Treating and Preventing Adolescent Mental Health Disorders: Treating and Preventing Adolescent Mental Health Disorders

Book Title: Treating and Preventing Adolescent Mental Health Disorders > pp. [120]-[124]

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Treating and Preventing Adolescent Mental Health Disorders

Print ISBN 9780195173642, 2005
pp. [120]-[124]

(McGlashan, 1996). Despite this, most individuals recover symptomatically from the first episode. However, most patients proceed to have one or more subsequent episodes in the form of psychotic relapses from which some proportion fail to recover, at least to the same degree as they had during their first or prior episode (Lieberman et al., 1993, 1996; Robinson et al., 1999a). This process of psychotic relapses, treatment failure, and incomplete recovery leads many patients to a chronic course of illness. Finally, persistent disturbances and deficits in perceptions, thought processes, and cognition affect development (Lieberman, 1999; McGlashan, 1988). In this way, patients accumulate morbidity in the form of residual or persistent symptoms and decrements in function from their premorbid status. The process of accruing morbidity in the context of exacerbations and (relative) remissions has been attributed to progression of the illness (Kraepelin, 1919) and described as “clinical deterioration” (Bleuler, 1980). Interestingly, the deterioration process occurs predominantly in the early phases of the illness, in the prepsychotic prodromal period and during the first 5 to 10 years after the initial episode (see Figure 5.1). For these reasons, early intervention is highly indicated. In this context, treatment serves two purposes: first, it is remedial for active symptoms of whatever level of severity or syndromal criteria; second, it may be preventive of the deterioration, which can occur and is the most devastating consequence of the illness. However, there are several challenges for treating patients optimally in the earliest stages of schizophrenia. First, patients usually do not seek (or are not brought in for) treatment until they have had the symptoms for often lengthy periods of time. Second, the symptoms by which persons in the prodromal stage and at imminent risk for psychosis are identified are not highly specific or sufficiently validated to use in clinical practice. Third, the optimal treatment agents and strategies for prodromal patients have not been determined. Fourth, patients in the prodromal stages and experiencing first episodes of schizophrenia are reluctant to take medications for sustained periods of time, as they have limited insight into the nature of their illness and are sensitive to and often object to side effects.

Acute Treatment

There have been relatively few studies on first-episode schizophrenia and very few on patients in the prodromal phase. There are currently two published studies of controlled or standardized acute treatment of patients with prodromal symptoms of schizophrenia and eight published studies of controlled or standardized acute treatment of patients with first-episode schizophrenia (summarized in Tables 6.1 and 6.2; Emsley, 1999; Kopala et al., 1996; Lieberman et al., 1993; May, Tuma, Yale, Potepan, & Dixon, 1976; Sanger et al., 1999; Scottish Schizophrenia Research Group, 1987; Szymanski et al., 1994). From these data and those from some uncontrolled studies and secondary analyses, several principles can be suggested to provide guidance for the treatment of patients experiencing a first episode of schizophrenia and for future research on improving the standard of care for this critical stage of psychotic disorders. With such limited data available on the management of prodromal and first-episode schizophrenia, practice will be guided by a hybrid of clinical trials evidence, real-life studies, and clinical experience.

Dosing and Selection of Pharmacologic Agents for Early Stages of Schizophrenia

The pharmacology of treating the prodromal stages of schizophrenia and related psychotic disorders has not been sufficiently well developed. Many agents have been suggested (by theories of pathogenesis) as preventive agents for schizophrenia to be used in the prodromal stage. These include a wide variety of treatments (antioxidants, benzodiazepines, phospholipids, lithium and mood-stabilizers, antidepressants, glutamatergic and nicotinic agents, selective DRD 1, 3, 4 dopamine receptor antagonists, and antipsychotic drugs). For both prodromal and first-episode patients, if an antipsychotic drug is to be used, the general consensus is that this be one of the second-generation antipsychotic drugs (Addington, 2002; Bhana, Foster, Olney, & Plosker, 2001; Bustillo, Lauriello, & Keith, 1999; Green & Schildkraut, 1995; Lieberman, 1996; NICE, 2002; Sartorius et al., 2002). Currently,

