Call Girls Ludhiana Just Call 9907093804 Top Class Call Girl Service Available
Antimanic drugs and mood stabilizing agents
1. DR. D. K. Brahma
Associate Professor
Department of Pharmacology
NEIGRIHMS, Shillong
2. Also called mood stabilizers or drugs for Bipolar
disorders
A mental condition marked by alternating periods of
elation and depression (high and low)
Bipolar disorder: also known as manic-depressive
illness, is a brain disorder that causes unusual shifts
in mood, energy, activity levels, and the ability to
carry out day-to-day tasks
◦ Range from periods of extremely “up,” elated, and
energized behavior (known as manic episodes)
◦ to very sad, “down,” or hopeless periods (known as
depressive episodes)
◦ Less severe manic periods are known as hypomanic
episodes
3. Bipolar I Disorder: defined by manic episodes that last at least 7
days, or by manic symptoms that are so severe that the person
needs immediate hospital care
◦ Usually, followed by depressive episodes, typically lasting at least 2 weeks
Episodes of depression with mixed features
◦ May also have mixed type - having depression and manic symptoms at the
same time
Bipolar II Disorder: pattern of depressive episodes and
hypomanic episodes, but not the full-blown manic episodes
described above
Cyclothymic Disorder or cyclothymia: defined by numerous
periods of hypomanic symptoms as well numerous periods of
depressive symptoms lasting for at least 2 years (1 year in
children and adolescents) - the symptoms do not meet the
diagnostic requirements for a hypomanic episode and a
depressive episode
Other Specified and Unspecified Bipolar and Related Disorders:
do not match the three categories listed above
4. Bipolar I Bipolar II
high self-esteem
little need for sleep
increased rate of speech
(talking fast)
flight of ideas
getting easily distracted
an increased interest in
goals or activities
psychomotor agitation
(pacing, hand wringing,
etc.)
increased pursuit of
activities with a high risk of
danger
changes in appetite or
weight, sleep, or
psychomotor activity
decreased energy
feelings of worthlessness
or guilt
trouble thinking,
concentrating, or making
decisions
thoughts of death or
suicidal plans or
attempts
7. No acute effects in bipolar and normal person
Neither sedative nor euphorient
But, on prolong administration – stabilizes mood in bipolar
disorder
In acute mania – gradually suppresses episodes (1 – 2
weeks) – continued treatment prevents cycle of mood
changes
Reduced sleep time normalized
MOA:
1. Effects on Electrolyte and ion transport
2. Effects on Neurotransmitters
3. Effects on 2nd Messenger generation
8. Li is the lightest of the alkali metal atoms
Na+ and K+ are important in this family
Li partly replaces Na+ and distributes evenly
in extracellular and intracellular fluids
(contrast to Na+ and K+)
Affects ionic fluxes across brain cells or
modify property of cell membranes
However, conc. of Li in comparison to Na+
and K+ is very low
9. Li decreases the presynaptic NA and DA
release in the brain (animals) – no affect on
5-HT release
Corrects the imbalance in the turn over of
brain mono-amine
10. Li has no effects on persons without mania ???
Li inhibits hydrolysis of inositol-1-phosphate by inositol
phosphatase
Supply of free inositol for regeneration of Phosphatidyl inositides
(source of IP3 and DAG) reduced - IP3 and DAG are important
2nd messengers
Hyperactive neurones involved in manic state preferentially get
affected - - supply of inositol from extracellular source is very
low
Thus spare normally operating receptors and “search out”
selectively overactive receptors – dampen signal transduction
Valproic acid – Li like effects in mania – inhibits conc. of inositol
in human brain by inhibiting de novo inositol synthesis
11. Inhibits actions of ADH - DI like state
Insulin like action on glucose metabolism
Increase in Leukocyte count
Inhibits release of thyroid hormone –
feedback stimulation of thyroid –
compensated euthyroid state
12. Well absorbed orally, but slowly
Not metabolized and not protein bound
First extracellular – enters brain - attains uniform distribution in
total body water
CSF conc. is half of plasma - apparent Vd – 0.8L/kg at steady
state
Li is actively reabsorbed from proximal tubule in the kidney
similar to Na+
When Na+ is restricted larger portion of Na+ is reabsorbed -
similar is in case of Li
2 half-life of excretion - Initially rapid excretion, then slower in
later phase – 10-12 hours Vs 16-30 hours
Clearance is 20% of creatinine
Steady state is attained in 5-7 days – elderly and renal
insufficiency
Available as 300 and 400 mg tablets
13. Individual variation in the rate of excretion
Narrow margin of safety - monitoring
Done 5 days after the start of treatment
Measurement is done 12 Hrs after the last dose
- steady state (0.5 to 0.8 mEq/L for maintenance)
- 0.8 to 1.1 mEq/L for acute attack
Toxicity above 1.5 mEq/L
Dosing is usually in divided doses 2 -3 times of a
tablet
Excreted in sweat, saliva, breast milk etc.
