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  1. 1. LITHIUM A Mood Stabilizer
  2. 2. Overview <ul><li>Facts about lithium </li></ul><ul><li>Brief overview of Bipolar Disorder </li></ul><ul><li>Augmenting combinations </li></ul><ul><li>How lithium may work </li></ul><ul><li>Side Effects </li></ul><ul><li>Special Populations </li></ul><ul><li>Drug Interactions </li></ul><ul><li>Pharmacokinetics and important dosing tips </li></ul>
  3. 3. Facts About Lithium (Li) <ul><li>It is an ion whose mechanism of action is not certain </li></ul><ul><li>Identified as the 1 st treatment for Bipolar Disorder </li></ul><ul><li>Less effective for rapid cycling or mixed episodes </li></ul><ul><li>It’s the 1 st psychotropic drug proven to have an effect in prevention of future episodes </li></ul>
  4. 4. Overview of Bipolar Disorder
  5. 5. Bipolar Disorder (cont’d) <ul><li>About 1% of the population are diagnosed with Bipolar Disorder (2-3 million) </li></ul><ul><li>It is believed to be genetic </li></ul><ul><ul><li>Monozygotic– 80% </li></ul></ul><ul><ul><li>Dizygotic– 8-10% </li></ul></ul><ul><li>No specific gene has been established </li></ul><ul><li>Believed that no single genetic abnormality within the DNA causes psychiatric disorders </li></ul><ul><li>Multiple sites in DNA must interact to produce the causation of a psychiatric disorder. </li></ul>
  6. 6. Augmenting Combinations <ul><li>Lithium can be used with the following, in cases of partial response or treatment resistance: </li></ul><ul><ul><li>Valproate </li></ul></ul><ul><ul><li>Atypical antipsychotics (risperdone, olanzapine, aripiprazole) </li></ul></ul><ul><ul><li>Some antidepressants </li></ul></ul><ul><ul><ul><li>CAUTION: antidepressants could potentially cause the patient to go into rapid cycling episodes or increase suicidal ideation (Avoid TCA’s and MAOI’s) </li></ul></ul></ul><ul><ul><li>Benzodiazepines </li></ul></ul>
  7. 7. How Lithium is Thought to Work <ul><li>It alters Na+ transport across cell membranes in nerve and muscle cells </li></ul><ul><li>It alters metabolism of NT’s including catecholamines and serotonin </li></ul><ul><li>It alters intracellular signaling through actions on 2 nd messenger systems </li></ul><ul><li>It inhibits inositol monophosphatase, affecting the phosphatidyl inositol 2 nd messenger system </li></ul>
  8. 8. How Lithium is Thought to Work (cont’d) <ul><li>It reduces protein kinase C activity </li></ul><ul><li>It increases cytoprotective proteins </li></ul><ul><li>It increases gray matter content, possibly by activating neurogenesis and enhancing trophic actions that maintain synapses </li></ul>
  9. 9. Side Effects <ul><li>Ataxia </li></ul><ul><li>Dysarthria </li></ul><ul><li>Delirium </li></ul><ul><li>Tremor </li></ul><ul><li>Memory problems </li></ul><ul><li>Diarrhea, Nausea </li></ul><ul><li>Weight Gain </li></ul><ul><li>Polyuria & Polydipsia </li></ul><ul><li>Leukocytosis </li></ul><ul><li>Acne, rash, alopecia </li></ul><ul><li>Sedation </li></ul><ul><li>LIFE THREATENING </li></ul><ul><ul><li>Li toxicity </li></ul></ul><ul><ul><li>Renal impairment </li></ul></ul><ul><ul><li>Arrhythmia </li></ul></ul><ul><ul><li>Bradycardia </li></ul></ul><ul><ul><li>Hypotension </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>Pseudotumor cerebri (intracranial pressure) </li></ul></ul><ul><li>Many cannot be improved by other medications </li></ul><ul><li>Propranolol (ataxia) </li></ul><ul><li>Diuretics </li></ul>
  10. 10. Do Not Prescribe to the Following <ul><li>Renal impairment </li></ul><ul><li>Cardiac impairment </li></ul><ul><li>Elderly </li></ul><ul><li>Children under 12 </li></ul><ul><li>Pregnant women </li></ul><ul><li>Women that are breast feeding </li></ul>
  11. 11. Drug Interactions with Lithium <ul><li>Anti-inflammatory agents (ibuprofen), diuretics, and angiotensin-converting enzyme inhibitors can cause increased plasma lithium concentrations </li></ul><ul><li>Carbamazepine (tegretol) and phenytoin (dilantin) can increase lithium toxicity </li></ul><ul><li>Calcium channel blockers may also increase lithium toxicity </li></ul><ul><li>SSRI’s may increase the risk of dizziness, confusion, diarrhea, agitation, and tremor </li></ul>
  12. 12. Pharmacokinetics <ul><li>Half life </li></ul><ul><ul><li>18-30 hours </li></ul></ul><ul><li>How long until it works </li></ul><ul><ul><li>1-3 weeks </li></ul></ul><ul><ul><li>For immediate results, an atypical antipsychotic is recommended </li></ul></ul><ul><li>Forms of Li </li></ul><ul><ul><li>Tablet (300 mg, slow release; 450 mg, controlled release) </li></ul></ul><ul><ul><li>Capsule (150 mg, 300 mg, 600 mg) </li></ul></ul><ul><ul><li>Liquid (8 mEq/5 mL) </li></ul></ul><ul><li>Up to 1800 mg/day can be given in acute cases (divided) </li></ul><ul><li>900-1200 mg/day for maintenance (divided) </li></ul><ul><li>10 mL 3 times/day for acute mania; 5 mL 3-4 times/day for long-term use </li></ul>
  13. 13. Dosing Tips <ul><li>Kidney function tests and thyroid function tests MUST be done before adminisering </li></ul><ul><li>Rapid discontinuation increases the risk of relapse and suicidal ideation. It needs to be tapered over 3 months </li></ul><ul><li>Long-term use can cause reduced kidney function, so 1-2 times a year it should be checked </li></ul><ul><li>Overdose can result in death or serious side effects (tremor, dysarthria, delirium, coma, seizures, and autonomic instability) </li></ul>
  14. 14. Any Questions? <ul><li>References </li></ul><ul><li>Stahl, S. M. (2000). Essential psychopharmacology: neuroscientific basis and practical applications (2nd ed.). New York: Cambridge University Press. </li></ul><ul><li>Stahl, S. M. (2005). The prescriber’s guide . New York: Cambridge University Press. </li></ul>