Practical Strategies for the Treatment of Patients with Schizophrenia

Leslie Citrome, MD, MPH

Adjunct Professor of Psychiatry & Behavioral Sciences, New York Medical College, Valhalla, NY
Sponsored by The France Foundation. Supported by an educational grant from Sunovion.

Faculty Disclosure
It is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty, activity planners, content reviewers, and staff participating in this activity will disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this educational activity.

The intent of this disclosure is not to prevent a person with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has identified and resolved any and all conflicts of interest prior to the release of this activity.

Disclosure Leslie Citrome, MD, MPH

Leslie Citrome, is a consultant for, has received honoraria from, or has conducted clinical research supported by the following:
Abbott, AstraZeneca*, Avanir, Azur, Barr, Bristol-Myers Squibb*, Eli Lilly*, Forest, GlaxoSmithKline, Janssen*, Jazz, Merck*, Novartis*, Noven*, Pfizer*, Shire*, Sunovion*, Valeant*, and Vanda.

* Denotes a relationship in effect anytime during the past 12 months

Learning Objectives
Recognize criteria for remission and recovery in patients with schizophrenia. Evaluate patients for the potential to achieve these outcomes and implement strategies directed towards these goals Recognize how clinical practice guidelines relate to the individualized treatment of patients with schizophrenia Integrate strategies that will help to improve the effective use of medications by patients with schizophrenia

Please take pretest now

Schizophrenia A Set of Symptoms

Positive Symptoms
Suspiciousness/paranoia Grandiosity/Delusions Unusual thought content

Negative Symptoms
Blunted affect Emotional withdrawal Active social avoidance Lack of spontaneity Poor rapport

Disorganized Symptoms
Poor attention Conceptual disorganization Difficulty in abstract thinking Disorientation

Clinical and Pathophysiological Course of Schizophrenia

Lieberman JA, et al. Biol Psychiatry. 2001;50(11):884-897.

What is Response?
Speed? Magnitude? Proportion responding? Effect in refractory patients?

Measuring Efficacy - Decrease in PANSS

Lieberman JA, et al. N Engl J Med. 2005;353(12):1209-1223.

Decrease in PANSS Factors

Heresco-Levy U, et al. Biological Psychiatry. 2004;55:165-171.

Arbitrary Categorical Changes in PANSS

Response defined as at least a 30% decrease from the baseline PANSS to the last observation

Daniel DG, et al. Neuropsychopharmacology.1999;20:491-505.

Functionality
Distribution of patients achieving 1 change in Personal and Social Performance (PSP) Scale category at end point. Intentto-treat population; PSP scale scores at end point for individual patients to show a clinically relevant change in personal and social functioning as represented by improvement of 1 category (classified as one 10-point interval); PSP = Personal and Social Performance Scale.
Kane J, et al. Schizophr Res. 2007;90:147-161.

What is remission and recovery in patients with schizophrenia?

Response vs Remission
Disease Response Remission Depression 50% HAM-D HAM-D 7 Mania 50% YMRS YMRS 12 Schizophrenia 20-30% PANSS ?

Andreasen N, et al. Am J Psychiatry. 2005;162:441-449.

Remission Definitions

Andreasen N, et al. Am J Psychiatry. 2005;162:441-449.

Proposed Criteria for Remission

Andreasen N, et al. Am J Psychiatry. 2005;162:441-449.

Recovery
Davidsons Nine Common Elements of Recovery
1. Renewing hope and commitment

SAMHSA Fundamental Components of Recovery

1. 2.

2.
3. 4. 5. 6. 7.

8.
9.

Consumer self-direction Individualized and person-centered Redefining self treatment Incorporating illness into life as a whole 3. Empowerment 4. A holistic treatment focus Involvement in meaningful activities 5. A nonlinear perspective of change Overcoming stigma 6. Treatment focused on strengths instead of deficits Assuming control 7. The inclusion of peer support in Becoming empowered and exercising treatment citizenship 8. Respect for consumers and consumer self-respect Managing symptoms 9. Consumer acceptance of personal Finding social support responsibility 10. Hope in recovery

Peebles S, et al. Psych Clin N Am. 2007;30:567-583.

