EVIDENCE BASED PRACTICE Clinical Pharmacology- HNG 540
Tina Goodrow MSN/ED, RN Faye Taber MSN, RN Kathleen Scott BSN, RN Carla Tipton BSN, RN-BC
Professor Frawley April 2, 2012
PART I- Overview of Schizophrenia I.Definition, Epidemiology, Etiology II.Diagnosis, Types, Differential Diagnosis III.Pathophysiology IV.Laboratory and Psychological Tests V.Psychodynamic Factors, Course Prognosis PART II- Treatments for Schizophrenia I.Non-pharmacological II.Pharmacotherapy
Goodrow, Taber, Scott & Tipton
• What it is • What it is not
. must have two or more of the following for more then 1 month:
• Delusions • Hallucinations • Disorganized Speech
• Grossly disorganized or catatonic behavior • Negative symptoms
• (flat affect. alogia)
• Must R/O substance abuse or a medical condition
(Ebert. Nurcombe. p.DEFINITION. Loosen. ETIOLOGY
• Schizophrenia: pt. EPIDEMIOLOGY. & Leckman.
auditory or visual hallucinations. • Subtypes of schizophrenia include: paranoid. Other possibilities include Addison’s disease. TYPES. or hyperthyroidism. Taber.
4/5/2012 Goodrow. • Schizophrenia often presents as delusional thinking. and negative symptoms may resemble depression. The positive symptoms of schizophrenia can present as mania. DIFFERENTIAL DIAGNOSIS
• Symptoms used to diagnose schizophrenia can vary depending on type and progression of the disease.DIAGNOSIS. head trauma. along with disorganized speech and flat affect. undifferentiated. catatonic. • In order to diagnose schizophrenia. disorganized. Scott & Tipton 5
. up to and including catatonia. Mood disorders and schizo-affective disorder must also be ruled out. and residual. one must rule out Bipolar I. alcohol-related psychosis.
Scott & Tipton
• No consistent structural defects • Changes noted
• • • ↓ # neurons ↑ gliosis Disorganization of neuronal architecture Degeneration in limbic system • CT • MRI • Magnetic Resonance spectroscopy • PET • Cerebral blood flow
• Minor Neuro findings
• • • •
↑ primitive reflex Abnormal Stereognosis Dysdiadochokinesia Paraxysmal saccadic eye movements
• ↑ Resting HR
brain imaging. cerebral abscesses. Taber. vasculitis. and tumors • Neuropsychological testing often shows poor executive functioning • Determination of the patient's cognitive weaknesses and strengths can be helpful in treatment planning • It is possible. 2012)
Goodrow.LABORATORY AND PSYCHOLOGICAL TESTS
• No characteristic laboratory results are found in schizophrenia • Diagnosis is made based on symptoms • Monitoring of certain laboratory tests at the beginning of illness and periodically afterwards • Brain imaging to rule out subdural hematomas. Scott & Tipton
. however. and other indicators that are still undefined — could someday be helpful in diagnosing and predicting the outcome of the disease. that a pattern of test results — perhaps including genetic. (Frankenburg.
2008. • Frequently occurs with substance abuse disorders. p. Loosen.PSYCHODYNAMIC FACTORS.
(Ebert. anxiety. COURSE PROGNOSIS
• Supportive therapy is recommended with a strong emphasis on skill building and teaching patient’s to deal with hallucinations. 261-268)
. Nurcombe. • Earlier onset usually a poorer outcome. delusions and negative symptoms • CBT (cognitive behavioral therapy)is indicated • Schizophrenia is usually involved recurrent acute exacerbation of psychosis • With each relapse with is an increase in deterioration. and depressive symptoms. & Leckman.
• Non-Pharmacological • Pharmacotherapy
and have a synergistic effect along with psychotropic medications. Support in this process leads to better outcomes and fewer instances of relapse.NON-PHARMACOLOGICAL
• Psychotherapy and social skills therapy work in conjunction with pharmacotherapy to provide optimal outcomes and social functioning for the schizophrenic client.
Goodrow. dialectical behavioral therapy. • Assertive Community Treatment (ACT) supports community integration as a way to prevent re-institutionalization • Group therapy. 2007). and individual psychotherapy all provide support. • Social and behavioral skills therapy directly address the life-skills needed to live independently by studying and practicing functional behavioral patterns. with the goal of independent or supported living in the community. cognitive behavioral therapy. and medication compliance leads to better social functioning if proper support is present. theory helps the client stick with his or her medication regime. In other words. Scott & Tipton
. Taber. (Saddock. • Family centered therapies help family learn how to support the client • Case management coordinates all services for the client.
