2. No consensus definition.
Any medication that is able to decrease
vulnerability to subsequent episodes of
mania or depression; and not exacerbate the
current episode or maintenance phase of
treatment. (Sachs -1996)
“There is no such thing as a mood stabilizer”
-FDA
3. 1817 – Lithium was discovered as a chemical
element.
1871 – First recorded use as a treatment of mania.
1876 – Li2CO3 used in the prevention of depression.
By the beginning of 20th century - use of Lithium
largely abandoned due to its toxicity.
1949 – Use of Lithium for mania rediscovered by
John Cade.
1970- FDA approved use of Lithium for mania.
1995- Sodium valproate approved for acute mania.
4. Soft drink 7up had
contained Lithium
citrate from 1929-
1950.
Marketed as good
for relieving
alcoholic hangouts.
6. Indications for use:
1. Acute treatment of mania
2. Prophylaxis of bipolar affective disorder ( More
effective in preventing manic than depressive
relapse)
3. Augmentation of antidepressants in resistant
depression
4. Prevention of aggressive behaviour in patients
with learning difficulties
7. Estimated suicide rate in bipolar patients :
10-15%
Lithium reduces both attempted and completed
suicide by , 80%
8. May work by affecting
signal transduction
1. Through inhibition of 2nd
messenger enzymes (eg:
inositole monophosphate)
2. By modulation of G proteins
3. By interaction at various
sites within downstream
signal transduction
cascades. ( eg: inhibition of
GSK3, PKC)
Exact mechanism of action is not certain.
9. Renal functions
Thyroid functions
ECG for patients with risk factors / existing
cardiac disease.
10. Narrow therapeutic index
Essential to measure plasma concentrations
during treatment.
1st- 4-7 days
2 weekly until the plasma level is satisfactory
6 weekly
3 monthly when plasma level is very stable unless
more frequent monitoring is indicated.
GFR,TFT – 6 monthly
11. For prophylaxis
Minimum effective level : 0.4 mmol/L
Optimal range : 0.6 - 0.75 mmol/L
Treatment of acute mania
0.8 - 1.0 mmol/L
12. Fine tremour/ Dry mouth/ Metallic taste/ Fatigue
Weight gain (esp. women)
Hair loss/ coarsening of hair texture
Polyuria/ polydipsia ( due to blocking of ADH)
Nephrogenic diabetes insipidus ( reversible in short to medium
term Rx)
Reduction in GFR ( 1/3 of young patients – GFR < 60mL/min)
Interstitial nephritis ( Rarely)
Thyroid enlargement ( 5% - reversible )
Hypothyroidism ( 20% of women)
Hyperparathyroidism – hypercalcaemia
Reversible ECG changes :T wave flattening, inversion/widening of
QRS
Reversible leucocytosis
Fetal abnormalities (esp. cardiac – Ebstein anomaly)
13. Human teratogen.
Continuation during pregnancy should be
considered carefully ( with likelihood of relapse
during pregnancy)
If continued, plasma levels should be monitored
closely.
15. Mostly involve reduced plasma Na levels
Low salt diet
Dehydration
Drug interactions
▪ diuretics (esp.Thiazides)
▪ NSAIDS
▪ ACE inhibitors
▪ Angio.2 receptor blockers
▪ some antibiotics like metronidazole
16. Stop lithium immediately.
High intake fluids.
Extra NaCl to stimulate osmotic diuresis.
If level > 3.0 mmol/L
Peritoneal / haemodialysis is indicated.
17. Risk of manic relapse ( even in patients
symptomless for 5 years)
Recommended not to start Lithium without
an intention to continue for at least 3 years.
Discontinuation should done slowly at least
over 1 month.
18. Indications in mood disorders
1. Treatment of acute mania
2. Prophylaxis of bipolar disorder
Effectiveness in prophylaxis of unipolar/
bipolar depression is not well established.
Overall efficacy is less than that of Lithium.
19. Blocks voltage sensitive Na+ channels (VSSC)
-At a site within the channel on alpha subunit
Reduces glutamate release
Decreases turnover of norepinephrine and
dopamine.
Facilitates 5HT neurotransmission.
20. Drowsiness, dizziness, ataxia, diplopia, nausea –
common at the beginning of treatment
Agranulocytosis – Rare -1:10000 to 1:25000.
