side-effects,
orthostatic hypotension, cardiotoxicity,
photosensitivity, OTCs, MAOIs, TCAs,
antihistamines, alcohol, benzodiazepines,
opioids, amphetamines, and pregnancy
Take as prescribed to maintain therapeutic
serum levels
May take up to 3 months to reach desired
effect
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Selective Serotonin Reuptake

Inhibitors SSRIs
Indications - major depression, obsessivecompulsive disorder, panic disorder &
bulimia nervosa
Mode of Action - act to block reuptake of
serotonin
Serotonin is thought to affect mood
Reduced serotonin has been noted in the brain of
some depressed individuals and some who have
committed suicide

Examples:
fluoxetine (Prozac), sertraline (Zoloft), paroxetine
(Paxil), citalopram (Celexa), escitalopram
(Lexapro), and fluvoxamine (Luvox)
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SSRIs Side Effects

Nausea, anorexia
Insomnia
Some EPSE (akathisia), anxiety, drowsiness
Sexual dysfunction (loss of libido, erectile
dysfunction, ejaculatory dysfunction or anorgasmia)
Diaphoresis
Hyponatremia older adults monitor electrolytes
Increased risk of bleeding with anticoagulants
Serotonin syndrome
Withdrawal/Discontinuation syndrome

19

SSRIs- Interactions
Toxic, sometimes fatal reactions have
occurred with concomitant use of MAOIs
effects of SSRIs with cimetidine, Ltryptophan, and lithium
Concomitant use of SSRIs may effects
of hydantoin, tricyclics, benzodiazepines,
beta-blockers, carbamazepine, clozapine,
haloperidol, phenothiazines, St. Johns
wort, sumatriptan, sympathomimetics,
tacrine, theophylline, and warfarin
Concomitant use of SSRIs may effects
of buspirone and digoxin
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Serotonin syndrome
Hyperserotonergic state
Can occur by combining drugs that affect
serotonin neurotransmission or w/ use of
single drug
Especially, but not limited to, SSRIs & MAOIs
Other drugs that have a powerful effect upon
serotonin, i.e., clomipramine (Anafranil),
trazodone (Deseryl), etc.
Combination of Lithium with SSRIs.
Tricyclic antidepressants, lithium, MAOIs,
SSRIs, ECT, tryptophan, and the serotonin
agonists (e.g., Buspar) enhance serotonin
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neurotransmission.

Serotonin Syndrome
(Cont.)

S&S

Rapid onset within minutes - activity of serotonin

neuroreceptors at CNS & PNS
Restlessness, euphoria/hypomania, mental status
changes, drowsiness, confusion, loss of
consciousness and death
temperature, BP, shivering, diaphoresis, diarrhea
Sustained rapid eye movement, overreaction of
reflexes
Rapid muscle contraction & relaxation in the ankle
causing abnormal movements of the foot, muscle
contraction and relaxation in the jaw
22

Treatment-Serotonin
Syndrome
Discontinuation of the offending medication
or medications, offer supportive measures,
and wait for the symptoms to resolve.
Usually resolves on its own within a 24 hour
period.
If medication not discontinued, can
progress rapidly to a more serious state and
become fatal.

23

Selective Serotonin Norepinephrine

Reuptake Inhibitors
While serotonin is thought to affect mood,
norepinephrine thought to be more
involved with alertness and energy
SNRIs significantly reduce reuptake of
norepinephrine & serotonin w/ mild
dopamine reuptake blockade effects
Examples: Effexor (venalafaxine), Effexor
XR, Cymbalta (duloxetine), Pristiq
(desvenlafaxine)(Other SNRIs not
approved for treatment of depression)
24

SNRIs, cont.
Examples - Effexor (venlafaxine), Effexor
XR, Cymbalta (duloxetine), Pristiq
(desvenlafaxine)
Side effects - Many similar to SSRIs
More CNS sedation, anticholinergic S&S,
cardiac conduction abnormalities than SSRIs

Should be taken with food, and at the

same time of day

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Atypical Antidepressants

Bupropion (Wellbutrin)
Bupropion (Wellbutrin SR)
Bupropion (Wellbutrin XL)
Mirtazapine (Remeron, or Remeron, SolTab)
Desyrel (Trazodone)

26

Atypical Antidepressant Agents, cont.

Bupropion (Wellbutrin) - differs in

mechanism of action by blocking
reuptake of dopamine, norepinephrine, &
serotonin
Less sedation, anticholinergic, cardiac
conduction side effects
Agitation and insomnia are most common
Increased risk of seizures
Also used for smoking cessation

27

Atypical Antidepressant Agents, cont.

Mirtazapine (Remeron) - Text identifies
as serotonin-norepinephrine
disinhibitor (SNDI) blocks presynaptic
2 adrenergic receptors; it causes
increase in norepinephrine & serotonin;
blocks serotonin2 & serotonin3
receptors & histamine receptors
Side effects include somnolence,
increased appetite, weight gain &
dizziness; liver enzymes should be
monitored periodically
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Atypical Antidepressant Agents, cont.