Treatment Effectiveness

Efficacy
Does Rx reduce Sx?

Tolerability and Safety

Combines all measures

Adherence/ Persistence
Will Pt take Rx?

Treatment Effectiveness

Does Rx cause SE?

Lehman AF, et al. Am J Psychiatry. 2004;161(2 suppl):1-56. Swartz MS, et al. Schizophr Bull. 2003;29(1):33-43.

Lieberman JA, et al. N Engl J Med. 2005;353(12):1209-1223.

CATIE Primary Outcome Measure: All-Cause Treatment Discontinuation

Efficacy All-Cause Discontinuation Clinician Input Patient Input Tolerability

Effectiveness
Time to Any-Cause Discontinuation
CATIE Clozapine Pathway Results

McEvoy JP, et al. Am J Psychiatry. 2006;163:600-610.

Effectiveness
Any-Cause Discontinuation: NNT
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%

CATIE Clozapine Pathway

86% 71% 56%
NNT 4 NNT 3

93%

OLZ

RIS

CLO

QUE

McEvoy JP et al. Am J Psychiatry. 2006;163:600-610; Citrome L. Psychiatry MMC. 2007;4(10):23-29; Citrome L and Stroup TS. Int J Clin Pract.2006;60:933-940.

What else do I need to know about recovery?

Hierarchies of Outcome: Recovery is at Top

Recovery

Remission

Stabilization

Criteria for Recovery?

Symptom remission Vocational functioning Independent living Peer relationships Duration 2 years Is recovery best viewed as an outcome or a process?

Liberman P, et al. Int Rev Psychiatry. 2002;14:256-272. Liberman P, Kopelowicz. Psychiatr Serv. 2005;56:735-742.

Recovery A Matter of Perspective

Recovery from Illness
Cure of illness, absence of illness

versus
Recovery in Illness: being in recovery
Process of managing illness more effectively Having a meaningful life in the community
Moving ahead with ones life despite illness

Davidson L, et al. Schizophr Bull. 2008;34:5-8.

Process of Recovery
The Person Play

The Illness
The Person

The Person Work Family The Illness Friends The Illness

Factors Associated with the Potential for Positive Clinical and Functional Outcomes
Short duration of untreated psychosis Good early response to antipsychotic treatment Collaborative therapeutic alliance Supportive family/caregivers Access to comprehensive, coordinated, and continuous treatment Opportunities to engage in functional activities and receive specialized interventions Absence of substance abuse

What about cognition in patients with schizophrenia?

Cognitive Deficits Are the Bridge Between Brain Functioning and Functional Impairments in Day-to-Day Life
Cognitive deficits are a frequent and robust feature of the illness Cognitive deficits are present at illness onset and persist throughout the illness Cognitive deficits directly contribute to poor functional outcome in schizophrenia

Normative Data Compared to a Schizophrenia Sample on the RBANS Neuropsychological Test

35 30

Schizophrenia (n = 575) Normal controls (n = 540) from standardization sample

25.0% 22.8% 20.6% 22.6% 25.0%

% of Cases

25 20 15 10
7.2%

16.5%

16.0%

16.0%

7.0% 0.4% 0% 1.6%

7.9% 2.2% 0.4% 0%

7.0% 0.4% 0% 1.6% 0%

5
0

< 50-50

51-60

61-70

71-80

81-90

91-100 101-110

111-120 121-130

131-140 140+

Total Scale Score

RBANS: Repeatable Battery for Assessment of Neuropsychological Status
Wilk CM, et al. Schizophr Res. 2004;70(2-3):175-186.

Components of Psychosocial Rehabilitation

Motivational Aspects External Intrinsic Outcomes Functional Subjective

Neurocognition Attention Processing Memory Reasoning Verbal learning Visual learning

Social Cognition Emotion processing Social perception Attributional bias Theory of mind

Kurzban S, et al. Curr Psychiatry Rep. 2010;12:345-355.

