Bola, John R., Mosher, Loren R.

Treatment of acute psychosis without neuroleptics: two-year outcomes from the Soteria project

The Soteria project (1971- 1983) compared residential treatment in the community and minimal use of antipsychotic medication with \"usual\" hospital treatment for patients with early episode schizophrenia spectrum psychosis. Newly diagnosed DSM-II schizophrenia subjects were assigned consecutively (1971 to 1976, N = 79) or randomly (1976 to 1979, N = 100) to the hospital or Soteria and followed for 2 years. Admission diagnoses were subsequently converted to DSM-IV schizophrenia and schizophreniform disorder. Multivariate analyses evaluated hypotheses of equal or better outcomes in Soteria on eight individual outcome measures and a composite outcome scale in three ways: for endpoint subjects (N = 160), for completing subjects (N = 129), and for completing subjects corrected for differential attrition (N = 129). Endpoint subjects exhibited small to medium effect size trends favoring experimental treatment. Completing subjects had significantly better composite outcomes of a medium effect size at Soteria (+.47 SD, p =.03). Completing subjects with schizophrenia exhibited a large effect size benefit with Soteria treatment (+.81 SD, p =.02), particularly in domains of psychopathology, work, and social functioning. Soteria treatment resulted in better 2-year outcomes for patients with newly diagnosed schizophrenia spectrum psychoses, particularly for completing subjects and for those with schizophrenia. In addition, only 58% of Soteria subjects received antipsychotic medications during the follow-up period, and only 19% were continuously maintained on antipsychotic medications.

Journal of Nervous & Mental Disease, 191(4) : 219-29

vanBruggen, Johanna, Tijssen, Jans, Dingemans, Petrus, Gersons, Berthold, Linszen, Donald

Symptom response and side-effects of olanzapine and risperidone in young adults with recent onset schizophrenia

The symptom response and side-effects of olanzapine and risperidone were compared in patients with recent onset schizophrenia. Actively symptomatic patients (n=44) randomly received olanzapine 15 mg (median dose) or risperidone 4 mg (median dose). Symptom response and side-effects were measured during a 6-10-week treatment study. No major differences were observed between the two treatment groups. Symptoms improved significantly on the Positive and Negative Syndrome Scale total score, positive subscale and general psychopathology subscale for both treatment groups. Using five symptom dimensions, both drugs were effective in treating positive symptoms and agitation/excitement symptoms, and neither olanzapine or risperidone influenced disorganization and depression symptoms. Results on the negative symptoms subscale and symptom dimension were inconclusive. No major differences were found in the frequency of the reported side-effects akathisia, parkinsonism and weight gain. These data indicate that the differences between olanzapine and risperidone in symptom response are small. In spite of the relatively low power of the study, we could exclude the presence of substantially different treatment effects between olanzapine and risperidone.

International Clinical Psychopharmacology, 18(6) : 341-6

Woods, Scott W., Breier, Alan, Zipursky, Robert B., Perkins, Diana O., Addington, Jean, Miller, Tandy J., Hawkins, Keith A., et-al

Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome.

BACKGROUND: The prodromal phase of schizophrenic disorders has been described prospectively. The present study aimed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo. METHODS: This was a double-blind, randomized, parallel-groups, placebo-controlled trial with fixed-flexible dosing conducted at four sites. Sixty patients met prodromal diagnostic criteria, including attenuated psychotic symptoms, as determined by structured interviews. Olanzapine 5-15 mg daily or placebo was prescribed for 8 weeks. RESULTS: In the mixed-effects, repeated-measures analysis, the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant, and post hoc analyses revealed that the olanzapine-placebo difference reached p<.10 by week 6 and p<.05 at week 8. Ratings of extrapyramidal symptoms remained low in each group and were not significantly different. Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients (p<.001). CONCLUSIONS: This short-term analysis suggests olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients. Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo. Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment.

Biological Psychiatry, 54(4) : 453- 64

Castilla, R.