Desyrel (Trazodone) mechanism of action
similar to tricyclics & tetracyclics,
however high doses = poor choice for
management of depressive S&S. Used
most frequently as hypnotic or
anxiolytic.
Common side effects include
somnolence, dizziness, cardiac
conduction px, & priapism(prolonged
erection).
Instruct client to follow guidelines for
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cyclics

Atypical Antidepressant Agents, cont.

Vilazodone (Viibryd) - serotonin partial
agonistreuptake inhibitor (SPARI)
approved by the FDA in 2011
Mechanism of action enhances release
of serotonin by inhibiting the serotonin
transporter (similar to SSRIs) and by
stimulating serotonin (5-HT1A) receptors
via partial agonism
Side effects unknown (only clinical trial
data- nausea, vomiting, insomnia)
Take with food for better bioavailability
30
in AM

Antidepressant Therapy
Pointers

Lag time before symptoms improve

Monitor for increased suicidal tendencies
Monitor for cheeking and hoarding
Monitor vital signs
Observe for signs of early toxicity
Monitor sexual side effects of SSRIs
Be aware of drug-drug and drug-food
interactions
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The Nursing Process:

Antidepressants
Nursing diagnoses:
Risk for suicide
Risk for injury
Social isolation
Constipation

32

Nursing Process:
Planning/Implementation:
Antidepressants
Monitor client for the following physiological side
effects
May occur with all chemical classes
Dry mouth, sedation, nausea
Discontinuation syndrome with abrupt
withdrawal
Most commonly occur with SSRIs
Insomnia, agitation, headache, weight loss,
sexual dysfunction, serotonin syndrome
Most commonly occur with MAOIs
Hypertensive crisis
Miscellaneous side effects
Priapism (with trazodone)

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The Nursing Process: MoodStabilizing Agents

Background assessment data
Indications: prevention and treatment of
S&S of bipolar disorder (Mode of action not
completely understood.)
Examples: Lithium carbonate (Eskalith)
Anticonvulsants approved by FDA:
carbamazepine (Tegretol), lamotrigine
(Lamictal), valproic acid (Depakote)

34

The Nursing Process: MoodStabilizing Agents, cont.

Background assessment data
Examples: Anticonvulsants, cont.:
Used but not approved by FDA:
gabapentin (Neurontin), topiramate
(Topamax), oxcarbazepine (Trileptal)
Anxiolytics occasionally used to treat
agitation in acute mania
(see pharmacology text)
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The Nursing Process: MoodStabilizing Agents, cont.

Background assessment data
Examples: Antipsychotics
Approved by FDA to manage agitation, &
psychosis frequently seen in the psychotic
client with mania: aripiprazole (Abilify),
quetiapine (Seroquel), risperidone (Risperdal),
olanzapine (Zyprexa) and ziprasidone
(Geodon)
(see pharmacology text)
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The Nursing Process: MoodStabilizers:

Planning/Implementation
Monitor for side effects of anticonvulsants
Nausea and vomiting
Drowsiness; dizziness
Blood dyscrasias
Prolonged bleeding time (with valproic acid)
Risk of severe rash (with lamotrigine)
Decreased efficacy with oral contraceptives
(with topiramate)

37

The Nursing Process: MoodStabilizers:

Planning/Implementation, cont.
Monitor for side effects of

antipsychotics
Somnolence, dizziness, asthenia (loss of
muscle strength)
Fever; tachycardia or bradycardia,
postural hypotension
Dry mouth, nausea, constipation
Increased appetite; weight gain
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Antimanic Agent - Lithium

Lithium used for 100 years for medical uses simplest possible drug, single ion
Indications treatment of bipolar disorder;
70-80% of clients respond to lithium for
treatment of acute mania and maintenance tx
Commonly used as treatment for
schizoaffective disorder & as adjunct to
antidepressant therapy
Also used in impulse-control disorders, selfinjurious behavior, pervasive developmental
disorder, and mental retardation
39

Lithium - Mode of Action

Not known, but appears to affect multiple
neurotransmitters: DA, NE, 5-HT
Inositol depletion hypothesis: Inhibition of
myo-inositol turnover in the phosphatidylinositol
second messenger system
Intracellular calcium signaling is also dependent on
this system

Not metabolized 80% reabsorbed in renal

tubules dependent upon Na present - Na
in tubules = Li reabsorbed = chance of
toxicity

40

Lithium - Clinical Use and Efficacy

Narrow tx window - potential for toxicity
requires rigorous baseline laboratory
monitoring
Levels should be monitored 1-2x/wk until
stable, then monthly
Therapeutic range is 0.4-1.3mEq/L
measured 12 hrs after last dose
Toxicity - > 1.5 - Life threatening - >
2.0
41

Lithium - Side Effects

GI S&S (dry mouth, mild nausea, alteration
in taste, diarrhea)
Increased thirst, mild polyuria (If diarrhea or
excessive urination lead to dehydration,
toxicity possible)
Fine hand tremor
Weight gain
Impotence, decreased libido
Increased WBC count, hypothyroidism,
alopecia, kidney damage
EKG changes, BP & P

42

Lithium Side Effects, cont.