Cognitive Remediation
Behavioral treatments that specifically target:
Memory Attention Executive functioning Reasoning

Restorative cognitive techniques drill and practice

Paper & pencil tasks Computerized training software COGPACK, Posit Science Brain Fitness, etc. Individual Groups Compensatory cognitive training promote adaptive behavior

Enhance daily functioning

School, work, social interactions, independent living

Enhance skills pertinent to recovery goals

Medalia A, Choi J. Neuropsychol Rev. 2009;19:353-364.

Work and Schizophrenia

~20% employed

80% Unemployed

Barriers

5570% identify employment as a goal

Cognitive impairments Psychiatric symptoms Episodes of illness Stigma from employers Internalized stigma/low self-confidence Fear of losing disability benefits

McGurk S, et al. Schizophr Bull. 2009;35:319-335. Kurzban S, et al. Curr Psychiatry Rep. 2010;12:345-355.

Vocational Rehabilitation
Skills training Sheltered workshops Transitional employment Supported employment Vocational rehabilitation + cognitive remediation best results Employment = Increased self esteem Reduction in symptoms and hospitalizations Enhanced social functioning Improvement in overall quality of life
McGurk S, et al. Schizophr Bull. 2009;35:319-335. Kurzban S, et al. Curr Psychiatry Rep. 2010;12:345-355.

Supported Employment
Basic Principles 1. Zero exclusion; eligibility based on consumer choice 2. Focus on competitive jobs in integrated community settings 3. Rapid job search 4. Respect for consumers preferences in terms of the nature of the job and types of support services 5. Ongoing job support 6. Close integration with a psychosocial rehabilitation team approach 7. Benefits counseling (disability benefits, social security, medical insurance)
McGurk S, et al. Schizophr Bull. 2009;35:319-335.

Optimizing Employment Outcomes

Vocational Rehabilitation (VR) + Cognitive Remediation (CR)
45 40 35

* **

3000 2500

VR VR + CR

Weeks Worked

30 25 20 15 10 5

Wages Earned

2000 1500 1000 500

Competitive Hospital-based Community Internship Work

Total

0 Competitive Hospital-based Community Internship Work

Total

* P < 0.05; ** P < 0.01 VR + CR: Greater improvements in verbal learning, memory, executive functioning vs VR only
McGurk S, et al. Schizophr Bull. 2009;35:319-335.

Cognitive remediation with COGPACK training software

What can guidelines tell us?

Management of Schizophrenia
Patient-focused therapeutic alliance Individualized approach Reduce or eliminate symptoms Optimize quality of life Assist patients in attaining personal life goals (work, housing, relationships) Guidelines and algorithms provide a framework for decision making

Guideline/Algorithm Recommendations
APA 2004 TMAP 2006 PORT 2009

First episode
Second choice Third choice Fourth choice Fifth choice Combinations

SGA
SGA, FGA, C C (C+)

SGA
SGA, FGA C C+ A,T CF

SGA, FGA
SGA, FGA C

FGA: first-generation antipsychotic SGA: second-generation (atypical) antipsychotic C: Clozapine C+: Clozapine augmentation CF: Clozapine failure
Practice Guideline for the Treatment of Patients with Schizophrenia. 2nd Edition. APA. 2004. Moore T, et al. J Clin Psychiatry. 2007;68:1751-1762. Kreyenbuhl J, et al. Schizophr Bull. 2010;36:94-103.

PORT Psychosocial Treatment

Patient Outcomes Research Team Recommendations for:
Assertive community treatment

Supported employment Skills training Cognitive behavioral therapy Token economy interventions Family-based services Interventions for alcohol and substance abuse disorders Interventions for weight management
Dixon L, et al. Schizophr Bull. 2010;36:48-70.

What is it that we actually do?

