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Haloperidol
Selected AbstractsRetrospective database analysis on the effectiveness of typical and atypical antipsychotic drugs in an outpatient clinic settingHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2007Cengiz Akkaya Abstract Objective To report the outcomes of a retrospective database analysis to compare the effectiveness of atypical and typical antipsychotic drugs. Methods Medical records of patients admitted to the psychiatry outpatient clinic between January 1998 and October 2005 were retrospectively reviewed. Data obtained from patient records were noted on a special form assessing four aspects of the treatment history: socio-demographic features, disease characteristics, initial treatment at the time of admission, and course of treatment. Patient groups (typical/atypical and Risperidone/Haloperidol/Olanzapine) were compared for time to all-cause medication discontinuation and rate of discontinuation. Results There was no statistically significant difference in the duration of treatment between patients using atypical (n,=,150) and typical (n,=,124) antipsychotics. The duration of treatment was significantly longer in patients on Haloperidol (n,=,91) compared with those on Risperidone (n,=,63). Rates of discontinuation over 18 months were 59.3% for patients on atypical antipsychotics and 57.3% for those on typical antipsychotics, and 68.3% for patients on Risperidone, 51.6% for patients on Haloperidol and 54.3% for patients on Olanzapine. Conclusion Despite our hypothesis patients with chronic schizophrenia discontinued their atypical and typical antipsychotics, at a high rate with no significant difference indicating substantial limitations in the effectiveness of these drugs. Copyright © 2007 John Wiley & Sons, Ltd. [source] Which neuroreceptors mediate the subjective effects of MDMA in humans?HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2001A summary of mechanistic studies Abstract In preclinical studies, 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') has been shown to release serotonin (5-HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5-HT2 antagonist ketanserin (50 mg orally) in 14 subjects, and the D2 antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double-blind placebo-controlled within-subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self-confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier-mediated 5-HT release, while the more stimulant-like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D2 receptor stimulation. The mild hallucinogen-like perceptual effects of MDMA appear to be due to serotonergic 5-HT2 receptor stimulation. Copyright © 2001 John Wiley & Sons, Ltd. [source] Haloperidol Prophylaxis for Elderly Hip-Surgery Patients at Risk for Delirium: A Randomized Placebo-Controlled StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2005Kees J. Kalisvaart MD Objectives: To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium. Design: Randomized, double-blind, placebo-controlled trial. Setting: Large medical school,affiliated general hospital in Alkmaar, the Netherlands. Participants: A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium. Intervention: Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients. Measurements: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay. Results: The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6,1.3); the mean highest DRS-R-98 score±standard deviation was 14.4±3.4 and 18.4±4.3, respectively (mean difference 4.0, 95% CI=2.0,5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0,8.0; P<.001); and the mean number of days in the hospital was 17.1±11.1 and 22.6±16.7, respectively (mean difference 5.5 days, 95% CI=1.4,2.3; P<.001). No haloperidol-related side effects were noted. Conclusion: Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated. [source] Identification of a new functional target of haloperidol metabolite: implications for a receptor-independent role of 3-(4-fluorobenzoyl) propionic acidJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Hyeon Soo Kim Abstract Haloperidol, a dopamine D2 receptor blocker, is a classical neuroleptic drug that elicits extrapyramidal symptoms. Its metabolites include 3-(4-fluorobenzoyl) propionic acid (FBPA) and 4-(4-chlorophenyl)-4-piperidinol (CPHP). Until now, the biological significance of these metabolites has remained largely unknown. Here, we report that the administration of FBPA to mice effected a suppression of locomotor activity and induced catalepsy in a manner similar to that observed with haloperidol, whereas CPHP had no significant effects. Neither of these two metabolites, however, exhibited any ability to bind to the dopamine D2 receptor. FBPA blocked dopamine-induced extracellular signal-regulated kinase 1/2 phosphorylation, and it specifically affected mitogen-activated protein kinase kinase (MEK)1/2 activity in hippocampal HN33 cells. Moreover, FBPA was capable of direct interaction with MEK1/2, and inhibited its activity in vitro. We demonstrated the generation of haloperidol metabolites within haloperidol-treated cells by mass spectrometric analyses. Collectively, our results confirm the biological activity of FBPA, and provide initial clues as to the receptor-independent role of haloperidol. [source] ,-Opioid receptor knockout mice are insensitive to methamphetamine-induced behavioral sensitizationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 10 2010Xine Shen Abstract Repeated administration of psychostimulants to rodents can lead to behavioral sensitization. Previous studies, using nonspecific opioid receptor (OR) antagonists, revealed that ORs were involved in modulation of behavioral sensitization to methamphetamine (METH). However, the contribution of OR subtypes remains unclear. In the present study, using ,-OR knockout mice, we examined