14. Side effects are tolerable – but toxicity ….
Nausea, vomiting and mild diarrrhoea – low dose start
Thirst and polyuria and mild fluid retention
Fine tremor frequently
CNS toxicity: in rise in plasma conc.
◦ Coarse tremor, giddiness, ataxia, motor incoordination, nystagmus,
mental confusion, slurred speech and hyper-reflexia etc. etc. – delirium,
coma
◦ Occurs mainly when plasma level is high (2 mEq/L)
◦ Acute intoxication: muscle twitching, drowsiness, delirium, coma and
convulsion, vomiting, diarrhoea, albuminuria, hypotension and cardiac
arrhythmia
◦ Symptomatic treatment – osmotic diuretics, Sodium bicarbonate and
haemodialysis – also propranolol, atenolol etc.
Long term use – diabetes insipidus, weight gain and goiter and
hypothyroidism (supplement thyroid hormone)
Contraindicated in pregnancy – foetal goiter and cardiac
abnormalities
Dermatitis and acne
15. Diuretics (thiazide, furosemide): Na+ loss and
promote proximal tubular reabsorption of Na+
and Li – plasma Li rise (K+ sparing diuretics)
Tetracyclines, NSAIDS and ACEIs: Renal clearance
of Lithium is reduced
Reduces pressor action of NA
Enhance Insulin/Sulfonyurea induced
hypoglycaemia
Succinylcholine and pancuronium – prolonged
paralysis
All Neuroleptics (haloperidol), except clozapine –
increased EPS
16. Acute mania: Inappropriate cheerfulness or irritability, motor
restlessness, high energy, nonstop talking, flight of ideas, little
sleep, progressive loss of contact with reality and violent
behaviour – effective in controlling – but slow response – atypical
antipsychotic and BZD (clonazepam) – followed by Li
Prophylaxis of Bipolar disorder: efficacious in 0.5 to 0.8 mEq/L
dose – lengthens interval between cycles of mood swings:
episodes of mania and depression reduced
◦ Risk benefit ration to be judged in individual cases for prolonged therapy
– depends on type of bipolar disorder (type 1 or type II)
◦ Over a decade therapy – relapse after discontinuation
Recurrent unipolar depression: combination with antidepressants
Recurrent neuropsychiatric illness, cluster headache and
adjuvant to antidepressants in nonbipolar major depression
Cancer chemotherapy induced leukopenia and inappropriate
ADH secretion syndrome
17. 1st line in acute mania
High dose acts faster than Li
Alternative to antipsychotic ± BZD
Lithium resistance cases or not tolerating cases
Lithium + Valproate – resistance to monotherapy
Prophylactic in bipolar disorders
Atypical antipsychotic + Valproate - high
efficacy in acute mania
Divalproex
18. Carbamazepine: Prolong the remission of bipolar
disorder
◦ Less popular and less effective than valproate and Li
◦ Acute mania – quickly acting drug required and also high
doses – Carbamazepine limitation
◦ Long term prophylaxis and prevention of suicide –
therapeutic value not proven
◦ However, Alternative to Li
Lamotrigine: Prophylaxis of depression in bipolar
disorder
◦ Not effective in treatment and prevention of mania
◦ Used in type 2
◦ Can be combined with Li
19. Acute mania: 1st line drug now - Olanzapine,
risperidone, aripiprazole, quetiapine with or without
BZD except cases requiring urgent parenteral
administration
Aripiprazole: fovoured drug for Bipolar type 1
maintenance as monotherapy or in combination with
Li and Valproate
◦ Prevents mania but not depressive episodes
Olanzapine: Mainenance therapy of bipolar disorder –
both depressive and manic phase
◦ Long term therapy – weight gain and hyperglycaemia
Combination of Valproate or Li with antipsychotic -
acute phases and maintenance therapy of bipolar
disorder