The Patient Cases: Psychosis -...

The Patient Cases: Psychosis

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Every effort has been made in preparing this book to provide accurate and up-to-date information that is in accord with accepted standards and practice at the time of publication. Nevertheless, the author, editors, and publisher can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The author, editors, and publisher therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use.

PUBLISHED BY NEI PRESS, an imprint of NEUROSCIENCE EDUCATION INSTITUTECarlsbad, California, United States of America

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Copyright © 2011 Neuroscience Education Institute. All rights reserved.

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Printed in the United States of AmericaFirst Edition, November 2011Electronic versions, December 2011

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CME Information ................................................................................................ i The Case: The 38-Year-Old WomanWith Schizophrenia Who Wants to Die ...................................................... 1

The Case: The 34-Year-Old WomanWith Hyperprolactinemia FollowingTreatment With a Depot Antipsychotic ..................................................... 13

The Case: The 45-Year-Old Woman Who Refuses Treatment ............. 19

The Case: The 50-Year-Old “Hydrophilic” Patient ................................... 29

The Case: The 37-Year-Old Woman Who Set Fire to Her Bed ............. 37

CME Posttest and Certificate ......................................................................... 47

Table of Contents


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Overview Schizophrenia encompasses positive, negative, cognitive, and affective symptom domains and can have a very different presentation for each individual patient. Additionally, patients with schizophrenia often suffer from various comorbid conditions. This booklet is a series of five case studies in psychosis, all adapted from real practice, and provides a glimpse into what cases look like after the first consultation, and over time, living through the treatments that work, the treatments that do not work, the mistakes, and the lessons to be learned.

Target Audience This activity has been developed for prescribers specializing in psychiatry. There are no prerequisites. Health care providers in all specialties who are interested in psychopharmacology, especially primary care physicians, nurses, psychologists, and pharmacists, are welcome for advanced study.

Statement of Need The following unmet needs regarding psychosis and schizophrenia were revealed following a literature review and through new medical knowledge:

• Schizophrenia is a debilitating disorder associated with poor quality of life, low remission rates, and huge adherence issues.• Several new medications are soon to be introduced and research into additional new treatment methods is ongoing; clinicians need to be educated on these new treatment strategies as data accumulate so that they are prepared to implement these tools once they become available.• A treatment plan that considers recovery a process of achieving individual life goals may be more likely to lead to success than one focused on eliminating all symptoms.

To help fill these unmet needs, quality improvement efforts need to provide education regarding: • Differentiation of therapeutic and side effect profiles of the various medications available for the treatment of schizophrenia.• New treatment strategies for schizophrenia, including novel mechanisms of action, and how these new options can help fill unmet needs within the current treatment of schizophrenia.• Optimization of functional outcomes for schizophrenia, including strategies to monitor and maximize adherence, methods to address cognitive and negative symptoms, and working with patients to set and track recovery-oriented goals.

Learning Objectives After completing this activity, participants should be better able to:

• Integrate novel treatment approaches into clinical practice according to best practice guidelines• Implement evidence-based treatment strategies that are aligned with recovery goals set by the patient• Include strategies for monitoring and addressing adherence as part of the treatment plan for all patients

Accreditation and Credit Designation Statements The Neuroscience Education Institute is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The Neuroscience Education Institute designates this enduring material for a maximum of 3.5 AMA PRA Category 1 Credits TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

CME Information

CME Information

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Nurses: for ALL of your CE requirements for recertification, the ANCC will accept category 1 credits from organizations accredited by the ACCME.

Physician Assistants: the AAPA accepts AMA PRA Category 1 Credit ™ from organizations accredited by the ACCME.

Also available will be a certificate of participation for completing this activity.

Please note: the content of this electronic book activity also exists as a print monograph under the same title. If you received CME credit for the print monograph version, you will not be able to receive credit again for completing this electronic book version.

Activity Instructions This CME activity is available in the form of a printed monograph and an electronic book and incorporates instructional design to enhance your retention of the information and pharmacological concepts that are being presented. You are advised to go through each case from beginning to end, including the brief tutorial at the end of each case, and then complete the posttest and activity evaluation. The estimated time for completion of this activity is 3.5 hours.

Instructions for CME Credit To receive your certificate of CME credit or participation, please complete the posttest and activity evaluation, available only online, by clicking the link found at the end of this electronic book or at www.neiglobal.com/CME under “Book”. If a passing score of 70% or more is attained (required to receive credit), you can immediately print your certificate. There is no fee for CME credits for this activity.

NEI Disclosure Policy It is the policy of the Neuroscience Education Institute to ensure balance, independence, objectivity, and scientific rigor in all its educational activities. Therefore, all individuals in a position to influence or control content development are required by NEI to disclose any financial relationships or apparent conflicts of interest that may have a direct bearing on the subject matter of the activity. Although potential conflicts of interest are identified and resolved prior to the activity being presented, it remains for the participant to determine whether outside interests reflect a possible bias in either the exposition or the conclusions presented.

These materials have been peer-reviewed to ensure the scientific accuracy and medical relevance of information presented and its independence from commercial bias. The Neuroscience Education Institute takes responsibility for the content, quality, and scientific integrity of this CME activity.

Individual Disclosure Statements Authors

Debbi Ann Morrissette, PhDAdjunct Professor, Biological Sciences, California State University, San MarcosMedical Writer, Neuroscience Education Institute, Carlsbad, CANo other financial relationships to disclose.

Stephen M. Stahl, MD, PhDAdjunct Professor, Department of Psychiatry, University of California, San Diego School of Medicine Honorary Visiting Senior Fellow, University of Cambridge, UKGrant/Research: AstraZeneca; BioMarin; Dainippon Sumitomo; Forest; Genomind; Lilly; Merck; Pamlab; Pfizer; PGxHealth/Trovis; Schering-Plough; Sepracor; Servier; Shire; TorrentConsultant/Advisor: Abbott; Advent; Alkermes; Arena; AstraZeneca; BioMarin; Boehringer Ingelheim; Bristol-Myers Squibb; Cypress; Dainippon Sumitomo; Forest; Genomind; Janssen, Division of Ortho-McNeil-Janssen; Jazz; Labopharm; Lilly; Lundbeck; Merck; Neuronetics; Novartis; Ono; Orexigen; Otsuka America; Pamlab; Pfizer; PGxHealth/Clinical Data; Rexahn; Royalty; Schering-Plough; Servier; Shire; Valeant; VIVUS Speakers Bureau: Dainippon Sumitomo; Lilly; Merck; Pamlab; Sepracor; Sunovion


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Peer ReviewerSteven S. Simring, MD, MPHClinical Associate Professor, Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York CityNo other financial relationships to disclose.

Program DevelopmentThe following are employed by the Neuroscience Education Institute in Carlsbad, CA, and have no other financial relationships to disclose.Rory Daley, MPH, Associate Director, Program Development Steve Smith, President and COO

Disclosed financial relationships have been reviewed by the Neuroscience Education Institute CME Advisory Board to resolve any potential conflicts of interest. All faculty and planning committee members have attested that their financial relationships do not affect their ability to present well-balanced, evidence-based content for this activity.

Disclosure of Off-Label Use This educational activity may include discussion of products or devices that are not currently labeled for such use by the FDA. Please consult the product prescribing information for full disclosure of labeled uses.

Disclaimer The information presented in this educational activity is not meant to define a standard of care, nor is it intended to dictate an exclusive course of patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this educational activity should not be used by clinicians without full evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Primary references and full prescribing information should be consulted.

Participants have an implied responsibility to use the newly acquired information from this activity to enhance patient outcomes and their own professional development. The participant should use his/her clinical judgment, knowledge, experience, and diagnostic decision-making before applying any information, whether provided here or by others, for any professional use.

Sponsorship Information This activity is sponsored by the Neuroscience Education Institute.

Support This activity is supported by an educational grant from Sunovion Pharmaceuticals Inc.

Date of Release/Expiration Print Monograph Release: November 1, 2011Electronic Books Released: December, 2011CME Credit Expires: October 31, 2014

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The Case: The 38-Year-Old Woman With Schizophrenia Who Wants to Die

The Dilemma: Treating Depression in Patients With Schizophrenia Self-assessment Pretest

Jeremy is a 27-year-old patient with schizoaffective disorder and comorbid kidney disease. He has had unsuccessful trials of 4 different antipsychotics and is interested in a trial of clozapine. Clozapine is contraindicated in patients with:

A. Cardiac impairmentB. Renal impairmentC. Hepatic impairmentD. All of the aboveE. None of the above

Patient Intake

• 38-year-old woman with ongoing psychosis• The patient complains of increased anxiety and tension during the daytime• She endorses depressed mood and feelings of hopelessness and helplessness, and she recently expressed a passive wish to die

· The patient reports that her mood began deteriorating following her father’s sudden death due to cardiac disease 1 month ago

• The patient indicates that she has ideas of hanging herself with a bed sheet · These thoughts have been especially intense during the past 3 nights

• The patient states that she has difficulty falling asleep and staying asleep• She reports feeling exhausted and fatigued during the daytime

· The patient notes that trazodone has been helpful in treating her insomnia in the past

• The patient is currently institutionalized following arrest · She attacked a man on a bicycle, demanding money for sex · When the man refused to give her money, the patient pushed him off the bicycle · The patient searched the man’s pockets, and a struggle broke out over money · When the money tore in half, the patient attempted to flee

