MOOD STABLIZING AGENTS:

A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and

sustained mood shifts, typically bipolar disorder. Mood Stabilizers are commonly listed as Anti-
Convulsant because of their calming effect and action dealing with seizures. They have
lately become very effective in treating such things as Bipolar Disorder, Depression, Anxiety
Disorders.

Lithium:

It is lightest of the alkali metals and was discovered by Arfuedson. In 1917, J.F.J. cade first
reported the use of lithium as an antimanic drug in 1949, in Australia. As it is very effective in
treatment of mania. The word antimanic is often used to describe it, but since it is equally
effective in preventing mood swings in biplolar disorder, the better term is mood stabilizing
agent. it is affective to control manic phase of psychosis, ‘’smoothing out” the wide swings in
mood between mania and depression. Its toxicity is very closely related to its serum levels, and
effective therapeutic dose in many instances in near the toxic level. Therefore repeated and
accurate serum lithium levels should be determined in all patients taking drug.

Mechanism :

Specific mechanism of control of mania is unknown. The drug can alter sodium transport at the
nerve ending, thereby changing the electrophysiological characteristics of nerve cells. It
promotes neuronal uptake of norepinephrine and serotonin thereby causing their more rapid
inactivation, and may also reduce norepinephrine release and inhibit catecholamine- activated
cycle AMP formation.

Available in market in the form of:

1. Lithium carbonate 300mg tablets, 400mg sustained release tablets.

2. Lithium citrate 300mg/5ml liquid.

Lithium carbonate:

Lithium carbonate is a salt of alkali metal lithium.

Pharmacotherapeutics:

It is recommended in treatment for bipolar affective disorder. It is also effective in treatment of

recurrent unipolar depression, obsessive-compulsive disorder, aggression, cluster headaches, and
alcoholism.
Pharmacokinetics:

The pharmacokinetic properties of drug are linked to the physiology of sodium, chloride,
potassium, and fluid balance in the individual. Absorption of lithium is rapid after a oral dose
and is complete with in 6 to 8 hrs. peak plasma levels occur within 30 min to 2hrs after the dose.
No protein binding occur. Lithium is distributed in the total body water, shifting slowly into
cells. The slow entry into cells may account for the delay of several days before full clinical
responses are noted.

Exit from cell is also slow. lithium levels in the cerebrospinal fluid peak 24 hrs later then levels
in the extracellular fluid. The concentration is 50% of plasma concentration. It is well absorbed
and gets distributed throughout the total body water. The drug is mainly excreted in urine , the
renal clearance being proportional to its plasma concentration. Lithium decreases the sodium
reabsorption by renal tubules leading to sodium depletion. patient on lithium treatment therefore
should maintain adequate salt and water intake.

Pharmacodynamics:

Lithium alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal
metabolism of catecholamines. It decreases in the synthesis of dopamine and NA in the brain and
facilitating of their neuronal re – uptake. It modify GABA concentration in the brain. It inhibit
depolarization provoked calcium- dependent release of NA and dopamine but not of 5-HT in the
brain. It decreases in the function of brain protein kinases leading to alterations in the release of
neurotransmitter and hormone.

Pharmaceutics:

Lithium carbonate is available in capsule, sustained-action tablet, uncoated tablet. Initial dose is
300mg twice daily. the initial dose of is 300mg until adequate serum concentration levels are
achieved. Optimal client response is usually established and maintained with 1800 mg per day in
divided doses. Immediate release capsules and tablets are usually administered three to foutimes
daily. Doses of controlled release tablets are administered twice a day.

Indication:
A. Mood (affective ) disorders:
1. Mania : lithium is effective in acute phase of mania, and its prophylaxis, through
in acute mania some psychiatrist prefer to use lithium in combination with
neuroleptics.
2. Major depression : lithium has antidepressant effects in some patient with major
depression ( without history of mania or hypomania, unipolar illness
B. Schizoaffective disorder: lithium has been tried in the prophylaxis of recurrent
schizoaffective disorders.
C. Alcoholism :lithium probably effective but only in those alcoholics where there is
affective symptomatology.
D. Uncontrolled aggressive behaviours: there is a significant reduction is aggressive
behaviours among prisoners on lithium.
E. Abnormal mood swings: in children and adolescents lithium has been effectively
used.
F. Other uses : lithium has been in treatment of migraine, premenstrual tension, thyroid
disease (hyperthyroidism), huntington’s chorea.

