Transcript Mood Stabilisers - Monash University

Mood Stabilisers
Psychopharmacology
Mood Stabilisers
 The
treatment of bipolar disorder
may be divided into three
overlapping phases
– Acute manic episode
– Depressive episode
– Prophylactic treatment
 Only
1/3 of bipolar patients
experience adequate relief with a
monotherapy.
How they work?
 They
have no clear effect on
dopamine?? So why are they
effective in mania?
 They
have no clear effect serotonin??
So why are they effective in
depressive episodes?
Pregnancy categories
Lithium
 First
original mood stabiliser
 Underutilised
 Appears most effective in treating
acute mania
 First psychiatric drug that required
blood level monitoring
Lithium
 Manic
episodes of bipolar disorder
 Maintenance treatment for bipolar
disorder
 Bipolar depression
 Major depressive disorder
 Vascular
headache
 Neutropenia
Mechanisms
 Generally
unknown
 Complex in action
 Alters sodium transport across cell
membranes
 Alter metabolism of
neurotransmitters catecholamines,
serotonin, GABA and glutamate
- May alter intracellular signalling through actions
on second messenger systems
Second messenger systems
 Method
of cellular signalling
 Cyclic adenosine monophosphate
(cAMP)
 intracellular signal transduction
 A different process of
neurotransmission
Lithium
 Effective
within 1-3 weeks
 Goal of treatment is a remission in
symptoms
 Many patients only have a partial
response
Concept of Augmentation
 the
combination of two or more
drugs to achieve better treatment
results
 Failure of monotherapy
 Better tolerability
Pre-testing
 Kidney
function( should be repeated
1-2)
 Thyroid function
 ECG for patients over 50
 Metabolic monitoring
– Fasting plasma glucose level
– Cholesterol and triglycerides
– BMI
Side Effects
 The
reason to why lithium causes
side effects is complex
 Excessive actions at the same or
similar sites that mediate actions
 Renal side effects= acts on
transportation of ions
Side Effects
 Polyuria
 Polydipsia
 Diarrhoea
 Nausea
 Weight
gain
 Goiter
 Acne,
rash, alopecia
 leukocytosis
Life Threatening Side Effects
 Lithium
toxicity
 Renal impairment
 Nephrogenic diabetes insipidus
 Arrhythmias
 Cardiovascular changes\sick sinus
rhythm
 Sick Sinus syndrome
 Bradycardia
 hypotension
 T wave flattening and inversion
Toxicity
 Toxic
Levels are very close to
therapeutic levels
Symptoms;
– Diarrhoea
– Vomiting
– Course tremor
– Delerium
– Coma
– Seizures

Monitoring for dehydration
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 upward
as indicated by plasma levels
Dosing
 Slow
release= less gastric irritation,
lower peak plasma levels and peak
dose side effects
 Use the lowest dose of lithium
associated with adequate therapeutic
response
 Go low in the elderly
 Rapid discontinuation= increase
relapse
Monitoring
 Therapeutic
Levels
Drug interaction
Increase plasma levels;
 NSAIDS
 Diuretics
 Angiotensin-converting enzymes
 Anticonvulsants (carbemazepine and phenytoin)
 Metronidazole
 Calcium channel blockers
Increase side effects
 SSRI’s
 Haloperidol
Special Populations
 Elderly
 Pregnancy
 Breast
feeding
Anticonvulsant medications
 Sodium
Valproate
 Carbemazepine
 Lamotrogine
Sodium Valproate
A
first line treatment for bipolar
disorder especially mixed state or
rapid cycling bipolar.
 Prescribed for;
– Mania
– Maintenance treatment of Bipolar Disorder
– Seizures
– Migraine prophylaxis
How does it work?
 Blocks
voltage- sensitive sodium
channels
 Increases brain concentrations of
gamma-aminobutyric acid (GABA)
 Relatively unknown why it does this
Sodium Valproate
 Effects
occur within a few days
 Optimised at several weeks to one
month
 The
goal is to see a remission in
symptoms
 Augmentation
Pre-testing
 Platelet
counts
 Liver function testing
 Coagulation tests
 Metabolic monitoring
Sides Effects
Due to Excessive actions at voltage sensitive
sodium channels
Include;