• She recently committed an aggressive act against another inpatient while

The Case:

The 38-Year-Old Woman

With Schizophrenia Who

Wants to Die


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in the courtyard• Her judgment and insight appear to be limited• BMI is currently 37.6• Serum glutamic pyruvic transaminase (SGPT; a measure of liver function, also known as alanine aminotransferase or AST) level is somewhat elevated at 44 units/L

Patient History

• The patient has a history of psychosis beginning at age 15 years• She attempted suicide at age 15 because “God told her to”• Symptoms have included:

· Auditory hallucinations · Persecutory and sexual delusions · Severe psychomotor agitation · Assaultive behavior

• Although the patient has had episodes of severe psychomotor agitation as well as episodes of depressed mood and suicidal ideation, it is unclear if she has ever met the criteria for either mania or major depression• Previous medications and the patient’s responses include:

· Aripiprazole: poor response · Ziprasidone: developed slurred speech · Haloperidol: developed extrapyramidal symptoms (EPS)

• The patient has had numerous hospitalizations over the course of her illness• Medical history is positive for:

· Obesity · Dyslipidemia · Hepatitis C · Seizure disorder (tonic-clonic in nature)

• The seizure disorder began following a motor vehicle accident in which she suffered a head injury with loss of consciousness

· The patient recently experienced a grand mal seizure• The patient has an extensive history of substance dependence, including:

· Alcohol · Marijuana · Cocaine · Methamphetamine · Heroin

• Family history · Positive for a mother with alcohol dependence · The patient notes that many family members are prone to addictive disorders · The patient denies any family history of mental disorder

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Current Medications

• Risperidone 4 mg/day (2 mg twice per day)• Olanzapine 40 mg/day (10 mg during the day and 30 mg at bedtime)• Zolpidem 10 mg at bedtime• Citalopram 40 mg at bedtime• Divalproex ER 1500 mg at bedtime• Levetiracetam 2000 mg/day (1000 mg twice per day)• Stool softener 250 mg in the morning• Lactulose 60 mL/day (30 mL twice per day) for constipation• Aspirin 81 mg in the morning• Olanzapine IM as needed

Question

How would you adjust this patient’s medication in order to improve her psychotic symptoms?

• Increase olanzapine dose• Increase risperidone dose• Switch to a different atypical antipsychotic• Switch to a conventional antipsychotic

Question

How would you adjust this patient’s medication in order to improve her depressive symptoms?

• Increase citalopram dose• Switch from citalopram to another SSRI• Switch from citalopram to an SNRI

Clinician’s Notes

• This patient is not having a good response to her current antipsychotic treatment regimen; she continues to exhibit psychotic symptoms despite treatment with both risperidone and olanzapine• It is possible that increasing the dose of risperidone may offer more relief from psychotic symptoms• This patient is currently on a high dose of olanzapine; increasing the dose of olanzapine may cause more weight gain and cardiometabolic side effects• Olanzapine plasma level should be obtained to ensure that concentration is in upper half of the reference range• A pharmacological agent, such as metformin, which acts by increasing


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insulin sensitivity, may help with weight reduction• As a class, conventional antipsychotics carry a greater risk of extrapyramidal side effects (EPS); given the patient’s history of EPS on haloperidol, a conventional antipsychotic may not be the best choice • The selection of a psychotropic treatment for this patient is complicated by liver damage due to hepatitis C• The 2 atypical antipsychotics that carry the least risk for those with hepatic impairment are aripiprazole and ziprasidone; unfortunately, this patient has not had success with either of these 2 agents• Asenapine and iloperidone would be contraindicated in this patient due to hepatic impairment; the remaining atypical antipsychotics (clozapine, lurasidone, olanzapine, paliperidone, risperidone, and quetiapine) should be used with caution in patients with hepatic impairment but are not contraindicated• The patient is currently depressed with suicidal ideation; treatment of her symptoms of depression is key for optimal outcomes• The patient does not seem to be responding to the SSRI citalopram; a different SSRI or an SNRI may be more beneficial for this patient• Replacing levetiracetam with lamotrigine may be helpful for this patient due to the actions of lamotrigine as an anticonvulsant, antidepressant, and adjunctive support for antipsychotic treatment

Case Outcome

• Risperidone is increased to 6 mg and given as a single bedtime dose• Lamotrigine 25 mg is initiated at bedtime and increased by 25 mg/week to 175 mg/day (75 mg in the morning and 100 mg at bedtime) • Levetiracetam is discontinued• Duloxetine 30 mg in the morning is initiated, then increased to 60 mg after 1 week • Citalopram is discontinued by tapering 20 mg/week• Metformin 500 mg in the morning is added• Lab results indicate that the olanzapine plasma level is 59 ng/mL, which is within the therapeutic range• The patient continues to exhibit psychotic signs and symptoms

· She states, “Devil babies are just in my mind”• The patient has become more anxious as she has become aware that some of her psychotic symptoms are not based in reality• She acknowledges auditory hallucinations but denies visual hallucinations• Ideas of reference as well as persecutory ideation and religious delusions are present• Her mood is described as intermittently dysphoric • She acknowledges feeling hopeless and wishing that she were dead, but

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she denies current suicidal intent or plan• The patient is still obese with a BMI of 37.0 • Her SGPT level has continued to rise and is now 72 units/L• Tremor is becoming evident in both hands

Current Medications

• Olanzapine 40 mg/day (10 mg during the day and 30 mg at bedtime)• Risperidone 6 mg at bedtime• Lamotrigine 175 mg/day (75 mg in the morning and 100 mg at bedtime)• Divalproex ER 1500 mg at bedtime• Duloxetine 60 mg in the morning• Zolpidem 10 mg at bedtime• Metformin 599 mg in the morning• Lactulose 60 mL/day (30 mL twice per day) for constipation• Aspirin 81 mg in the morning • Stool softener 250 mg in the morning• Olanzapine IM as needed

Question

How would you adjust this patient’s psychotropic medications?

• Increase olanzapine• Increase risperidone• Increase lamotrigine• Increase divalproex• Increase duloxetine• Add hydroxyzine

Clinician’s Notes

• This patient is showing no improvement in the treatment-related metabolic side effects; of the atypical antipsychotics, olanzapine is specifically noted for carrying an increased risk of adverse cardiometabolic effects; increasing the olanzapine dose may exacerbate the patient’s struggle with obesity• Increasing the risperidone dose may result in further improvement in psychosis; however, it is important to note that risperidone also carries an increased risk of weight gain• Given the observed hand tremor, the valproic acid plasma concentration should be obtained; it is also important to note that valproic acid reduces the clearance of lamotrigine and can consequently increase lamotrigine levels


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• Adding hydroxyzine may help alleviate some of the patient’s anxiety and dysphoria symptoms

Case Outcome

• Risperidone is increased to 8 mg/day (2 mg in the morning and 6 mg at bedtime)• Olanzapine is consolidated to 40 mg at bedtime• Lamotrigine is increased to 200 mg/day• Hydroxyzine 100 mg every 6 hours as needed is added for anxiety• Lab results indicate that the valproic acid concentration is 100 ug/mL, which is within the optimal range for mood stabilization (80-120 ug/mL)• Ideas of reference, persecutory ideation, and bizarre delusional ideation continue

· The patient states that she “[fell] below the earth but was able to crawl back up”

• The patient also exhibits sexual delusions · She reports experiencing vaginal pain and concludes that she must have been “raped many times”

• The patient’s thinking is disorganized and tangential · She frequently responds to questions with answers that are irrelevant

• She reports a feeling of internal pressure, which she attributes to being anxious about other people

· “Others pick fights with me, hold grudges, and may harm me”• She has sad affect and continues to intermittently experience suicidal thoughts

· She is placed under enhanced observation due to worsening suicidal ideation

• The patient continues to exhibit psychomotor agitation and assaultive behavior• The patient gains 18 lbs over 4 months (BMI is now 44.6)• Her SGPT level has continued to rise and is now 90 units/L, indicating increasingly poor liver function• The patient’s primary care physician would like to begin treatment with interferon-alpha (IFN-α) and ribavirin for her hepatitis C

Question

Would you advise proceeding with IFN-α and ribavirin treatment at this time?

• Yes, initiate treatment with IFN-α and ribavirin at this time• No, do not initiate treatment with IFN-α and ribavirin at this time

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Question

How would you adjust this patient’s psychotropic medications?

