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MOOD
STABILIZERS
BY: Nur Liyana binti ABD Malek
Supervisor: Prof Ramli
Outlines
Pharmacologic actions
Dosage and clinical guidelines
Precautions and adverse
reactions
Therapeutic indications
The examples
MOOD STABILISERS
Lithium Valproate LamotrigineCarbamazepine
Anti psychotic
agent
Others
Lithium
◦ Used for short-term and prophylactic treatment of bipolar I disorder.
◦ Absorbed by GIT
◦ Does not bind to plasma proteins, not metabolized in liver
◦ ½ life: 20 hours, equilibrium: 5-7 d of regular intake
◦ Excretion:
◦ through kidney (decreased clearance in renal insufficiency & after delivery,
◦ increased in pregnancy
BBB permits only slow passage of lithium (a single overdose of Li
does not necessarily toxicity)
Pharmacologic actions
Therapeutic indications
◦Bipolar 1 disorder
◦Major depressive disorder
◦Schizoaffective disorder and
schizophrenia
 Manic episodes : control acute
mania and prevent relapse, slow
onset of action and exerts its
antimanic effect over 1 to 3
weeks
 Bipolar depression: effective in
the treatment of depression
associated with bipolar type 1
 Maintenence : decreases the
frequency, the severity and the
duration of manic and
depressive episodes.
 Effective against in the long
treatment of major depressive
disorder
 Not more effective than
antidepressant drug
 Person with predominant mood
symptom in schizoaffective are
more likely react to Lithium
rather than those with
predominant psychotic
symptom.
 As augmentation agent.
 As the treatment of choice for
schizoaffective are dopamine
receptor antagonist, serotonin-
dopamine antagonist
 For schizophrenia patient that
do not tolerate with anti-
psychotic drug
Precaution and adverse effect
• Start with low dose firstElderly person
• Don’t start Lithium in 1st trismester (Ebstein anomaly (20
x HR)
Pregnant lady
• Need to evaluate potential risk and benefit as lithium is
excreted into breast milk
Breastfeed mother
• Nausea, decreased appetite, vomiting and diarrheaGIT
• Lithium induce hypothyroidism, lithium induced edemaWeight gain
• Tremor, cognitive effect (dysphoria, lack of spontaneousity, slowed reaction times and impaired
memory)
Neurological
• Polyuria and polydipsia, Nonspecific interstitial fibrosis (10 years), renal failure, nephrotic
syndrome
Renal
• Benign reversible exophthalmos, hyperthyroidism, hypothyroidismThyroid
• ECG: resemble of hypokalemia, T- wave flattening or inversion
• Sinus dysrhythmias, heart block and syncope.
Cardiac
• Dose dependent: acneiform, follicular and muculopapular eruption, pretibial ulceration,
worsening psoriasis
Dermatological
Dosage and clinical guideline
Baseline
investigations
• Renal profile
• Thyroid function
• Full blood count
• ECG
• Pregnancy test
Serum & plasma
concentrations of
lithium
• Every 2 to 6
months
• Except :
• Non-
compliant
• Toxicity
• Dosage
adjustment
*1 to 1.5mEq/L in acute mania
0.4 to 0.8 mEq/L in maintenance
Acute mania: 600 – 1800
mg/day in divided doses
Maintenance dose: 300 –
1200 mg/day in divided
doses
(Desired serum level : 0.6 -
1.2 mEq/L not exceeding
1.5 mEq/L) To be used
with caution and correlate
clinically
#CPG Bipolar disorder
Valproate
◦ More preferable than lithium
◦ Epilim
◦ Also being used in treatment of seizure and migraine prophylaxis
◦ Absorbed 1 to 2 hours after oral administration,
◦ Plasma half life: 10 to 16 hours
◦ Highly protein bound
◦ Metabolized in liver
Pharmacologic actions
Therapeutic indications
Bipolar 1 disorder
Acute mania, mixed episodes, acute bipolar depression, prophylaxis
Schizophrenia and schizoaffective (accelerate response to AP’s drug)
Other mental disorder
(alcohol withdrawal and relapse prevention, panic disorder, PTSD,
impulse control disorder, behavioural agitation and dementia)
Precautions and adverse reaction
• Please avoid use it. May cause spina bifida (1st trimester)Pregnant lady
• Not contraindicationBreastfeeding mother
• Please avoid use itHepatic disease patient
• Hepatotoxicity (rare cause of death in patient older than 10 years old)Liver
• Pancreatitis (rare)Pancreas
• Thrombocytopenia, platelet dysfunctionHaematological
• Nausea, vomiting, dyspepsia, diarrheaGIT
• Tremor, sedation, ataxia, dysarthriaNervous
• In long term treatmentWeight gain
Hair loss
Dosage and clinical guideline
◦ Acute Mania: 600 - 2500
mg/day in divided doses
◦ Maintenance dose: 400 -
2000 mg/day in divided
doses
◦ (Desired serum level 50-
100 µg/mL @ 347-693
µmol/L)
◦ #CPG Bipolar disorder
Baseline
investigations
• Liver function
test
• Serum amylase
After 1 month of
therapy
• Full blood count
• Liver function
test
• Pregnancy test
Carbamezapine
◦ Tegral
◦ Also used in partial and generalized onset epilepsy and trigeminal
neuralgia.
