Reversal of Haloperidol-Induced Orofacial Dyskinesia and Neuroinflammation by Isoflavones

Schizophrenia is a serious mental illness, and its pharmacological treatment consists in the administration of antipsychotics, such as haloperidol. However, treatment with haloperidol often causes extrapyramidal motor disorders such as tardive dyskinesia (TD). TD is a movement disorder characterized by involuntary movements, which can be studied in animals. So far, there is no effective treatment for TD and alternatives have been sought. Thus, the objective was to evaluate the possible protective effect of isoflavones against the induction of involuntary movements induced by haloperidol in an animal model. Male Wistars rats were treated with haloperidol (1 mg/ kg/day) and/or isoflavones (80 mg/kg) for 28 days. Rats were submitted to behavioral evaluation to quantify vacuous chewing movements (VCM) and the locomotor activity. In addition, the levels of pro-inflammatory cytokines were measured in the striatum. Haloperidol treatment reduced the locomotor activity and increased the number of VCM in rats. Co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of VCM to the levels of the control group. Besides, haloperidol caused significant increase in the proinflammatory cytokines (interleukin-1β:IL-1β, tumor necrosis factor-α:TNF-a and IL-6 and the co-treatment with isoflavones was able to reduce the levels of IL-1β and TNF-α, but not IL-6. It is believed that the beneficial effect found with this treatment is related to their anti-inflammatory potential and also to the action on estrogen receptors (based on findings in the scientific literature). Finally, further studies are needed to elucidate the mechanisms of isoflavones in reducing motor disorders induced by antipsychotic.

Total Cholesterol Levels in Men with Schizophrenia Receiving Risperidone and Haloperidol Treatment

AIM: The objectives of the study were to compare total cholesterol levels in men with schizophrenia receiving risperidone and haloperidol treatment. METHODS: We conducted on treatment analysis experiment study involving 30 subjects who received risperidone and 30 subjects who received haloperidol. Total cholesterol levels were examined at week 0 and week 8. RESULTS: There were no statistically significant differences in baseline characteristics. At week 8, mean of total cholesterol level in the risperidone group was 207.23 ± 21.49 compared to 188.17 ± 17.00 in the haloperidol group. A difference of 19.06 ± 5.00 (95% CI 9.05–29.08) was observed, which is statistically significant (p < 0.001). CONCLUSIONS: There was a statistically significant increase in total cholesterol levels in men with schizophrenia receiving risperidone compared to haloperidol.

Neuroprotective Effect of Filgrastim in Animal Models of 3-Nitropropionic Acid & Haloperidol Induced Neurotoxicity in Rats

Movement disorders are the heterogeneous group of disorders characterized by the progressive and selective impairment in motor function. Movement disorders like Huntington's disease (HD) and Tardive dyskinesia (TD) share many common features at both cellular and subcellular levels. Filgrastim is a recombinant methionyl granulocyte colony-stimulating factor (GCSF), shows neuroprotective properties in in-vivo models of movement disorders. The present study was designed to evaluate the neuroprotective effect of filgrastimin the animal models of haloperidol and 3-NP induced neurotoxicity in rats. Study was divided in two different protocol, in study one, rats were administered with haloperidol for 21 days, and filgrastim at the dose of (20, 40 & 60 µg/kg,s.c.) was administered once a day, before haloperidol treatment and the following parameters (orofacial movements, rotarod, actophotometer) were assessed for TD. Similarly, in second study rats were administered with 3-NP for 21 days and filgrastimat the dose of (20 & 40 µg/kg, s.c.) was administered, and following parameters (rotarod, narrow beam walk and open field test) were assessed for HD. In each study, on 22nd day, animals were sacrificed, to isolate cortex and striatum for oxidative stress (LPO, GSH, SOD, catalase, and nitrate) parameters. The result revealed that haloperidol and 3-NP treatment significantly impaired motor coordination, oxidative defense and induce TD and HD like symptoms. Filgrastim pre-treatment significantly averted haloperidol & 3-NP induced behavioral and biochemical alterations, respectively. Conclusively, neuroprotective effect of filgrastim is credited to its antioxidant properties, hence filgrastim might be a novel therapeutic candidate to manage TD & HD.

