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Psychotic Prodrome: Are Antipsychotics Effective? Ethical? Evidence Is Mixed but Risk Is High When Abnormal Cognition Falls Short of Schizophrenia

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Psychotic Prodrome: Are Antipsychotics Effective? Ethical? Evidence Is Mixed but Risk Is High When Abnormal Cognition Falls Short of Schizophrenia Psychotic prodrome: Are antipsychotics effective? Ethical? Evidence is mixed but risk is high when abnormal cognition falls short of schizophrenia Meera Narasimhan, MD Director, psychopharmacology division Associate professor of clinical psychiatry Department of neuropsychiatry and behavioral sciences University of South Carolina School of Medicine Columbia Peter F. Buckley, MD Chairman and professor Department of psychiatry and behavioral health Medical College of Georgia, Augusta ecause 40% of individuals with a psy- B chotic prodrome develop schizophrenia, detecting and preventing this transition could improve many patients’ lives. Unfortunately: • psychotic prodrome lacks clear-cut symp- toms and is difficult to identify • little evidence exists to help clinicians select psychotropics and decide how long to use them • treating all prodromal patients would expose those who never develop psychosis to the risk of psychotropics’ side effects. How, then, can psychiatrists help patients who present with possible prodromal symptoms? Based on research and our experience, this article describes the psychotic prodrome and offers a © Marc Bruce / Images.com 32 Current VOL. 4, NO. 3 / MARCH 2005 p SYCHIATRY Current p SYCHIATRY pragmatic, evidence-based approach to Box 1 diagnosis and treatment. Neuroimaging detects brain changes during psychotic prodrome WHAT CAUSES PSYCHOTIC CONVERSION? Reduced gray matter volumes in certain educed gray matter volumes in certain brain brain regions may be associated with con- Rregions may be associated with conversion to version to psychosis (Box 1). Stress also may psychosis. Imaging studies have found medial play a role; elevated stress-reactive cortisol temporal lobe changes—specifically, hippocampal volume alterations—in persons with schizophrenia, levels are associated with positive symptom genetic high-risk groups, and those thought to be at 1 severity in the prodrome. Other factors risk for imminent psychosis.11 being investigated include obstetric compli- MRI imaging of patients with prodromal signs has cations at birth, maternal age >30, premor- shown less gray matter in the right medial temporal, bid schizotypal personality disorder, and lateral temporal, inferior frontal cortex, and bilateral impaired olfaction. cingulate regions in those who have developed Symptoms. Nearly 80% of patients with psychosis, compared with those who have not. schizophrenia experience a psychotic pro- In the psychotic patients, 12-month longitudinal drome that lasts a few months to several follow-up has found reduced gray matter in the left hippocampal, fusiform, orbitofrontal, cerebellar 2 years. Common features include: cortices, and cingulate gyrus.12 • gradual worsening of perceptual dis- Brain structure is related to genetic liability turbance for schizophrenia in high-risk patients, who seem to • referential thinking have smaller right and left prefrontal lobes and smaller • paranoia right and left thalami. These findings are consistent • mild cognitive deficits with the prodrome’s neurocognitive deficits, which • mood lability are less than those reported in schizophrenia and • impulsivity greater than those seen in healthy subjects. • suicidality • declining social function and acade- mic performance.3,4 predict outcome. A longer prodrome is thought to Patients with these symptoms may be at immi- indicate a poor prognosis,6 such as in patients nent risk; if untreated, an estimated 40% progress to who wait a year before seeking treatment.7 A schizophrenia within 1 year.5 review of 22 studies of first-episode psychosis A premorbid phase often precedes the pro- found early psychosocial and pharmacologic drome, with symptoms such as impaired atten- interventions improved long-term prognosis, and tion, soft neurologic signs, and subtle social medication discontinuation predicted more- deficits. These changes may be harbingers of the severe and chronic disease.8 prodrome but are too nonspecific to be diagnos- Genetic risk. Schizophrenia has a strong genetic tic. Other functional impairments—including predisposition, although not everyone in the anxiety, depression, drug abuse, and psychosocial genetic high-risk group develops schizophrenia. factors such as school stress—may mimic schizo- Persons with a family history of schizophrenia phrenic prodrome. have a 10% to 20% risk of psychotic conversion.9 Prognosis. Studies of patients’ first schizophrenia Pioneering work by McGorry et al10 identi- episodes suggest that prodrome duration may fied an “ultra high-risk group” with a psychotic VOL. 4, NO. 3 / MARCH 2005 33 Psychotic