syndrome
-
Sedation
Tremor
ataxia
tremor
-
headache
Abdominal pain
nausea/vomiting
reduced appetite
constipation
-
-
dyspepsia
weight gain
alopecia
polycystic ovarian
hyperandrogenisam
hyperinsulinemia
Lipid dysregulation
decreased bone density
Life threatening/Dangerous Side
Effects
 Hepatotoxicity
 Liver
failure
 Pancreatitis
 Overdose
–
–
–
–
–
Restlessness
Hallucinations
Sedation
Heart block
Coma
Dosage and Use
 Range;
 Mania;
1200-1500mg/day
 Migraine; 500-1000mg/day
 Epilepsy; 10-60mg/day
 100mg,
200mg and 500mg tablets
 Dosages are increased rapidly in the
case of mania.
 May need divided dose due to half
life
 Terminal
mean half life of 9-16 hours
 Metabolised by the liver
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
Warnings

Hepatotoxicity
 Malaise
 Weakness
 Lethargy
 Facial
edema
 Anorexia
 Vomiting
 Jaundice skin and eyes

Pancreatitis
 Abdominal
 Nausea
 vomiting
pain
Special Populations
 Elderly
 Pregnancy
 Breast
feeding
 Post partum issues
Carbamazepine
 More
commonly used to treat
seizures
 First anticonvulsant to be widely
used in the treatment of Bipolar
disorders
 Potentially an advantage in
treatment resistant bipolar and or
psychotic disorders
How it works
 Blocks
voltage sensitive sodium
channels
 Interacts with the open channel
conformation of sodium channels
 Inhibits release of glutamate
Carbamazepine
 Goal
of treatment is remission of
symptoms
 Effect usually occur within a few
weeks
 Can be used a augment other
medications
Pre testing
 Blood
count
 Liver function
 Kidney function
 Thyroid function
Side effects











Sedation
Dizziness
Confusion
Unsteadiness
Headache
Nausea and vomiting
Diarrhoea
Blurred vision
Benign leukopenia
Rash
Weight gain
Dangerous side effects
 Rare
aplatic anemia
 Agranulocytosis
– Ususal bleeding
– Infections
– Fever
– Sore throat
Steven Johnson syndrome (RASH)
 Cardiac issues
 SIADH

Dosage and Use
 400-1200
mg/day
 Comes in slow release
 Should always be taken with food
Pharmacokinetics
 Metabolised
in the liver by CYP450
 Half life of 26-65 hours initially then
drops with repeated doses
Drug interactions
 Other
antiepileptic medications
 Fluvoxamine, fluoxtetine
 Decrease efficacy of
benzodiazepines, clozapine,
haloperidol, lamotrogine, epilum and
warfarin
 Can decrease effectiveness of the
contraceptive pill
 Lithium
Special Populations
 Pregnancy
Category D
 Breast Feeding
Lamotrigine
 Seems
to be more effective in
treating depressive episodes of
bipolar
 Used less than other anticonvulsants
for Bipolar Disorder
How it works?
 Voltage-
gated sodium channel
agonist
 Inhibits the release of glutamate
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
Stevens Johnson’s Syndrome

Rare serious rash




Acute fever
Bullae on the skin
Ulcers on the mucous
membranes on lip,
eyes, mouth and nasal
passages
Management



Stop medication
Monitor and investigate
organ involvement
May require admission
Dosage and Use
 Monotherapy
100- 200 mg/day
 Halved if used with other medication
 Monitor
for rash
Pharmacokinetics
 Elimination
half life 33 hours
 Higher if used concurrently with
other anticonvulsant medication
 Metabolised through the liver
Drug interactions
 Depressive
effects may be increased
by other CNS depressants
Special populations
 People
with renal impairment
 Hepatic Impairment
 Elderly
 Children and Adolescents
 Pregnancy
 Breast feeding
Atypical Antipsychotic Medication
 Increasing
use of antipsychotic
medication
 Olanzapine, Risperidone, Quetiapine,
Ziprasidone and Aripripazole