Survey of APA Practice Research Network: Schizophrenia Treatments

100
90

Percent Receiving Recommended Treatment

80 70 60 50

40
30 20 10 0
Use of Dose in Range Antipsychotic Illness education Vocational Rehabilitation Substance Abuse Treatment Any Psychosocial Treatment

West J, et al. Psych Services. 2005;56:283-291.

 Second-generation antipsychotics are used in over 70% of individuals with schizophrenia (use may be higher in first-episode patients) Rate of clozapine use is much lower than the incidence of treatment-resistant schizophrenia Antipsychotic polypharmacy
~10 to 30% of individuals with schizophrenia FGA + SGA most common combinations

Real-World Antipsychotic Treatment Practices

Use of adjunctive medications

Baseline data from CATIE
Antidepressants (38%), anxiolytics (22%), sedative hypnotics (19%), lithium (4%), other mood stabilizers (15%)

Dosage of antipsychotic medications within therapeutic range 64 to 83% of the time during inpatient treatment
Moore T, et al. Psychiatr Clin N Am. 2007;30:401-416.

What do we know about efficacy and tolerability of antipsychotic medication?

Meta-Analyses Demonstrate the Heterogeneity for Antipsychotic Response

All antipsychotics are equal, but some are more equal than others - Volavka J, Citrome L. J Clin Psychiatry. 2009;70:429-430.

SGA versus FGA

Amisulpride Aripiprazole Clozapine Olanzapine Quetiapine Risperidone Sertindole Ziprasidone Zotepine

Leucht S, et al. Lancet. 2009;373(9657):31-41.

Meta-Analyses Demonstrate the Heterogeneity for Antipsychotic Response

All antipsychotics are equal, but some are more equal than others - Volavka J, Citrome L. J Clin Psychiatry. 2009;70:429-430.

SGA versus SGA Advantages for:

Clozapine Olanzapine Risperidone

Leucht S, et al. Am J Psychiatry. 2008;166(2):152-163.

Antipsychotics Heterogeneity for Tolerability

EPS, Prolactin, Weight, Glucose/Lipids, Sedation, Hypotension

Volavka J, Citrome L. Expert Opin Pharmacother. 2009;10(12):1917-1928.

CATIE Reasons for Discontinuation

80% 70% 60% 50% 40% 30% 20% 10% 0%
ALL CAUSE LACK OF EFFICACY INTOLERABILITY PATIENT DECISION OTHER REASONS
WEIGHT GAIN - METABOLIC EFFECTS

74%

N=1432
EXTRAPYRAMIDAL EFFECTS SEDATION

4.0% 4.0% 1.8% 4.9%

24%

30% 6%

OTHER

15%

Lieberman JA, et al. N Engl J Med. 2005;353(12):1209-1223.

How do we manage this heterogeneity?

We Can Use Evidence-Based Medicine

Clinical Judgment EBM Relevant Scientific Evidence

Patients Values and Preferences

Sackett DL, et al. BMJ. 1996;312(7023):71-72. Citrome L, Ketter TA. Int J Clin Pract. 2009;63(3):353-359.

What Is Treatment Effectiveness?

Efficacy
Does Rx reduce Sx?

Tolerability and Safety

Does Rx cause SE?

Treatment Effectiveness
Adherence/ Persistence
Will Pt take Rx?

Combines all measures

Lehman AF, et al. Am J Psychiatry. 2004;161(2 suppl):1-56. Swartz MS, et al. Schizophr Bull. 2003;29(1):33-43. Lieberman JA, et al. N Engl J Med. 2005;353(12):1209-1223.

Effective Use of Medication

Medication is a tool that a person with schizophrenia can use to take greater control over his or her life The goal should be to maximize the effectiveness of medication to help the person live the kind of life that he or she wants to live

The medicine has work well enough, be tolerated well enough, and the patient has to take it

Medication Nonadherence
Prevalence ~30 to 50% (and higher); rates vary depending on clinical setting, definitions, study duration, study population Relatively short gaps in medication coverage can increase the risk of relapse Nonadherence is associated with poor outcomes
Relapse Hospitalization Suicide attempts
Lacro J, et al. J Clin Psychiatry. 2002;63:892-909. Novick D, et al. Psychiatry Res. 2010;176:109-113. Masand P, et al. Prim Care Companion J Clin Psychiatry. 2009;11:147-154.