◦ Absorption is slow and unpredictable
◦ Protein bound
◦ Metabolised in liver
Pharmacologic actions
Therapeutic indications
Bipolar disorder
(acute mania, prophylaxis, acute depression)
Other disorders
(alcohol withdrawal)
• Nausea, vomiting, constipation, diarrhea, anorexiaGIT
• sedation, ataxiaNervous
Not cause weight gain
• Blood dyscriasis (aplastic anemia, agranulocytosis)haematological
• hepatitisLiver
• Benign maculopapular rash, exfoliative dermatitis, erythema multiforme, steven Johnson
syndrome, toxic epidermal necrolysis
Dermatological
Renal
Cardiac effect
• Hyponatremia, water intoxication
• Exacerbate cardiac disease
Dosage and clinical guideline
◦ Mania/mixed episodes
◦ 200 to 1600 mg/day in
divided doses (Desired
serum level 4-12 mg/L @
1750 µmol/L)
◦ #CPG Bipolar disorder
Laboratory
monitoring
 Full blood count
 Liver function test
 Renal profile
 ECG
Antipsychotic: act as mood stabilizers
◦Olanzapine (can be used in maintenance phase)
◦Respiridone
◦Aripripazole
◦Quatiapine
◦Paliperidone
◦Asenapine
Other mood stabilizing agent
◦ Symbax (olanzapine and fluoxetine)
◦ Levitiracetam (keppra)
◦ Oxcarbazepine (trileptal)
Take home messages
1. Mood stabilizers is one of the treatment of bipolar
disorder
2. Lithium and valproate are contraindication in
pregnancy
3. Carbamezapine can cause steven Johnson syndrome
4. It is important to remember the side effect of the
medication as it will alter the management.
References
◦ Kaplan & Saddock’ s pocket handbook of clinical psychiatrist
◦ CPG Management of Bipolar Disorder in Adults
THANK YOU 

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MOOD STABILIZERS: AN OVERVIEW

  • 1. MOOD STABILIZERS BY: Nur Liyana binti ABD Malek Supervisor: Prof Ramli
  • 2. Outlines Pharmacologic actions Dosage and clinical guidelines Precautions and adverse reactions Therapeutic indications The examples
  • 3. MOOD STABILISERS Lithium Valproate LamotrigineCarbamazepine Anti psychotic agent Others
  • 4. Lithium ◦ Used for short-term and prophylactic treatment of bipolar I disorder. ◦ Absorbed by GIT ◦ Does not bind to plasma proteins, not metabolized in liver ◦ ½ life: 20 hours, equilibrium: 5-7 d of regular intake ◦ Excretion: ◦ through kidney (decreased clearance in renal insufficiency & after delivery, ◦ increased in pregnancy BBB permits only slow passage of lithium (a single overdose of Li does not necessarily toxicity) Pharmacologic actions
  • 5. Therapeutic indications ◦Bipolar 1 disorder ◦Major depressive disorder ◦Schizoaffective disorder and schizophrenia  Manic episodes : control acute mania and prevent relapse, slow onset of action and exerts its antimanic effect over 1 to 3 weeks  Bipolar depression: effective in the treatment of depression associated with bipolar type 1  Maintenence : decreases the frequency, the severity and the duration of manic and depressive episodes.  Effective against in the long treatment of major depressive disorder  Not more effective than antidepressant drug  Person with predominant mood symptom in schizoaffective are more likely react to Lithium rather than those with predominant psychotic symptom.  As augmentation agent.  As the treatment of choice for schizoaffective are dopamine receptor antagonist, serotonin- dopamine antagonist  For schizophrenia patient that do not tolerate with anti- psychotic drug
  • 6. Precaution and adverse effect • Start with low dose firstElderly person • Don’t start Lithium in 1st trismester (Ebstein anomaly (20 x HR) Pregnant lady • Need to evaluate potential risk and benefit as lithium is excreted into breast milk Breastfeed mother
  • 7. • Nausea, decreased appetite, vomiting and diarrheaGIT • Lithium induce hypothyroidism, lithium induced edemaWeight gain • Tremor, cognitive effect (dysphoria, lack of spontaneousity, slowed reaction times and impaired memory) Neurological • Polyuria and polydipsia, Nonspecific interstitial fibrosis (10 years), renal failure, nephrotic syndrome Renal • Benign reversible exophthalmos, hyperthyroidism, hypothyroidismThyroid • ECG: resemble of hypokalemia, T- wave flattening or inversion • Sinus dysrhythmias, heart block and syncope. Cardiac • Dose dependent: acneiform, follicular and muculopapular eruption, pretibial ulceration, worsening psoriasis Dermatological
  • 8.