• Increase risperidone dose• Decrease risperidone dose• Increase olanzapine dose• Decrease olanzapine dose• Switch to clozapine

Clinician’s Notes

• Given the increasing liver failure (as indicated by rising SGPT levels), this patient may soon require treatment for hepatitis C• However, IFN-α treatment can induce depression in patients with hepatitis C; given this patient’s current depressed mood and suicidality, it may not be prudent to start IFN-α treatment until symptoms of depression and suicidal ideation have been resolved• If IFN-α treatment is pursued, it will be prudent to maintain brief checks for suicidality several times per week throughout the course of treatment• The recent increase in risperidone dose does not seem to be providing any benefit for the patient, and it may be exacerbating her cardiometabolic state• Increasing the olanzapine dose may offer some additional therapeutic benefit; however, this patient is already on a high dose of olanzapine and is experiencing severe metabolic effects• Decreasing the olanzapine dose may reduce metabolic side effects, but there is a risk of losing what little therapeutic gains the patient is currently deriving from olanzapine• Suicide accounts for 10% of patient deaths in schizophrenia; clozapine is recommended for treatment-resistant schizophrenia and has been shown to reduce suicidality• Clozapine may work as a monotherapy, and it does not pose a greater metabolic risk than olanzapine; however, there are some safety concerns with clozapine use that make extensive blood monitoring required

Case Outcome

• Treatment with IFN-α and ribavirin is delayed pending the absence of depressed mood and suicidal ideation for at least 3 months• Risperidone is reduced to 6 mg and consolidated to a single bedtime dose• Lamotrigine is consolidated to a single bedtime dose• Topiramate 25 mg at bedtime is initiated and increased by 25 mg/week until reaching 400 mg/day


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• Metformin is titrated to 2000 mg/day (1000 mg twice per day), and the patient is referred to a nutritionist; her weight begins to decrease (BMI 38.1)• The patient continues to exhibit symptoms of psychosis• She reports moderate depression, and suicidal ideation persists• Clozapine 25 mg/day (12.5 mg twice per day) is initiated and increased by 25 mg/day until reaching 450 mg/day; both olanzapine and risperidone are cross-tapered and discontinued over a period of 8 weeks

Case Debrief

• Approximately 15% of patients with schizophrenia are unresponsive to traditional antipsychotic therapy; this can pose several challenges in clinical practice• Many patients present with comorbid disorders that must be taken into account when developing a treatment plan• Although it is important to address the patient’s symptoms of schizophrenia, it is equally important to minimize disturbing side effects• Compared to atypical antipsychotics, conventional antipsychotics carry an increased risk of movement disorders • Although atypical antipsychotics carry a relatively reduced risk of extrapyramidal side effects, they do carry increased cardiometabolic risks• The clinician must weigh the risks and benefits of treatments on an individual patient basis• Monitoring drug levels and metabolic parameters is essential for the fine- tuning of any treatment regimen• Suicidality is a common problem in schizophrenia with devastating consequences for the patient and his/her family• Clozapine has been shown in numerous studies to be beneficial in the prevention of suicide in schizophrenia and is FDA-approved for treatment- resistant schizophrenia and the reduction of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder

Performance in Practice Assessment

• What could have been done better here? · Earlier intervention with metformin and nutritional advice · Earlier switch to clozapine

• Possible action items for improvement in practice · Patients with schizophrenia should be regularly assessed for drug- induced cardiometabolic effects, and all efforts should be made to reduce these side effects · In patients who have had unsuccessful treatment with 2 or more

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antipsychotics, clozapine should be considered an option; this is especially true for patients with suicidal ideation

Brief Tutorial: Special Populations

Cardiac Renal Hepatic

Aripiprazole May increase risk of orthostatic hypotension

Dose adjustment not necessary

Dose adjustment not necessary

Asenapine May increase risk of orthostatic hypotension

Dose adjustment not generally necessary

• Mild/Moderate: Dose adjustment not generally necessary• Severe: Not recommended

Clozapine Use with caution, particularly if taken with concomitant medication

Use with caution Use with caution

Iloperidone • Mild/Moderate: May increase risk of orthostatic hypotension• Severe: Not recommended


Not recommended for patients with hepatic impairment

Lurasidone May increase risk of orthostatic hypotension

Moderate/Severe: Maximum dose should not exceed 40 mg

Moderate/Severe: Maximum dose should not exceed 40 mg

Olanzapine May increase risk of orthostatic hypotension

• No dose adjustment required for oral formulation• Not removed by hemodialysis• Consider lower starting dose (5 mg) for IM formulation

• May need to lower dose• Mild/Moderate/ Severe: Liver function tests several times a year recommended• Moderate/Severe: Start oral and IM dose at 5 mg and increase with caution

Paliperidone May increase risk of orthostatic hypotension

• Mild: Maximum recommended dose is 6 mg/day• Moderate/Severe: Maximum recommended dose is 3 mg/day

• Mild/Moderate: No dose adjustment necessary• Severe: Use in individuals with severe impairment has not been studied

Quetiapine May increase risk of orthostatic hypotension


Downward dose adjustment may be necessary


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Risperidone • May increase risk of orthostatic hypotension• When administered to elderly patients with atrial fibrillation, may increase the risk of stroke

• Initial 0.5 mg orally 2X/ day for 1st week; increase to 1 mg 2X/day during 2nd week• Depot should not be administered until patient has shown tolerability of at least 2 mg/day orally• Depot should be dosed at 25 mg every 2 weeks; oral administration should continue for 3 weeks after the 1st injection

• Initial 0.5 mg orally 2X/ day for 1st week; increase to 1 mg 2X/day during 2nd week• Depot should not be administered until patient has shown tolerability of at least 2 mg/day orally• Depot should be dosed at 25 mg every 2 weeks; oral administration should continue for 3 weeks after the 1st injection

Ziprasidone • May increase risk of orthostatic hypotension• Contraindicated in patients with a history of QTc prolongation, recent myocardial infarction, and uncompensated heart failure

• Dose adjustment not necessary• Not removed by hemodialysis• IM formulation should be used with caution


The use of antipsychotics in special populations (those with cardiac, renal, or hepatic impairment) often requires careful consideration. Red = contraindicated in cases of severe impairment; yellow = use caution; green = no special consideration necessary.

Brief Tutorial: Monitoring Sucidality

• Advise parents to remove lethal means and monitor for risk factors (be explicit, do not rely on “common sense”)

· Clean old and unused medications out of medicine cabinet · Severely limit amount of alcohol kept in house · Lock up or remove all weapons · In emergency, call 911 or bring the child to the nearest ER if practical · 1-800-lifenet (give them a card with this number to keep on the refrigerator)

• Engage a concerned third party• Establish mutually agreeable emergency contacts in the event of increasing suicidality• Establish clear follow-up• Do not rely on safety contracts• Behavioral warning signs of suicidality

· Expressing self-destructive thoughts

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· Drawing morbid or death-themed pictures · Engaging in death-themed activity (music, video games, books, etc.) · Giving away possessions

Brief Tutorial: Clozapine Reduces Suicidality in Patients With Schizophrenia

In a study of 88 neuroleptic-resistant patients prospectively evaluated for periods of 6 months to 7 years, clozapine was associated with improvement on Hamilton Depression Scale scores, including reduction in suicidality. ** p<0.05 compared to baseline; *** p<0.01 compared to baseline. Data from Meltzer HY, Okayli G. Am J Psychiatry 1995;152(2):183-90.

Self-assessment Posttest

Jeremy is a 27-year-old patient with schizoaffective disorder and comorbid kidney disease. He has had unsuccessful trials of 4 different antipsychotics and is interested in a trial of clozapine. Clozapine is contraindicated in patients with:

A. Cardiac impairmentB. Renal impairmentC. Hepatic impairmentD. All of the aboveE. None of the above


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(Answer: E. Although caution should be used when administering clozapine to patients with liver, heart, or kidney impairment, clozapine is not contraindicated in any of these conditions.)

ReferencesBuchanan et al. 2009 PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull 2010,36(1):71-93.

Hauser P et al. A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C. Mol Psychiatry 2002;7(9):942-7.

Kerwin RW, Bolonna AA. Is clozapine antisuicidal? Expert Rev Neurother 2004;4(2):187-90.

Meltzer HY. Suicide in schizophrenia, clozapine, and adoption of evidence-based medicine. J Clin Psychiatry 2005;66(4):530-3.

Meltzer HY et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003;60(1):82-91.

Meltzer HY, Okayli G. Reduction of suicidality during clozapine treatment of neuroleptic-resistant schizophrenia: impact of risk-benefit assessment. Am J Psychiatry 1995;152(2):183-90.

Stahl SM. Stahl’s essential psychopharmacology: the prescriber’s guide. 4th ed. New York, NY: Cambridge University Press; 2009.

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The Case: The 34-Year-Old Woman WithHyperprolactinemia Following Treatment With a Depot Antipsychotic

The Dilemma: Maximizing Drug Efficacy and Minimizing Adverse Effects in Order to Optimize Treatment Adherence Self-assessment Pretest

Rhea is a 45-year-old patient with schizophrenia and a history of treatment nonadherence. Currently, she is getting some benefit from depot haloperidol, but she has developed signs of tardive dyskinesia, and you would like to see her switched to an atypical antipsychotic. Which of the following atypical antipsychotics is currently being developed as a 12-week depot formulation?

A. QuetiapineB. AsenapineC. PaliperidoneD. Ziprasidone

Patient Intake

• 34-year-old-woman • She was recently arrested after setting fire to her apartment• The patient is actively psychotic and assaultive• She is superficially cooperative, friendly, and polite• Her mood is jovial with full affect• The patient’s thinking is generally linear but notable for derailment

· For example, while discussing medication side effects, she suddenly switched the subject to how products might deplete the rainforests

• She often exhibits mood lability Patient History

• The patient met criteria for conduct disorder prior to age 15• She has continued a criminal lifestyle as an adult• The patient was diagnosed at age 18 with bipolar mood disorder• Over the course of her illness, the patient has exhibited social withdrawal, selective mutism, tangential and disorganized thinking, loosening of logical associations, bizarre delusions, grandiose delusions, and labile mood

The Case:

The 34-Year-Old Woman With

Hyperprolactinemia Following

Treatment With a Depot Antipsychotic


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• She has a history of assaultive behavior, self-injurious behavior, and suicidality• The patient has a history of substance abuse that has been minimized; substance abuse has included a variety of substances

· Alcohol · Marijuana · Methamphetamine · Cocaine · Heroin · LSD · Inhalants

• She also has a history of treatment nonadherence • The patient denies suffering from a mental disorder and often fails to attend her group therapy sessions• During a previous trial of depot risperidone, prolactin became elevated• The patient was switched from depot risperidone to oral olanzapine• Prolactin level has remained elevated but has been declining since the switch to olanzapine• The patient is currently actively psychotic and assaultive despite ongoing antipsychotic treatment• She is not exhibiting any abnormal involuntary movements or tics• The patient’s medical history is significant for being overweight, but her BMI is currently normal at 23.7• She denies any family history of mental illness

Current Medications

• Olanzapine 10 mg at bedtime (IM ordered if oral refused)• Benztropine 1 mg/day (0.5 mg twice per day)• Multivitamin (1 tablet in the morning)

Question

How would you adjust this patient’s current medication?