How can we manage non-adherence?

Step 1: Admit the possibility of partial or nonadherence

We Overestimate Adherence
Nonadherence viewed as failure consistent bias to overestimate adherence/underestimate nonadherence We assume lack of adequate response as treatment-resistance and lack of efficacy for the antipsychotic for that patient
This is a possible explanation for high dosing of antipsychotics, polypharmacy with other antipsychotics and combination treatment with anticonvulsants This is a no-win cycle: adherence is even more of a challenge with complex regimens
Velligan DI, et al. Psychiatr Serv. 2007;58(9):1187-1192.

Step 2: Identify the specific barriers to adherence present for your patient

Risk Factors for Nonadherence

Patient-related1
Poor insight Negative attitude toward medication Prior nonadherence Substance abuse Cognitive impairment

Environment/Relationship-related1
Lack of family/social support Problems with therapeutic alliance Practical problems (financial, transportation, etc)

Treatment-related1
Side effects Lack of efficacy/ continued symptoms

Societal-related2
Stigma attached to illness Stigma caused by medication side effects

1. Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46. 2. Lee S, et al. Soc Sci Med. 2006;62(7):1685-1696.

Risk Factors for Nonadherence

Patient-related1
Poor insight Negative attitude toward medication Prior nonadherence Substance abuse Cognitive impairment

Environment/Relationship-related1
Lack of family/social support Problems with therapeutic alliance Practical problems (financial, transportation, etc)

Treatment-related1
Side effects Lack of efficacy/ continued symptoms

Societal-related2
Stigma attached to illness Stigma caused by medication side effects

1. Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46. 2. Lee S, et al. Soc Sci Med. 2006;62(7):1685-1696.

Barriers to Therapeutic Alliance in Schizophrenia

Patient barriers1
Communication difficulties Difficulty forming an alliance because of negative symptoms Difficulty learning from experience because of cognitive symptoms Rejection of diagnosis due to stigma

Clinician barriers2
Underestimating importance of relationship Hopelessness conveyed to patient Lack of interest in life goals and other issues important to patient
1. Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46. 2. Pitschel-Walz, G, et al. J Clin Psychiatry. 2006;67(3):443-452.

Relationship Between Early Alliance and Later Medication Adherence: The Boston Collaborative Study
Adherence After 6 Months, %
80 60 40 20 0
< 0.001

74

26a

28a

Good

Fair Alliance at 6 Months

Poor

aP

Frank AF, Gunderson JG. Arch Gen Psychiatry. 1990;47:228-235.

Assessing Medication Adherence: Interview Style

Ask for the patients view about medications1,2 Obtain sufficient information before responding3 Do not jump to conclusions; take comments at face value3 Explain that you want to hear what the patient really thinks, not what he/she thinks you want to hear1-3 If you want to respond, do not try to do too much and make sure you do not go beyond what the patient can accept for now As much as you can, try to keep the discussion about medication adherence positiveeven enjoyable1 Above all, try to maintain and even strengthen the alliance, even if there is disagreement about the need for medication1
1. Weiden, PJ. J Psychiatr Prac. 2002;8(6):386-392. 2. McCabe R, et al. BMJ. 2002;325(7373):1148-1151. 3. Weiden PJ. J Clin Psychiatry. 2007;68(suppl 14):14-19.

Assessing Medication Adherence: Interview Style

Have you been taking your medications? or You have been taking your medicines, right? Everyone misses doses of their medicines. Can you give me some idea of how many doses do you usually miss in any given week? I just need a ball-park figure, you dont have to be exact. This is followed by, What doses do you miss the most morning? evening? with meals? in between meals? This way we can figure out the best time of day to use these medications so we can minimize the number of times you may miss them.