Early medication intervention in the treatment of psychosis in children (Conference abstract)

International Journal of Neuropsychopharmacology, 5(Suppl 1) : S51

McGorry, Patrick D., Yung, Alison R., Phillips, Lisa J., Yuen, Hok Pan, Francey, Shona, Cosgrave, Elizabeth M., Germano, Dominic, Bravin, Jenny, McDonald, Tony, Blair, Alison, Adlard, Stephen, Jackson, Henry

Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms

BACKGROUND: Most disability produced by psychotic illnesses, especially schizophrenia, develops during the prepsychotic period, creating a case for intervention during this period. However, only recently has it been possible to engage people in treatment during this phase. METHODS: A randomized controlled trial compared 2 interventions in 59 patients at incipient risk of progression to first-episode psychosis. We termed this group ultra-high risk to emphasize the enhanced risk vs conventional genetic high-risk studies. Needs-based intervention was compared with specific preventive intervention comprising low- dose risperidone therapy (mean dosage, 1.3 mg/d) and cognitive behavior therapy. Treatment was provided for 6 months, after which all patients were offered ongoing needs-based intervention. Assessments were performed at baseline, 6 months, and 12 months. RESULTS: By the end of treatment, 10 of 28 people who received needs-based intervention progressed to first-episode psychosis vs 3 of 31 from the specific preventive intervention group (P=.03). After 6-month follow-up, another 3 people in the specific preventive intervention group became psychotic, and with intention-to-treat analysis, the difference was no longer significant (P=.24). However, for risperidone therapy-adherent patients in the specific preventive intervention group, protection against progression extended for 6 months after cessation of risperidone use. CONCLUSIONS: More specific pharmacotherapy and psychotherapy reduces the risk of early transition to psychosis in young people at ultra-high risk, although their relative contributions could not be determined. This represents at least delay in onset (prevalence reduction), and possibly some reduction in incidence.

Archives of General Psychiatry, 59(10) : 921-8

Merlo, Marco C. G., Hofer, Helene, Gekle, Walter, Berger, Gregor, Ventura, Joseph, Panhuber, Ingrid, Latour, Gabriela, Marder, Stephen R.

Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: treatment efficacy and effects on fine motor functioning

BACKGROUND: The aim of this study was to examine differences in the improvement of clinical psychopathology and in fine motor functions at 2 doses of risperidone in first-episode, acutely psychotic patients. METHOD: In a double-blind, fixed-dose study, 49 acutely psychotic, neuroleptic-naive patients who were admitted for the first time and who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder were randomly assigned to 2 or 4 mg/day of risperidone. Treatment efficacy was measured using the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, The Clinical Global Impressions scale, and the Social and Occupational Functioning Assessment Scale. Fine motor functions were assessed using a computerized device (the Vienna Test System) and were compared with those of a control group of 20 healthy subjects who were matched for age, gender, and educational level. RESULTS: Treatment with doses of 2 and 4 mg of risperidone daily significantly reduced positive (p < .0001) and negative (p < .01) symptoms at 8 weeks. Although there were no significant differences in motor movements as measured using the Barnes Akathisia Scale and the Simpson-Angus Scale, computerized fine motor assessment showed significantly less motor dysfunction in the 2-mg/day group at 8 weeks. No significant correlations to plasma concentration of active moiety were found for data on psychopathology and fine motor functions. CONCLUSION: The 2 doses of risperidone did not differ in terms of clinical improvement, but the 2-mg/day dose produced fewer fine motor dysfunctions. These results suggest that a dose as low as 2 mg/day of risperidone may be effective for patients with first-episode psychosis.

Journal of Clinical Psychiatry, 63(10) : 885-91

Lenior, Marie E., Dingemans, Peter M., Schene, Aart H., Hart, Augustinus A., Linszen, Don H.

The course of parental expressed emotion and psychotic episodes after family intervention in recent-onset schizophrenia. A longitudinal study

The stability of parental expressed emotion (EE) is analysed over about 9 yrs, and related to course of illness in patients (aged 15- 26 yrs at intake) with recent-onset schizophrenia in The Netherlands. Families, who participated in a 15-mo intervention, were randomised over two intervention conditions. Psychotic episodes were measured over 5 yrs after discharge. The Five Minute Speech Sample (FMSS) EE was elicited 2 times during the 12-mo outpatient intervention and 2 times over 8 yrs after discharge on average. EE is expressed as criticism/dissatisfaction (CRIT), emotional overinvolvement (EOI), and as the classical dichotomous index. EE is not stable over the years. Intervention condition had no differential effect on EE as measured with CRIT and the dichotomous index. For EOI, an interaction between intervention condition and time was found. EE as assessed during intervention does not predict psychotic episodes during follow-up. An association was found between psychotic episodes and CRIT as assessed at 34 mo after discharge. Family intervention may inhibit the development of high EOI for a limited period. Our results may be in support of the hypothesis that psychotic episodes in patients can affect the critical attitude in parents. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Schizophrenia Research, 57(2-3) : 183-190