Know these:
Expected (not toxic) S&S=fine hand
tremor, mild thirst, mild polyuria (resulting
from mild thirst), transient & mild nausea.
Early S&S of toxicity may include:
vomiting, persistent nausea, diarrhea,
ataxia (lack of coordination), slurred
speech, drowsiness/mental confusion.

43

Lithium - Client Education

To avoid GI upset instruct client to take
w/meals.
Avoid Ibuprofen (causes lithium toxicity)
aspirin is better.
Client should not decrease or increase Na
intake.
Avoid OTC meds, especially diuretics, and
any meds that may alter Na:K cell ratios.
Drink approximately 6-12 (8 oz.) glasses of
water/day. Avoid caffeine, which promotes
diuresis.
Do not stop medication without PCPs advice.
44

carbamazepine (Tegretol)
Indications: Acute mania
Common side effects: Anticholinergic, orthostasis,
sedation, and ataxia
Adverse/rare: Stevens-Johnson syndrome
potentially life-threatening rash in 10% of
patients, which develops during the 1st 20 weeks
of treatment
Recommended baseline labs - liver function tests,
CBC, electrocardiogram, and electrolytes
Serum levels monitored (toxicity = > 12 mcg/mL)no therapeutic range for bipolar disorder
45

lamotrigine (Lamictal)
Indications: maintenance therapy
of depression in bipolar disorder,
but not effective in acute mania
Common side effects: Anticholinergic,
orthostasis, sedation, and ataxia
Adverse/rare: Stevens-Johnson
syndrome potentially lifethreatening rash
46

valproic acid (Depakote)

Indications: mixed episodes and/or rapid
cycling
Common side effects: tremor, weight gain,
and sedation
Adverse effects: thrombocytopenia,
pancreatitis, hepatic failure, and birth defects
Baseline and periodic LFTs, CBC & platelets.
Liver function should be monitored for 1 st six
months
Serum blood levels
Take with food at the same time every day
47

Treatment Modalities for Mood

Disorders, cont. Electroconvulsive
Therapy (ECT)
For depression and mania
Mechanism of action: Unclear - thought
to increase levels of biogenic amines
Side effects: temporary memory loss
and confusion
Risks: mortality; permanent memory
loss; brain damage, cardiac arrest
Medications: pretreatment medication;
muscle relaxant; short-acting anesthetic
48

Electroconvulsive Therapy (ECT), cont.

Procedure:
Informed consent obtained
EKG & CBC (minimally) obtained before procedure
NPO for 8 hours prior to tx
Anticonvulsants & anxiolytics usually held 24
hours prior
Important to visually inspect clients mouth for
partial or full dentures bite guard
EEG, EKG, O2 sat, & VS monitored throughout
procedure (tachycardia & hypertension common
arrhythmias possible)

49

ECT: Procedure, cont.

Short-acting anesthetic (e.g., methohexital, or
propofol), muscle relaxant (succinylcholine) &
02 administered
One series = 2-3x/week for a total of 12 tx
some clients have multiple series
(maintenance ECT) electrodes placed on
scalp (unilaterally or bilaterally) and electrical
stimulus induces seizure threshold
determined by administrator
Standard pulse width bilateral ECT most common

50

Electroconvulsive Therapy (ECT), cont.

Side-effects:
Nausea, vomiting, headache, muscle aches, or
jaw pain
Cognitive impairment confusion may be
minutes, hours, or days. with successive tx
Memory loss retrograde amnesia (most
common) inability to recall memories prior to
ECT Anterograde amnesia memory loss
following ECT
Cardiac complications
Respiratory complications

51

Electroconvulsive Therapy (ECT), cont.

ECT remains a controversial tx
Recent studies suggest decreased efficacy
compared to placebo esp. after 6 mos.
Other studies show evidence of sustained
cognitive impairment and memory loss
Some researchers suggest that changing
the administration of stimulus (reducing the
width of the electrical pulse and by using
the right unilateral electrode placement)
may decrease adverse cognitive effects

52

Transcranial Magnetic Stimulation

(TMS)
Noninvasive stimulates areas of the
cerebral cortex using strong magnetic
pulses thereby temporarily
accelerating neural activity in a
localized area of the cortex
Approved by FDA for treatment
resistant depression or as an
alternative to anti-depressants for
pregnant women
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54

TMS Procedure
Patient is awake during procedure,
which takes about 30 minutes - 5
days a week for 4 to 6 weeks
Fewer side-effects than ECT
headache, discomfort at administration
site
No memory loss

55