Sustained long-term improvement with clozapine in schizophrenia

Abstract

SUMMARY -The present paper reports the long-term use of clozapine in a prospective sample of 46 chronic schizophrenics. In six months, 21 subjects had been excluded for a number of reasons. In four of them the reasons for exclusion were related to lack of response or adverse effects. The median daily clozapine dose was 400 mg in the remaining 25 patients. As a whole, there were remarkable improvements in core dimensions of psychopathology, global cognitive status, and level of functioning. We confirmed that clozapine is effective in a subgroup of schizophrenics with the severest forms of the disease. If tolerated after the first few months it leads to progressive gains in several domains of behavior. Clozapine should be tried in every patient with schizophrenia in whom positive symptoms, disorganization, or bizarre behavior are a matter of incapacitation despite efforts to keep them under control with other drugs.KEY WORDS: clozapine, schizophrenia, psychosis, psychopathology. Clozapina na esquizofrenia grave: melhora duradoura e sustentadaRESUMO -O presente estudo, prospectivo, relata o uso de longo-prazo da clozapina em 46 esquizofrênicos graves, com mais de cinco anos de doença. Com seis meses de uso da droga, 21 indivíduos haviam sido excluídos por diversas razões. Em quatro, a exclusão se deveu a efeitos adversos ou ausência de resposta. A dose mediana de clozapina foi de 400 mg nos demais 25 pacientes. No todo, observamos melhora em dimensões de psicopatologia, estado cognitivo global, e nível funcional. Concluímos que a clozapina é eficaz em um subgrupo de esquizofrênicos com formas graves da doença. Se tolerada depois dos primeiros meses, produz benefícios progressivos em diversos domínios do comportamento. Clozapina deve ser tentada em todo paciente com esquizofrenia incapacitado por sintomas positivos, desorganização, e/ou comportamentos bizarros, que persistem a despeito de esforços para mantê-los sob controle com outras drogas.

Clozapine for severe ("kraepelinian") schizophrenia: Sustained improvement over 5 years

“…In a previous article we reported our experience with the first 6 months of treatment of schizophrenia using clozapine. 4 The results of this earlier study were in strong agreement with those involving larger series of patients. For example, one of the first studies on the time for clozapine response in a series of 50 patients with refractory schizophrenia showed that those who eventually improved, i.e., 68% of patients, did so within the first 8 weeks of treatment.…”

“…Previous work by the authors 4 and others 18 , 19 has indicated that clozapine promotes a noticeable improvement in patients with severe schizophrenia by the end of 6-12 months. The present investigation further indicates that, following this initial response, an enduring period of clinical stability ensues which does not seem to appreciably change in the long-term ( Figure ).…”

Risk of readmission in patients with schizophrenia and schizoaffective disorder newly prescribed clozapine

“…Despite these safety concerns, studies have reported that clozapine is associated with a decreased mortality risk, compared with other antipsychotics (Hayes et al, 2014; Wimberley et al, 2017). There are also corresponding improvements in symptoms and functioning (De Oliveira-Souza et al, 1999; Wahlbeck et al, 2009), which are the ideal measures of assessing the efficacy of clozapine, in accordance to usual clinical practice.…”

The dementias of schizophrenia

“…The main neuropsychological pattern is characterized by impairments in attention, executive performance, learning and memory with relative sparing of verbal knowledge and complex visual perception. 32 Major challenges for future studies include (i) a better understanding of the patterns of dementia and cognitive impairments in schizophrenia, 43 and (ii) how they relate to psychopathological status, (iii) how they adversely affect socio-occupational functioning, (iv) how they may differentially respond to pharmacological and cognitive-behavioral treatment, 44 and (v) how schizophrenia can improve our understanding about the cerebral organization presiding the human mind and behavior. 45 …”