Mood Stabilisers

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Mood Stabilisers

• Psychopharmacology

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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.

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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?

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Pregnancy categories
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Lithium

• First original mood stabiliser
• Underutilised
• Appears most effective in treating acute mania
• First psychiatric drug that required blood level
  monitoring

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Lithium

• Manic episodes of bipolar disorder
• Maintenance treatment for bipolar disorder
• Bipolar depression
• Major depressive disorder
• Vascular headache
• Neutropenia

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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

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Second messenger systems

• Method of cellular signalling
• Cyclic adenosine monophosphate (cAMP)
• intracellular signal transduction
• A different process of neurotransmission

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Lithium

• Effective within 1-3 weeks
• Goal of treatment is a remission in symptoms
• Many patients only have a partial response

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Concept of Augmentation

• the combination of two or more drugs to achieve
  better treatment results
• Failure of monotherapy
• Better tolerability

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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

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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

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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 toxicity
• Renal impairment
• Nephrogenic diabetes insipidus
• Arrhythmias
• Cardiovascular changes\sick sinus rhythm
• Sick Sinus syndrome
• Bradycardia
• hypotension
• T wave flattening and inversion

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Toxicity

• Toxic Levels are very close to therapeutic 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 upward as indicated
  by plasma levels

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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

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Monitoring

• Therapeutic Levels

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Drug interaction

• Increase plasma levels
• NSAIDS
• Diuretics
• Angiotensin-converting enzymes
• Anticonvulsants (carbemazepine and phenytoin)
• Metronidazole
• Calcium channel blockers
• Increase side effects
• SSRIs
• Haloperidol

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Special Populations

• Elderly
• Pregnancy
• Breast feeding

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Anticonvulsant medications

• Sodium Valproate
• Carbemazepine
• Lamotrogine

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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

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How does it work?

• Blocks voltage- sensitive sodium channels
• Increases brain concentrations of
  gamma-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 one month
• The goal is to see a remission in symptoms
• Augmentation

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Pre-testing

• Platelet counts
• Liver function testing
• Coagulation tests
• Metabolic monitoring

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Sides Effects

• Due to Excessive actions at voltage sensitive
  sodium 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
• Pancreatitis
• Overdose
• 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 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

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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

• Hepatotoxicity
• Malaise
• Weakness
• Lethargy
• Facial edema
• Anorexia
• Vomiting
• Jaundice skin and eyes
• Pancreatitis
• Abdominal pain
• Nausea
• vomiting

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Special Populations

• Elderly
• Pregnancy
• Breast feeding
• Post partum issues

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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

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How it works

• Blocks voltage sensitive sodium channels
• Interacts with the open channel conformation of
  sodium channels
• Inhibits release of glutamate

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Carbamazepine

• Goal of treatment is remission of symptoms
• Effect usually occur within a few weeks
• Can be used a augment other medications

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Pre testing

• Blood count
• Liver function
• Kidney function
• Thyroid 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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Pharmacokinetics

• Metabolised in the liver by CYP450
• Half life of 26-65 hours initially then drops
  with repeated doses

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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

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Special Populations

• Pregnancy Category D
• Breast Feeding

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Lamotrigine

• Seems to be more effective in treating depressive
  episodes of bipolar
• Used less than other anticonvulsants for Bipolar
  Disorder

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How it works?

• Voltage- gated sodium channel agonist
• 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 mucous membranes on lip, eyes,
  mouth and nasal passages
• Management
• Stop medication
• Monitor and investigate organ 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 with other
  anticonvulsant medication
• Metabolised through the liver

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Drug interactions

• Depressive effects may be increased by 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 antipsychotic medication
• Olanzapine, Risperidone, Quetiapine, Ziprasidone
  and Aripripazole