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Seven Keys To Relapse Prevention
in Schizophrenia
Relapse prevention is a primary goal in the treat-
ment of schizophrenia. Relapse can cause signifi-
cant personal distress, interfere with rehabilitation
efforts, and result in psychiatric hospitalization.
The emergence of psychotic symptoms and disrup-
tive behaviors can also lead to arrest and incarcer-
ation, particularly among patients who are not
engaged in treatment. This article focuses on the
process of relapse in schizophrenia and theoretical
foundations of relapse prevention. The Program for
Relapse Prevention is presented, along with the
results of a recently completed controlled prospec-
tive evaluation. Based upon this study and the cur-
rent literature, the author presents a series of seven
clinical strategies for optimal relapse prevention.
(Journal of Psychiatric Practice 2001;7: XXX–XXX)
KEY WORDS: schizophrenia, relapse prevention, prodro-
mal symptoms, early intervention, nonadherence.
chizophrenia is usually a relapsing and remitting
S disorder, with periods of acute psychosis alternat-
ing with periods of relative stability. Unfortunately,
psychotic relapse is common, with up to 40% of all
patients suffering a relapse within a year of being hospi-
talized.1, 2 With the total cost of hospital care for patients
with schizophrenia exceeding two billion dollars annually,3
relapse represents a significant public health problem. The
personal costs associated with relapse—including
impaired role functioning, disrupted interpersonal rela-
tionships, and demoralization—are also considerable. This
article begins with a brief review of what is known about
relapse in schizophrenia. The results of a study comparing
a specific relapse prevention program with treatment as
usual are then presented. The article concludes with a
presentation of key strategies that appear to be effective in
preventing relapse in schizophrenia.
LAMBERTI: University of Rochester Medical Center.
Copyright © Lippincott Williams & Wilkins Inc.
Please send correspondence and reprint requests to: J. Steven Lamberti, MD,
Director, Strong Ties Community Support Program, 1650 Elmwood Avenue,
Rochester, NY 14620.
The author thanks Marvin I. Herz, MD, for his input and guidance.
Journal of Psychiatric Practice
J. STEVEN LAMBERTI, MD
AN OVERVIEW OF RELAPSE IN
SCHIZOPHRENIA
Although operational definitions exist,4 relapse in schizo-
phrenia may be clinically defined as the emergence of
psychotic symptoms to the point that crisis intervention
or hospitalization is required. Understanding the relaps-
ing and remitting course of schizophrenia is central to
relapse prevention. Figure 1 illustrates the longitudinal
course of illness and how the pattern of relapse can vary
significantly between groups of patients.5 It is notewor-
thy that DSM-IV has introduced a useful classification of
the course of schizophrenia, including categories of single
episode, episodic with interepisode symptoms, episodic
without interepisode symptoms, and continuous.6
Relapse in schizophrenia should not be viewed as
occurring “spontaneously.” According to the vulnerability-
stress model, individuals with schizophrenia have a bio-
logically mediated vulnerability to stressful events that
can result in acute psychosis.7, 8 Whether a full-blown
relapse occurs depends upon a complex interaction
between an individual’s degree of vulnerability, the
nature of the stressful event, and the presence or absence
of protective factors.9 Protective factors include an indi-
vidual’s coping skills, family and social supports, and
therapeutic interventions. The role of protective factors
was emphasized in the development of the Program for
Relapse Prevention described in the next section.10
A PROGRAM FOR RELAPSE PREVENTION
IN SCHIZOPHRENIA
The Program for Relapse Prevention (PRP) was devel-
oped as a state-of-the-art approach incorporating a num-
ber of interventions shown to be effective in preventing
relapse in schizophrenia.10, 11 In addition to maintenance
pharmacotherapy, PRP includes four primary compo-
nents:
1. Monitoring for prodromal symptoms of relapse by
treatment providers, patients, family members, and
others in frequent contact with the patient
2. Prompt clinical intervention whenever prodromal
symptoms of relapse are detected
3. Weekly supportive group therapy meetings, with indi-
vidual sessions as needed
4. Multifamily psychoeducation group meetings, bi-week-
ly for 6 months and monthly thereafter.
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SEVEN KEYS TO RELAPSE PREVENTION IN SCHIZOPHRENIA
Group 1
Group 2
Group 3
Group 4
Figure 1. Variations in longitudinal course of
schizophrenia.
Reprinted with permission from Shepard et al. 19895
To assess the effectiveness of the program, it was com-
pared to treatment as usual (TAU) consisting of biweekly
individual supportive therapy and family contact on an
“as needed” basis.10 Eighty-two outpatients with schizo-
phrenia or schizoaffective disorder were randomly
assigned to receive PRP or TAU, and were followed in an
18-month prospective study. Subjects in both groups
received standard doses of antipsychotic medications.
Over 18 months, 17% of patients relapsed and 22% were
hospitalized in the PRP group compared to 34% of
