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; - Sedation - dyspepsia - Tremor - ataxia - tremor - weight gain - alopecia polycystic ovarian syndrome - headache - Abdominal pain - nausea/vomiting - reduced appetite - constipation 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 pain Nausea vomiting
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