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Treatment Challenges in Schizophrenia: A Multifaceted Approach to Relapse Prevention

Treatment Challenges in Schizophrenia: A Multifaceted Approach to Relapse Prevention

While prescription of an antipsychotic
medication for
schizophrenia is the first step
of treatment and for the resolution of
an acute episode of psychosis, it is
increasingly recognized that comprehensive
care requires the integration
of adjunctive therapies and attention to
long-term treatment goals, including
relapse prevention and psychosocial
rehabilitation. In the absence of a cure
for schizophrenia, clinicians can optimize
outcomes by combining pharmacotherapy
with a treatment approach
that incorporates symptom monitoring,
assessment of treatment adherence and
medication side effects, management
of medical and psychiatric comorbidities,
and nonpharmacologic therapies
directed at functional rehabilitation and
improved quality of life.

Relapse prevention and treatment adherence

The main goal in the treatment of schizophrenia is to reduce symptoms and minimize the risk of relapse or the reappearance of symptom exacerbations. Although there is no single definition of relapse, rehospitalization, symptomatic worsening, self-injury, and suicidal or homicidal ideation are all factors used in determining relapse in research and clinical settings.1

Schizophrenia is a complex and
chronic disorder that requires long-term
treatment. Although other treatment
methods such as psychotherapy, stress
management, and education can help
in delaying the occurrence of relapse,
antipsychotic therapy is the cornerstone
of relapse prevention. Consequently,
adherence to a drug regimen is crucial
for reducing the risk of relapse.

There are 3 basic ways of assessing medication adherence. First, clinicians can elicit reports from patients, family members, and caregivers regarding adherence, although such reports can be inaccurate. A more reliable technique is to have patients bring in their medication bottles at each visit to perform pill counts. Finally, plasma levels of certain antipsychotics may be obtained to determine whether a medication is being taken, although this method might fail to detect partial adherence. Switching to an injectable, long-acting antipsychotic may be suitable for certain patients and produce beneficial results in efficacy, tolerability, and relapse prevention.2 Injectable antipsychotics are not a panacea for maintaining adherence, but their administration in the clinic allows for verification that each dose has been received.

Patients and family members should be informed about the benefits and side effects of medications so that they can actively participate in the treatment effort.3 In long-term studies of schizophrenia conducted in the 1980s, family education was the most effective psychosocial treatment available. Adherence therapy and psychosocial skills training are also highly regarded.

Managing comorbidities

Alcohol and drug abuse, social anxiety, and depression are all conditions prevalent among patients with schizophrenia. Each can negatively affect a patient's quality of life and treatment outcome and should be attended to as a regular component of aftercare. Between one third and one half of schizophrenic patients use alcohol and/or other substances; this puts them at increased risk for relapse, treatment nonadherence, hospitalization, violence, and suicide.4 Shaner and coinvestigators5 found that the combination of cognitive-behavioral drug relapse prevention strategies and social and independent living skills training improved drug and alcohol abstinence, medication adherence, and quality of life.

Dual-diagnosis programs are more likely to produce beneficial results for patients with schizophrenia than any 12-step program alone because they are designed to take into account the various symptomatic, cognitive, and social limitations of patients with schizophrenia.6 Accordingly, dual-diagnosis programs typically follow a "harm-reduction" model in which a decrease in drug use and its associated consequences, rather than total abstinence, is the goal of treatment. An ideal dualdiagnosis program is shaped on 2 basic principles:

  • Simultaneous treatment of schizophrenia
    and substance abuse.
  • An integrated treatment program in
    which a set of clinicians (eg, physicians,
    nurses, case managers) work as a team
    on both disorders.

Other important elements include
intensive case management, motivational interventions, counseling, staged
interventions, social support interventions,
and regular urine drug screens.7

In a study conducted by Pallanti and colleagues,8 36.3% of the schizophrenic patients were found to be suffering from social anxiety disorder. These patients had higher rates of past suicide attempts and alcohol and drug dependence. They also rated poorly in employment, socialization, and personal well-being as measured by the Social Adjustment Scale. Symptoms of social anxiety, such as social withdrawal, are similar to but distinct from negative symptoms of schizophrenia.8 The added burden of anxiety may cause further decline in a patient's quality of life.9,10 According to Kingsep and associates,11 because social anxiety is multifaceted, multiple assessments can be used to measure its symptoms more directly.

