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Transcript
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