patients relapsing and 39% being hospitalized in the TAU
group (P = 0.01 and 0.03, respectively). A preliminary
analysis of total direct costs of care showed that PRP
actually cost less than TAU, although the difference was
not statistically significant. Based on experience with the
PRP model and a review of the current literature on
relapse prevention, a list of seven strategies for relapse
prevention has been developed. Although they were
derived from intensive treatment programs including
PRP and assertive community treatment (ACT), these
strategies can be used successfully in a variety of treat-
ment settings.
RELAPSE PREVENTION STRATEGIES
Strategy 1: Be Available and Flexible
Availability and flexibility are the cornerstones of relapse
prevention. Patients and their support persons should be
able to reach clinicians easily, particularly during
evenings and weekends. Patients and family members in
the PRP study group were given a pager number for their
treatment team, with instructions to call whenever they
were concerned about the possibility of relapse. Although
clinicians may be reluctant to provide this level of access
2 July 2001
for several reasons, including the possibility of receiving
multiple calls after hours, the experience of the PRP team
suggests that such calls are infrequent, especially with
ongoing instruction and practice. While an answering
service or other system of reaching treatment providers
after hours may be adequate, arrangements that require
patients to work with unfamiliar clinicians are not opti-
mal.
Whenever possible, patients with schizophrenia who
may be relapsing should be evaluated within 24 to 48
hours. Many relapses have resulted from the common
practice of assigning such patients the “next available
appointment”—even when the appointment is several
days or weeks away. Clinicians can achieve flexibility in
their daily work schedules by maintaining regular time
slots for crisis appointments or by overbooking crisis
appointments when needed.
Along with personal qualities such as warmth and gen-
uineness, availability and flexibility can promote a strong
therapeutic alliance. Since a positive therapeutic rela-
tionship is associated with improved adherence to treat-
ment,12 it is likely that being available and flexible will
have therapeutic benefits that extend beyond enabling
prompt clinical intervention.
Availability and flexibility are the corner-
stones of relapse prevention and can
promote a strong therapeutic alliance.
Strategy 2: Watch for Prodromal Symptoms
Prodromal symptoms—often called early warning signs—
are the earliest noticeable signs of relapse. The regular
occurrence of prodromal symptoms before relapse in
schizophrenia has been established by several investiga-
tors.13–18 Common examples of prodromal symptoms are
insomnia, tension and nervousness, eating less, difficulty
concentrating, social withdrawal, auditory hallucina-
tions, depressed mood, loss of interest, decreased person-
al hygiene, and irritability.13 Prodromal symptoms vary
considerably among patients, but tend to remain rela-
tively consistent within a given individual from relapse to
relapse.
Effective monitoring for prodromal symptoms requires
frequent contact and careful evaluation. Open-ended
questions such as “How are things going?” or “Are there
any problems?” are not adequate for detecting prodromal
symptoms. A shortened version of the Early Signs
Questionnaire11, 13 (see Appendix) was administered to
patients in the PRP study at the start of each weekly
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SEVEN KEYS TO RELAPSE PREVENTION IN SCHIZOPHRENIA
Symptoms and Role Impairment
Prodromal Phase
Prodromal-Type
Symptoms
BASELINE
STRESSOR
Figure 2. Process of relapse in schizophrenia and opportunities for intervention.
group therapy meeting. This tool can be administered to
patients in any treatment setting where regular contact
is maintained. It is important to note that patients may
report various symptoms on the questionnaire even dur-
ing a stable phase of illness. Since many patients experi-
ence interepisode symptoms such as insomnia, anxiety,
and auditory hallucinations, a thorough knowledge of
each patient is necessary to distinguish these “baseline”
symptoms from prodromal symptoms.
Strategy 3: Intervene Early
The process of relapse in schizophrenia is usually a grad-
ual one that presents a window of opportunity for early
intervention (Figure 2). Although prodromal symptoms
typically precede full relapse by at least a week,9 inter-
vention often does not occur until late in the course of
relapse when an emergency room visit or hospitalization
is necessary. In the PRP study, 40% of patients in the
TAU group required hospitalization by the time that the
treatment providers became aware that the patients were
relapsing.
The relapse process in schizophrenia is reversible if
intervention occurs early enough in its course.4, 10, 19–21
When prodromal symptoms are detected, intervention
should consist of supportive therapy visits, increased
medication as needed, and crisis problem solving. The
likely precipitating cause of the prodromal episode
should be identified and addressed through appropriate
measures. For instance, a patient who begins to relapse