  • 9. Dosage and clinical guideline Baseline investigations • Renal profile • Thyroid function • Full blood count • ECG • Pregnancy test Serum & plasma concentrations of lithium • Every 2 to 6 months • Except : • Non- compliant • Toxicity • Dosage adjustment *1 to 1.5mEq/L in acute mania 0.4 to 0.8 mEq/L in maintenance Acute mania: 600 – 1800 mg/day in divided doses Maintenance dose: 300 – 1200 mg/day in divided doses (Desired serum level : 0.6 - 1.2 mEq/L not exceeding 1.5 mEq/L) To be used with caution and correlate clinically #CPG Bipolar disorder
  • 10. Valproate ◦ More preferable than lithium ◦ Epilim ◦ Also being used in treatment of seizure and migraine prophylaxis ◦ Absorbed 1 to 2 hours after oral administration, ◦ Plasma half life: 10 to 16 hours ◦ Highly protein bound ◦ Metabolized in liver Pharmacologic actions
  • 11. Therapeutic indications Bipolar 1 disorder Acute mania, mixed episodes, acute bipolar depression, prophylaxis Schizophrenia and schizoaffective (accelerate response to AP’s drug) Other mental disorder (alcohol withdrawal and relapse prevention, panic disorder, PTSD, impulse control disorder, behavioural agitation and dementia)
  • 12. Precautions and adverse reaction • Please avoid use it. May cause spina bifida (1st trimester)Pregnant lady • Not contraindicationBreastfeeding mother • Please avoid use itHepatic disease patient
  • 13. • Hepatotoxicity (rare cause of death in patient older than 10 years old)Liver • Pancreatitis (rare)Pancreas • Thrombocytopenia, platelet dysfunctionHaematological • Nausea, vomiting, dyspepsia, diarrheaGIT • Tremor, sedation, ataxia, dysarthriaNervous • In long term treatmentWeight gain Hair loss
  • 14.
  • 15. Dosage and clinical guideline ◦ Acute Mania: 600 - 2500 mg/day in divided doses ◦ Maintenance dose: 400 - 2000 mg/day in divided doses ◦ (Desired serum level 50- 100 µg/mL @ 347-693 µmol/L) ◦ #CPG Bipolar disorder Baseline investigations • Liver function test • Serum amylase After 1 month of therapy • Full blood count • Liver function test • Pregnancy test
  • 16. Carbamezapine ◦ Tegral ◦ Also used in partial and generalized onset epilepsy and trigeminal neuralgia. ◦ Absorption is slow and unpredictable ◦ Protein bound ◦ Metabolised in liver Pharmacologic actions
  • 17. Therapeutic indications Bipolar disorder (acute mania, prophylaxis, acute depression) Other disorders (alcohol withdrawal)
  • 18. • Nausea, vomiting, constipation, diarrhea, anorexiaGIT • sedation, ataxiaNervous Not cause weight gain • Blood dyscriasis (aplastic anemia, agranulocytosis)haematological • hepatitisLiver • Benign maculopapular rash, exfoliative dermatitis, erythema multiforme, steven Johnson syndrome, toxic epidermal necrolysis Dermatological Renal Cardiac effect • Hyponatremia, water intoxication • Exacerbate cardiac disease
  • 19.
  • 20. Dosage and clinical guideline ◦ Mania/mixed episodes ◦ 200 to 1600 mg/day in divided doses (Desired serum level 4-12 mg/L @ 1750 µmol/L) ◦ #CPG Bipolar disorder Laboratory monitoring  Full blood count  Liver function test  Renal profile  ECG
  • 21. Antipsychotic: act as mood stabilizers ◦Olanzapine (can be used in maintenance phase) ◦Respiridone ◦Aripripazole ◦Quatiapine ◦Paliperidone ◦Asenapine
  • 22. Other mood stabilizing agent ◦ Symbax (olanzapine and fluoxetine) ◦ Levitiracetam (keppra) ◦ Oxcarbazepine (trileptal)
  • 23. Take home messages 1. Mood stabilizers is one of the treatment of bipolar disorder 2. Lithium and valproate are contraindication in pregnancy 3. Carbamezapine can cause steven Johnson syndrome 4. It is important to remember the side effect of the medication as it will alter the management.
  • 24. References ◦ Kaplan & Saddock’ s pocket handbook of clinical psychiatrist ◦ CPG Management of Bipolar Disorder in Adults