• Increase olanzapine• Switch to another oral atypical antipsychotic• Switch to an oral conventional antipsychotic• Switch to a depot formulation of an atypical antipsychotic• Switch to a depot formulation of a typical antipsychotic

Clinician’s Notes

• Although this patient exhibits mood lability, there is no clear evidence

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that she has met full criteria for hypomania, mania, or major depression• Her current diagnosis seems to fit with schizophrenia, disorganized type• The patient’s current treatment regimen seems to be ineffective• Increasing olanzapine dose may yield improvement in positive symptoms; however, many atypical antipsychotics (including olanzapine) are associated with an increased risk for metabolic side effects; however, most studies do not show a dose-related increase in side effects• Given this patient’s history of being overweight, caution must be taken so that her physical health is not compromised in treating her mental illness• As a class, conventional antipsychotics carry less risk for cardiometabolic side effects; however, they are associated with elevated risks of extrapyramidal symptoms (EPS) and hyperprolactinemia due to dopamine D2 receptor antagonism • The use of a conventional antipsychotic in this patient may not be the best choice due to her history of hyperprolactinemia • Although atypical antipsychotics also bind to D2 receptors, some of the adverse side effects associated with such binding (e.g., EPS, hyperprolactinemia) are mitigated by binding to additional receptors, including serotonin 5-HT1A and 5-HT2A receptors• Of the atypical antipsychotics, quetiapine has one of the lowest risks for hyperprolactinemia• Given the patient’s history of treatment nonadherence, the ensured delivery of a depot antipsychotic would be beneficial• There are several conventional and atypical antipsychotics available as depot formulations; however, this patient does not seem to be a good candidate for treatment with a conventional antipsychotic due to the risk of hyperprolactinemia• The only atypical antipsychotics currently available as depot formulations are risperidone, paliperidone, and olanzapine; unfortunately, this patient has already shown intolerance for risperidone and would likely show the same intolerance for paliperidone, the active metabolite of risperidone • Oral olanzapine has been ineffective for this patient, and it is likely that she would have the same inadequate response to depot olanzapine; however, it may be that the patient has been nonadherent to her oral olanzapine treatment; if nonadherence is the issue, the patient may have better results with the depot formulation of olanzapine• There are many other depot atypical antipsychotics currently in development that may be more effective for this patient; however, risperidone, paliperidone, and olanzapine are the only ones currently available


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Case Outcome

• The patient is initiated on quetiapine XR (200 mg/day at bedtime), and the dose is increased by 200 mg every week until reaching 800 mg/day at bedtime• Oral olanzapine is discontinued with maintenance of IM olanzapine as needed• Prolactin levels are monitored every 3 months and continue to decline until reaching a steady baseline• Benztropine is discontinued• Although her positive symptoms of psychosis are mildly improved after 6 weeks on quetiapine 800 mg/day, she continues to have bizarre delusions • Quetiapine is further titrated to 1200 mg/day (taken at bedtime)• The patient continues to have psychotic symptoms, although she seems less aggressive• Quetiapine is further titrated to 1800 mg/day• Psychotic symptoms are further resolved but mood continues to be labile at times• Lamotrigine (25 mg at bedtime) is initiated and titrated by 25 mg/week to 400 mg/day

Case Debrief

• Optimal care for patients with schizophrenia includes finding the most effective treatment with the fewest side effects• There are many pharmacological treatment options available; the challenge is finding which one works best for the individual patient• Although depot formulations may be effective for patients with a history of treatment nonadherence, conventional antipsychotics may not be the best choice for some patients (due to D2 antagonism-based side effects), and the number of atypical antipsychotics currently available is somewhat limited

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Brief Tutorial: Long-Acting Depot Formulations of Atypical Antipsychotics

Dosing and Side Effect Factors That May Affect AdherenceMedication non-adherence has been linked to poor functional outcome in schizophrenia. Several factors including adverse side effects and dosing schedule may affect patient adherence to a particular antipsychotic. In addition to long-acting depot formulations of conventional antipsychotics, several atypical antipsychotics are also available in long-acting depot formulations that may be especially useful for treating individuals with a history of medication non-adherence.

Atypical Antipsychotic

Dosing Schedule

of Oral Formulation

Alternative Formulations Side Effects*

Additional CaveatsLong-Acting Depot Other Sedating Weight

Gain EPS

Aripiprazole 1X day 4 wk in trials 10 and 15 mg oral disintegrating tablets; 9.75 mg/1.3 injection (can cause

akathisia)

May be activating rather than sedating

Asenapine 2X day Only available in 5 and 10 mg sublingual tablets

Patient should not eat or drink immediately after drug administration

Iloperidone 1X day 4 wk in trials Very gradual titration

Olanzapine 1X day 2 wk4 wk

Oral disintegrating tablet

No titration needed. Oral supplementation of depot may be needed

Paliperidone 1X day 4 wk 12 wk in trials

Only available in extended release formulation

No titration needed

Quetiapine 1X day Extended release formulation available

Risperidone 1X day 2 wk4 wk in early trials

0.5, 1, and 2 mg oral disintegrating tablets; 1 mg/mL liquid (dose-

dependent)

Titration needed

Ziprasidone 2X day 10-20 mg IM formulation available

Lurasidone 1X day Titration to initial 40mg do

*Side effects scale: Unusual = reported in few patients; Not unusual = occurs in a significant minority; Common = many experience or can be in significant amount; Problematic = occurs frequently, can be in a significant amount, and may be a health problem in some patients

Several of the atypical antipsychotics are currently available as long-acting injectable formulations. There are additional depot formulations currently in development. The use of depot formulations may improve adherence; the patient need only decide and remember to take their medication once or twice a month rather than once or twice a day.


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Rhea is a 45-year-old patient with schizophrenia and a history of treatment nonadherence. Currently, she is getting some benefit from depot haloperidol, but she has developed signs of tardive dyskinesia, and you would like to see her switched to an atypical antipsychotic. Which of the following atypical antipsychotics is currently being developed as a 12-week depot formulation?

A. QuetiapineB. AsenapineC. PaliperidoneD. Ziprasidone

(Answer: C. Paliperidone is currently available as a 4-week depot formulation and is in development as a 12-week formulation.)

ReferencesOlfson M, Mechanic D, Hansell S et al. Predicting medication noncompliance after hospital discharge among patients with schizophrenia. Psychiatr Serv 2000;51(2):216-22.


Tiihonen J, Haukka J, Taylor M et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011; E-pub ahead of print.

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The Case: The 45-Year-Old Woman Who Refuses Treatment

The Dilemma: Forming a Treatment Alliance Self-assessment Pretest

Charlie is a 52-year-old patient with schizophrenia. Due to a history of alcohol abuse, Charlie now has moderate cirrhosis of the liver. He is currently taking halo-peridol, but he has begun to display parkinsonian movements, and you would like to switch him to an atypical antipsychotic. Which atypical antipsychotic is contra-indicated for this patient with hepatic impairment?

A. OlanzapineB. AripiprazoleC. AsenapineD. Paliperidone

Patient Intake

• 45-year-old woman • Recently admitted to psychiatric ward following arrest for assault with a deadly weapon

· While riding a city bus, she stabbed a stranger with a pair of scissors and yelled that she was going to kill him

• The patient is thin and disheveled with poor hygiene · The patient describes her poor grooming as an attempt to keep others away; at the same time, she claims to be “very social”

• She presents with persecutory delusions as well as blunted and flat affect• The patient also presents with lethargy and muscle rigidity• Her Global Assessment of Functioning (GAF) score is 30

Patient History

• The patient has a history of chronic psychotic disorder, with illness onset in her early 20s• Past symptoms have included:

· Ideas of reference · Persecutory ideation

The Case:


Who Refuses Treatment


20

· Psychomotor agitation · Assaultiveness

• The patient has a history of bizarre behaviors, including: · Hoarding urine and feces in juice boxes · Refusing to brush her teeth · Using shirts as tampons · Eating her own feces

• She has required numerous hospitalizations over the past 20 years• The patient has a history of alcohol, marijuana, and cocaine abuse occurring between ages 16 and 18• She also has a history of suicidal ideation, although she is not presently suicidal• The patient often refuses to eat adequately or take prescribed medications because she believes the staff are trying to poison or harm her• She reports that her father physically abused her between the ages of 6 and 10 but denies any family history of psychiatric disorders

Medical History

• BMI = 19.6• Aplastic anemia

· The patient has required periodic transfusions and erythropoietin (Procrit) treatment

• Hypothyroidism• Folic acid deficiency• Pituitary enlargement• Generalized dermatitis of unknown etiology characterized by large patches of dry, erythematous skin

Current Medications

• Levothyroxine 35 ug/day taken in the morning for hypothyroidism • Folic acid 1 mg/day taken in the morning• Megace 400 mg/day to increase appetite• Procrit 40,000 units/week subcutaneously• The patient is not currently taking an antipsychotic

Question

Based on what you have been told so far about this patient’s history and current symptoms, what do you think her primary diagnosis is?

