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Mental Health Pharmacology II

Mental Health Pharmacology II. Chelsea Mannebach Pharmacy Resident August 17 th , 2011. Topics. Schizophrenia Bipolar Disorder Anxiety Disorders Eating Disorders. Schizophrenia. Psychiatric disorder characterized by profound disruption in perception, cognition, and emotion

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Mental Health Pharmacology II

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  1. Mental Health Pharmacology II Chelsea Mannebach Pharmacy Resident August 17th, 2011

  2. Topics • Schizophrenia • Bipolar Disorder • Anxiety Disorders • Eating Disorders

  3. Schizophrenia • Psychiatric disorder characterized by profound disruption in perception, cognition, and emotion • ~1% of the United States population • Types • Paranoid • Disorganized • Catatonic • Undifferentiated • Residual

  4. What symptoms are associated with schizophrenia?

  5. Diagnosis • DSM-IV Criteria • Two or more of the following in a one month period • Hallucinations • Delusions • Disorganized speech • Grossly disorganized or catatonic behavior • Negative symptoms

  6. Pathophysiology • Dopamine hyperactivity in limbic system • Dopamine hypo-functioning in the prefrontal cortex • Decreased glutamate • NMDA receptor dysfunction

  7. Four Dopamine Pathways • Mesolimbic • Nigrostriatal • Mesocortical • Tuberoinfundibular

  8. Drug Therapy • What are some common drugs used to treat schizophrenia?

  9. Conventional Antipsychotics • Chlorpromazine (Thorazine) • Thioridazine (Mellaril) • Perphenazine (Trilafon) • Fluphenazine (Prolixin) • Haloperidol (Haldol)

  10. Atypical Antipsychotics • Clozapine (Clozaril) • Risperidone (Risperdal) • Olanzapine (Zyprexa) • Quetiapine (Seroquel) • Ziprasidone (Geodon) • Aripiprazole (Abilify) • Paliperidone (Invega)

  11. Mechanism of Action • Conventional • Dopamine-2 Receptor Antagonist • Non-selective • Atypical • Dopamine-2 Receptor and Serotonin Antagonist • Selective mesolimbic D2 blocking • Serotonin blockade causes decreased extrapyramidal side effects and is beneficial with negative symptoms

  12. Side Effects • Sedation • Orthostasis • Weight gain • Anticholinergic effects • Dystonic reactions • Akathisia • Pseudoparkinsonism • Tardive dyskinesia • Neuroleptic malignant syndrome • Dermatologic effects • Hypothalmic effects • Cardiac effects • Opthalmologic effects

  13. Side Effect Management • Dystonic reactions • benztropine (Cogentin) 1-2 mg IM or diphenhydramine (Benadryl) 25-50 mg IM every 30 minutes until reaction resolved • Akathisia • Beta blockers (propranolol), benzodiazepines, clonidine, anticholinergics • Pseudoparkinsonism • Amantadine (Symmetrel) 100 mg BID or anticholinergics • TardiveDyskinesia • No effective treatment

  14. NMS Treatment • Stop offending agent • Administer supportive therapy • Fluid and electrolyte replacement • Temperature reduction • Support of cardiac, respiratory and renal function • Pharmacological therapy • Bromocriptine (Parlodel) • Dantrolene (Dantrium)

  15. Acute Schizophrenia Treamtment • Haloperidol or fluphenazine IR 5-10 mg IM and lorazepam 2 mg IM q4h prn • Olanzapine 10 mg IM may also be used and can be repeated in 2 hrs and again 4 hours later (max 30 mg/d) • Ziprasidone 10 mg IM every 2 hours or 20 mg IM every 4 hours (max 40 mg/d)

  16. Maintenance Therapy • Lifelong therapy usually indicated • Use lowest effective dose to decrease risk of side effects • Monitor • Fasting glucose • Lipids • Blood pressure • Weight • Waist circumference

  17. Expert Consensus Treatment Guidelines • Monotherapy • Switch • Clozapine • Combination

  18. Treatment Pearls • All antipsychotics are equally effective if used properly • Clozapine is the only agent approved for refractory schizophrenia • Use past history to help guide therapy • Administer a trial of at least 4-6 weeks when initiating therapy • Alternative dosage forms and compliance • Haloperidol decanoate, Fluphenazine decanoate, Risperidone injection