Lenior, M. E., Dingemans, P. M., Linszen, D. H., deHaan, L., Schene, A. H.,

Social functioning and the course of early-onset schizophrenia: Five-year follow-up of a psychosocial intervention

BACKGROUND: Schizophrenia implies severe social impairments. Since the treatment of patients with schizophrenia shifted from long-term hospital admissions to community services, research on social functioning has become increasingly important. AIMS: Follow-up assessment of social functioning in young patients with schizophrenia during a 5-year period after intervention. METHOD: During intervention, families were randomised into two conditions: standard intervention and standard plus family intervention. RESULTS: Although no differential treatment effect with regard to the course of the illness was found, patients from the standard plus family intervention condition stayed for fewer months in institutions for psychiatric patients than patients from the standard intervention condition. CONCLUSIONS: Family intervention has helped parents to support their children, thereby diminishing institutional care.

British Journal of Psychiatry, 179 : 53-8

Emsley, R. A., RisperidoneWorkingGroup

Risperidone in the treatment of first episode psychotic patients: A double blind multicenter study

An international, multicenter, double-blind study was conducted in 183 patients with a first psychotic episode (provisional schizophreniform disorder or schizophrenia; DSM-III-R) treated with flexible doses of risperidone or haloperidol for 6 weeks. At endpoint, 63 percent of risperidone-treated patients and 56 percent of haloperidol-treated patients were clinically improved (> or = 50% reduction in Positive and Negative Syndrome Scale total scores). Risperidone was better tolerated than haloperidol: the severity of extrapyramidal symptoms was significantly lower in the risperidone-treated patients; significantly fewer risperidone-treated patients required antiparkinsonian medication; and significantly fewer discontinued treatment because of adverse events. A post hoc analysis revealed that low doses of these antipsychotics were efficacious in some patients. Furthermore, the severity of extrapyramidal symptoms and the use of antiparkinsonian medications were significantly lower in patients receiving low doses (maximum, < or = 6 mg/day) than high doses (maximum, > 6 mg/day) of risperidone or haloperidol. These findings are consistent with the suggestion that patients with a first psychotic episode may require low doses of antipsychotic medications. Studies designed specifically to compare low and high doses of antipsychotics are warranted to help optimize treatment for these patients.

Schizophrenia Bulletin, 25(4) : 721-9

Linszen, D. H., Dingemans, P. M., Lenior, M. E., Scholte, W. F., Goldstein, M.

Early family and individual interventions and relapse in recent-onset schizophrenia and related disorders

The present study was designed to test the effectiveness of delivering two intervention programs with patients with recent onset schizophrenia and related disorders. The 76 patients in the study were young (mean age 20.5 SD 2.5). Overall relapse rates during the two intervention programs were low (16%). Adding a family intervention to the standard intervention did affect the relapse rate. Patients from low EE families relapsed slightly more in the intervention group with additional behavioral family therapy. Behavioral family intervention in low EE families may increase stress, thus influencing relapse. Inpatient family involvement may be a critical ingredient in successful individually oriented outpatient relapse prevention programs. Collaboration between professionals and relatives may form an optimal basis for extended continuity of care.

Italian Journal of Psychiatry & Behavioural Sciences., 8(2) : 77- 84

Ferrari, M. C. L., Elkis, H.

A six month trial of risperidone versus conventional neuroleptics in young patients with early onset schizophrenia conference abstracts

Schizophrenia Research, 1, 2(special) :

Nugter, A., Dingemans, P., VanDoes, J. W. D., Linszen, D., Gersons, B.

Family treatment, expressed emotion and relapse in recent onset schizophrenia

A controlled longitudinal treatment study was carried out to investigate the effect of a behavioral family treatment on Expressed Emotion (EE) and to examine the correspondence between EE changes and relapse rates. Subjects were 52 patients with recent onset schizophrenia or related disorders and their parents. After completion of inpatient treatment they were randomly allocated to individual treatment or individual treatment plus family treatment. The family treatment consisted of education and training in communication and problem-solving skills. Expressed Emotion was measured with the Five- Minute Speech Sample (FMSS). The findings show that family treatment did not have a significant positive effect on EE level. The dichotomous FMSS/EE did not systematically change and these findings were comparable with the results of prior EE research. A scoring system that included all subscores of the FMSS was somewhat more sensitive to changes. In the individual treatment condition relapse rates tended to co-occur with a change in FMSS/EE level, irrespective of the direction of this change.

Psychiatry Research., 72(1) : 23- 31