• Schizophrenia, paranoid type• Schizophrenia, disorganized type

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• Schizophrenia, undifferentiated type Clinician’s Notes

• Schizophrenia, paranoid type is described in the DSM-IV as preoccupation with one or more delusions or frequent auditory hallucinations, without prominent disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect• Schizophrenia, disorganized type is described in the DSM-IV as disorganized speech, disorganized behavior, and flat or inappropriate affect, without catatonic symptoms• Schizophrenia, undifferentiated type is described in the DSM-IV as not meeting criteria for paranoid, disorganized, or catatonic types• The patient does have persecutory delusions, which might be indicative of schizophrenia, paranoid type• However, given the presence of abnormal affect, bizarre behavior (e.g., hoarding urine and feces), and severe psychosocial deterioration, a diagnosis of schizophrenia, disorganized type might be more accurate

Case Outcome

• The patient is diagnosed with schizophrenia, disorganized type• She is prescribed oral risperidone 2 mg BID but continues to refuse treatment• The patient also continues to refuse other prescribed medications, with the exception of Procrit

· She cooperates with erythropoietin injections but claims that the treatment rather than her anemia makes her tired

• Over a period of 1 month, she requires 2 blood transfusions for severe anemia• She also continues to display aggression and have poor hygiene

· She strikes another patient due to persecutory ideation · She often engages in yelling and threatening verbal behaviors toward both staff and fellow inpatients

• The patient reports that staff are still trying to poison and harm her, and she refuses to eat food offered to her

Question

What would you do now?

• Continue to encourage the patient to take oral risperidone• Switch to another atypical antipsychotic• Switch to a depot formulation of an antipsychotic


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• Pursue authorization for involuntary antipsychotic treatment based on the patient’s assaultiveness toward a fellow inpatient

Clinician’s Notes

• Nonadherence is a major challenge in patients with schizophrenia and is often attributed to stigma, negative attitude toward medication, substance use, lack of treatment efficacy, poor illness insight, and cognitive impairment• Given the patient’s history of medication nonadherence, a depot formulation may provide more therapeutic benefits than an oral antipsychotic• In addition to numerous depot conventional antipsychotics, there are several depot formulations of atypical antipsychotics available, including a 4-week paliperidone palmitate injection and a 2-week risperidone injection• The initiation of depot antipsychotics is best done in patients who have shown prior tolerance of the oral formulation of the same drug• Treatment adherence strategies are perhaps as important as the treatment regimen itself• In addition to pharmacological treatment, psychosocial interventions may be beneficial to patients with schizophrenia, especially those with little illness insight and poor adherence

Further Investigation

What additional information regarding this case would be helpful in determining the best course of action for increasing medication adherence in this patient?

• How is the patient’s current relationship with individual members of the treatment team?

· She is generally mistrustful of virtually all of the staff• Is there any particular staff member of whom she is particularly trustful or distrustful?

· She is particularly mistrustful of one of the treating physicians · She has developed a rapport with one of the social workers in the hospital

Case Outcomes

• The patient is maintained on oral risperidone but continues to refuse medication• She is also recommended to a substance abuse group therapy program but refuses to attend

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• Permission for involuntary antipsychotic treatment is sought and denied by an involuntary medication panel

· The authorization is denied because no staff witnessed the alleged assault, and the patient claims she acted in self-defense

• The patient continues to exhibit deficits in personal hygiene, including a suspected chronic oral infection

· This is especially concerning because the patient often threatens to spit on staff and fellow patients; however, the staff admits that these incidents are poorly documented

• The patient is compliant with blood transfusions when her hemoglobin levels become low enough to cause severe weakness

· She delays treatments as long as possible · The ongoing transfusions are leading to excess iron storage, and they carry a risk of liver failure

• However, the patient refuses to comply with other medical treatments and evaluations

· She ripped an intravenous line out of her arm when she realized that it was being used to administer levothyroxine to suppress a suspected TSH-secreting tumor

• She also continues to refuse food, and her BMI drops from 19.6 to 19.0• The patient denies all psychotic symptoms and describes herself as a “reasonable person”

Question

What would you do now?

• Continue to encourage the patient to take oral risperidone• Switch to another atypical antipsychotic• Switch to a depot formulation of an antipsychotic• Continue to pursue authorization for involuntary antipsychotic treatment • Enlist hospital staff members who have a good rapport with the patient into the treatment team

Clinician’s Notes

• Given this patient’s possible hepatic deterioration, it is important to consider which antipsychotics are contraindicated in patients with liver impairment• Atypical antipsychotics that are not recommended for patients with severe liver impairment include iloperidone and asenapine; additionally, caution should be used with most other atypical antipsychotics • The initiation of depot antipsychotics is best done in patients who have shown prior tolerance of the oral formulation of the same drug; this is


24

especially true for risperidone in patients with liver impairment• Forming a strong therapeutic alliance between the patient and the treatment team has been shown to greatly increase medication adherence; this may be especially true for patients with persecutory ideation and low illness insight• Involuntary treatment may be necessary if treatment alliance fails; a more complete record of threatening or assaultive incidents will be useful in determining if involuntary medication is necessary

Case Outcomes

• The hospital staff is instructed and encouraged to carefully document all episodes of threatening or assaultive behavior• The hospital social worker with whom the patient has a positive rapport is enlisted into the treatment team

· Under the supervision of an experienced psychologist, the social worker begins to work with the patient · The social worker also accompanies the patient to medical evaluations and treatments as a “phobic companion”

• Given the patient’s mistrust of the treating physician, a teaching nurse is enlisted to explain medical evaluations and treatments to the patient• With encouragement and reassurance from the social worker, the patient begins to take oral risperidone• One week following the initiation of oral risperidone, the patient shows no medication-related side effects; however, she will only take the antipsychotic when the social worker is present• Depot risperidone 37.5 mg every 2 weeks is initiated, with the social worker present for the administration• The patient also begins to eat food that is offered to her by the social worker; she gains 3 lbs over a 3-week period• She continues to have persecutory ideation, but her symptoms are improving, and she is beginning to trust more members of the treatment team

Case Debrief

• This patient is her own worst enemy; unfortunately, this is often the case for patients with schizophrenia• As the alliance between the patient and the treatment team improves, it may be possible to further evaluate and treat the medical comorbidities seen in this patient• Continued treatment with an antipsychotic may improve illness insight, leading to more willingness to accept treatment and thus more symptom

25


improvement

Take-Home Points

• Medications do not work if they are not taken• Medication nonadherence has a tremendous impact on the treatment of schizophrenia, and it often has dire consequences for the patient’s recovery efforts• Studies have shown that the use of long-acting injectable antipsychotics in patients with schizophrenia and medication adherence problems can significantly impact patient outcomes• It is imperative that the patient be comfortable with the treatment regimen in order to maximize treatment adherence and optimize recovery efforts• Despite major advancements in our understanding of the neurobiology of schizophrenia and numerous available treatments, schizophrenia poses several challenges in clinical practice• Forming a treatment alliance with the patient is a key factor in developing an effective treatment plan• An integrated approach that involves psychosocial interventions and individualized pharmacotherapy with the most efficacy and the fewest side effects offers the best strategy for improving adherence in patients with schizophrenia


• What could have been done better here? · Earlier attempts to create an alliance between members of the treatment team and the patient · Better documentation of the incidents that could warrant involuntary treatment

• Possible action items for improvement in practice · Individuals both inside and outside of the treatment team should be encouraged to work with the patient, especially in cases in which the patient presents with persecutory ideation · In patients who refuse medication, careful incident documentation should be standard, especially when the patient is a potential danger to him/herself and/or others


26

Brief Tutorial: Illness Insight May Improve With Antipsychotic Treatment

Following 50 weeks of treatment with depot risperidone, 199 patients (32.4%) had improved insight scores compared to baseline (Gharabawi GM et al, 2006).

Brief Tutorial: Factors That May Influence Treatment Adherence in Patients With Schizophrenia

Positive symptoms

Negative symptoms

Poor treatment alliance

Alcohol and drug use

Low therapeutic efficacy

Side effects

Complicated or frequent dosing schedules

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Charlie is a 52-year-old patient with schizophrenia. Due to a history of alcohol abuse, Charlie now has moderate cirrhosis of the liver. He is currently taking haloperidol, but he has begun to display parkinsonian movements, and you would like to switch him to an atypical antipsychotic. Which atypical antipsychotic is contraindicated for this patient with hepatic impairment?

A. OlanzapineB. AripiprazoleC. AsenapineD. Paliperidone

(Answer: C. Asenapine is not recommended for use in patients with hepatic impairment.)

ReferencesGharabawi GM et al. Insight and its relationship to clinical outcomes in patients with schizophrenia or schizoaffective disorder receiving long-acting risperidone. Int Clin Psychopharmacol 2006;21(4):233-40.