prodrome Table 1 3 patient groups considered at ‘ultra high risk’ to develop schizophrenia Patients with… Symptoms Attenuated psychotic symptoms Overvalued ideas, perceptual disorders Present at least 1 week; not >5 years At least 1 symptom several times a week Brief intermittent psychotic episodes Frank psychotic features Resolve spontaneously within 7 days Can be drug-induced Genetic risk and recent deterioration syndrome Psychotic disorder in a first-degree relative Schizotypal personality disorder Present at least 1 month; not >5 years Significant functional decline Source: Adapted from reference 10 conversion rate of 40% to 60%. These patients • Bonn Scale for the Assessment of Basic present with three symptom patterns: Symptoms (BSABS): captures subtle • attenuated positive symptoms changes in thinking, feeling, and perception. • brief intermittent psychotic episodes • Schizophrenia Prediction Instrument for • genetic risk and recent deterioration syn- Adults (SPI-A): defines prepsychotic drome (Table 1). deviations and rates symptoms that are Early identification of these high-risk indi- subjectively experienced by the patient. viduals with perceptual distortions, frank psy- • Comprehensive Assessment of At Risk chotic symptoms, family history of psychosis, Mental State (CAARMS): defines ultra and schizotypal personality disorder may aid in high-risk criteria and incorporates eight early recognition and treatment. dimensions of psychopathology. The Edinburgh High Risk Study of 162 indi- • Scale of Prodromal Symptoms (SOPS): viduals ages 16 to 25 showed more marked psy- rates psychosis severity. When embedded chopathology in those with at least two close rel- within the Structured Interview for atives with schizophrenia, compared with con- Prodromal Syndromes (SIPS), the SOPS trol groups. A direct correlation was seen determines the presence or absence of psy- between genetic liability and poor neurocogni- chosis and predicts progression to psy- tive performance.11 chopathology. • Criteria for Prodromal Symptoms PRODROME RATING SCALES (COPS): defines ultra high-risk categories. Researchers are using outcome measures to diag- • Presence of Psychosis Scale (POPS): rates nose prodromal symptoms and assess their severity. severity, intensity, and duration of positive Operational, validated assessment tools include: prodromal symptoms.12 continued on page 37 34 Current VOL. 4, NO. 3 / MARCH 2005 p SYCHIATRY Current p SYCHIATRY continued from page 34 These instruments may identify pro- Table 2 dromal symptoms in psychiatric practice, Should you intervene with patients but further validation of clinical criteria in suspected psychotic prodrome? is needed before they could be recom- Arguments for: mended for routine patient assessment. • Early treatment may prevent psychosocial decline PROPHYLACTIC ANTIPSYCHOTICS? • Treatment may delay or ameliorate psychosis onset Atypical antipsychotics may be the stan- • Treatment may improve patient awareness dard of care for patients with a first psy- and acceptance of diagnosis chotic episode, but this intervention is • Antipsychotics are effective for symptoms based on few double-blind controlled trials. and may be neuroprotective Not surprisingly, only a handful of studies • Medications may improve overall outcome have examined antipsychotic therapy for • Neuroimaging findings may predict psychosis the prodrome’s less clear-cut symptoms. • Outcome scales have improved diagnosis Risperidone. An 8- to 12-week open-label • Treatment may reduce prodrome duration study in adolescents with first- and second- and improve prognosis degree relatives with schizophrenia13 Arguments against: included four prodromal and six first- episode psychosis patients who met criteria • Treatment would likely be given to persons for a cluster A personality disorder. who would not develop psychosis Risperidone, 1.0 mg/d and 1.8 mg/d, • Treatment would unnecessarily stigmatize individuals respectively, improved thought disorder who do not have schizophrenia and attention symptoms, as measured with • Exposing patients with uncertain diagnoses the Child Behavior Checklist. Verbal to treatment risks is an ethical dilemma memory improved minimally, and no • Antipsychotics are associated with side effects medication side effects were reported. • Psychotic prodrome studies are inconclusive, An open-label observational study14 with small sample sizes and short follow-up identified four middle-aged subjects • No biological markers exist to predict psychosis with a genetic risk of schizophrenia who reported negative symptoms and neu- rocognitive deficits. Risperidone, started at 0.25 ing antipsychotics, and supportive psy- mg/d and gradually increased to a maximum of 2 chotherapy mg/d, improved negative symptoms, attention, • or a specific preventive intervention (SPI) that and working memory. Mild side effects including included risperidone, 1 to 2 mg/d, and a mod- tremors,
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