About 10% of schizophrenic patients successfully complete suicide.12,13 Multiple risk factors have been identified, ranging from previous suicide attempts, substance abuse, hopelessness, depression, and male sex2 to lack of social support, lack of problem-solving skills, and stress.13 While patients who have recently been released from the hospital are more likely to attempt suicide, Desai and colleagues14 were not able to find a correlation between suicide risk and quality of mental health care. They report that suicide rates are too unstable to clearly be attributed to the quality of a treatment facility or its delivery of care.

The most common indicator of suicide risk is depression. Illness insight can lead to depression and hopelessness in some patients.15 Anhedonia and anergia are among the negative symptoms common to schizophrenia and depression. Difficulties in making a distinction between the 2 disorders may result in a patient's depression being left untreated. Assessments such as the Hamilton Rating Scale for Depression and the Montgomery-Asberg Depression Rating Scale may aid physicians in diagnosing depression and instituting treatment earlier.

Clinicians should monitor patients at baseline and throughout treatment for changes in insight regarding their condition15 and be alert to the possibility of suicide if they begin feeling hopeless motivaabout their recovery.12 In 2002, clozapine (Clozaril) was approved by the FDA for reducing the risk of suicide in schizophrenic and schizoaffective patients. Meltzer16 has recently reviewed studies supporting the use of clozapine to reduce suicidal behaviors and examining reasons for its lack of use (ie, adverse effects such as agranulocytosis, metabolic abnormalities, seizures, hypotension, and hypersalivation).

Managing medication-related comorbidities

A large number of reports have linked atypical antipsychotics to weight gain and associated health outcomes.17 Excess body weight also puts patients with schizophrenia at increased risk for stroke, gallbladder disease, osteoarthritis, and some forms of cancer.18 According to the American Diabetes Association (ADA) consensus statement,19 clozapine and olanzapine (Zyprexa) appear to cause the greatest amount of weight gain among the atypical antipsychotics. These medications are also associated with an increased risk of dyslipidemia and diabetes. Type 2 diabetes may occur because of insulin resistance caused by weight gain or altered fat distribution, or as a result of direct effects of the drugs on insulin receptors. Carefully monitoring patients' blood glucose levels may ultimately prevent diabetes and significant illnesses associated with diabetes, particularly cardiovascular disease, renal disease, peripheral neuropathy, and limb loss.

The ADA suggests obtaining several
screening measures when a patient
starts taking an atypical antipsychotic.
These include baseline assessment of
personal and family history of obesity,
diabetes, dyslipidemia, hypertension,
and cardiovascular disease, as well as
baseline and subsequent monitoring of
body mass index, waist circumference,
blood pressure, and fasting plasma
glucose and lipid measurements.
Patients at risk for diabetes (fasting
glucose level of 100 to 125 mg/dL) and
patients with diabetes (fasting plasma
glucose level of 126 mg/dL or more)
should in particular be monitored for
symptoms of diabetes and diabetic
ketoacidosis, including polyuria, excessive
thirst, weight loss, nausea or vomiting,
dehydration, rapid respiration, and
clouding of sensorium.

Fortunately, behavioral approaches to weight control, such as nutritional intervention and increased activity, can prevent or counter antipsychoticinduced weight gain.20-22 Patients should be encouraged to weigh themselves and exercise regularly. Even a simple exercise, such as brisk walking for a half hour per day, can be beneficial in maintaining or reducing weight. We encourage our patients to learn how to control their portions and reduce their fat intake, as opposed to cutting carbohydrates or counting calories, because fat requires a greater amount of energy to burn off. Keeping food and exercise diaries is helpful for both patients and clinicians in managing caloric intake, determining problem foods, and crafting healthier eating habits.

We are currently testing a series of classes adopted from the Diabetes Prevention Program23 in our research. Thus far,20 participants in our program have enjoyed the Healthy Lifestyles classes and have lost or maintained weight. The key is to establish lifestyle changes because even weight-loss medications are ineffective without changes in eating and exercise habits. We are also working with caregivers to help our participants achieve the changes necessary to reach their weight loss goals. Weight management can improve quality of life and self-image20 and can halt a downward spiral leading to other health problems and depression.

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