mood stablizer
TRANSCRIPT
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Mood StabilisersPsychopharmacology
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Mood Stabilisers
The treatment of bipolar disordermay be divided into threeoverlapping phases
Acute manic episode
Depressive episode
Prophylactic treatment
Only 1/3 of bipolar patientsexperience adequate relief with amonotherapy.
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How they work?
They have no clear effect ondopamine?? So why are theyeffective in mania?
They have no clear effect serotonin??So why are they effective indepressive episodes?
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Pregnancy categories
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Lithium
First original mood stabiliser
Underutilised
Appears most effective in treatingacute mania
First psychiatric drug that required
blood level monitoring
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Lithium
Manic episodes of bipolar disorder
Maintenance treatment for bipolardisorder
Bipolar depression
Major depressive disorder
Vascular headache
Neutropenia
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Mechanisms
Generally unknownComplex in action
Alters sodium transport across cell
membranesAlter metabolism of
neurotransmitters catecholamines,
serotonin, GABA and glutamate- May alter intracellular signalling through actions
on second messenger systems
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Second messenger systems
Method of cellular signalling
Cyclic adenosine monophosphate(cAMP)
intracellular signal transduction
A different process of
neurotransmission
http://en.wikipedia.org/wiki/Signal_transductionhttp://en.wikipedia.org/wiki/Signal_transduction -
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Lithium
Effective within 1-3 weeks
Goal of treatment is a remission insymptoms
Many patients only have a partialresponse
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Concept of Augmentation
the combination of two or moredrugs to achieve better treatmentresults
Failure of monotherapy
Better tolerability
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Pre-testing
Kidney function( should be repeated1-2)
Thyroid function
ECG for patients over 50
Metabolic monitoring Fasting plasma glucose level
Cholesterol and triglycerides
BMI
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Side Effects
The reason to why lithium causesside effects is complex
Excessive actions at the same orsimilar sites that mediate actions
Renal side effects= acts ontransportation of ions
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Side Effects
Polyuria
Polydipsia
Diarrhoea
Nausea
Weight gain
Goiter
Acne, rash, alopecia
leukocytosis
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Life Threatening Side Effects
Lithium toxicityRenal impairment
Nephrogenic diabetes insipidus
ArrhythmiasCardiovascular changes\sick sinus
rhythm
Sick Sinus syndromeBradycardia
hypotension
T wave flattening and inversion
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Toxicity
Toxic Levels are very close totherapeutic levels
Symptoms;
Diarrhoea Vomiting
Course tremor
Delerium
Coma
Seizures
Monitoring for dehydration
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Dosing and Using
1800mg/day in divided doses (acute)
900-1200mg/day in divided doses(maintenance)
Dosage forms 450mg (slow release)
250mg tablets
start low and adjust dosage upwardas indicated by plasma levels
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Dosing
Slow release= less gastric irritation,lower peak plasma levels and peakdose side effects
Use the lowest dose of lithiumassociated with adequate therapeuticresponse
Go low in the elderly
Rapid discontinuation= increaserelapse
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Monitoring
Therapeutic Levels
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Anticonvulsant medications
Sodium Valproate
Carbemazepine
Lamotrogine
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Sodium Valproate
A first line treatment for bipolardisorder especially mixed state orrapid cycling bipolar.
Prescribed for; Mania
Maintenance treatment of Bipolar Disorder
Seizures
Migraine prophylaxis
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How does it work?