All rights reserved. except higher doses of risperidone Yes. hyperglycemia or hyperlipidemia Repeated nonadherence to pharmacological TX
Date of download: 3/25/2012
Yes Yes Yes.PHARMACOTHERAPY
Table 3 Choice of Medication in the Acute Phase
Group 1: 1st Generation Group 2: 2nd Generation Group 3: Clozapin e Group 4: LongActing Injectable Antipsychotic Agents
Persistent SI or behavior Persistent hostility & Aggressive behavior Tardive dyskinesia HX of Sensitivity to EPS HX of Sensitivity to Prolactin elevation HX of Sensitivity to Wt gain. except Risperidone Ziprasidone or Aripiprazole Yes
Copyright © American Psychiatric Association.
. all group 2 drugs may not be equal in their lower or no tardive dyskinesia liability Yes.
From: Chapter 4.
. All rights reserved. 2010
FIGURE 1. Somatic Treatment of Schizophrenia
Date of download: 3/25/2012
Copyright © American Psychiatric Association.
TREATING SCHIZOPHRENIA: A Quick Reference Guide
APA Practice Guidelines.
Goodrow. or apple juice Multiple side effects Less sedation/hypotension Greater risk of EPS Tardive dyskinesia. 97-101 & 225-229)
.PHENOTHIAZINES FIRST-GENERATION AGENTS
• • • • • • • • • • • • Conventional Antipsychotic Dopamine 2 antagonist Antiemetic Low potency phenothiazine Several FDA uses Approved in children w caution Reduces positive symptoms IM available for emergency Rectal suppository available Sedation for behavior control Multiple side effects. tea. Scott & Tipton (Stahl. 2011.EPS Tardive dyskinesia.irreversible • • • • • • • • • • •
Conventional Antipsychotic Dopamine 2 antagonist High potency phenothiazine Reduces positive symptoms IM available for emergency IM Long-acting Decanoate Do not mix oral solution with caffeine. Taber.
• Not addicting
(Olson. Wilson. 2008. 42-43) (Shannon. & Strang. analgesics. p. sedatives. analgesic. anti histamines and morphine. 1494-1495)
. central depressants. antihistimines alcohol and morphine. Shields. 2006. Not addicting
(Trilafon) • FDA approved • Used more frequently • Given orally to adults-4-16 mg BID to ID • Causes anti-cholinergic side effects & hypotension • Monitor liver and kidney functioning • Enhances effects of alcohol.FIRST-GENERATION AGENTS
• FDA approved • Not frequently used • Potential for serious cardiac issues Can be given orally or IM Patients are at risk for EPS or NMS Causes anti-cholinergic effects Enhances effect of central depressants. sedatives. p.
Goodrow. Taber. and less cost (Stahl.FIRST-GENERATION AGENTS
• Conventional antipsychotic • Blocks dopamine-2 receptors • Serious cardiac and drug-interaction effects • Contraindicated for most patients unless all other options have failed (Stahl. Scott & Tipton
• Conventional antipsychotic • Blocks dopamine-2 receptors • Augmented pharmacotherapy possible • Greater efficacy and tolerability.
or decanoate 10-20 times previous daily dose of oral
• Side effects/ TX
• EPS.BUTYROPHENONE FIRST-GENERATION AGENTS
• Conventional Antipsychotic • Several FDA uses • Dosage• Oral: 1-40mg. • Cogentin/trihexypheni dylAtypical
• Antipsychotic monitoring required • Special populations
Goodrow. Akathesia. Taber. sedation etc. Immediaterelease IM 2-5mg each. Scott & Tipton
. wt gain.
327-331 & 405-408)
. EPS. 2011.irreversible • • • • • • • •
Goodrow. galactorrhea • Tardive dyskinesia. loss
Conventional antipsychotic Dopamine 2 antagonist Reduces positive symptoms Titration over 3-4 days Very short half-life ~1. ? daily dosing One active metabolite is the antidepressant.OTHER FIRST-GENERATION AGENTS
• • • • • • • • • • Conventional antipsychotic Dopamine 2 antagonist Serotonin dopamine antagonist Reduces positive symptoms IM faster onset of action & superior efficacy than Haldol Requires titration over 7-10 d Studies have shown that may be atypical at low doses Multiple active metabolites w longer half-lives. Taber.5h 3-4 divided daily doses May cause less weight gain Multiple side effects: anticholinergic. akathisia. p. gain & may cause wt.amoxapine wt. Scott & Tipton (Stahl. antihistamine effects.