the role of ,-OR in the development of METH sensitization. Mice received daily intraperitoneal injection of drug or saline for 7 consecutive days to initiate sensitization. To express sensitization, animals received one injection of drug (the same as for initiation) or saline on day 11. Animal locomotor activity and stereotypy were monitored during the periods of initiation and expression of sensitization. Also, the concentrations of METH and its active metabolite amphetamine in the blood were measured after single and repeated administrations of METH. METH promoted significant locomotor hyperactivity at low doses and stereotyped behaviors at relative high doses (2.5 mg/kg and above). Repeated administration of METH led to the initiation and expression of behavioral sensitization in wild-type mice. METH-induced behavioral responses were attenuated in the ,-OR knockout mice. Haloperidol (a dopamine receptor antagonist) showed a more potent effect in counteracting METH-induced stereotypy in the ,-OR knockout mice. Saline did not induce behavioral sensitization in either genotype. No significant difference was observed in disposition of METH and amphetamine between the two genotypes. Our study indicated that the ,-opioid system is involved in modulating the development of behavioral sensitization to METH. © 2010 Wiley-Liss, Inc. [source] Combined Scopolamine and Ethanol Treatment Results in a Locomotor Stimulant Response Suggestive of Synergism That is Not Blocked by Dopamine Receptor AntagonistsALCOHOLISM, Issue 3 2009Angela C. Scibelli Background:, Muscarinic acetylcholine receptors (mAChRs) are well positioned to mediate ethanol's stimulant effects. To investigate this possibility, we examined the effects of scopolamine, a receptor subtype nonselective mAChR antagonist, on ethanol-induced stimulation in genotypes highly sensitive to this effect of ethanol. We also investigated whether the dopamine D1-like receptor antagonist, SCH-23390 or the dopamine D2-like receptor antagonist, haloperidol, could block the extreme stimulant response found following co-administration of scopolamine and ethanol. Methods:, Scopolamine (0, 0.0625, 0.125, 0.25, or 0.5 mg/kg) was given 10 minutes prior to saline or ethanol (0.75 to 2 g/kg) to female FAST (Experiment I) or DBA/2J (Experiment II) mice that were then tested for locomotion for 30 minutes. In Experiments III and IV, respectively, SCH-23390 (0, 0.015, or 0.03 mg/kg) was given 10 minutes prior, and haloperidol (0, 0.08, or 0.16 mg/kg) was given 2 minutes prior, to scopolamine (0 or 0.5 mg/kg), followed 10 minutes later by saline or ethanol (1.5 g/kg) and female DBA/2J mice were tested for locomotion for 30 minutes. Results:, FAST and DBA/2J mice displayed a robust enhancement of the locomotor effects of ethanol following pretreatment with scopolamine that was suggestive of synergism. SCH-23390 had no effect on the response to the scopolamine + ethanol drug combination, nor did it attenuate ethanol- or scopolamine-induced locomotor activity. Haloperidol, while attenuating the effects of ethanol, was not able to block the effects of scopolamine or the robust response to the scopolamine-ethanol drug combination. Conclusions:, These results suggest that while muscarinic receptor antagonism robustly enhances acute locomotor stimulation to ethanol, dopamine receptors are not involved in the super-additive interaction of scopolamine and ethanol treatment. They also suggest that in addition to cautions regarding the use of alcohol when scopolamine is clinically prescribed due to enhanced sedative effects, enhanced stimulation may also be a concern. [source] Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's diseaseMOVEMENT DISORDERS, Issue 11 2006Naomi P. Visanji PhD Abstract Investigation of the pathophysiology of psychosis in Parkinson's disease (PD), as well as the assessment of potential novel therapeutics, has been limited by the lack of a well-validated animal model. MPTP-lesioned primates exhibit abnormal behaviors that are distinct from dyskinesia and parkinsonism and may represent behavioral correlates of neural processes related to psychosis in PD. Here we assess four types of behavior,agitation, hallucinatory-like responses to nonapparent stimuli, obsessive grooming, and stereotypies that are termed "psychosis-like",and define their pharmacology using a psychosis-like behavior rating scale. By assessing the actions of drugs known to enhance or attenuate psychosis in PD patients, we find that the pharmacology of these behaviors recapitulates, in several respects, the pharmacology of psychosis in PD. Thus, levodopa and apomorphine elicited psychosis-like behaviors. Amantadine significantly decreased levodopa-induced dyskinesia but exacerbated psychosis-like behaviors. Haloperidol reduced psychosis-like behaviors but at the expense of increased parkinsonian disability while the atypical neuroleptics clozapine and quetiapine reduced psychosis-like behaviors without significant effect on parkinsonian disability. The response of different components of the psychotomimetic behavior suggested the involvement of both dopaminergic and nondopaminergic mechanisms in their expression. © 2006 Movement Disorder Society [source] Methamphetamine psychosis in which tardive dystonia was successfully treated with clonazepamPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2007NOBUTOMO YAMAMOTO md Abstract Reported herein is a case of methamphetamine psychosis in which tardive dystonia was treated successfully with clonazepam. The patient was a 69-year-old man who had taken methamphetamine habitually for approximately 40 years. Auditory hallucinations had developed 25 years previously, for which haloperidol had been prescribed. Tardive dystonia had developed in December 2005. Haloperidol was withdrawn and risperidone or olanzapine alone had been administered, but neither