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Mood Stabilisers

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?.

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Mood Stabilisers

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  1. Mood Stabilisers Psychopharmacology

  2. 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.

  3. 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?

  4. Pregnancy categories

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

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

  7. 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

  8. Second messenger systems • Method of cellular signalling • Cyclic adenosine monophosphate (cAMP) • intracellular signal transduction • A different process of neurotransmission

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

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

  11. 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

  12. 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

  13. Side Effects • Polyuria • Polydipsia • Diarrhoea • Nausea • Weight gain • Goiter • Acne, rash, alopecia • leukocytosis

  14. 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

  15. Toxicity • Toxic Levels are very close to therapeutic levels Symptoms; • Diarrhoea • Vomiting • Course tremor • Delerium • Coma • Seizures • Monitoring for dehydration

  16. 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

  17. 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

  18. Monitoring • Therapeutic Levels

  19. Drug interaction Increase plasma levels; • NSAIDS • Diuretics • Angiotensin-converting enzymes • Anticonvulsants (carbemazepine and phenytoin) • Metronidazole • Calcium channel blockers Increase side effects • SSRI’s • Haloperidol

  20. Special Populations • Elderly • Pregnancy • Breast feeding

  21. Anticonvulsant medications • Sodium Valproate • Carbemazepine • Lamotrogine

  22. 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

  23. How does it work? • Blocks voltage- sensitive sodium channels • Increases brain concentrations of gamma-aminobutyric acid (GABA) • Relatively unknown why it does this

  24. 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

  25. Pre-testing • Platelet counts • Liver function testing • Coagulation tests • Metabolic monitoring

  26. 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

  27. Life threatening/Dangerous Side Effects • Hepatotoxicity • Liver failure • Pancreatitis • Overdose • Restlessness • Hallucinations • Sedation • Heart block • Coma

  28. 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

  29. 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

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

  31. Special Populations • Elderly • Pregnancy • Breast feeding • Post partum issues

  32. 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

  33. How it works • Blocks voltage sensitive sodium channels • Interacts with the open channel conformation of sodium channels • Inhibits release of glutamate

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

  35. Pre testing • Blood count • Liver function • Kidney function • Thyroid function

  36. Side effects • Sedation • Dizziness • Confusion • Unsteadiness • Headache • Nausea and vomiting • Diarrhoea • Blurred vision • Benign leukopenia • Rash • Weight gain

  37. Dangerous side effects • Rare aplatic anemia • Agranulocytosis • Ususal bleeding • Infections • Fever • Sore throat • Steven Johnson syndrome (RASH) • Cardiac issues • SIADH

  38. Dosage and Use • 400-1200 mg/day • Comes in slow release • Should always be taken with food

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

  40. 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

  41. Special Populations • Pregnancy Category D • Breast Feeding

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

  43. How it works? • Voltage- gated sodium channel agonist • Inhibits the release of glutamate

  44. 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

  45. 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

  46. Dosage and Use • Monotherapy 100- 200 mg/day • Halved if used with other medication • Monitor for rash

  47. Pharmacokinetics • Elimination half life 33 hours • Higher if used concurrently with other anticonvulsant medication • Metabolised through the liver

  48. Drug interactions • Depressive effects may be increased by other CNS depressants

  49. Special populations • People with renal impairment • Hepatic Impairment • Elderly • Children and Adolescents • Pregnancy • Breast feeding

  50. Atypical Antipsychotic Medication • Increasing use of antipsychotic medication • Olanzapine, Risperidone, Quetiapine, Ziprasidone and Aripripazole

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