Wilson. sedative. 2006. & Strang. such as chlorpromazine • Can be given PO or IM • Not addicting • Inhibits action of levadopa and & dopamine agonists
• Enhances the effect of central depressants. p. 2008. 1494-1495)
. Shields.OTHER FIRST-GENERATION AGENTS
• Blocks Dopamine Receptors • Less sedating and hypotension then other agents. alcohol & morphine • High incidence of akathisia
(Olson. antihistamines. p. 42-43) (Shannon. analgesics.
• Atypical antipsychotic: dopamine partial agonist • Improves cognitive. not indicated for diabetics • Augmentation possible
Goodrow. Taber. and mood symptoms • Low risk for lifethreatening side effects • Compatible with other antipsychotics
• Atypical antipsychotic: Serotonin-dopamine antagonist • Reduces but does not eliminate both positive and negative symptoms • Significant risk for hyperglycemia. negative. Scott & Tipton
• FDA approved for
• Tx-Resistant Schizophrenia • Reduction in risk of recurrent suicidal behavior w/schizophrenia or schizoaffective d/o
• Intensive monitoring parameters –CBC/ANC
• Wkly x 6mo. 2011)
• Dose 300-450mg/day • Agranulocytosis • Cardiomyopathy
Goodrow. Scott & Tipton
. biwkly x 6mo. q4wks thereafter • AIMS assessment • blood glucose • LFTs • neurologic function • serum cholesterol profile • weight (Stahl. Taber.
BID dosing positive & improves negative symptoms Monitor BMI. and fasting lipid profile Orthostatic hypotension Reduced risk of TD or NMS Prolongs QTc interval Less EPS or akathisia
• Atypical antipsychotic • Serotonin dopamine antagonist • Mood stabilizer. Scott & Tipton (Stahl. FBS.mono or adjunct & prevent recurrence • Several FDA & off label uses • Approved age 13 & up • 5HT2C antagonists plus serotonin blockade of Prozac • IM agitation in 15-30 min • Oral disintegrating tablet • + & improves . Taber. 267-271 & 427-433)
. waist circum. 2011. BP.symptoms • risk diabetes & dyslipidemia • May dose for smokers
Goodrow. p.SECOND-GENERATION AGENTS
• • • • • • • • • • • Atypical antipsychotic Serotonin dopamine antagonist Inhibitors of CYP450 2D6 3A4 Multiple off label uses Slow titration.
orthostatic hypotension. 2008. 130-1311)
. TD and EPS then traditional antipsychotics
(Olson. Shields.SECOND-GENERATION AGENTS
• PO and IM long acting use • Not for use with elderly dementia-induced psychosis • May prolong QT interval
• Higher affinity for 5 HT2 receptors then D2 receptors • Less risk of anticholinergic S/E. 42-43) (Shannon. 2006. & Strang. p. Wilson. sedation. p.
• Atypical antipsychotic. 2011)
Goodrow. continue oral agents for 3 weeks after first injection • Must be administered by qualified professional • Must stay refrigerated (Stahl. Scott & Tipton
. serotonin-dopamine antagonist • Blocks dopamine 2 receptors • Reduces both positive and negative symptoms • Higher risk for side effects over 6mg/day orally • Augmentation possible (Stahl. 2011)
• Ideal for non-compliant clients • Two week lead time.
absorption • Slow cross-titration
• Atypical antipsychotic • Serotonin dopamine antagonist • Mood stabilizer • Metabolized by CYP450 3A4. Taber. and fasting lipid profile • Less wt.BID dosing at >120mg/d • Take w meal. 2011. BP. 427-433)
. p. Scott & Tipton (Stahl.no significant affect • Several FDA & off label uses • IM can reduce agitation in 15 minutes • positive & improves negative symptoms
• Monitor BMI. waist circum. gain (uncommon) • S/E at low doses for some • Best efficacy. FBS.
requires strict compliance with plasma level monitoring due to high risk for toxicity (Stahl. 2011).
Goodrow. can also reduce anxiety • Must use extreme caution when used with lithium due to its potentiating effect. Taber. monitor closely for early s/sx toxicity (Stahl.OTHER DRUGS
(Lithium) • Mood stabilizer • Alters sodium transport across cell membranes • Can lead to full remission of both mania and depressive symptoms • Can augment both typical and atypical antipsychotics • Narrow therapeutic range.
