How long clinicians should wait before considering an antipsychotic ineffective and changing treatment in schizophrenia is an unresolved clinical question. Guidelines differ substantially in this ...regard. The authors conducted a diagnostic test meta-analysis using mostly individual patient data to assess whether lack of improvement at week 2 predicts later nonresponse.
The search included EMBASE, MEDLINE, BIOSIS, PsycINFO, Cochrane Library, CINAHL, and reference lists of relevant articles, supplemented by requests to authors of all relevant studies. The main outcome was prediction of nonresponse, defined as <50% reduction in total score on either the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) (corresponding to at least much improved) from baseline to endpoint (4-12 weeks), by <20% PANSS or BPRS improvement (corresponding to less than minimally improved) at week 2. Secondary outcomes were absent cross-sectional symptomatic remission and <20% PANSS or BPRS reduction at endpoint. Potential moderator variables were examined by meta-regression.
In 34 studies (N=9,460) a <20% PANSS or BPRS reduction at week 2 predicted nonresponse at endpoint with a specificity of 86% and a positive predictive value (PPV) of 90%. Using data for observed cases (specificity=86%, PPV=85%) or lack of remission (specificity=77%, PPV=88%) yielded similar results. Conversely, using the definition of <20% reduction at endpoint yielded worse results (specificity=70%, PPV=55%). The test specificity was significantly moderated by a trial duration of <6 weeks, higher baseline illness severity, and shorter illness duration.
Patients not even minimally improved by week 2 of antipsychotic treatment are unlikely to respond later and may benefit from a treatment change.
Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. ...Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce.
To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil.
A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider's perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated.
147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs.
Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially in low and middle income countries.
Abstract
Background
Poor social skills are a core characteristic of schizophrenia and are highly associated with the progression of negative symptoms. While positive symptoms have a good response to ...antipsychotics, the treatment of negative symptoms remains an unmet need.
Methods
A randomized controlled trial to assess the efficacy of a 20-week social skills training (SST) program for the improvement of negative symptoms in patients with treatment-resistant schizophrenia (TRS) with predominantly negative persistent symptoms, with a score > 4 (moderate) in at least 3 items of the Negative Symptom Factor Score (NSFS) (blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation and active social avoidance).
Each session lasted 60 minutes and included 6 to 9 participants. The SST sessions were conducted by trained psychologists, following topics previously outlined in a manual, and role-playing activities. The non-directive control group was conducted by nurses specialists in mental health, with the same duration but without role-playing activities. Control groups’ therapists were instructed not to give directions to the patients but to listen and redirect questions to the group.
TRS was defined as the persistence of psychotic symptoms after at least two adequate trials with two different antipsychotics, All patients were taking clozapine. Blinded raters evaluated the patients at baseline, 20 weeks and after 6 months follow-up by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) and the Social Skills Inventory (SSI). Longitudinal comparisons between groups were carried out using a linear mixed-effects model at pre, post and follow-up to assess differences between groups. Cohen’s d effect size was computed at each time point. Primary outcome measure was the PANSS negative subscale score.Social skill were assessed with the Social Skills Inventory.
Results
62 patients were randomized to SST (N=29) and control group (N=33). Subjects were predominantly male (70.96%) and single (88.70%). At baseline, groups showed no differences in terms of demographic variables and illness duration. Patients were moderately ill, with mean CGI = 4.10 (SD 0.78) in SST group and 4.34 (0.90) in the control group, and had a high baseline PANSS score, with a mean total PANSS 71.90 (10.83) in the SST group and 70.4 (13.8) in the control group. The mean PANSS negative subscale score was 25.48 (4.56) in SST group and 25.13 (6.34) in control group; in the SST group 28 patients completed the 20-week intervention and 24 were assessed after 6 months; in the control group, 18 completed the treatment and 16 were assessed at the follow-up. After the 20-week intervention period, the PANSS negative scores were 24.57 (4.92) in the SST group and 22.67 (6.59) in the control group. At the follow-up, the negative score was 23.92 (5.85) in the SST group and 22.97 (5.32) in the control. There was no improvement at any timepoint (p= 0.162) or any difference between groups (p= 0.864). Patients remained clinically stable during the study. The only symptom which showed a significant improvement was the control of aggressiveness (Cohen’s d at week 20 = 0.445 IC 95% -0.140; 1.030), which was maintained at follow-up (Cohen’s d = 0.682 IC 95% 0.037; 1.327).
Discussion
The study has limitations: the SSI was not designed to assess social skills in patients with psychosis, and we have not assessed the adherence to pharmacological treatment. Our findings suggest that SST is not effective to improve negative symptoms in patients with TRS with predominantly negative symptoms, but may be potentially useful for the control of aggressiveness in situations such as criticism and mockery, which frequently occur in social interactions.
•This randomized trial evaluated the efficacy of social skills training (SST) in improving negative symptoms in patients with treatment-resistant schizophrenia in comparison with a control group.•The ...patients were all taking clozapine and had predominantly negative symptoms.•SST was not efficacious for improvement of negative symptoms in patients with TRS with predominantly negative symptoms, but caution is required to interpret these results due to the study's limitations.
We conducted a randomized controlled trial to assess the effectiveness of social skills training (SST) in improving negative symptoms in patients with treatment-resistant schizophrenia with predominantly negative symptoms. Patients were randomized to receive SST (n = 29) or to a control group (n = 33), in a 20-week program with weekly group sessions. Patients were assessed at baseline, post-treatment (20 weeks) and 6-month follow-up with the Positive and Negative Syndrome Scale. There was no significant improvement in the negative symptoms in either group, at any timepoint. Caution is warranted to interpret the results due to small sample size.