  19. Bipolar Disorder • Bipolar I • manic episodes and major depressive episodes • Bipolar II • hypomanic episodes and major depressive episodes • Cyclothymia • numerous episodes of hypomania and depression that cannot be classified as major depressive episodes; at least a 2 year period

  20. Diagnosis • DSM-IV • Mania • Heightened mood, flight of ideas, rapid speech, grandiosity, increased energy, decreased sleep, impulsivity, social or occupational impairment • Hypomania • Less severe form of mania (no social impairment) • Dysphoric (mixed mania) • Manic and depressive features, agitation, suicidal ideation, appetite disturbances • Major depression • Rapid cycling • > 4 mood episodes in a year

  21. Pathophysiology • Neurotransmitter imbalance • Decreased serotonin • Increased norepinephrine • Decreased GABA • Increased glutamate

  22. What pharmacological agents are used to treat bipolar disorder?

  23. Mood Stabilizers • Lithium (Lithobid) • Divalproex sodium (Depakote) • Carbamezapine (Tegretol) • Lamotrigine (Lamictal)

  24. Lithium (Lithobid) • Indicated for acute treatment and prophylaxis for both manic and depressive episodes • Mechanism of Action • facilitates GABA function, normalizes transmission of norepinephrine, serotonin and dopamine • Contraindications • renal disease, 1st trimester pregnancy, severe CV disease, hx leukemia; caution in patients with thyroid disease, dehydration • Monitoring • TSH, SCr, CBC, electrolytes, ECG, pregnancy status, Lithium level (acute: 0.6-1.2 mEq/L; maintenance: 0.8-1.0 mEq/L)

  25. Lithium cont. • Side Effects • tremor, polydipsia, N/D, weight gain, hypothyroidsim, mental dulling, acne • Toxicity • Mild: Levels 1.5 – 2.0 mEq/L • GI, muscle weakness, fatigue, tremor • Moderate: Levels 2.0-2.5 mEq/L • Ataxia, lethargy, confusion, severe GI upset • Severe: Levels > 3.0 mEq/L • Impaired consciousness, coma, seizures, death

  26. Lithium Toxicity Management • Discontinue lithium • Gastric lavage • Supportive care • Dialysis

  27. Lithium Drug Interactions • Increase Lithium level • NSAIDS • ACE inhibitors • Fluoxetine • Metronidazole • Diuretics • Sodium depletion • Decrease lithium level • Theophylline • Caffeine • Pregnancy • Osmotic diuretics (mannitol and urea)

  28. Divalproex Sodium • First line indication for acute manic episodes; effective in rapid cyclers • Mechanism of Action • thought to increase GABA or mimic its action at the postsynaptic receptor site • Contraindications • hepatic dysfunction*, pregnancy (if risk outweighs benefit supplement with folic acid 4-5 mg/d to decrease risk of neural tube defects) • Monitoring: LFTs, CBC, VPA level ( 50-125 mcg/mL)

  29. Divalproex sodium cont. • Side Effects • GI upset, weight gain, alopecia, increased LFTS, pancreatitis, sedation • Drug Interactions • CYP450 2C19 inhibitor • increased sedation with phenobarbital and benzos • Pearls • take with food • take a multivitamin with selenium and zinc if alopecia occurs

  30. Carbamazepine (Tegretol) • Second line therapy for acute treatment and prophylaxis of bipolar disorder; more effective in rapid cyclers and mixed episodes • Mechanism of Action • Unknown; inhibits transmission at Na channel • Contraindication • previous bone marrow suppression • Monitoring • CBC, electrolytes, LFTs, SCr, levels (optimal 4-12 mcg/mL)

  31. Carbamazepine cont. • Side Effects • dizziness, sedation, slurred speech, aplastic anemia, rash • Drug Interactions • CYP 450 1A2, 2C, and 3A4 inducer • CYP 450 2C8 and 3A4 substrate • Induces metabolism of benzodiazepines, clozapine, corticosteroids, oral contraceptives, VPA, warfarin, phenytoin, TCAs and more! • Is inhibited by cimetidine, clarithromycin, diltiazem, verapamil, propoxyphene, metronidazole, lamotrigine and more!

