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

Abstract Clozapine has become a keystone in the treatment of schizophrenia because of its efficacy as an antipsychotic with negligible neuroleptic effects. The long-term stability of its effects, however, is poorly understood, because most studies have probed the usefulness of clozapine over a period of weeks to several months at the most. Knowing whether clozapine's benefits are sustained over the very long-term, i.e., more than 5 years, may be critical for cost-benefit analyses. Objective: To report the results of an open study on the efficacy of clozapine over the very long-term. Methods: Thirty-three adults (26 men) with severe (kraepelinian) schizophrenia were assessed at regular intervals using a brief neuropsychiatric battery over a 5-year period. Results: A significant improvement was observed between the pre-clozapine and the first "on-clozapine" evaluation. This improvement was paralleled by a remarkable conversion of schizophrenia from "active" (mostly paranoid) into "residual" in 70% of all patients. Eight patients became functionally productive to the point of being capable of living an independent life. Roughly one-third of our cases showed no improvement. Conclusions: Clozapine is a safe and effective drug for patients with severe schizophrenia who have failed to improve on other antipsychotic drugs. Clozapine's maximal benefit is established by the end of the first year of treatment and continues unabated for many years thereafter. Clozapine-resistant patients remain a major challenge calling for the discovery of new treatments for schizophrenia

The dementias of schizophrenia

Abstract Cases of "adolescent insanity" were known to Kraepelin's forerunners and lay at the core of his concept of dementia præcox. In the post-neuroleptic era it became clear that dementia may also occur in schizophrenia as a fully reversible state depending on psychopathological status. In the present review we discuss the validity of applying the concept of dementia to schizophrenia. We concur with the view that schizophrenia may lead to a true dementia both (i) as a fixed end-stage consequence of the disease process itself, or (ii) as a drug-responsive reversible state. There is an urgent need to examine the patterns of dementia in other common neuropsychiatric disorders, employing current methods of neurobehavioral investigation

Dissociation of depression from apathy in traumatic brain injury: A case report

ABSTRACT Although not evident clinically, lesions to the prefrontal cortex cause great social and functional impairment to patients. The anterior cingulate cortex is intimately involved with motivational behavior and after injury to this area the onset of an apathetic state can be observed. This paper describes the case of a patient with traumatic brain injury to the prefrontal lobe presenting with a depressive syndrome associated with apathetic symptoms. After appropriate treatment for depression, intense apathy was revealed, an irreversible sequelae of the traumatic brain injury, constituting the main barrier to the patient's return of lifestyle and independence

All that glitters is not gold: When motor and vocal tics in a child do not match Tourette syndrome: A case report

ABSTRACT The atypical form of Pantothenate Kinase-Associated Neurodegeneration (PKAN) tends to present at around the age of 14 years, has a heterogeneous presentation with extrapyramidal symptoms, and approximately one third of patients exhibit psychiatric problems. This paper reports the case of a patient with apparent typical symptoms of Tourette syndrome. However, the severity and poor response to treatment led to further investigation and the diagnosis of PKAN as a secondary cause of Tourettism was reached

Trail making and cognitive set-shifting

We tested the hypothesis that Part B of the Trail Making Test (TMT) is a measure of cognitive set-shifting ability in 55 normal subjects with the conventional (written) TMT and a verbal adaptation, the "verbal TMT" (vTMT). The finding of a significant association between Parts B of TMT and vTMT (r = 0,59, p < 0,001), after correcting for age and education, supports the view that Part B of TMT is a valid measure of the ability to alternate between cognitive categories

Sustained long-term improvement with clozapine in schizophrenia Clozapina na esquizofrenia grave: melhora duradoura e sustentada

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.<br>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