Effect of 5-HT2A receptor antagonism on levels of D2/3 receptor occupancy and adverse behavioral side-effects induced by haloperidol: a SPECT imaging study in the rat

Several studies suggested that 5-HT2A receptor (5-HT2AR) blockade may provide a more favorable efficacy and side-effect profile to antipsychotic treatment. We hypothesized that a combined haloperidol (a D2/3 receptor (D2/3R) antagonist) and MDL-100,907 (a 5-HT2AR antagonist) treatment would reverse the side effects and the neurochemical alterations induced by haloperidol alone and would potentialize its efficacy. We thus chronically treated male Mdr1a knock-out rats with several doses of haloperidol alone or in combination with a saturating dose of a MDL-100,907. Receptor occupancy at clinically relevant levels was validated with a dual-radiotracer in-vivo SPECT imaging of D2/3R and 5-HT2AR occupancy. Experimental tests of efficacy (dizocilpine-disrupted prepulse inhibition (PPI) of the startle reflex) and side effects (catalepsy, vacuous chewing movements) were performed. Finally, a second dual-radiotracer in-vivo SPECT scan assessed the neurochemical changes induced by the chronic treatments. Chronic haloperidol failed to reverse PPI disruption induced by dizocilpine, whilst administration of MDL-100,907 along with haloperidol was associated with a reversal of the effect of dizocilpine. Haloperidol at 0.5 mg/kg/day and at 1 mg/kg/day induced catalepsy that was significantly alleviated (by ~50%) by co-treatment with MDL-100,907 but only at 0.5 mg/kg/day dose of haloperidol. Chronic haloperidol treatment, event at doses as low as 0.1 mg/kg/day induced a significant upregulation of the D2/3R in the striatum (by over 40% in the nucleus accumbens and over 20% in the caudate-putamen nuclei), that was not reversed by MDL-100,907. Finally, an upregulation of 5-HT2AR after chronic haloperidol treatment at a moderate dose only (0.25 mg/kg/day) was demonstrated in frontal cortical regions and the ventral tegmental area. Overall, a partial contribution of a 5-HT2AR antagonism to the efficacy and side-effect profile of antipsychotic agents is suggested.

An Obsessive-Compulsive Symptom-Related Headache in a Patient with Schizophrenia

Obsessive-compulsive symptoms are prevalent, manifold, and sometimes insidious in patients with schizophrenia. In this case study, we reported an intractable headache that bears a close relationship with obsessive-compulsive symptoms in a schizophrenia patient. In a series of treatments, the headache was miraculously susceptible to haloperidol treatment.

T167. QUALITATIVE DIFFERENCES IN LONG ACTING INJECTABLE ANTIPSYCHOTIC MEDICATIONS AMONG SCHIZOPHRENIA PATIENTS

Background The purpose of this presentation is to investigate qualitative differences associated with treatment of Schizophrenia spectrum disorder patients with long acting injectable (LAI) antipsychotics, including adverse effects and efficacy. Methods Literature around LAI antipsychotics and their comparative data was reviewed and evaluated via all electronic databases up to December 2018. Results Metabolic, hepatic and cardiovascular complications in olanzapine treatment have been the major concern in most studies, despite the effectiveness of the medication, as coronary heart disease is strongly associated with a decrease in the life expectancy of schizophrenia patients (coupled with higher levels of smoking and malnutrition). Treatment with risperidone was associated with a worsening of depressive affect and suicidal ideation (except prolactin-related and extrapyramidal adverse effects), as well as sexual dysfunction. Hyperprolactinemia, extrapyramidal / neurological symptoms, and sexual dysfunction were the major problems with haloperidol treatment despite a good efficacy profile with respect to positive symptoms of schizophrenia. Sporadic effectiveness, agitation and, to a lesser extent, weight gain were some of the concerns in palimperidone treatment. Aripiprazole treatment was associated with a comparatively milder and in the long term more preferable adverse effect profile, while exhibiting similarly high levels of efficacy with olanzapine in controlling schizophrenia symptoms, but with a reported relatively higher rate in treatment discontinuation (drop-outs) in comparison to olanzapine and haloperidol in case of schizophrenia (in contrast to schizoaffective disorder in which high levels of both compliance and effectiveness are exhibited). Discussion The need for an individualized approach in psychiatric treatment highlighted so that the needs of each patient be taken into account by the therapist in choosing the optimal treatment within a given time frame.