  32. Lamotrigine (Lamictal) • Maintenance treatment of bipolar I disorder • Requires dose titration to avoid rash • Side effects • dizziness, headache, nausea, rash, sedation, anxiety • Caution • Black box warning for severe rash (Stevens-Johnson syndrome) • Drug Interactions • Carbamazepine, phenytoin, oral contraceptives, rifampin, and phenobarbital decrease Lamictal concentrations • VPA increases Lamictal concentrations

  33. Other Potential Therapies • Atypical antipsychotics • All have proven efficacy • Need to dose on higher end • Gabapentin (Neurontin) • Adjunctive therapy • Oxcarbazepine (Trileptal) • Topiramate (Topamax) • Calcium Channel Blockers (last line) • Verapamil for mania

  34. Treatment Guidelines • Acute • Lithium, divalproex sodium, carbamezapine, or antipsychotic • Short term use of a benzo • Maintenance • Monotherapy if possible • Lithium, divalproex sodium, lamotrigine • Depressed phase • Use antidepressants with caution

  35. Anxiety Disorders • Generalized Anxiety Disorder • Panic Disorder • Obsessive-Compulsive Disorder • Social Anxiety Disorder • Simple Phobias • Post-Traumatic Stress Disorder • Substance-Induced Anxiety Disorder

  36. What drugs are commonly associated with anxiety?

  37. What drugs have anxiety associated with their withdrawal?

  38. What drugs are commonly used to treat anxiety disorders?

  39. Benzodiazepines • Alprazolam (Xanax) • Chlordiazepoxide (Librium) • Clonazepam (Klonopin) • Clorazepate (Tranxene) • Diazepam (Valium) • Estazolam (ProSom) • Flurazepam (Dalmane) • Halazepam (Paxipam) • Lorazepam (Ativan) • Oxazepam (Serax) • Prazepam (Centrax) • Quazepam (Doral) • Temezapam (Restoril) • Triazolam (Halcion)

  40. Mechanism of Action • Potentiate the inhibitory actions of GABA • Reduce neuronal firing and therefore symptoms of anxiety • Onset • More lipophilic = faster onset of action • Alprazolam • Diazepam • Clorazepate • Flurazepam

  41. Side Effects • Sedation • Dizziness • Confusion • Blurred vision • Psychomotor and cognitive disturbances

  42. Metabolism and Drug Interactions • Patients with hepatic dysfunction or elderly • Use lorazepam, oxazepam, temazepam (LOT) • Metabolized by CYP 3A4 • Alprazolam, diazepam, triazolam • Watch if taken with 3A4 inhibitors (ketoconazole, erythromycin, nefazodone)

  43. Clinical Pearls • Paradoxical reactions in children and cognitively impaired elderly patients • Never abruptly discontinue benzodiazepines, can cause status epilepticus; taper gradually • Use “LOT” in elderly patients to avoid against falls • Avoid use in pregnancy (cleft palate risk) • Abuse potential high • Tolerance is common

  44. Buspirone (Buspar) • Mechanism of Action • Non-benzodiazepine anxiolytic • 5HT-1A partial agonist • No action on GABA • Antianxiolytic effect takes longer to achieve • 2-3 weeks • Side Effects • GI upset, headache, nervousness • Less sedating than benzos, no psychomotor or cognitive impairment, no withdrawal symptoms, little abuse potential

  45. Other therapies • Antidepressants • SSRIs and SNRIs are first line for many patients with comorbid depression and substance abuse problems • Titrate doses slowly • Higher doses are needed to treat anxiety than depression • TCAs and MAOIs are third line • Poor side effect profile • Beta blockers (propranolol, atenolol) • Hydroxyzine

  46. Treatment Guidelines • Start in combination with a serotonergic drug • Taper benzodiazepine after 4-12 weeks • once benefit from SSRI or SNRI has been achieved • Taper slowly over 4-10 weeks • Risk of withdrawal • Often used on PRN basis

  47. Eating Disorders • Anorexia nervosa • Bulimia nervosa • Binge eating disorder

  48. Drug Therapy • SSRIs • Help patients maintain weight after it has been gained • May be more effective in patients with bulima • Fluoxetine (Prozac): higher doses up to 60 mg/day • Topiramate (Topamax) and Zonisamide (Zonegran) • Beneficial in binge-eating disorder and bulima nervosa

  49. Questions?

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