Dosage:
Acute mania:
600mg 3 times /day( desired serum level is 1meq/liter – 1.5meq/liter) adjust oral
dosage to optimal clinical response as well as desired serum level ,clinical effects
begin to appear within 4to7 days.
Prophylaxis:
300mg 3to 4 times/day (serum levels .6meq/liter-1.4 meq/liter)

Fate:
Rapidly absorbed orally, peak serum levels in 1 hrs to 2hrs clinical response may take
a week or more to develop, widely distributed in body; very little is protein bound;
crosses blood-brain barrier, excreted through the kidneys( half-life about 24hr) ,the
rate being directly proportional to its plasma concentration, excretion is diminished
by low sodium levels ,for eg those resulting from diminished salt intake.

Preliminaries to lithium treatment :

The base line renal, cardiac, and thyroid function and body weight are taken before
starting lithium for this purpose:
1. A full blood count, plasma, electrolytes and urea , creatinine, EGG ,and serum T4
& TSH level are required.
2. The lithium treatment is monitored initially by weekly serum levels. ( an
estimation in dose 5-7 days after any dose change) followed by monthly and then
every 2-3 months.
3. Thyroid function test should be checked every six months.
4. 24 hrs urine volume should be done every months and a ECG should be
performed every year.
5. Routine general and systemic physical examination to be done.

Serum level:
 Measured by any time between 12 and 24 hrs after the last dose of lithium. Usually
morning fasting level is taken.
Therapeutic levels: .8to 1.4meq/liter
Prophylaxis levels : .5 to 1.0meq/liter
Children & elderly: .4 to .8meq/ liter

Intoxicity :
It usually appears when the serum lithium is above 2.0meq/liter

Common signs:
1. Tremors
2. Disorientation
3. Ataxia
4. Convulsion
5. Aphasia
6. Coma
7. Slumming of speech
8. Confusion
9. Death

Management:

1. Stopping lithium
2. High fluid intake
3. If level is above 3.0meq/liter peritoneal or haemodialysis is done

Common side effects:

Fine hand tremors, nausea, thirst, polyuria, fatigue, and mild muscle weakmess.
Adverse reaction:
(usually observed at serum levels above 1.5meq/liter)
Neuromuscular :
lack of coordination, ataxia, muscle hyperirritability, and twitching, extra pyramidal –
like symptoms.
CNS:
Drowsiness, dizziness, restlessness ,tremor, ataxia, muscular weakness, confusion,
seizure.
Gastrointestinal :
Nausea, metallic taste, vomiting, abdominal pain, diarrhea.
Cardiovascular :
Arrhythmia, hypothyroidism, bradycardia, weight gain, endocrine, goiter.
Urinary:
 Albuminuria, glycosuria, ologuria.
Dermatology:
Rash, pruritus, thinning hair, folliculitis, acneiform eruptions, cutaneous ulceration.
Other :
Hypothyroidism, transient hyperglycemia, weight gain, proriasis.
Contraindication:
Severe renal , cardiovascular disease, organic brain syndrome, sodium depletion,
early pregnancy, and children under 12.

Contraindication :

1. Marked rental failure

2. Myasthenia gravis
3. Asdision’s disease
4. Pregnancy (first trimester) lactation
5. Acute myocardial infraction

Drug –drug interactions:

1. When given with fluoxetine serum lithium levels concentration increases and
lithium toxicity is possible.
2. With nonsteroidal anti-inflammatory drugs it also increases serum lithium
concentrations.
3. Combinations of lithium and haloperidol may produce severe encephalopathic
symptoms such as parkinsonism, dyskinesia, and dementia.
4. Thiazide diuretics and furosemide increases sodium and potassium excretion and
lithium reabsorption ,leading to increased serum lithium concentration.
5. Potassium saving diuretics decreases renal clearance of lithium and may also
increase lithium serum concentration.

Nurses’s role:

1. Check that toxic effects frequently develop when the serum levels rise above
1.5meq/liter. Perform periodic blood tests to determine precise serum levels.
2. Tell the patient to consult physician immediately should signs of toxicity
appear such as diarrhea, vomiting, drowsiness, muscle weakness, ataxia.
3. Take adequate salt and fluid intake during lithium therapy.(2500-3000ml/day)
4. Not to be involved in activities requiring alertness until reaction to lithium has
been established. Drug may causes drowsiness and impaired coordination.
5. Use cautiously in elderly, dehydrated patients, and presence of thyroid
disease.
6. Be aware that optimum therapeutic effects usually occur 7to 14 days after
initiation of treatment. do not prolonged therapy past 4 weeks if no response is
evident.
7. Test urine for specific gravity and check signs of polydipsia, and polyurea. If
severe therapy is discontinued.
8. Provide supplemental fluid and salt in case of sweating or diarrhea.
9. Salt should not be restricted in the diet unless instructed by the physician.
10. Note symptoms of developing hypothyroidism eg weight gain fatigue, puffy
face.) symptoms are reversible upon cessation of therapy but may be
controlled by supplemental throxine without discontinuation of lithium
therapy.
11. Checks the signs of edema and any sudden weight gain.
12. Weight should be recorded before lithium therapy . weekly weight should be
maintained.
13. Intake and output to be balanced because because relation of fluid will
increases weight.
14. Give drugs with meals, use sustain release form , divided doses to maintain
GI irritation. It will reduce the metallic taste in the mouth. Ensure serum level
being maintained.

