Effectiveness of rivastigmine on positive, negative, and cognitive symptoms of schizophrenia: a double-blind clinical trial

Abstract

Background: Several lines of evidence suggest that the cholinergic system may be disrupted in schizophrenia and so this may contribute to the cognitive impairments of schizophrenic patients. Because such deficits do not respond to neuroleptic treatment, different approaches have been done by acetylcholinesterase inhibitors (AChEIs). The objective of the present assessment was to evaluate the safety and clinical effects of rivastigmine, as an adjunctive drug, on the clinical symptoms of schizophrenia. Methods: A total of 46 patients with a diagnosis of schizophrenia entered into a 12-week, double-blind, clinical trial for random assignment to rivastigmine or placebo, as adjuvant to their current antipsychotic medication. Positive and Negative Symptom Scale (PANSS) and Mini Mental State Examination (MMSE) had been used as the primary outcome measures. Clinical Global Impressions-Improvement (CGI-I) Scale and Extrapyramidal Symptom Rating Scale (ESRS) had been used as the secondary measures. Treatment efficacy was evaluated by a Student's t test and repeated-measures analysis of variance (ANOVA). Statistical significance was defined as a two-sided p value ⩽ 0.05. Cohen's standard (d) and correlation measures of effect size (r) had been calculated for comparing baseline to endpoint changes. Results: According to the findings, except for significant enhancement of MMSE by rivastigmine (p < 0.001), no significant improvement in PANSS (negative symptoms), PANSS (positive symptoms), and PANSS (general psychopathology) was evident in the target group. Also, except for significant improvement of CGI-I by rivastigmine in intragroup analysis, no significant effectiveness was evident in between-group analysis or repeated-measures ANOVA. ESRS, also, did not show any significant alteration in either group. Effect size (ES) analysis showed a large improvement in MMSE by rivastigmine. Conclusions: According to the findings, while rivastigmine could not induce significant improvement of positive and negative symptoms of schizophrenia, it caused significant enhancement of cognitive function in this group of patients.

Effectiveness of clozapine, oxcarbazepine and rivastigmine combination in a bipolar disorder patient with initial cerebral atrophy

“…Rivastigmine is a cholinesterase inhibitor widely employed in the treatment of mild to moderate AD and PD, with a good efficacy in psychiatric symptoms frequently co‐occurring in these neurological disorders . In addition, scattered data would also suggest its possible use in visual hallucinations of schizophrenic patients …”

“…Clozapine is the prototype of second‐generation antipsychotics (SGAs) commonly used in refractory psychoses and BD, while oxcarbazepine is prescribed as mood stabilizer in resistant BDI, although controlled studies are meager . The combination of clozapine and rivastigmine is considered as an effective symptomatic treatment in neurodegenerative disorders characterized by a possible underlying decreased functioning of the cholinergic system, such as PD, AD and LBD, and even schizophrenia, but not considered a conventional intervention in BDI. The present paper reports the positive response of a patient suffering from BDI with mixed features and fronto‐temporal atrophy treated with an association of clozapine, oxcarbazepine, and rivastigmine.…”

The role of nicotinic cholinergic neurotransmission in delusional thinking

“…Consequently, a hypocholinergic state would be expected to slow belief updating (as in delusional belief) and an increase in cholinergic tone would improve it, as shown with galantamine 191 . Acetylcholinesterase inhibitors (which increase ACh neurotransmission) have been used off-label to improve cognition in schizophrenia [192][193][194][195] . The obvious inference is that the decreased cholinergic neurotransmission, consistent with what is seen in α7 nAChR loss-of-function mutations in animal models, would result in decreased ability to adapt to environments based on predictability and consistent low weight placed on unexpected data in predictable environments, relative to topdown beliefs.…”

Natural Corynanthe-Type Cholinesterase Inhibitors from Malaysian Uncaria attenuata Korth.: Isolation, Characterization, In Vitro and In Silico Studies

“…Cholinesterase inhibitors block the action of cholinesterase, increasing acetylcholine availability and, subsequently, its duration of action in the brains of AD patients, which is essential for arousal, attention, learning, memory, muscle activation, etc. [ 9 , 10 ]. Nonetheless, cholinesterase inhibitors are symptomatic treatments that neither halt the disease course nor reverse the disease progression [ 11 , 12 ].…”