due to anxiety about moving into a group home could be
given transitional visits in order to get acquainted with
the facility. Pharmacological intervention usually con-
sists of increasing a patient’s standing dose of antipsy-
chotic medication or of adding an extra dose on an
as-needed basis. The additional medication should be con-
Journal of Psychiatric Practice
Page 3
Relapse
Psychotic Exacerbation
Hospitalization
Intervention
Emergency
Treatment
Treatment
Early
Personal
Coping
Crisis Intervention
Time
Reprinted from Herz and Lamberti 19959
tinued until the precipitating factors have been
addressed and the prodromal symptoms have fully
resolved. Adjunctive benzodiazepines may also be consid-
ered for the treatment of prodromal symptoms.22
Strategy 4: Work Closely With Families and Other
Supports
Some patients are unable to detect or report the onset of
relapse, despite education about prodromal symptoms
and considerable personal experience. For such individu-
als, it is critical to enlist the help of family members and
supportive others, including friends, employers, group
home counselors, and day treatment program staff. These
individuals, who have frequent contact with the patient,
can become the “eyes and ears” of the treatment team in
detecting the onset of relapse. They can also have a pro-
tective effect by helping patients manage stressful situa-
tions and by supporting adherence to treatment.23
In recent years, family psychoeducational approaches
have been developed to assist families and others in pro-
viding support for persons with schizophrenia.24 As a
group, these approaches emphasize providing education
about schizophrenia, teaching problem solving and com-
munication skills, and developing social networks.
Several research studies have demonstrated the effec-
tiveness of family psychoeducation in reducing relapse
rates in schizophrenia.25 The strength of the evidence for
the effectiveness of family psychoeducation in preventing
relapse is perhaps second only to that for antipsychotic
medications. Despite the evidence, the Patient Outcomes
Research Team (PORT) study26 and a recent review of the
literature27 have suggested that family psychoeducation
interventions are highly underutilized.
The multifamily group format was chosen for the PRP
intervention because it lends itself to teaching about
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SEVEN KEYS TO RELAPSE PREVENTION IN SCHIZOPHRENIA
relapse prevention, it promotes formation of family net-
works, and it may be more cost effective than single fam-
ily models. Although only 29% of PRP patients’ families
participated in the multifamily groups, only one patient
from these families relapsed and was hospitalized during
the study period. Interested clinicians are referred to the
excellent practical overview of multifamily group psy-
choeducation by McFarlane and Cunningham.28
Family members and supportive others can
become the “eyes and ears” of the treat-
ment team in detecting the onset of relapse.
They can also have a protective effect by
helping patients manage stressful situations
and by supporting adherence to treatment.
Strategy 5: Use Assertive Outreach When
Necessary
When they are relapsing, patients often withdraw from
their usual activities, including attending outpatient
appointments. Assertive outreach to such patients, car-
ried out in a positive, confident, and persistent way, can
promote engagement in treatment. Forms of outreach
may include letters, phone calls, and home visits. In the
PRP study, all patients in the experimental group who
missed an appointment received a follow-up phone call,
and home visits were conducted if clinically indicated.
The assertive community treatment (ACT) model has
been developed for patients who consistently require out-
reach in order to engage in treatment.29 It consists of
mobile multidisciplinary treatment teams with a high
staff-to-patient ratio and around the clock availability.
ACT places a strong emphasis on delivering comprehen-
sive services in community settings, outside the walls of
outpatient clinics.
Strategy 6: Address Nonadherence
It has been estimated that nonadherence to treatment
with antipsychotic medications accounts for approxi-
mately 40% of all relapses in schizophrenia.30, 31
Medication nonadherence was also the single strongest
predictor of relapse in the PRP study. Causes of medica-
tion nonadherence include denial of illness, perceived
lack of benefit from treatment, financial and environ-
mental obstacles, and motivational factors. The self-
4 July 2001
determination theory of human motivation32 suggests
that medication adherence is most likely to occur and
persist if the patient experiences the behavior as
autonomous—as emanating from within him- or herself.
Recent studies of adherence to weight loss regimens,33
diabetes diets,34 and medications in outpatient medical
settings35 have highlighted the impact of clinicians’
behaviors on patient motivation. The following clinical
strategies, which are based on the self-determination
model, should be considered for patients who are nonad-
herent with antipsychotic medications:
1. Listen: elicit the patient’s experiences and concerns.
2. Empathize: acknowledge the patient’s perspective.