CARBAMAZEPINE: OR (TAGRETOL):

Carbamazepine was synthesized in 1950s. it was introduce in clinical practice

as an antiepileptic drug in united states in 1960s. it is available in tablet and
suspension form.

Pharmacotherapeutics:

Carbamazepine was used as treatment of trigeminal and glossopharyngeal

neuralgia. Later used as antiepileptic drug. It is indicated in treatment of
psychomotor and temporal lobe seizures. It also indicated in the treatment of
generalized tonic clonic seizures , complex seizures, and mixed seizures. Later
in 1970s it is used in combination with lithium in treatment of bipolar
affective disorder. , impulse control disorder and aggression, psychosis with
epilepsy, schizo-affective disorder, borderline personality disorder.

Indications:

Bipolar disorder:
Manic episode:
Carbamazepine is effective in treatment of acute mania. It is second line agent
in both manic and depressive episode in bipolar disorder, after lithium and
valporic acid. It is effective antimanic agent in 50 to 70% of person within 2to
3 weeks of intiation and effective in persons whoare not responces to lithium
such as dysphoric mania, negative family history of mood disorder. Some
persons respond to carbamazepine but not lithium,or valporic acid.

Depressive patient:
It is effective in treatment for depression. About 25 to 33% of depressed
person respond to carbamazepine. It is alternative drug for depressed persons
who have not responded to conventional treatment, including ECT or who
have rapid period of depressive episodes.

Schizophrenia and schizoaffective disorder:

It is effective in treatment of schizophrenia and schizoaffective disorder.
Person with positive symptoms (hallucination) is respond and who display
impulsive aggressive outbursts.

Impulsive control disorder:

It is effective in controlling impulsive, aggressive behavior in non psychotic
person of all ages. Diagnosis is ruled out before initiating treatment with
carbamazepine include akathisia, and neuroleptic malignant syndrome.

Posttraumatic stress disorder:

It is been suggested along with antidepressant, benzodiazepines, beta
adrenergic receptor antagonists as treatment for PTSD.
Alcohol and benzodiazepine withdrawal:
It is effective in control of symptoms associated with alcohol withdrawal. It is
also assist in withdrawal of benzodiazepines use especially in seizure prone
person.

Pharmacokinectics:
It has poor water solubility ,and absorption of drug from GI tract is slow.
Since eating increases the secretion of bile and gastric juice taking the drug
with meals enhances its absorption. peak serum levels occur in within 5hrs of
oral administration . a steady rate is reached with in 2 to 4 days and
therapeutic levels are 4 to 12 ug/ml. It takes several days to maintains
therapeutic serum levels (4to 12 ug/ml). the drug metabolizes in liver and
excreted by kidneys 28% of drug is excreted by feces.
Pharmacodynamics:
It is chemically unrelated to other antiepileptics. It may reduce chemically and
electrically induced seizures by reducing polysynaptic responses in CNS and
depressing nerve transmission, subsequently preventing seizures activity.

Adverse reactions:
1. Most frequent: dizziness, drowsiness, unsteadiness, vomiting. To
minimize such reactions therapy is started at low doses.
2. Hematopoietic: aplastic anemia, leucopenia, agranulocytosis,
thrombocytopenia.
3. Hepatic: abnormal hepatic function, hepatocellular jaundice.
4. GU: urinary frequency, acute urinary retention, oliguria with
hypertension, renal failure, albuminuria, glycosuria, elevated BUN levels.
5. CNS: dizziness, drowsiness, disturbance of coordination, confusion,
headache, blurred vision, fatigue, occulomotar and speech disturbances,
peripheral neuritis, tinnitus, diplopia, visual hallucination.
6. Pulmonary: hypersentivity pneumonitis.
7. Dermatology: pruritic, and erythematous rashes, urticaria,
photosensitivity reactions, pigmentations, dermatitis, diaphoresis,
aggravation of lupus erthematosus.
8. Digestive: nausea, vomiting, gastric distress, diarrhea, constipation,
anorexia, dryness of mouth, glossitis, stomatitis.
9. Cardiovascular: congestive heart failure, hypotension, syncope, edema,
thromophelebitis, arrhythmias, myocardial infraction.
10. Ophthalmologic: scattered, punctuate cortical lens opacities,
conjunctivitis.
11. Musculoskeletal : aching joints, and muscles, leg cramps.
12. Metabolic: fever, chills, inappropriate antidiuretic hormone syndrome,
alterations in functions.

