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Brain on Drugs 1 - Julien pp 306 336 Chapter 10 Drugs Used...

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Julien pp. 306 – 336 Chapter 10 – Drugs Used to Treat Bipolar Disorder (Mood Stabilizers) Bipolar Disorder Characterized by recurrent episodes of mania and depression, associated with cognitive deficits Occurs in up to 5 percent of population If episode of mania or hypomania required hospitalization bipolar I Less severe bipolar II Higher suicide rates in untreated bipolar individuals than normal population Higher death rates due to substance abuse Two episodes of mania is enough to require long-term mood-stabilization treatment Treatment Issues Ideal mood stabilizer: o Stabilizes acute mania, mixed, and depressive symptoms o Does not induce switch from mania to depression/depression to mania o Prevents relapse to symptoms Classic mood stabilizer: Lithium o Effective, but has bad side effects/high risk of toxicity Neuronal Injury and Mechanisms of Drug Action Bipolar disorder a neurochemical disorder Evidence that bipolar disorder is accompanied by regional differences in neuronal density and reduction in number of neurons in specific brain areas Progressive illness, recurs, deteriorates brain if left untreated Lithium Lithium increases levels of a cellular-protective protein, reduces brain damage, and facilitates neurological recovery after brain injury. o Li shares properties with sodium (Na) o Effective in treating 60-80 percent of manic episodes o Peak blood levels at 3 hours, complete absorption 8 hours o Crosses blood/brain barrier slowly and incompletely o Completely leaves body in 1-2 weeks, homeostasis reached after 2 weeks of treatment o Very narrow therapeutic range o Toxic at relatively low levels, Li replaces salt, so patients not supposed to alter sodium intake concurrent with treatment o Pharmacodynamics: exhibits few effects on brain other than action on mania o Antimanic mechanism still under research
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o Side effects: GI tract (i.e. nausea, vomiting, diarrhea), lethargy, dizziness, impaired concentration, memory, weight gain. All with high plasma levels, 1.5 – 2 mEq/l. Long-term: thyroid enlargement, rashes, increased urine output o >2.5 mEq/l can lead to death o Side effects non-compliance o Combination therapy is the rule Neuromodulator Anticonvulsants Alternatives to lithium/candidates for treatment with lithium o Carbamazepine, Valporic Acid, Lamotrigine, Gabapenntin, Topiramate, Aripiprazole, Haloperidol, Olanzapine, Risperidone, Quetiapine, Ziprasidone, Omega-3 o See Table 10.1, p. 308 for the grades these medications receive on treatment of actue mania, mood stabilization, and actue bipolar depression Atypical Antipsychotics Traditional Antipsychotics use to treat bipolar disorder pre-dates Lithium by 20 years Little use against depressive symptoms Could not prevent recurrence “Atypical” are effective against mania, and prevent relapse o Clozapine, risperidone, and olanzapine o Olanzapine considered as effective as lithium Most effective with fluoxetine Acetylcholinesterase Inhibitors
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