Leucht C, Heres S, Kane JM et al. Oral versus depot antipsychotic drugs for schizophrenia—a critical systematic review and meta-analysis of randomized long-term trials. Schizophr Res 2011;127:83-92.


Zygmunt A, Olfson M, Boyer CA et al. Interventions to improve medication adherence in schizophrenia. Am J Psychiatry 2002;159:1653-64.


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29

The Case: The 50-Year-Old “Hydrophilic” Patient

The Dilemma: Simplifying a Complicated Treatment Regimen Self-assessment Pretest

Isabella is a 34-year-old patient with schizophrenia who is currently taking 2 different antipsychotics (olanzapine and risperidone), an antidepressant (fluoxetine), and the mood stabilizer lamotrigine. Her positive symptoms of schizophrenia are fairly well controlled, but she has a lot of difficulty remembering to take all of her medications. According to recent data from the 2009-2010 Physician Drug and Diagnosis Audit, approximately how many patients with schizophrenia are prescribed more than 1 medication?

A. 10%B. 25%C. 50%D. 75%

Patient Intake

• 50-year-old patient with psychosis diagnosed with schizophrenia with bipolar features and developmental delay (IQ =63)• Accompanied by his twin sister• The patient has developed a fascination with water over the past year

· Leaves faucets running and watches water flow• This fascination has become excessive—to the point that he has had to be transferred from a board and care facility to a locked unit

Patient History

• The patient has done poorly on treatments for obsessive compulsive disorder (OCD), including fluvoxamine, added to his general antipsychotic regimen• He recently started clozapine, and this seems to be somewhat effective• For reasons that are unclear, he was started on bupropion at the same time as clozapine despite the fact that he was not depressed• The patient was previously diagnosed with borderline average

The Case:

The 50-Year-Old "Hydrophilic"

Patient


30

intelligence and chronic paranoid schizophrenia• He has been treated with numerous psychotropic drugs over the course of his illness• The patient has a history of seizures at high doses (>400 mg/day) of clozapine

Current Medications

• Clozapine 300 mg/day (100 mg in the morning, 200 mg at night)• Bupropion 200 mg/day (100 mg twice per day)• Fluphenazine 60 mg/day• Trihexyphenidyl 10 mg/day (5 mg twice per day)• Lamotrigine 50 mg/day• Lorazepam 1 mg/day (0.5 mg twice per day)• Trazodone 100 mg/day

Question

How would you adjust this patient’s medication?

• Increase clozapine dose• Increase lamotrigine dose • Discontinue clozapine• Discontinue lamotrigine • Discontinue trazodone • Discontinue bupropion• Discontinue lorazepam• Discontinue trihexyphenidyl• Discontinue fluphenazine

Clinician’s Notes

• With the patient currently in a locked facility under close care, it is an excellent time to try simplifying his medication regimen• The patient seems to be benefiting from clozapine• Increasing clozapine may allow for further improvement in the patient’s fascination with water• A downward taper of bupropion may be prudent, as there seems to be no need for it; once bupropion is discontinued, one could determine if the patient is getting any benefit from lamotrigine. He is currently on a very low dose of lamotrigine (50 mg/day), which could be discontinued without tapering• If the patient shows worsening of mood after discontinuation of lamotrigine, the lamotrigine could be added back in

31


• Because clozapine is sedating, trazodone is likely unnecessary; if some or all of the clozapine dose were given in the evening, trazodone could be slowly tapered, and if no insomnia resulted from the trazodone reduction, it could be discontinued• Given that clozapine is also an anxiolytic, lorazepam could also be discontinued and used as needed for agitation• Trihexyphenidyl, an anticholinergic medication, is likely being taken by this patient for motor side effects from fluphenazine• The polypharmacy of clozapine and fluphenazine may not be necessary for this patient. Discontinuation of fluphenazine may be possible; this would eliminate the need for trihexyphenidyl• By systematically discontinuing medications from the patient’s treatment regimen, it can be discovered which medications are truly necessary

Case Outcome

• Clozapine is increased to 400 mg/day by 50-mg increments, with 300 mg given at night• Bupropion is tapered to 100 mg/day for 1 week; no adverse consequences are observed. After another week at 100 mg/day, bupropion is discontinued completely• Trazodone is slowly tapered by reducing the dose from 100 mg to 50 mg for 7 nights; the patient experiences no consequent insomnia• Lorazepam is tapered to 0.5 mg/day for 1 week and then stopped altogether• Lamotrigine is discontinued without tapering• The patient shows some signs of depression 1 week after discontinuing lamotrigine; lamotrigine is reinitiated at 50 mg/day• Fluphenazine is very slowly tapered over a period of 8 weeks with careful observation for worsening of psychotic symptoms• With fluphenazine discontinued, trihexyphenidyl is no longer needed and is discontinued• The patient remains stable on this simplified medication regimen of clozapine 400 mg/day and lamotrigine 50 mg/day• He still shows some fascination with water, although this is now somewhat improved; his sister buys an inexpensive recirculating fountain for her home; the fountain is found to be effective in displacing the patient’s interest during several visits to his sister’s home• He is transferred back to the board and care facility, and his sister purchases a second fountain for him to keep in his room


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Case Debrief

• Simplifying this patient’s medication regimen allowed for the most effective treatment with the fewest side effects and created a baseline for the patient to be returned to a board and care facility• Although it is a common practice, there is little evidence to support the use of antipsychotic polypharmacy; many patients who are prescribed more than 1 antipsychotic would likely do just as well with monotherapy• Antipsychotic polypharmacy not only complicates the treatment regimen, but also increases the risk of side effects; it may even increase mortality and worsen cognitive impairment• Complex dosing schedules and medication regimens are often predictors of treatment nonadherence. Although this patient is currently in a care facility where he does not necessarily need to remember and be responsible for taking his medication, future recovery efforts for this patient may include more independent living; a simplified medication regimen will lend itself nicely to such recovery efforts• Recovery in schizophrenia can be viewed as a dynamic process with setbacks and accomplishments• Recovery can mean different things to different patients; it is not a fixed, “one size fits all” bar that all patients should be expected to reach, but rather a set of goals for optimizing functional outcomes and quality of life that is unique to each individual patient• Symptom relief with minimal side effects is often a goal in recovery; employment, independent housing, and acceptance in the community are also cited by many patients as essential to their recovery• It is possible that optimal outcomes for this particular patient may never include independent living beyond a board and care facility; however, residence at a board and care facility where he can easily visit with family rather than remaining in a locked unit is preferable to both the patient and his family

33


Brief Tutorial: Recovery in Schizophrenia

Recovery in schizophrenia encompasses many elements. Recovery for the individual patient may differ according to which of these elements are deemed essential.


34

Brief Tutorial: Polypharmacy in Schizophrenia

Nearly half of patients with schizophrenia are on more than 1 medication. Antidepressants, mood stabilizers, anxiolytics, anticholinergics, and additional antipsychotics are often prescribed along with antipsychotic medications (data from SDI’s Physician Drug and Diagnosis Audit (PDDA) database from May 2009 to April 2010).


Isabella is a 34-year-old patient with schizophrenia who is currently taking 2 different antipsychotics (olanzapine and risperidone), an antidepressant (fluoxetine), and the mood stabilizer lamotrigine. Her positive symptoms of schizophrenia are fairly well controlled, but she has a lot of difficulty remembering to take all of her medications. According to recent data from the 2009-2010 Physician Drug and Diagnosis Audit, approximately how many patients with schizophrenia are prescribed more than 1 medication?

A. 10%B. 25%C. 50%D. 75%

(Answer: C. According to recent data from SDI’s Physician Drug and Diagnosis Audit, nearly 50% of patients with schizophrenia are taking more than 1 medication.)

ReferencesBarnes TRE, Paton C. Antipsychotic polypharmacy in schizophrenia: benefits and risks. CNS Drugs 2011;25(5):383-99.

Buckley PF. Factors that influence treatment success in schizophrenia. J Clin Psychiatry 2008;69(Suppl 3):4-10.

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Davidson L, O’Connell M, Tondora J et al. The top ten concerns about recovery encountered in mental health system transformation. Psychiatr Serv 2006;57(5):640-5.

Dussias P, Kalali AH, Citrome L. Polypharmacy in schizophrenia. Psychiatry 2010;7(8):17-9.

Economou M, Palli A, Peppou L et al. Recovery from schizophrenia: a four-year study of an inner city cohort. Community Ment Health J 2011; Epub ahead of print.

Mitchell AJ, Selmes T. Why don’t patients take their medicine? Reasons and solutions in psychiatry. Adv Psychiatr Treat 2007;13:336-46.

Noiseux S, Ricard N. Recovery as perceived by people with schizophrenia, family members and health professionals: a grounded theory. Int J Nurs Stud 2008;45(8):1148-62.

Remington G, Foussias G, Agid O. Progress in defining optimal treatment outcome in schizophrenia. CNS Drugs 2010;24(1):9-20.

Stahl SM, Grady MM. A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation. Curr Med Chem 2004;11:313-27.

Suzuki T et al. Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia. Int J Neuropsychopharmacol 2004;7:133-42.

Warner R. Recovery from schizophrenia and the recovery model. Curr Opin Psychiatry 2009;22:374-80.