Contraindication and precautions:

Carbamazepine is not recommended for clients with history og bone
marrow depression, hypersensitivity to drug or any tricyclic compound
(desipramine, imipramine).

Drug to drug interactions:

1. In combination with furosemide it produce symptomatic
hyponatremia.
2. With cimetidine, isoniazid and proxyphene is potential for toxicity.
3. Calcium channels blockers such as verapamil, and antibiotic
erythromycin decreases hepatic metabolism of carbamazepine.

Nurses role:
1. Check the result of baseline CBC and liver function test before
administering the initial dose of drug.
2. Weight should be recorded.
3. If WBC count is below 3000 discontinue the drug.
4. Clients receiving carbamazepine with diuretics should have serum
electrolyte determination.
5. If dizziness, drowsiness may occur avoid client to operating
dangerous machinery or motor vehicle.
6. Tell client to take drug with food to minimize GI discomfort and to
enhance absorption.
7. Advise client not to adjust drug doses without consulting primary
care provider.
8. Notify physician if any change in blood pressure, pulse rate, or
rhythm.
9. Periodic eye examination, renal and hepatic function test should
be done.
10. Record vital signs measure intake output ,observe side effects,asses
the response of patient to drug.
11. Do not discontinue the drug without order by physician, abrupt
discontinuation may leads to seizures, and even status epillepticus.
12. Notify physician if any bleeding, bruising, jaundice, abdominal
pain, pale stools, darkened urine, swelling on hand & feet, fever,
chills, sore throat, and ulcer in mouth.

VALPROIC ACID:
It is indicated in treatment of absence, myoclonic, grandmal
seizures. It is effective against atonic,complex partial, elementary
seizures. it is used in preventing recurrent febrile seizure in
children. It is also given as an alternative to lithium in treatment of
acute mania, and as for bipolar disorder.

ACTIONS:
It is rapidly absorbed after oral indigestion. Peak level occur less
than 4 hrs. the serum therapeutic level is 50 to 100ug/ml. the
starting dose for both adult and children is 15mg/kg perday.
Maintenance dose is 20 to 60mg/kg per day.
Its activity is related to increased brain levels of gamma-
aminobutyric acid ( GABA).it decreases high frequency repetitive
firing action potentials in the CNS. This action is enhanced by
sodium channel inactivation. There is slight delay in absorption
occurs when administer with meals, but does not affect total
absorption. It is metabolized by liver and elimination in urine
minor with feces.

Indications:
Bipolar disorder:
It controls in two third of person with acute mania. It also reduces
overall psychiatric symptoms and need for supplemental doses of
benzodiazepines. Person with mania usually respond 1to4 days
after valproate serum concentration rises to 50ug/ml. it is effective
against in person with rapid cycling and ultrarapid cycling bipolar
disorder, dysphoric and mania due to general medical condition. It
reduces frequency of manic episode.

Schizoaffective disorder:
It is effective in treating the short term phase of bipolar type of
schizoaffective disorder. Valporate is effective with lithium,
carbamazepine or serotonin –dopamine anatognist by person with
schizoaffective disorder.

Other:
It control physical aggression, agitation, verbal aggression
associated with dementia, organic brain diseases.

CONTAINDICATION:
Hepatic disease.

ADVERSE REACTION:
1. GI: nausea, vomiting, indigestion, diarrhea, abdominal cramps,
and constipation.
2. CNS: ataxia, headache, diplopia, asterixis( spots before eyes),
tremor, dizziness, incoordination, and insomnia.
3. Dermatologic: hair loss, skin rash, petechiae.
4. Psychiatric: emotional upset, depression, psychosis,
aggression, hyperactivity, behavioural deterioration.
5. Musculoskeletal: weakness
6. Hematopoietic: altered bleeding time, thrombocytopenia,
bruising, hematoma, frank hemorrhage, anemia, bone marrow
aspiration.
7. Hepatic: elevation in SGOPT, SGPT increases in bilirubin
levels, abnormal changes in hepatic function test,
hepatotoxicity .
8. Endocrine: irregular menses, amenorrhea, abnormal thyroid
function test.