3. Educate: provide a clear rationale for the recommend-
ed treatment.
4. Provide choices: promote choice whenever possible.
5. Minimize control: minimize controlling behaviors.
Despite this approach, some patients with schizophre-
nia will continue to refuse medications. These patients
are at risk for entering a “revolving door” cycle of repeat-
ed relapse and hospitalization.36 For patients whose
refusal of medication consistently results in behaviors
that pose a risk of harm to themselves or others, involun-
tary outpatient commitment should be considered.37, 38
Outpatient commitment has been shown to reduce hospi-
tal readmission rates and medication nonadherence
among patients with psychotic disorders, although its
effectiveness may depend upon the ability of outpatient
programs to engage such individuals.38
Patients with schizophrenia who are not engaged by
existing treatment programs present difficult challenges
for relapse prevention. These patients often have co-
occurring substance use disorders, and many experience
homelessness, arrest, and incarceration.39, 40 New models
of outpatient service delivery are being developed to pre-
vent relapse and recidivism among such individuals. An
example is Project Link, an integrated approach that
spans healthcare, social service, and criminal justice sys-
tems.41 The program incorporates elements of the ACT
model and features a mobile treatment team with a
forensic psychiatrist, a dual diagnosis residence, and cul-
turally diverse staff. It also involves active collaboration
between treatment team members and criminal justice
system representatives, including jail staff, judges, and
probation and parole officers. While preliminary program
evaluations have suggested that this model may be effec-
tive, controlled studies are needed to further examine the
impact of this approach on relapse and recidivism.41, 42
Strategy 7: Optimize Pharmacotherapy
Pharmacotherapy can be optimized by simplifying drug
regimens, by considering the use of atypical and
decanoate antipsychotic medications, and by minimizing
drug side effects.30, 31 Although side effects are a major
cause of medication nonadherence among patients with
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SEVEN KEYS TO RELAPSE PREVENTION IN SCHIZOPHRENIA
schizophrenia, patients may not report side effects unless
asked about them directly. Clinicians should therefore
carefully assess all patients for side effects on a regular
basis. While most medication side effects have the poten-
tial to affect adherence, extrapyramidal side effects (EPS)
such as akathisia and akinesia may be especially prob-
lematic.43 Since novel “atypical” antipsychotic medica-
tions produce noticeably fewer EPS than standard
antipsychotic medications, they have the potential to
improve adherence and help prevent relapse.
Recent studies have suggested that atypical antipsy-
chotic medications are superior to standard medications
in preventing psychotic relapse. In a review of three large
international studies of olanzapine versus haloperidol,
the Kaplan-Meier estimated 1-year risk of relapse was
28% with haloperidol compared to 19.7% with olanzapine
(p < 0.05).44 In a study comparing risperidone and
haloperidol in a group of 365 patients, 34.6% of patients
on haloperidol and 23.2% of patients on risperidone
relapsed after 1 year (p < 0.01).45 In addition to studies
that have examined relapse rates, a number of pharma-
coeconomic studies have shown decreased rates of hospi-
talization associated with atypical antipsychotic drugs
compared to standard drugs.46, 47 Although these phar-
macoeconomic studies have methodological limitations,48
the results to date are encouraging.
Long-acting decanoate medications should also be con-
sidered for reducing the risk of relapse in schizophrenia.
Decanoate medications have been found to lower relapse
rates by approximately 15% compared to standard oral
antipsychotic medications.49 These injectable medications
have the additional advantage of allowing clinicians to
detect nonadherence, thus providing an opportunity for
early intervention. No randomized controlled studies
have been published comparing the effectiveness of
decanoate and atypical antipsychotic medications in pre-
venting relapse and hospitalization in schizophrenia.
Recent studies have suggested that atypical
antipsychotic medications are superior to
standard medications in preventing psy-
chotic relapse.
SUMMARY AND CONCLUSIONS
Although effective approaches to relapse prevention in
schizophrenia have been developed, they remain largely
underutilized.26 This paper has presented seven funda-
mental principles for relapse prevention that are based
Journal of Psychiatric Practice
upon existing approaches and can be flexibly applied in
outpatient treatment settings. A consideration of these
principles calls to mind the expression “simple but not
easy”—the principles are simple to understand, but their
application requires persistence and practice for optimal
effectiveness. However, these efforts are worthwhile
investments, because effective relapse prevention can
provide a foundation for rehabilitation and recovery
among those who suffer from schizophrenia.
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SEVEN KEYS TO RELAPSE PREVENTION IN SCHIZOPHRENIA

