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Slide 2 MOOD STABILIZER DR.Mohamadbeigi Psychiatrist Slide 3 Bipolar Disorder (Manic-Depressive Illness) Mania: 1 wk of (hypomania 4 days) Mania: 1 wk of (hypomania 4 days) Elevated, Expansive, Irritable Mood +3 (4): Elevated, Expansive, Irritable Mood +3 (4): inflated self-esteem or Grandiosity inflated self-esteem or Grandiosity need for sleep (rested with 2.5 mEq/L) Generalized convulsions Oliguria and renal failure Death Slide 15 Drug Interactions with Lithium Antipsychotics: Case reports of encephalopathy, worsening of extrapyramidal adverse effects, and neuroleptic malignant syndrome; inconsistent reports of altered red blood cell and plasma concentrations of lithium, antipsychotic drug, or both Antidepressants: Occasional reports of a serotonin-like syndrome with potent serotonin reuptake inhibitors Anticonvulsants :No significant pharmacokinetic interactions with carbamazepine or valproate; reports of neurotoxicity with carbamazepine; combinations helpful for treatment resistance NSAIDs May reduce renal lithium clearance and increase serum concentration; toxicity reported (exception is aspirin) Thiazides: Well-documented reduced renal lithium clearance and increased serum concentration; toxicity reported Potassium sparing Limited data, may increase lithium concentration ACE inhibitors Reports of reduced lithium clearance, increased concentrations, and toxicity Calcium channel inhibitors Case reports of neurotoxicity; no consistent pharmacokinetic interactions Metronidazole Increased lithium concentration Methyldopa Few reports of neurotoxicity Propranolol Used for lithium tremor; possible slight increase in lithium concentration Slide 16 Routine Laboratory Monitoring TSH concentrations should be measured every 6 to 12 months. check serum creatinine concentration, and 24-hour urine volume at 6-month intervals Lithium levels should be obtained every 2 to 6 months, except when signs of toxicity are seen, during dosage adjustments, and in persons suspected to be noncompliant with the prescribed dosages. Baseline ECGs are essential and should be repeated annually. Slide 17 Correlates of Relative Lithium Responsiveness Episode characteristics Rapid or faster cycling Episode contiguity Intermittent, that is, with a well interval Sequence pattern Mania depression well interval Number of episodes before starting prophylaxis Three or fewer Quality of mania Euphoric Comorbidities History of substance abuse History of anxiety disorder Genetic background Family history of anxiety disorder Family history of bipolar illness and especially lithium response Slide 18 Valproate Valproate or valproic acid, is used for the treatment of acute manic or mixed episodes associated with bipolar I disorder. Other indications include seizure disorder and migraine prophylaxis. Slide 19 valproate is rapidly and completely absorbed 1 to 2 hours after oral administration, with peak concentrations occurring 4 to 5 hours after oral administration. The plasma half-life of valproate is 10 to 16 hours. Valproate is highly protein bound. Slide 20 Therapeutic Indications Bipolar I Disorder Acute Mania Mixed Episodes Acute Bipolar Depression Prophylaxis Schizophrenia and Schizoaffective Disorder Other Mental Disorders Slide 21 Adverse Effects of Valproate Common GI irritation Nausea Sedation Tremor Weight gain Hair loss Uncommon Vomiting Diarrhea Ataxia Dysarthria Persistent elevation of hepatic transaminases Rare Fatal hepatotoxicity (primarily in pediatric patients) Reversible thrombocytopenia Platelet dysfunction Coagulation disturbances Edema Hemorrhagic pancreatitis Agranulocytosis Encephalopathy and coma Respiratory muscle weakness and respiratory failure Slide 22 Recommended Laboratory Tests During Valproate Therapy Prior to treatment Standard chemistry screen with special attention to liver function tests CBC, including white cell and platelet count During treatment CBC and Liver function tests at 1 month, then every 6 to 24 months if no abnormalities are found Liver function test results become abnormal Mild transaminase elevation (less than three times normal): monitoring every 1 to 2 weeks: if stable and patient is responding to valproate, results are monitored monthly to every 3 months Pronounced transaminase elevation (more than three times normal): dosage reduction or discontinuation of valproate; increase dose or rechallenge if transaminases normalize and if the patient is a valproate responder Slide 23 For treatment of acute mania, an oral loading strategy of initiation with 20 to 30 mg/kg a day can be used to accelerate control of symptoms. Slide 24 Carbamazepine Carbamazepine is absorbed slowly. Bioavailability is 80 percent Peak plasma levels are reached 2 to 8 hours after a single dose. Carbamazepine is 70 to 80 percent bound to plasma protein. The average half-life after a single dose is 26 hours, with a range of 18 to 54 hours. autoinduction Slide 25 Therapeutic Indications Bipolar Disorder Acute Mania Prophylaxis Other Disorders Slide 26 Dosage-Related Adverse Effects Double or blurred vision Vertigo Gastrointestinal (GI) disturbances Task performance impairment Hematologic effects Idiosyncratic Adverse Effects Hepatic failure Agranulocytosis Aplastic anemia Rash Stevens-Johnson syndrome Pancreatitis Slide 27 Carbamazepine occasionally activates vasopressin receptor function (SIADH), characterized by hyponatremia and, rarely, water intoxication. Emergence of confusion, severe weakness, or headache in a person taking carbamazepine should prompt measurement of serum electrolytes. Slide 28 Routine Laboratory Monitoring Complete laboratory blood assessments may be performed every 2 weeks for the first 2 months of treatment and quarterly thereafter. Carbamazepine treatment should be discontinued: WBC below 3,000/mm 3, erythrocytes below 4.0 10 6 /mm 3, neutrophils below 1,500/mm 3, hematocrit less than 32 percent, hemoglobin less than 11 g/100 mL, platelet count below 100,000/mm 3 reticulocyte count below 0.3 percent serum iron concentration below 150 mg/100 mL Slide 29 Lamotrigine Lamotrigine (Lamictal) was originally developed as an antiepileptic drug used as adjunctive therapy for general and partial seizures in adults and pediatric patients. It was approved by the US Food and Drug Administration (FDA) for maintenance treatment of bipolar I disorder in 2003. In clinical trials, it was shown to keep patients euthymic longer and was particularly effective in preventing depressive episodes. Slide 30 Therapeutic Indications Bipolar Disorder Lamotrigine is indicated in the maintenance treatment of bipolar disorder and may prolong the time between episodes of depression and mania. It is more effective in lengthening the intervals between depressive episodes than manic episodes. It is also effective as treatment for rapid-cycling bipolar disorder. Other Indications Slide 31 Precautions and Adverse Reactions The most common adverse effectsdizziness, ataxia, somnolence, headache, diplopia, blurred vision, and nausea are typically mild. Cognitive impairment and joint or back pain may occur. Rash: Benign maculopapular rash :8% Stevens-Johnson syndrome or toxic epidermal necrolysis 0.08%- 0.13% Slide 32 Drug Interactions The most potentially serious lamotrigine drug interaction involves concurrent use of valproic acid, which doubles serum lamotrigine concentrations conversely. Slide 33 Lamotrigine Lamotrigine Topiramate Topiramate Gabapentin Gabapentin Antipsychotics Antipsychotics Classic (Haloperidol) Classic (Haloperidol) Novel (Clozapine, Olanzapine) Novel (Clozapine, Olanzapine)