NURSES ROLE:
1. Give medicine with food to avoid GI upset.
2. Monitor vital signs.
3. Drug may cause sedation assist the patient with ambulatory
activities.
4. If receive with Phenobarbital observe for CNS depression.
5. Periodic hepatic function test should be done.
6. Periodic CBC , platelet count, hb, bleeding time may be
performed during therapy.
7. If ketones is present in urine inform the physician.
8. Not to discontinue medicine without consult.
9. Do not drink alcohol, or CNS depressants while taking this
drug.
10. If bleeding tendencies, malaise, weakness, vomiting,
anorexia, sore throat, any infection, seizure report to
physician.
11. Carry Medic- Alert indicating medication, usage and
epilepsy.
12. It should not be used by pregnant women or nursing
women it causes neural tube defect.
13. It affects pancreas and liver.

Gabapentin, Lomotrigine & Topiramate:

These are alternative treatment of bipolar disorders, anxiety

disorder, agitation, pain and substance use.

Actions:

Gabapentine:

Is absorbed by the neural amino acid membrane transporter

system in the gut and it crosses the blood brain barrier. Doses
should not exceed from 1800mg per single dose. Food has no
effect on absorption and it does not bind to plasma proteins. It
is not metabolized and is excreted unchanged in the urine.

Lamotrigine:

It is completely absorbed . food not affect its absorption, it is

given twice day maintenance dosing. It has anticonvulsant
effect. It inhibit the enzyme that is responsible for generation
for folic acid. It increases plasma serotonin concentrations and
is weak inhibitor of serotonin 5-HT3 receptors.

Topiramate:

It is completely absorbed , food does not affect its absorption.

It is excreted unchanged in urine .it is an inhibitor of state
dependent sodium channels. It potentiates the action of GABA
at a benzodiazepine, non- barbiturate- sensitive GABA
receptor.

Indications:

These are indicated in the treatment of seizure disorders.

Gabapentin is widely used to treat chronic pain, in
polyneuropathy.

Bipolar disorder:

It is adjunctive medication for treatment with bipolar disorder.

These have both mood stabilizing and antidepressant effects. It
is added when person not respond to first line agents such as
lithium, carabamazepine.

Chronic pain:

Gabapentin is effective for treatment of postherpetic neuralgia

and painful diabetic neuropathy, lamotrigine has been effective
for treatment of HIV associated peripheral neuropathy and
reduction of postoperative analgesic use.

Other indication:
Gabapentin reduces the frequency and intensity of explosive
outbursts in person with dyscontrol disorder, person with
dementia, & person with traumatic brain injury. It is also
effective treatment for social phobia and panic disorder. It has
mildly sedative action and used in treating insomnia, agitation.
Treat tremor and parkinsonism.

Lomotrigine reduces symptoms of PTSD.

Topiramate used in treatment for obesity, binge eating, and

migraine.

Adverse reactions:

Gabapentin:

1. Somnolence
2. Dizziness
3. Ataxia
4. Fatigue
5. Nystagmus

Lamotrigine:
1. Dizziness
2. Ataxia
3. Headache
4. Diplopia
5. Blurred vision
6. Nausea
7. Vomiting
8. Rash
9. Pigmented retina
10. Epidermal necrolysis
11. Hypersensitivity reaction

Topiramate:
1. Psychomotor slowing
2. Speech and language problem
3. Paresthesias
4. Poor concentration
5. Confusion
6. Anorexia
 7. Mood problems
8. Weight loss
9. Tremor

Drug –drug interactions:

Gabapentin:

Antacids containing aluminium hydroxide and

magnesium hydroxide decreases its absorption.
Lomotrigine:

Its concentration decreases with carbamazepine ,

phenytoin, and increases with valporic acid.
Topiramate:

With acetazolamide (diamox) risk of renal

calculi.its concentration decreases with
carbamazepine, valporic acid.

Nurses role:
1. Assess the renal insufficiency and start at low dose.
2. Check for any rashes.

BIBLIOGRAPHY:
1. Normal L. Pinnell “ nursing pharmacology” saunders
company 1996.
2. Jeanne C. Scherer, “nurses Drug manual” Lippincott
company 1990.
3. Kaplan and Sadocks “synopsis of psychiatry” 9th edition
Lippincott Williams & wilikins 2003.
4. Mary C.Townsend “psychiatric mental health nursing”
5th edition 2006.