Relative lecopenia – common.
Rashes – 5% . Exfoliative dermatities- Rare.
Elevation of LFT. Hepatitis – Rare.
Disturbance of cardiac conduction.
Teratogenicity ( Neural tube defects)
Reduces plasma thyroxin level – clinical
hypothyroidism is rare.
21. Pre-treatment tests :
Baseline FBC, BU, SE, LFT - Recommended.
Baseline weight.
Monitoring:
Repeat FBC, BU, SE, LFT and Weight
measurement in 6 months.
Use in women of childbearing age :
If cannot be avoided , adequate contraceptive
method should be used.
Prophylactic folic acid 5mg/daily.
22. Structurally related to carbamazepine.
Prodrug.
Active form - eslicarbazepine.
Mechanism of action – similar to
carbamazepine.
Less sedating , less BM toxicity and less hepatic
enzyme inducing than carbamazepine.
Mood stabilizer effects not proven.
Used off label due to better tolerability than
carbamazepine. (esp. for mania)
23. Indications in mood disorders:
1.Treatment acute mania
2. Prophylaxis of bipolar disorder
Shown to be useful for patients unresponsive
to Lithium and carbamazepine .
Believed to be more effective than Lithium in
treating rapid cycling and mixed episodes of
mania.
24. Exact mechanism of action is uncertain.
Three possibilities:
1. Inhibition of voltage-sensitive Na+ channels
(VSSC) – Diminish excitatory glutamate
neurotransmission.
2. Enhancing actions of GABA – promote inhibitory
neurotransmission.
3. Regulating downstream signal transduction
cascades – promote neuroprotection and long term
plasticity.
25. GI disturbances, tremour, sedation, tiredness –
common.
Weight gain
Transient hair loss
Elevation of liver enzymes
Thrombocytopenia
Inhibition of platelet aggregation
Acute pancreatitis
Rashes
Polycystic ovarian disease
Teratogenicity – (Spina bifida, ASD, cleft palate,
hypospadias, polydactyly, craniosynostosis)
26. Pre- treatment tests:
Baseline FBC, LFTs and weight.
Monitoring:
Repeat FBC, LFTs after 6 months.
Monitoring of BMI.
Use in women of childbearing age :
should not be routinely used to treat bipolar illness in
women of childbearing age.
If used, lowest possible dose is advisable.
Prophylactic folic acid 5mg/daily.
27. Indications in mood disorders
1. Acute treatment of bipolar depression
2. Prophylaxis for bipolar depression
Used alone, it does not have significant acute
or prophylactic anti-manic actions.
28. Similar to carbamazepine
1. Blocks voltage sensitive Na+ channels
(VSSC) -At a site within the channel on alpha
subunit
2. Reduces excitatory glutamate
neurotransmission.
29. Rarely, serious side effects:
Angioedema
Steven Johnson syndrome
Toxic epidermal necrolysis
Use in women of
childbearing age :
Risk of cleft palate – (low
risk)
Skin rashes – 3% , usually maculopapular
Nausea/headache/diplopia/blurred vision/dizziness/ataxia/tremor
30. Structural analogues of GABA.
Mechanism of action :
inhibition of alpha-2 delta subunit of voltage-
gated Ca++ channels.
Not considered to be effective mood
stabilizers.
Anxiolytic, sedative and analgesic properties.
May be useful as adjunctive treatments to
other mood stabilizers.
31. Anticonvulsant and antimigraine drug.
Not clearly effective as a mood stabilizer.
Mechanism of action:
Enhance GABA function and Reduce glutamate
function by interfering with Na+ and Ca++
channels.
Useful as an adjunctive treatment in bipolar
disorder by reducing weight gain, insomnia
and anxiety.
32. Atypical antipsychotics proved to be effective
in preventing recurrence of mania.
New data suggest certain atypical
antipsychotics are effective in ,
treating bipolar depression
preventing recurrence of depression.
33. 5HT2A antagonism
Reduces glutamate hyperactivity – Action shared by
several anticonvulsants used as mood stabilizers.
Increasing trimonoamine neurotransmitters
(5HT, NA, DA)
Important in improving mood in depression.
34. Majority of bipolar patients need treatment
with several medications.
Doses of each agent can be lowered to tolerable
levels .
Synergy among agents provides greater efficacy
than a single agent in high dose.