(Inderal) • Beta Blocker • Blocks beta-adrenergic receptor sites • Reduces essential tremor and other motor side effects caused by antipsychotics and lithium. 2011). Scott & Tipton
p. diazepam. 232-234)
. 53 (Shannon. Alprazolam. 2008. Wilson. & Strang. 2008. Shields. p. Clonazepam.OTHER DRUGS
Many including. and Lorazepam Use cautiously with elderly Risk of addiction/excessive sedation Metabolized in liver-monitor liver enzymes
• Anticonvulsant tricyclic • Off label (FDA) for treatment resistant schizophrenia • Do not give within 14 day of an MAO Inhibitor • Pregnancy Class D • Can cause agranulocytosis or aplastic anemia (monitor blood counts)
Valproate family. and platelets • CNS and GI side effects • Rare fatal adverse effects • Hepatotoxicity • Rare sudden suicidal activation • Sedation and weight gain can be problematic • Abrupt withdrawal may cause seizures
Valproate sodium (Depacon). LFT. 2011.Divalproex sodium (Depakote). 625-630)
. Valproic Acid (Depakene) • • • • • • • • Anticonvulsant Mood stabilizer Migraine prophylaxis Voltage-sensitive sodium channel modulator Adjunctive tx in Schizophrenia Once a day or BID dosing Extended-release less bioavailability Pregnancy category D
• Multiple drug interactions • Monitor trough plasma drug levels.
Start with small doses and titrate based on response 7. Regularly consider that onset of new symptoms may be drug induced 6. nicotine. Ascertain all drugs being taken. Scott & Tipton
. Review Tx. Keep dosage regimens simple 8. Be sure that patient’s visual. Taber. Complete detailed pre-therapy assessment and re-assess periodically during therapy to monitor response to pharmacotherapy 2. Know the pharmacology of the drugs 4. including OTC’s. caffeine. or cognitive impairments will not result in errors or noncompliance
Goodrow. Plan and response regularly 5. ETOH and drugs of abuse 3. motor.CONCLUSION
Guidelines for Prescribing: 1.
M. Upper Saddle River. 1993.org content.. Scott & Tipton
.. (2008). Nurcombe.E. Goren. J... Buchanan. A. Inpatient antipsychotic drug use in 1998. Goodman and Gilman’s the pharmacological basis of therapeutics (10th ed. B.html Olson. A.... Limbird. NJ: Prentice Hall. FL: MedMaster.. Wilson. J. S.NY: McGraw-Hill Professional
Lehman. B.). (2007). F.). L.. C.Y.D. F.. (2006)..: McGraw Hill Medical. S. (2012). Loosen.D. Health professionals drug guide. Miami. Egli.medscape. B. Prescription writing course (lecture). Boerescu. & Sandson N. New York. Goldberg. from http://www. Kaplan and Saddock’s synopsis of psychiatry (10th ed..ccnmd. From nursing. Saddock. Kreyenbuhl. H. B. (2012). (2011). Dickerson... Eakin. Schizophrenia workup.. Salvatore.A.. Philadelphia. F.J. (2012). R. F.edu
Hardman. Practice guideline for the treatment of patients with schizophrenia Second Edition. P. J. Frankenburg. L.). Stahl. Funded by the National Institute of Mental Health. PsychiatryOnline (2012). M. Kelleher J. (2008). J. From http://www. M. Kaplan and Saddock’s pocket handbook of clinical psychiatry. P. Shields. New York.com/article/288259-workup#showall
Frawley. & Leckman. & Baldessarini..N. L. A. L. (eds. W. PA: Lippincott..edu/Pages/Research/researchbg. and 1989.G. M.).. Tek.J. Philadelphia.
Goodrow. (2002)..pitt.stonybrookmedicine. & Strang.J. University of Pittsburgh. W. American Journal of Psychiatry 159(3):1932–1935 Ebert. From http://emedicine. M. D. R.F. Williams and Wilkins Shannon.P. Taber.aspxbookid=28§ionid=1665359#46215 Saddock..)(2001). Stahl’s essential pharmacology: The prescriber’s guide (4th ed. New York..B. Clinical pharmacology made ridiculously simple (3rd ed. & Gilman. Green-Paden. J. Tenhula.. Dixon. (2010)..psychiatryonline. J.W. K. NY: Cambridge University Press. Conte Center for the Neuroscience of Mental Disorders. S. M. N.. Current diagnosis & treatment psychiatry (2nd ed. Bahk.).C. R. R.(2003): The Schizophrenia patient outcomes research team (PORT): Updated treatment recommendations
Centorrino.G.B.. T. PA: Lippincott Williams and Wilkins.