The Effect of Clozapine on Cognition and Psychiatric Symptoms in Patients with Schizophrenia

Abstract

Psychiatric symptoms and cognition were assessed in 13 patients with schizophrenia, one patient with schizoaffective disorder, and one patient with psychosis not otherwise specified while they received a conventional neuroleptic and again after an average of 15 months on clozapine. Despite improvements in psychiatric symptoms, attention, memory, and higher-level problem-solving were essentially unchanged. This suggests that certain cognitive deficits are relatively independent of psychotic symptoms in schizophrenia, and are probably central and enduring features of the disorder. Cognitive disability appeared to have been rate-limiting in the sample's rehabilitation, as patients' social and vocational adjustment remained marginal during the study. We also observed that treatment with clozapine was associated with a decline in some memory functions; the potent anticholinergic properties of the drug may have been responsible for this.

Effects of Atypical Neuroleptics on Sustained Attention Deficits in Schizophrenia A Trial of Risperidone Versus Haloperidol

“…In this regard, the present study had the merits that it was conducted with a sufficient interval between assessments to avoid practice effects (Epstein et al 1996) and to assess within-subject changes in CPT performance across different states. Our finding that CPT performance is relatively independent of the severity of clinical symptoms is consistent with the most recently published studies using longitudinal designs with sufficient follow-up times and information processing paradigms (Cornblatt et al 1997;Epstein et al 1996;Finkelstein et al 1997;Goldberg et al 1993; Nuechterlein et al 1992). Furthermore, our results showed that the atypical neuroleptic risperidone did not improve patients' CPT performance.…”

“…Furthermore, our results showed that the atypical neuroleptic risperidone did not improve patients' CPT performance. This finding is similar to those of studies that used traditional neuroleptics, and is consistent with a previous study of the effects of clozapine on cognition (Goldberg et al 1993). Despite the equivalence in CPT performance at baseline and no significant change from baseline to endpoint for both the risperidone and haloperidol groups, the undegraded CPT dЈ of the risperidone group was better than that of the haloperidol group.…”

Reversal of Subchronic PCP-Induced Deficits in Attentional Set Shifting in Rats by Sertindole and a 5-HT6 Receptor Antagonist: Comparison Among Antipsychotics

“…Novel antipsychotic compounds (second-generation or 'atypical' antipsychotics) such as clozapine (Fitton and Heel, 1990), olanzapine (Fulton and Goa, 1997), and sertindole (Kane and Tamminga, 1997;Azorin et al, 2006) have some beneficial effect on negative symptoms and reduced potential to produce extrapyramidal side effects, but these agents have demonstrated inconsistent effects on cognitive function in patients with schizophrenia. Depending on the type of cognitive domain measured, second-generation antipsychotics have been reported to produce improvement (Mortimer 1997;Meltzer and McGurk, 1999;Keefe et al, 2007), no effect (Hoff et al, 1996;Meltzer and McGurk, 1999), and impairment (Goldberg et al, 1993). The effect of sertindole on cognitive function has not been investigated extensively; however, a small clinical trial indicates a beneficial effect on some cognitive substrates, including executive function, in individuals diagnosed with schizophrenia (Gallhofer et al, 2007).…”

Reversal of Clozapine Effects on Working Memory in Rats with Fimbria–Fornix Lesions

“…Some studies of people with schizophrenia have shown clozapine-induced cognitive improvements in attentional tasks (Gallhofer et al, 1996;Hagger et al, 1993;Lee et al, 1999;Manschreck et al, 1999;Meltzer and McGurk, 1999;Sharma and Mockler, 1998). Other clinical studies, however, have demonstrated clozapine-induced memory deficits (Goldberg et al, 1993;Goldberg and Weinberger, 1996). Furthermore, rodent studies have shown clozapine-induced memory impairments in intact rats Skarsfeldt, 1996).…”