Blocks voltage- sensitive sodiumchannels
Increases brain concentrations ofgamma-aminobutyric acid (GABA)
Relatively unknown why it does this
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Sodium Valproate
Effects occur within a few days
Optimised at several weeks to onemonth
The goal is to see a remission in
symptomsAugmentation
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Pre-testing
Platelet counts
Liver function testing
Coagulation testsMetabolic monitoring
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Sides Effects
Due to Excessive actions at voltage sensitivesodium channels
Include;- Sedation - dyspepsia- Tremor - weight gain- ataxia - alopecia- tremor - polycystic ovarian
syndrome- headache - hyperandrogenisam- Abdominal pain - hyperinsulinemia
- nausea/vomiting - Lipid dysregulation- reduced appetite - decreased bone density- constipation
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Life threatening/Dangerous Side
Effects
Hepatotoxicity
Liver failure
PancreatitisOverdose
Restlessness
Hallucinations
Sedation
Heart block
Coma
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Dosage and Use
Range;Mania; 1200-1500mg/day
Migraine; 500-1000mg/day
Epilepsy; 10-60mg/day
100mg, 200mg and 500mg tabletsDosages are increased rapidly in the
case of mania.
May need divided dose due to halflife
Terminal mean half life of 9-16 hours
Metabolised by the liver
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Drug interactions
Lamotrogine should be reduced by 50%
Plasma levels lowered by drugs such as;Carbemazepine
Phenytoin Plasma levels are increased by drugs
such as; Aspirin
Chlorpromazine Fluoxetine
NSAIDS
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Warnings
HepatotoxicityMalaise
Weakness
Lethargy
Facial edema Anorexia
Vomiting
Jaundice skin and eyes
Pancreatitis Abdominal pain
Nausea
vomiting
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Special Populations
Elderly
Pregnancy
Breast feedingPost partum issues
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Carbamazepine
More commonly used to treatseizures
First anticonvulsant to be widelyused in the treatment of Bipolardisorders
Potentially an advantage in
treatment resistant bipolar and orpsychotic disorders
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How it works
Blocks voltage sensitive sodiumchannels
Interacts with the open channelconformation of sodium channels
Inhibits release of glutamate
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Carbamazepine
Goal of treatment is remission ofsymptoms
Effect usually occur within a fewweeks
Can be used a augment othermedications
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Pre testing
Blood count
Liver function
Kidney functionThyroid function
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Side effects
Sedation
Dizziness
Confusion
Unsteadiness
Headache
Nausea and vomiting
Diarrhoea
Blurred vision
Benign leukopenia
Rash
Weight gain
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Dangerous side effects
Rare aplatic anemia
Agranulocytosis Ususal bleeding
Infections Fever
Sore throat
Steven Johnson syndrome (RASH)
Cardiac issues
SIADH
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Dosage and Use
400-1200 mg/day
Comes in slow release
Should always be taken with food
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Drug interactions
Other antiepileptic medications
Fluvoxamine, fluoxtetine
Decrease efficacy of
benzodiazepines, clozapine,haloperidol, lamotrogine, epilum andwarfarin
Can decrease effectiveness of thecontraceptive pill
Lithium
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Special Populations
Pregnancy Category D
Breast Feeding
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Lamotrigine
Seems to be more effective intreating depressive episodes ofbipolar
Used less than other anticonvulsantsfor Bipolar Disorder
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How it works?
Voltage- gated sodium channelagonist
Inhibits the release of glutamate
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Side effects
Benign rash (10%) Sedation Blurred vision Dizziness
Ataxia Headache Tremor Insomnia Poor coordination Fatigue Nausea and vomiting Can cause flu like symptoms in some people
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Stevens Johnsons Syndrome
Rare serious rash Acute fever
Bullae on the skin
Ulcers on the mucousmembranes on lip,eyes, mouth and nasalpassages
Management Stop medication
Monitor and investigateorgan involvement
May require admission
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Dosage and Use
Monotherapy 100- 200 mg/day
Halved if used with other medication
Monitor for rash
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Pharmacokinetics
Elimination half life 33 hours
Higher if used concurrently withother anticonvulsant medication
Metabolised through the liver
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Drug interactions
Depressive effects may be increasedby other CNS depressants
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Special populations
People with renal impairment
Hepatic Impairment
Elderly
Children and Adolescents
Pregnancy
Breast feeding
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Atypical Antipsychotic Medication
Increasing use of antipsychoticmedication
Olanzapine, Risperidone, Quetiapine,
Ziprasidone and Aripripazole