Risk Factors for Nonadherence

Patient-related1
Poor insight Negative attitude toward medication Prior nonadherence Substance abuse Cognitive impairment

Environment/Relationship-related1
Lack of family/social support Problems with therapeutic alliance Practical problems (financial, transportation, etc)

Treatment-related1
Side effects Lack of efficacy/ continued symptoms

Societal-related2
Stigma attached to illness Stigma caused by medication side effects

1. Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46. 2. Lee S, et al. Soc Sci Med. 2006;62(7):1685-1696.

Medication-related Side Effects and Nonadherence

Potential drivers
Level of distress rather than severity Attribution to the medication Vary from patient to patient

Most commonly associated with nonadherence

Weight gain Sedation Akathisia Sexual dysfunction Parkinsonian symptoms Cognitive problems

Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46.

Reverberations From Side Effects

How Patient and Clinician Responses May Differ
Adherence Impact

Side effect appears

Subjective Distress
Objective Severity

Safety and Risk

Weiden PJ, Buckley PF. J Clin Psychiatry. 2007;68(suppl 6):14-23.

Considering Side Effect Profile When Choosing Treatment

Important because side effects may1: Contribute to treatment nonadherence Limit return to maximal levels of social functioning Potentially contribute to long-term morbidity Atypical antipsychotics are better tolerated than typical antipsychotics (mainly due to decreased EPS)2 Differences in drug-specific adverse effect profiles, including metabolic effects, may impact treatment adherence and long-term outcomes1,2
1. Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46. 2. Tandon R. Psychiatr Q. 2002;73(4):297-311.

Risk Factors for Nonadherence

Patient-related1
Poor insight Negative attitude toward medication Prior nonadherence Substance abuse Cognitive impairment

Environment/Relationship-related1
Lack of family/social support Problems with therapeutic alliance Practical problems (financial, transportation, etc)

Treatment-related1
Side effects Lack of efficacy/ continued symptoms

Societal-related2
Stigma attached to illness Stigma caused by medication side effects

1. Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46. 2. Lee S, et al. Soc Sci Med. 2006;62(7):1685-1696.

What Type of Intervention Is Appropriate?

If the adherence problem is that the patient WILL NOT, focus intervention on strengthening perceived benefits of medication and minimizing perceived costs
If the adherence problem is that the patient CANNOT, then address barriers to adherence

Pill boxes in obvious locations Self-monitoring tools Establishment of routines Consider long-acting injectable antipsychotic
Weiden P. J Clin Psychiatry. 2007;68(suppl 14):14-19.

Risk Factors for Nonadherence

Patient-related1
Poor insight Negative attitude toward medication Prior nonadherence Substance abuse Cognitive impairment

Environment/Relationship-related1
Lack of family/social support Problems with therapeutic alliance Practical problems (financial, transportation, etc)

Treatment-related1
Side effects Lack of efficacy/ continued symptoms

Societal-related2
Stigma attached to illness Stigma caused by medication side effects

1. Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46. 2. Lee S, et al. Soc Sci Med. 2006;62(7):1685-1696.

Step 3: Monitoring adherence

Monitoring Medication Adherence

There are no entirely satisfactory methods, but can count pills and measure plasma levels Ask if the patient is taking his/her medications Ask, are the medications doing any good? Any perceived benefit (eg, sleeping better) is a treasure If none, be worried Ask, are the medications doing any harm? Ask about being sleepy, slowed down, dulled Ask about weight changes Ask about constipation Ask about sex
Velligan DI, et al. J Clin Psychiatry. 2009;70(suppl 4):1-46.