Clozapine is considered the gold standard for the treatment of patients with treatment-resistant schizophrenia (TRS); however, randomized controlled trials (RCT) of olanzapine showed efficacy similar ...to clozapine in patients with TRS.
A systematic review was conducted comparing clozapine with olanzapine in patients with TRS. Meta-analyses were performed for single outcome measures. Response to treatment was measured by the percentage of responders, or mean change or endpoint values of psychotic symptoms scales. Effect sizes were shown as relative risks (RR), or standardized mean differences, with 95% confidence intervals.
Seven RCT were included, comprising 648 patients. Five meta-analyses were performed. Olanzapine and clozapine had similar effects on dropout rates (RR = 0.93, CI95% = 0.77-1.12), PANSS total endpoints (SMD = 0.21, CI95% = -0.04-0.46), and PANSS total mean changes (SMD = 0.08, CI95% = -0.01-0.027). Clozapine was superior to olanzapine for PANSS positive (SMD = 0.51, CI95% = 0.17-0.86) and negative (SMD = 0.50, CI95% = 0.16-0.85) subscales. There was a trend toward high doses of olanzapine producing higher effect sizes for this drug.
The results of this study suggest that clozapine is significantly more efficacious than olanzapine in improving positive and negative symptoms in TRS patients.
INTRODUÇÃO: Acredita-se cada vez mais que o tempo para se observar a resposta ao antipsicótico é curto, sendo possível nas primeiras duas semanas já prever se o paciente responderá em 12 semanas. ...Entretanto, a maior parte das evidências que sustentam tal hipótese provém da análise de dados de estudos controlados duplo-cegos, que não definiam o conceito de início de ação de antipsicóticos, o que pode gerar uma certa confusão quanto às expectativas de resposta. Neste estudo, testamos se a ausência de melhora mínima de 20% da PANSS nas primeiras duas semanas correlacionava-se a ausência de resposta em 12 semanas. MÉTODOS: Foi feita a avaliação do tempo de resposta ao tratamento antipsicótico, utilizando o algoritmo de tratamento do IPAP, que recomenda o uso de monoterapia por 4 a 6 semanas, e troca por outro antipsicótico em caso de ausência de resposta. Os pacientes incluídos tinham esquizofrenia de início recente pelos critérios DSM-IV e foram aleatorizados para receber tratamento com antipsicótico de primeira geração (APG) ou de segunda geração (ASG). Foi considerada resposta ao tratamento a redução média de pelo menos 30% dos sintomas, em comparação com a PANSS inicial.Os pacientes foram avaliados pela PANSS a cada 2 semanas, durante 12 semanas. RESULTADOS: Foram incluídos 22 pacientes (APG, N=10 e ASG, N=12). Não houve diferença quanto ao tempo ou taxa de resposta entre os grupos; 20% (4) dos pacientes não responderam ao tratamento, enquanto 65% (13) responderam; 15% (3) abandonaram um tratamento. Um paciente não pôde ser avaliado pela PANSS e não teve seus dados incluídos na análise. Não houve correlação entre melhora nas primeiras 2 semanas e resposta em 12 semanas. A mudança média da 11 PANSS em relação ao basal foi significante a partir da 4a semana (p=0,43), e houve melhora progressiva ao longo das 12 semanas. Ambos os grupos tiveram a mesma proporção de substituições de medicamentos, sendo que não houve diferença, em termos de porcentagem de respondedores, entre os que trocaram o medicamento e entre os que permaneceram com a mesma medicação inicial. CONCLUSÕES: A ausência de resposta nas primeiras duas semanas não prediz ausência de resposta em 12 semanas. O tempo para avaliar a resposta clínica a um medicamento antipsicótico é de pelo menos quatro semanas. Aguardar o efeito do medicamento parece ser mais importante que trocar de medicamento nas primeiras 4 semanas
INTRODUCTION: It has been widely accepted that time to observe response to antipsychotic is short, with a response in 2 weeks predicting response or nonresponse in 12 weeks. However, most evidence for this hypothesis come from controlled doubleblind trials, which did not assess the onset of action, but clinical response, generating some false expectancies regarding clinical response. In this study, we assessed whether the lack of improvement in 2 weeks would predict nonresponse in 12 weeks. METHODS: We assessed time to response to antipsychotic through a treatment algorithm IPAP, which recommends monotherapy during 4-6 weeks and switch to another antipsychotic in case of nonresponse. Subjects with recent onset schizophrenia according to DSM-IV criteria were included and randomized to receive first generation antipsychotic (FGA) or second generation (SGA). Response was considered as at least 30% reduction of PANSS. Subjects were assessed every 2 weeks, during the 12-week study period. RESULTS: 22 subjects were included (FGA: 10; SGA: 12). There was no difference between groups in terms of response rate; overall 20% (4) did not respond in 12 weeks and 65% responded; 15% (3) dropped out. Data from one patient was not included in the analysis due to impossibility of assessment with PANSS. No correlation was found between response in 2 weeks and response in 12 weeks. Significant mean change at PANSS was observed in the fourth week (p= 0,43). The need for switch was similar in both groups, and improvement was progressive throughout the 12 weeks. Response rate was similar in the group that switched and the group that remained with first antipsychotic. CONCLUSIONS: Lack of response in 2 weeks does not predict lack 13 of response in 12 weeks. Time to assess clinical response é at least four weeks. Looking forward to drug effect seems to be more important for the outcome in 12 weeks than switching the drug in the first 4 weeks
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