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37

The Case: The 37-Year-Old Woman Who Set Fire to Her Bed

The Dilemma: Involving the Patient in Treatment Decisions Self-assessment Pretest

Veronica is a 44-year-old patient with schizophrenia and a history of treatment nonadherence. She refuses to take her medication (clozapine) because she cannot tolerate the way it causes her mouth to feel dry (presumably due to the binding of muscarinic M1 and M3 receptors). She has agreed to try a depot formulation of an atypical antipsychotic. Based on binding profiles and the availability of a depot formulation, which atypical antipsychotic would you prescribe for this patient?

A. OlanzapineB. AsenapineC. AripiprazoleD. Paliperidone

Patient Intake

• 37-year-old woman with command auditory hallucinations to harm herself• The patient was recently arrested

· In an apparent suicide attempt, the patient set fire to her mattress while living in a residential psychiatric facility

• She has been cutting herself in an attempt to “let the devil out”• The patient also recently scratched her own hand with a staple and banged her head against the wall• She has been refusing medications

· The patient wants to take medications “her way” and frequently requests PRN medications

• She has been attending group therapy sessions, but she is often demanding, and she makes attempts to trade and barter with fellow inpatients• She has also been described as having poor impulse control• Previously, the patient was placed in 5-point restraints after attempting to hit a staff member and injure herself• She is currently under enhanced, one-to-one nursing observation

The Case:


Who Set Fire to Her Bed


38

following an attempt to hit a staff member with a pool cue• The patient is angry, irritated, and easily agitated• Her mood is described as dysphoric and hopeless• The patient is obese (BMI is 41.0)• She exhibits restlessness and tremor in both legs, and she repeatedly taps her left index finger• She indicates that her sleep is fragmented and that she is fatigued during the day

· She has nightmares of being chased by demons and spirits• The patient’s chief complaints are the presence of tremors and an objection to the dosing of her current quetiapine prescription

· She is unhappy that her prescription was recently consolidated from multiple doses to a single dose of quetiapine XR

Patient History

• The patient has a history of psychotic and mood disorders beginning at age 18• She has required 20 to 30 hospitalizations over the course of her illness due to severe psychomotor agitation; auditory hallucinations, including command auditory hallucinations; and suicide attempts• Prominent signs of mental disorder have also included persecutory ideation, self-injurious behavior, depressed mood, anhedonia, anergia, and a feeling of hopelessness• The patient also has a history of violence toward others, including:

· Assault with a deadly weapon · Cruelty to a child · Assault with a caustic agent

• Her illness has been complicated by a history of treatment nonadherence and substance abuse

· She began abusing marijuana at age 15 and added methamphetamine at age 18 · She has sporadically abused LSD, PCP, and solvents in the form of paint · The use of methamphetamines was associated with the onset of psychotic and mood disorders · She denies alcohol abuse

• She has exhibited a near-lifelong pattern of intense unstable mood, conflicted interpersonal relationships, self-mutilatory behavior, and frequent suicidality• The patient has a history of frequent head-banging, but without loss of consciousness, seizure, or neurological deficits• Medical history is significant for:

39


· Obesity · Dyslipidemia · Type II diabetes mellitus · Gastroesophageal reflux disease · Hypothyroidism · Asthma · Hypertension · Degenerative joint disease in the lumbar spine

• Family history is positive for: · Alcohol dependence in parents · Psychotic disorder and several suicide attempts in mother

Current Medications

• Quetiapine XR 1800 mg/day• Risperidone 2 mg/day (1 mg twice per day)• Topiramate 400 mg (200 mg twice per day)• Divalproex ER 250 mg in the morning and 2000 mg at bedtime• Duloxetine 120 mg (60 mg twice per day) • Naltrexone 50 mg in the morning for substance dependence• Levothyroxine 75 ug in the morning for hypothyroidism• Omeprazole 40 mg (20 mg twice per day) for acid reflux• Enalapril 20 mg in the morning for hypertension• Hydrochlorothiazide 12.5 mg in the morning for hypertension• Docusate 500 mg (250 mg twice per day) for constipation• Metamucil 2 tbsp (1 tbsp twice per day) for constipation• Atorvastatin 80 mg at bedtime for cholesterol• Aspirin 81 mg at bedtime• Primidone 100 mg at bedtime for tremors• Metformin 1700 mg/day (850 mg twice per day) for insulin resistance• Glipizide 2.5 mg in the morning to control blood sugar• Advair 2 inhalations per day for asthma

• PRN medications include: · o Ibuprofen · o Ziprasidone · o Guaifenesin (a cough suppressant)


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Question

How would you adjust this patient’s current medication regimen?

• Increase risperidone dose• Switch from divalproex to lamotrigine• Add a benzodiazepine hypnotic• Add a non-benzodiazepine hypnotic• Increase primidone• Switch from current antipsychotics to clozapine• Switch to a long-acting depot antipsychotic

Clinician’s Notes

• This patient is showing symptoms of psychosis despite her current medication regimen• However, in light of her treatment nonadherence, adjusting her current medications will likely not improve her condition • Factors that have been shown to affect treatment adherence in schizophrenia include a lack of medication efficacy, adverse side effects, cognitive deficits, and a lack of an alliance between the patient and the treatment team; many patients with schizophrenia cite a feeling of powerlessness with regard to their illness and its treatment as a barrier to adherence• This patient may derive some benefit from nonpharmacological interventions aimed at increasing illness insight and improving adherence, such as cognitive behavioral therapy• Incorporating this patient’s preferences into the development of a treatment plan will likely yield the best possible outcome• Although the use of quetiapine XR simplifies the dosing regimen, the patient has expressed a preference for divided dosing of the immediate- release quetiapine formulation; there seems to be no clinically compelling reason not to grant the patient’s request. Allowing the patient her say in the treatment plan when feasible may improve her willingness to adhere to the treatment• Increasing the dose of risperidone may offer additional relief from auditory hallucinations (if the patient will agree to adhere to the treatment plan)• Given the patient’s history of medication nonadherence, a depot formulation may provide more therapeutic benefits than an oral antipsychotic• In addition to numerous depot conventional antipsychotics, there are several depot formulations of atypical antipsychotics available, including a

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4-week paliperidone palmitate injection and a 2-week risperidone injection• Both divalproex and lamotrigine are mood stabilizers and anticonvulsants; divalproex is most effective in treating symptoms of mania, whereas lamotrigine is most effective in treating bipolar depression; because this patient is exhibiting depressive symptoms rather than manic ones, it may be prudent to switch her mood stabilizer from divalproex to lamotrigine• Additionally, valproate is associated with weight gain and may be particularly undesirable in a patient who is obese and diabetic; lamotrigine carries relatively little risk for weight gain and may be preferable for this particular patient• Adding a hypnotic agent may help with fragmented sleep and insomnia; however, given this patient’s history of drug abuse, using a benzodiazepine may not be prudent; a non-benzodiazepine, such as zolpidem, may be a wiser course of action • The patient’s extrapyramidal symptoms (EPS), including tremor, are not being adequately addressed and may be exacerbating her unwillingness to adhere to antipsychotic treatment• Increasing her primidone dose may offer further improvement in EPS and possibly lead to improvement in treatment adherence• If response to quetiapine plus risperidone continues to be inadequate, a trial with clozapine may be warranted. Clozapine is recommended for treatment-resistant cases, and it may offer superior benefits with respect to mood lability and suicidality. The challenge in this particular case would be risks relevant to metabolic syndrome and the need for adequate monitoring

Case Outcome

• Per her request, the patient is switched from quetiapine XR to quetiapine IR 400 mg twice per day and 1000 mg at bedtime• Risperidone dosing is switched to bedtime and increased by 2 mg per week until achieving a target of 6 mg at bedtime• Placated by the change in quetiapine dosing, the patient agrees to take her medication• She is also enrolled in group cognitive therapy specializing in treatment adherence• Divalproex is tapered and discontinued as lamotrigine is added (25 mg at bedtime); lamotrigine is increased by 25 mg per week to a target of 400 mg (200 mg twice per day)• Primidone is increased to 100 mg twice per day plus 100 mg at bedtime• The patient shows improvement in mood • Her tremors are reduced, and she reports less frequent awakenings and


42

less daytime sleepiness• Auditory hallucinations continue, and the patient persists in acts of self-harm• Following a discussion, the patient agrees to try clozapine• Quetiapine and risperidone are slowly tapered over 6 weeks while clozapine is added, starting at 25 mg/day and increasing by 25 mg/day to 450 mg/day (225 mg twice per day)• The patient is currently being monitored for metabolic side effects and absolute neutrophil count

Case Debrief

• Medications do not work if they are not taken• Many factors, including treatment alliance, perceived medication efficacy versus side effects, and illness insight can greatly affect a patient’s willingness to adhere to medication • Treatment adherence strategies are perhaps as important as the treatment regimen itself• Psychosocial interventions, including cognitive behavioral therapy, have been shown to improve medication adherence in patients with schizophrenia• Cognitive behavioral therapy involves the use of a pencil and paper or computerized mental exercises designed to improve cognitive functioning• An integrated approach that involves psychosocial interventions and individualized pharmacotherapy with the most efficacy and the fewest side effects offers the best strategy for improving adherence in patients with schizophrenia• Customizing treatments to fit the needs of the individual patient and empowering the patient as a decision-making partner are critical elements for recovery in schizophrenia


• What could have been done better here? · If the patient’s preference for quetiapine in divided doses had been known prior to switching to quetiapine XR, subsequent issues of nonadherence may have been avoided

• Possible action items for improvement in practice · Discussion with the patient prior to adjusting medications · Incorporation of patient preferences into treatment regimen when feasible

43


Brief Tutorial: Consequences of Nonadherence

Even partial nonadherence to antipsychotic medication is associated with an increased risk of rehospitalization.