Step 4: Consider a depot antipsychotic

Considering Efficacy When Choosing Treatment

Someone who isnt responding adequately to an oral medication is unlikely to then respond to its depot formulation
Unless they were a non-responder because of nonadherence

There is heterogeneity in efficacy outcomes among the different antipsychotics, and this heterogeneity is observed among groups in clinical trials and in individual patients

Potential Advantages of Long-acting Injectable Antipsychotics

Reduces dosage deviations1 Eliminates guessing about adherence status2,3 Shows start date of nonadherence2,3 Helps disentangle reasons for poor response to medication3 Eliminates need for the patient to remember to take a pill daily1 Enables prescribers to avoid first-pass metabolism, therefore a better relationship between dose and blood level exists1 Results in predictable and stable plasma levels1 Eliminates abrupt loss of efficacy if dose missed1,3 Many patients prefer them, especially if already receiving them4
1. 2. 3. 4. McEvoy JP. J Clin Psychiatry. 2006;67(suppl 5):15-18. Olfson M, et al. Schizophr Bull. 2007;33(6):1379-1387. Kane JM, et al. J Clin Psychiatry. 2003;64(suppl 12):5-19. Patel MX, et al. J Psychiatr Ment Health Nurs. 2005;12(2):237-244.

Potential Obstacles to Long-acting Injectable Antipsychotics

Lack of infrastructure in outpatient settings Need to refrigerate, store, reconstitute, etc. Overburdened public agencies Frequency of injections and consequent inconvenience for staff and patients Need to take concomitant medications orally Anti-shot sentiment

McEvoy JP. J Clin Psychiatry. 2006;67(suppl 5):15-18. Kane JM, et al. J Clin Psychiatry. 2003;64(suppl 12):5-19.

Determinants of Depot Use

Citrome L, et al. Psychopharmacol Bull. 1996;32(3):321-326.

Depot Antipsychotics Reduce Relapse in Long-term Studies

Study Barnes 1983 Falloon 1978 Hogarty 1979 Quitkin 1978 Rifkin 1977 Crawford 1974 DelGuidice 1975 Schooler 1973 Total (95% CI)

Treatment n/N
3/19 8/20 22/55 5/29 1/19 2/14 21/27 26/107 88/290

Control n/N
3/17 5/24 32/50 4/27 4/24 6/15 59/61 35/107 146/325

Relative Risk (95% CI Random)

Relative Risk (95% CI Random)

0.89 (0.21, 3.85) 1.92 (0.74, 4.95) 0.62 (0.43, 0.92) 1.16 (0.35, 3.89) 0.63 (0.06, 6.45) 0.36 (0.09, 1.48) 0.80 (0.65, 0.99) 0.74 (0.48, 1.14) 0.78 (0.66, 0.91)

Overall effect z = 3.06; P = 0.002 .1 .2 Favors Treatment

5 10 Favors Control

Mentschel C, et al. Presented at: The International Congress on Schizophrenia Research (ICOSR) 2003; March 29-April 2; Colorado Springs, Colorado.

Relapse-free Survival Rates With Oral and Depot Fluphenazine

10 9 8 7 6 5 4 3 2 1 0

Proportion Surviving

Fluphenazine decanoate (n = 55)

Oral fluphenazine (n = 50)

0 3 6 9 12 15 18 21 24

Months in Community
Hogarty GE, et al. Arch Gen Psychiatry. 1979;36(12):1283-1294.

Adherence Summary
Strategies to improve adherence include Admitting that partial or nonadherence is a possibility Identifying risk factors specific to the individual Addressing barriers to therapeutic alliance Tailoring interventions to adherence attitudes and behavior Pharmacologic strategies to improve adherence include Considering patient history, efficacy, and side effect profile when choosing treatment Considering utilizing long-acting injectable antipsychotics, if available, in patients with recurring relapses related to nonadherence

Summary
Response, remission and recovery are necessary goals of treatment, but each can be interpreted differently by clinicians, patients, and their families Clinical practice guidelines can provide advice regarding a comprehensive approach, unfortunately not often done Treatment effectiveness is dependent on a medication being efficacious enough, tolerable enough, and the patient has to take it Adherence can be the ultimate confounder regarding effectiveness

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