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Table 6.1 Studies of Acute Treatment in Prodromal Stages of Schizophrenia

Reference	Population	Inclusion/Exclusion	Design/Protocol	Response Criteria	Response Rates
McGorry et al., 2002	59 patients at incipient risk of progression to first-episode psychosis (“high risk”)	Ages 14–30, living in Melbourne metropolitan area; met criteria for 1 or more of 3 operationally defined “high-risk” categories	Single-blind, randomized, controlled trial with blinded interviews. Subjects were randomized to need-based intervention (according to presenting or existing problems) and specific preventive intervention, which included 1–2 mg risperidone and a modified CBT.	Progression to psychosis at 6 months (postintervention) and 12 months (follow-up) after study entry, defined by a predetermined threshold of positive symptoms sustained for 1 week or more (based on BPRS and comprehensive assessment of symptoms and history)	Needs-based intervention: 36% postintervention, 36% at 12 months Specific prevention intervention: 10% postintervention, 19% at 12 months
Woods et al., 2002	60 patients from 4 North American centers diagnosed by means of the Structured Interview for Prodromal Symptoms	Not available in published abstract	Randomized to 5–15 mg olanzapine daily or placebo	SOPS at 8 weeks; weight gain	Olanzapine: least-squares SOPS mean = −14.0 ± 3.3 versus −2.1 ± 3.4. Olanzapine patients gained significantly more weight (p = .001).

BPRS, Brief Psychiatric Rating Scale; CBT, cognitive behavior therapy; SOPS, Scale of Prodromal Symptoms.

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Table 6.2 Studies of Acute Treatment in First-Episode Schizophrenia

