Mood Stabilisers Psychopharmacology Mood Stabilisers u The treatment
Mood Stabilisers Psychopharmacology
Mood Stabilisers u The treatment of bipolar disorder may be divided into three overlapping phases – Acute manic episode – Depressive episode – Prophylactic treatment u Only 1/3 of bipolar patients experience adequate relief with a monotherapy.
How they work? u They have no clear effect on dopamine? ? So why are they effective in mania? u They have no clear effect serotonin? ? So why are they effective in depressive episodes?
Pregnancy categories
Lithium u First original mood stabiliser u Underutilised u Appears most effective in treating acute mania u First psychiatric drug that required blood level monitoring
Lithium u Manic episodes of bipolar disorder u Maintenance treatment for bipolar disorder u Bipolar depression u Major depressive disorder u Vascular headache u Neutropenia
Mechanisms u Generally unknown u Complex in action u Alters sodium transport across cell membranes u Alter metabolism of neurotransmitters catecholamines, serotonin, GABA and glutamate - May alter intracellular signalling through actions on second messenger systems
Second messenger systems u Method of cellular signalling u Cyclic adenosine monophosphate (c. AMP) u intracellular signal transduction u A different process of neurotransmission
Lithium u Effective within 1 -3 weeks u Goal of treatment is a remission in symptoms u Many patients only have a partial response
Concept of Augmentation u the combination of two or more drugs to achieve better treatment results u Failure of monotherapy u Better tolerability
Pre-testing u Kidney function( should be repeated 1 -2) u Thyroid function u ECG for patients over 50 u Metabolic monitoring – Fasting plasma glucose level – Cholesterol and triglycerides – BMI
Side Effects u The reason to why lithium causes side effects is complex u Excessive actions at the same or similar sites that mediate actions u Renal side effects= acts on transportation of ions
Side Effects u Polyuria u Polydipsia u Diarrhoea u Nausea u Weight gain u Goiter u Acne, rash, alopecia u leukocytosis
Life Threatening Side Effects u Lithium toxicity u Renal impairment u Nephrogenic diabetes insipidus u Arrhythmias u Cardiovascular changessick sinus rhythm u Sick Sinus syndrome u Bradycardia u hypotension u T wave flattening and inversion
Toxicity u Toxic Levels are very close to therapeutic levels Symptoms; – Diarrhoea – Vomiting – Course tremor – Delerium – Coma – Seizures u Monitoring for dehydration
Dosing and Using u 1800 mg/day in divided doses (acute) u 900 -1200 mg/day in divided doses( maintenance) u Dosage forms – 450 mg (slow release) – 250 mg tablets u start low and adjust dosage upward as indicated by plasma levels
Dosing u Slow release= less gastric irritation, lower peak plasma levels and peak dose side effects u Use the lowest dose of lithium associated with adequate therapeutic response u Go low in the elderly u Rapid discontinuation= increase relapse
Monitoring u Therapeutic Levels
Drug interaction Increase plasma levels; u NSAIDS u Diuretics u Angiotensin-converting enzymes u Anticonvulsants (carbemazepine and phenytoin) u Metronidazole u Calcium channel blockers Increase side effects u SSRI’s u Haloperidol
Special Populations u Elderly u Pregnancy u Breast feeding
Anticonvulsant medications u Sodium Valproate u Carbemazepine u Lamotrogine
Sodium Valproate u. A first line treatment for bipolar disorder especially mixed state or rapid cycling bipolar. u Prescribed for; – Mania – Maintenance treatment of Bipolar Disorder – Seizures – Migraine prophylaxis
How does it work? u Blocks voltage- sensitive sodium channels u Increases brain concentrations of gamma-aminobutyric acid (GABA) u Relatively unknown why it does this
Sodium Valproate u Effects occur within a few days u Optimised at several weeks to one month u The goal is to see a remission in symptoms u Augmentation
Pre-testing u Platelet counts u Liver function testing u Coagulation tests u Metabolic monitoring
Sides Effects Due to Excessive actions at voltage sensitive sodium channels Include; u 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 u Hepatotoxicity u Liver failure u Pancreatitis u Overdose – Restlessness – Hallucinations – Sedation – Heart block – Coma
Dosage and Use u Range; u Mania; 1200 -1500 mg/day u Migraine; 500 -1000 mg/day u Epilepsy; 10 -60 mg/day u 100 mg, 200 mg and 500 mg tablets u Dosages are increased rapidly in the case of mania. u May need divided dose due to half life u Terminal mean half life of 9 -16 hours u Metabolised by the liver
Drug interactions Lamotrogine should be reduced by 50% u Plasma levels lowered by drugs such as; u u Carbemazepine u Phenytoin u Plasma levels are increased by drugs such as; u Aspirin u Chlorpromazine u Fluoxetine u NSAIDS
Warnings u Hepatotoxicity u Malaise u Weakness u Lethargy u Facial edema u Anorexia u Vomiting u Jaundice skin and eyes u Pancreatitis u Abdominal u Nausea u vomiting pain
Special Populations u Elderly u Pregnancy u Breast feeding u Post partum issues
Carbamazepine u More commonly used to treat seizures u First anticonvulsant to be widely used in the treatment of Bipolar disorders u Potentially an advantage in treatment resistant bipolar and or psychotic disorders
How it works u Blocks voltage sensitive sodium channels u Interacts with the open channel conformation of sodium channels u Inhibits release of glutamate
Carbamazepine u Goal of treatment is remission of symptoms u Effect usually occur within a few weeks u Can be used a augment other medications
Pre testing u Blood count u Liver function u Kidney function u Thyroid function
Side effects u u u Sedation Dizziness Confusion Unsteadiness Headache Nausea and vomiting Diarrhoea Blurred vision Benign leukopenia Rash Weight gain
Dangerous side effects u Rare aplatic anemia u Agranulocytosis – Ususal bleeding – Infections – Fever – Sore throat Steven Johnson syndrome (RASH) u Cardiac issues u SIADH u
Dosage and Use u 400 -1200 mg/day u Comes in slow release u Should always be taken with food
Pharmacokinetics u Metabolised in the liver by CYP 450 u Half life of 26 -65 hours initially then drops with repeated doses
Drug interactions u Other antiepileptic medications u Fluvoxamine, fluoxtetine u Decrease efficacy of benzodiazepines, clozapine, haloperidol, lamotrogine, epilum and warfarin u Can decrease effectiveness of the contraceptive pill u Lithium
Special Populations u Pregnancy Category D u Breast Feeding
Lamotrigine u Seems to be more effective in treating depressive episodes of bipolar u Used less than other anticonvulsants for Bipolar Disorder
How it works? u Voltage- gated sodium channel agonist u Inhibits the release of glutamate
Side effects u u u 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 u Rare serious rash Acute fever u Bullae on the skin u Ulcers on the mucous membranes on lip, eyes, mouth and nasal passages u u Management Stop medication u Monitor and investigate organ involvement u May require admission u
Dosage and Use u Monotherapy 100 - 200 mg/day u Halved if used with other medication u Monitor for rash
Pharmacokinetics u Elimination half life 33 hours u Higher if used concurrently with other anticonvulsant medication u Metabolised through the liver
Drug interactions u Depressive effects may be increased by other CNS depressants
Special populations u People with renal impairment u Hepatic Impairment u Elderly u Children and Adolescents u Pregnancy u Breast feeding
Atypical Antipsychotic Medication u Increasing use of antipsychotic medication u Olanzapine, Risperidone, Quetiapine, Ziprasidone and Aripripazole
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