Appendix. Early Signs Questionnaire, Short Form

NAME___________________________________________ DATE___________________

Compared to last week, has there been an increase in any of the following symptoms?
YES NO
1. Problems with sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
2. Problems with appetite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
3. Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
4. Problems with concentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
5. Restlessness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
6. Tension or nervousness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
7. Use of alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
8. Use of street drugs (includes marijuana) . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
9. Hearing voices or seeing things that others can’t hear or see . . . . . . . . ________ ________
10. Less pleasure gained from things you usually enjoy . . . . . . . . . . . . . . . ________ ________
11. Feeling people were watching you, were against you,
or were talking about you . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
12. Preference for being alone and/or been spending less time
with other people . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
13. Arguments with others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ________ ________
14. Inability to get your mind off of one or two things . . . . . . . . . . . . . . . . . ________ ________

Have any other symptoms appeared or increased? . . . . . . . . . . . . . . . . . . . . ________ ________

If so, what were they?__________________________________________________

__________________________________________________________________

__________________________________________________________________
Did anything specific happen last week which upset you? . . . . . . . . . . . . . . ________ ________
If so, what was it?_____________________________________________________

__________________________________________________________________

__________________________________________________________________
Have you been taking your medication as it is prescribed for you? . . . . . . . ________ ________

Reprinted with permission from Marvin Herz, MD. Clinicians may reproduce this scale for use in their clinical practice. Researchers
who wish to use the Early Signs Questionnaire in multi-patient studies should contact Dr. Herz at University of Rochester Medical
Center, Strong Ties Community Support Program, 1650 Elmwood Avenue, Rochester, NY 14620, (716)275-0300, x2337,
marvin_herz@urmc.rochester.edu

Journal of Psychiatric Practice July 2001 7