Brief Tutorial: Receptor Binding Profiles of Antipsychotics

Dru

g

D2 Antag D2 PA D3 5HT1A PA

5HT2A Antag 5HT2C 5HT7 α1 M1 M3 H1

Arip

ipra

zole

+++ +++ +++ +++ ++ +++ ++

Ase

napi

ne

+++ +++ ++ ++++ ++++ ++++ +++ ++ ++ +++

Cloz

apin

e

++ + + ++ ++ ++ ++ ++ ++ +++

Ilope

ridon

e

++ ++ ++ ++++ ++ + ++++ ++

Lura

sido

ne

+++ ? +++ +++ ++++ ++ ?


44

Brief Tutorial: Receptor Binding Profiles of Antipsychotics (cont)D

rug

D2 Antag D2 PA D3 5HT1A PA

5HT2A Antag 5HT2C 5HT7 α1 M1 M3 H1

Ola

nzap

ine

++ ++ +++ ++ + ++ ++ ++ +++

Palip

erid

one

+++ +++ + ++++ ++ +++ +++ ++

Que

tiapi

ne

++ + + + +* + +++ + +++

Risp

erid

one

+++ +++ + ++++ ++ +++ +++ ++

Zipr

asid

one

+++ ++ ++ ++++ ++++ +++ +++ +

Ther

apeu

tic E

ffect

s

Reduced Pos

Reduced Pos

Reduced Pos;

Reduced Neg; Pro-cognitive; Antidep

Reduced EPS;

Reduced HP;

Antidep; Anxio-

lytic

Reduced EPS;

Reduced HP

Antidep

Reduced Circ dys-function; Reduced

Neg; Procogni-

tive

Reduced night-mares

Reduced EPS

Reduced EPS Hypnotic

Side

Effe

cts

EPS;HP;

Increased Neg;

Increased Cog;

Sedation

Relatively lower risk

of EPS Unknown Unknown Unknown CM Unknown

Dizziness;Sedation;Hypoten-

sion

Constipa-tion;

Sedation;Dry

mouth;Blurred vision

CM; Constipa-

tion;Sedation;

Dry mouth;Blurred vision

CM;Sedation

Binding affinities based on data from the National Institutes of Mental Health Psychoactive Drug Screening Program online Ki database. +Ki≥100nM; ++Ki≥10nM; +++ Ki≥1nM; ++++Ki<1nM. Note that a higher Ki is indicative of a lower binding affinity. *Represents the binding affinity of norquetiapine, the active metabolite of quetiapine. Abbreviations: Antidepresant (Antidep); Cardiometabolic (CM); Circadian rhythm (Circ); Cognitive deficits (Cog); Extrapyramidal symptoms (EPS); Hyperprolac-tinemia (HP); Negative symptoms (Neg); Partial agonist (PA); Positive symptoms (Pos)

The therapeutic benefits and side effects associated with antipsychotics may be related to their specific binding profiles. Maximizing the therapeutic benefits while minimizing the side effects that are most troubling for the individual patient may help improve treatment adherence.

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Self-Assessment Posttest

Veronica is a 44-year-old patient with schizophrenia and a history of treatment nonadherence. She refuses to take her medication (clozapine) because she cannot tolerate the way it causes her mouth to feel dry (presumably due to the binding of muscarinic M1 and M3 receptors). She has agreed to try a depot formulation of an atypical antipsychotic. Based on binding profiles and the availability of a depot formulation, which atypical antipsychotic would you prescribe for this patient?

A. OlanzapineB. AsenapineC. AripiprazoleD. Paliperidone

Answer: D. (Paliperidone is the only choice listed here that is available in a depot formulation and that exhibits virtually no binding at muscarinic M1 and M3 receptors.)

ReferencesAscher-Svanum H, Zhu B, Faries DE et al. Medication adherence levels and differential use of mental-health services in the treatment of schizophrenia. BMC Res Notes 2009;2:1-6.

Corrigan PW. Recovery from schizophrenia and the role of evidence-based psychosocial interventions. Expert Rev Neurother 2006;6(7):993-1004.

Docherty JP, Kozma C, Grogg A et al. Antipsychotic maintenance in schizophrenia: partial compliance and clinical outcome. Poster presented at: 41st Annual Meeting of the American College of Neuropsy-chopharmacology (ACNP); December 8-12, 2002; San Juan, Puerto Rico. 179 Abstract 154.

Lindenmayer J-P, Liu-Seifert H, Kulkarni PM et al. Medication nonadherence and treatment outcome in patients with schizophrenia or schizoaffective disorder with suboptimal prior response. J Clin Psychia-try 2009;70(7):990-6.

Llorca P-M. Partial compliance in schizophrenia and the impact on patient outcomes. Psychiatry Res 2008;161:235-47.

Noiseux S, Ricard N. Recovery as perceived by people with schizophrenia, family members and health professionals: a grounded theory. Int J Nurs Stud 2008;45(8):1148-62.

Nosé M, Barbui C, Tansella M. How often do patients with psychosis fail to adhere to treatment pro-grammes? A systematic review. Psychol Med 2003;33(7):1149-60.

Perkins DO, Gu H, Weiden PJ et al. Predictors of treatment discontinuation and medication nonad-herence in patients recovering from a first episode of schizophrenia, schizophreniform disorder, or schizoaffective disorder: a randomized, double-blind, flexible-dose, multicenter study. J Clin Psychiatry 2008;69:106-13.

Stahl SM. Stahl’s essential psychopharmacology: the prescriber’s guide. 4th ed. New York, NY: Cam-bridge University Press; 2009.

Tarrier N. Cognitive behavioral therapy for schizophrenia and psychosis: current status and future directions. Clin Schizophr Relat Psychoses 2010;4(3):176-84.

Weiden PJ, Kozma C, Grogg A et al. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv 2004;55(8):886-91.

Zygmunt A, Olfson M, Boyer CA et al. Interventions to improve medication adherence in schizophrenia. Am J Psychiatry 2002;159:1653-64.


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CME Posttest and Activity Evaluation

Release/Expiration Dates Print Monograph Released: November 1, 2011Electronic Books Released: December, 2011CME Credit Expires: October 31, 2014. If this date has passed, please contact NEI for updated information.

CME Posttest Study GuidePLEASE NOTE: The posttest can only be submitted online. The posttest questions have been provided below solely as a study tool to prepare for your online submission. Faxed/mailed copies of the posttest cannot be processed and will be returned to the sender. If you do not have access to a computer, please contact customer service at 888-535-5600.

1. Jeremy is a 27-year-old patient with schizoaffective disorder and comorbid kidney disease. He has had unsuccessful trials of 4 different antipsychotics and is interested in a trial of clozapine. Clozapine is contraindicated in patients with:

B. Cardiac impairmentC. Renal impairmentD. Hepatic impairmentE. All of the aboveF. None of the above

2. Rhea is a 45-year-old patient with schizophrenia and a history of treatment nonadherence. Currently, she is getting some benefit from depot haloperidol, but she has developed signs of tardive dyskinesia, and you would like to see her switched to an atypical antipsychotic. Which of the following atypical antipsychotics is currently being developed as a 12-week depot formulation?

C. QuetiapineD. AsenapineE. PaliperidoneF. Ziprasidone

3. Isabella is a 34-year-old patient with schizophrenia who is currently taking 2 different antipsychotics (olanzapine and risperidone), an antidepressant (fluoxetine), and the mood stabilizer lamotrigine. Her positive symptoms of schizophrenia are fairly well controlled, but she has a lot of difficulty remembering to take all of her medications. According to recent data from the 2009-2010 Physician Drug and Diagnosis Audit, approximately how many patients with schizophrenia are prescribed more than 1 medication?

D. 10%E. 25%F. 50%G. 75%

CME: Posttest and Certificate


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4. Veronica is a 44-year-old patient with schizophrenia and a history of treatment nonadherence. She refuses to take her medication (clozapine) because she cannot tolerate the way it causes her mouth to feel dry (presumably due to the binding of muscarinic M1 and M3 receptors). She has agreed to try a depot formulation of an atypical antipsychotic. Based on binding profiles and the availability of a depot formulation, which atypical antipsychotic would you prescribe for this patient?

E. OlanzapineF. AsenapineG. AripiprazoleH. Paliperidone

5. Charlie is a 52-year-old patient with schizophrenia. Due to a history of alcohol abuse, Charlie now has moderate cirrhosis of the liver. He is currently taking haloperidol, but he has begun to display parkinsonian movements, and you would like to switch him to an atypical antipsychotic. Which atypical antipsychotic is contraindicated for this patient with hepatic impairment?

F. OlanzapineG. AripiprazoleH. AsenapineI. Paliperidone

CME Online Posttest and CertificateTo receive your certificate of CME credit or participation, please complete the posttest and activity evaluation, available only online, by clicking the link found at the end of this electronic book or at www.neiglobal.com/CME under “Book”. If a passing score of 70% or more is attained (required to receive credit), you can immediately print your certificate. There is no fee for CME credits for this activity.

http://www.neiglobal.com/WebPosttest.aspx?action=webposttest&args=PT_AT-BOOK11-CASES-SCHIZ

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