DESCRIPTION
Risperidone is an atypical antipsychotic used to treat schizophrenia (including adolescent schizophrenia), schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in children with autism.
This drug belongs to a class of antipsychotic drugs known as atypical antipsychotics that have more pronounced serotonin antagonism than dopamine antagonism, but risperidone is unique in this class because it retains dopamine antagonism. It has high affinity for D2 dopaminergic receptors. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, 5-HT2A,linked to its antipsychotic action and relief of some of the extrapyramidal side effects (EPS) experienced with the typical neuroleptics. The EPS are a consequence of increased release of dopamine from nigrostriatal neurons in the brain.
CLASSIFICATION
- AA
- BB
INDICATIONS
PHARMACOKINETICS
MOLECULAR MECHANISM
PHARMACOGENOMICS
SIDE EFFECTS
- Risperidone-associated hyperprolactinemia. 2000
- To compare the prolactogenic effects of risperidone, clozapine, and typical antipsychotic agents in an outpatient community-based psychiatric population.
METHODS:
Prolactin and thyroid-stimulating hormone (TSH) concentrations were measured in 68 outpatients with schizophrenia who were receiving antipsychotic medications and were recruited from a community mental health clinic.
RESULTS:
The percentage of women with increased prolactin concentrations was significantly greater in the risperidone group (100%, 12 of 12 patients) than in the clozapine group (25%, 1 of 4) (P = 0.0071) but not in comparison with the typical antipsychotic agent group (83%, 5 of 6) (P = 0.333). The percentage of men with increased prolactin concentrations was significantly greater in the risperidone group (94%, 17 of 18) than in the clozapine group (18%, 3 of 17) (P<0.0001) and in comparison with the typical antipsychotic agent group (27%, 3 of 11) (P = 0.0003). The mean prolactin concentration (all ng/mL +/- standard deviation) was also significantly higher in patients taking risperidone (women, 125.0 +/- 56.6; men, 37.3 +/- 23.9) than clozapine (women, 22.0 +/- 25.9; men, 13.3 +/- 22.4) (female patients, P = 0.0004; male patients, P<0.0001) or typical antipsychotic agents (women, 69.0 +/- 59.8; men, 13. 3 +/- 9.1) (female patients, P = 0.036; male patients, P = 0.0003). In the risperidone group, gender affected prolactin level, with women having higher concentrations than men, but the duration of therapy did not. In this group, prolactin was inversely dependent on age. No difference was noted in TSH concentrations between medication groups.
CONCLUSION:
Risperidone is a potent inducer of hyperprolactinemia in outpatients with schizophrenia in a community population. The higher and more frequently increased prolactin concentrations caused by risperidone could adversely affect patient health and compliance.
TOXICITY
RESISTANCE
DEPENDENCE AND WITHDRAW
Glutamatergic dysfunction in schizophrenia: from basic neuroscience to clinical psychopharmacology, 2008
- The underlying cellular mechanisms leading to frontal cortical hypofunction (i.e., hypofrontality) in schizophrenia remain unclear. Both hypoactive and hyperreactive prefrontal cortical (PFC) states have been reported in schizophrenia patients. Recent proton magnetic resonance spectroscopy studies revealed that antipsychotic-na�ve patients with first psychotic episode exhibit a hyperactive PFC. Conversely, PFC activity seems to be diminished in patients chronically exposed to conventional antipsychotic treatments, an effect that could reflect the therapeutic action as well as some of the impairing side effects induced by long-term blockade of dopamine transmission. In this review, we will provide an evolving picture of the pathophysiology of schizophrenia moving from dopamine to a more glutamatergic-centered hypothesis. We will discuss how alternative antipsychotic strategies may emerge by using drugs that reduce excessive glutamatergic response without altering the balance of synaptic and extrasynaptic normal glutamatergic neurotransmission. Preclinical studies indicate that acamprosate, a FDA approved drug for relapse prevention in detoxified alcoholic patients, reduces the glutamatergic hyperactivity triggered by ethanol withdrawal without depressing normal glutamatergic transmission. Whether this effect is mediated by a direct modulation of NMDA receptors or by antagonism of metabotropic glutamate receptor remains to be determined. We hypothesize that drugs with similar pharmacological actions to acamprosate may provide a better and safer approach to reverse psychotic symptoms and cognitive deficits without altering the balance of excitation and inhibition of the corticolimbic dopamine-PFC system. It is predicted that schizophrenia patients treated with acamprosate-like compounds will not exhibit progressive cortical atrophy associated with the anti-dopaminergic effect of classical antipsychotic exposure.
Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract administration in mice. M2017":https://www.ncbi.nlm.nih.gov/pubmed/29034440
- Curcumin is a major component of traditional turmeric (Curcuma longa) which has been reported to improve lipid and glucose metabolism and to decrease weight in obese mice.