Reference	Population	Inclusion/Exclusion	Design/Protocol	Response Criteria	Response Rates
May et al., 1976	228 patients selected from consecutive admissions to a state psychiatric hospital between 1959 and 1962	Inclusions: first-admission patients with diagnosis of schizophrenia and “no significant prior treatment” Exclusions: those judged unlikely to be discharged and those who remitted fairly quickly (within 18 days)	Randomization to either individual psychotherapy, trifluoperazine, psychotherapy in combination with trifluoperazine, electroconvulsive therapy, or milieu therapy only	Release from hospital after a “fair trial” (6–12 months) of the assigned treatment	Individual psychotherapy (65%), trifluoperazine (96%), psychotherapy in combination with trifluoperazine (95%), ECT (79%), and milieu therapy only (58%)
Scottish Schizophrenia Research Group, 1987	46 patients with first-episode schizophrenia admitted to hospital	Inclusion: diagnosis of first-episode criteria on clinician's ICD-9	5-week, double-blind, randomized trial of flupenthixol versus pimozide Adjunctive medications allowed	“Responders”: able to enter maintenance treatment on their assigned drug therapy “Non-responders”: those who received further treatment, either ECT or another antipsychotic “Non-completers”: those who did not proceed to maintenance therapy but were clearly not “non-responders”	63% were “responders” overall Positive symptoms improved significantly (p < .01) for both drugs during the study period, but negative symptoms did not change
Lieberman et al., 1993; Robinson et al., 1999b	70 RDC-diagnosed patients with schizophrenia (N = 54) and schizoaffective disorder (N = 16)	1.No prior psychotic episodes 2.Age 16–40 years 3.No history of neurological or general medical illness that could influence diagnosis or biological variables being studied	Open, prospective study using a standardized antipsychotic protocol of sequential trials until response criteria were met with fluphenazine, haloperidol, molindone, and clozapine	Operationally defined as a CGI rating of “much” or “very much” improved and a rating of mild or less on specified SADS-C+PDI items with response sustained for at least 8 weeks	83% of patients remitted by 1 year with mean and median times to remission of 35.7 and 11 weeks, respectively
Szymanski et al., 1994	10 patients in the Lieberman et al. (1993) study	Patients in the above study who had failed treatment with a standardized protocol of 3 typical antipsychotics	After a 2-week washout period, patients were treated for 12 weeks on clozapine	20% reduction in BPRS score and a CGI severity of illness score of ≤3	30% (3 of 10)
Kopala et al., 1996	22 neuroleptic naive patients consecutively admitted for the first time; mean age of 25 years	DSM-IV diagnosis of a first episode of schizophrenia	Open trial of risperidone monotherapy for a mean duration of treatment was 7.1 weeks (SD = 3.2, range 1.8–14.1). Benzotropine for EPS and lorazepam or clonazepam for insomnia were the only adjunctives allowed.	20% reduction in total PANSS score	59% Negative symptoms improved less than positive symptoms.
Sanger et al., 1999	83 first-episode patients out of 1,996 patients enrolled in a multicenter trial of olanzapine versus haloperidol in psychotic disorders	1.First episode of psychosis with a DSM-II-R diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder 2.Duration of episode of <5 years 3.No more than 45 years old at episode onset 4.Minimum BPRS score of 18 or intolerant to current antipsychotic therapy	6-week, double-blind, randomized trial of olanzapine (N = 59) or haloperidol (N = 24) at mean modal doses of 11.6 (SD = 5.9) and 10.8 (SD = 4.8) mg/day, respectively	Defined a priori as a ≥40% reduction in total BPRS from baseline, also calculated for a 20% reduction	40% BPRS reduction in total BPRS: olanzapine 67.2% response rate, haloperidol 29.2% (Fisher's exact p = .003) 20% BPRS reduction: olanzapine 82.8% response rate, haloperidol 58.3% (Fisher's exact p = .03)
Emsley, 1999	183 patients recruited in multiple international sites	1.Ages 15–40 years 2.Diagnosis of provisional schizophreniform disorder or schizophrenia according to DSM-III-R 3.No prior treatment beyond 3 days of emergency antipsychotics 4.No clinically relevant medical abnormalities	6-week, double-blind study of risperidone versus haloperidol 2–16 mg/day Antiparkinsonian drugs or benzodiazepines administered only if essential	50% improvement in total PANSS scores was defined a priori as clinical response	Risperidone: 63% response rate Haloperidol: 56% response rate
Yap et al., 2001	24 patients recruited from Woodbridge Hospital and Geylang Psychiatric Outpatient Clinic	Previously untreated male and female patients aged 18–65 with DSM-IV schizophreniform disorder or DSM-IV schizophrenia for no longer than 12 months	Open-label, 8-week study of risperidone	20% reduction in total PANSS score, response for 50% reduction in total PANSS score was also calculated	Responder rate (≥20% reduction in total PANSS score) was 87.5% 13 patients (54.2%) exhibited ≥50% reduction in total PANSS score
Lieberman, Gu, et al., 2003	160 Chinese patients in first-episode schizophrenia	1.Ages 16–45 years 2.Diagnosis of provisional schizophreniform disorder or schizophrenia according to DSM-IV 3.No prior antipsychotic treatment 4.No clinically relevant medical abnormalities	52-week, double-blind RCT of clozapine and chlorpromazine and trihexyphenidyl
Lieberman, Tollefson, et al., 2003	263 patients recruited from 14 sites in N. America and W. Europe	1.Ages 16–40 years 2.Diagnosis of provisional schizophreniform disorder, schizophrenia, or schizoaffective disorder according to DSM-IV 3.Prior lifetime treatment <16 weeks 4.No clinically relevant medical abnormalities	12-week, acute treatment results of 2-year double-blind RCT of olanzapine (5–15 mg/day) and haloperidol (2–20 mg/day). Antiparkinsonian drugs or benzodiazepines administered only if essential	Total PANSS response defined as 30% reduction of PANSS and CGI severity <4 (moderately ill)	Significantly greater reduction in total PANSS and PANSS Negative Scale with olanzapine on mixed models but not LOCF analysis 55% of olanzapine and 46% of haloperidol met response criteria by week 12

BPRS, Brief Psychiatric Rating Scale; CGI, Clinical Global Impression; ECT, electroconvulsive therapy; LOCF, last-observation-carried-forward; PANSS, Positive and Negative Syndrome Scale for schizophrenia; RCT, randomized control trial; RDC, Research Diagnostic Criteria; SADS-C+PDI, Schedule for Affective Disorders and Schizophrenia Change Version with Psychosis and Disorganization Items rating scale; SD, standard deviation.

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doi:10.1093/9780195173642.003.0007