had improved the dystonic posture. However, when clonazepam was added, a gradual improvement in the dystonic posture became evident. Tardive dystonia is currently treated on a trial-and-error basis. Accumulation of further cases similar to the present one is very important for establishing an effective treatment. [source] Encephalopathy with combined lithium-risperidone administrationACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2008K. Boora Objective:, Lithium-neuroleptics induced encephalopathy is a rare drug interaction. Here I am reporting a patient who developed reversible encepatholopathy with lithium-risperidone combination. Method:, A single case report. Result:, A patient of bipolar disorder, who presented with manic symptoms with psychotic feature, started with a combination of lithium and risperidone. Within few days, the patient developed encepatholopathy, which reversed upon discontinuation of lithium and risperidone. Conclusion:, Combining lithium and neuroleptic is useful in treatment of bipolar disorder. However, encepatholapthy can be anticipated to result when lithium is used with high potency anti-psychotic such as haloperidol and risperidone and there are baseline EEG abnormalities. [source] Amisulpride: a review of its efficacyin schizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 400 2000H. J. Möller Objective: To assess the efficacy of the new atypical antipsychotic drug, amisulpride. Method: Studies comparing the efficacy of amisulpride with that of haloperidol and risperidone, respectively, are reviewed. Outcome measures were Clinical Global Impression, Brief Psychiatric Rating Scale (BPRS), and Positive And Negative Symptom Scale (PANSS) scores. Results: Amisulpride was at least as effective as haloperidol and risperidone in the improvement of positive symptoms, and significantly more efficacious than haloperidol in reducing PANSS negative subscores (P=0.038) in patients with acute exacerbations. Amisulpride demonstrated a greater improvement in BPRS total scores (P<0.05) and PANSS negative subscores (P=0.0001) than haloperidol after 12 months of treatment in chronic schizophrenic patients with acute exacerbations. Conclusion: Amisulpride can thus be considered for use as first-line treatment of acute and chronic schizophrenia. [source] Chronological Changes of Plasma Homovanillic Acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) Levels in 4 Patients with Temporal Lobe Epilepsy who Developed Psychosis-Like Symptoms (Hallucination and Delusion) During Zonisamide (ZNS) Administration.EPILEPSIA, Issue 2000Takuya Ueno Purpose: Zonisamide (ZNS) is a relatively new antiepileptic drug with an extensive therapeutic spectrum. However, ZNS can produce psychiatric side effects. In this study, we serially measured plasma hoinovaniliic acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels in 4 patients with epilepsy who developed psychosis-like symptoms (hallucinations and delusions) during ZNS administration. Methods: Subjects comprised 4 patients (3 males and 1 female) with temporal lobe epilepsy ranging in age from 18 to 28 years. Intervals from the start of ZNS administration to the appearance of psychiatric symptoms ranged from 36 to 707 days. Intervals from achievement of the maximal dose to the appearance of psychiatric symptoms ranged from 2 to 240 days. In these 4 patients, the maximal doses of ZNS ranged from 300 to 600 mg/day. In 3 cases, serum ZNS levels were within the effective therapeutic concentration range wlicn syinptoms appeared. However, in 1 case, the serum ZNS level exceeded thc therapeutic level. In all cases, psychiatric symptoms disappeared after ZNS was switched to other antiepileptic drugs and anti-psychotic agents (2-5 mg/day of haloperidol or 10 mg/day of thioridazine) were added. In these cases, we serially measured plasma HVA and MHPG concentrations. Results: Case 1 was a 28-year-old male. Delusions of persecution appeared 190 days after ZNS administration was started. HVA levels at the appearance of psychiatric symptoms were 12.7 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.4 ng/ml. MHPG levels at the appearance of psychiatric symptoms were 14.5 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 6. I ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, whereas the MHPG level was slightly increased. Case 2 was an 18-year-old female. Auditory hallucinations appeared 320 days after ZNS first was administered. HVA levels at the appearance of psychiatric symptoms were 9.6- 10.0 nghl and HVA levels at the disappearance of psychiatric symptoms were 5.3,6.1 ng/ml. MHPG levcls at the appearance of psychiatric symptoms were 4.14.2 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 3.1 ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, but there was no increase in MHPG. Case 3 was an 18-year-old male. Delusion of persecution appeared 707 days after ZNS administration was started. HVA levels at the appearance of psychiatric symptoms were 10.6 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.2 ngiml. MHPG levels at the appearance of psychiatric symptoms were 5.3 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 3.9 ng/ml. When psychiatric symptoms appeared, plasma HVA level was increased, while the MHPG level was slightly increased. Case 4 was a 20-year-old male. Auditory hallucination appeared 36 days after ZNS was administered. HVA levels at the appearance of psychiatric symptoms were 13.6 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.2 ng/ml. MHPG levels at the appearance of psychiatric symptoms were 5.4 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 6. I ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, but there was no increase in MHPG. Conclusions: In all patients, the plasma HVA levels at the appearance of psychiatric symptoms was higher than the corresponding level at time of disappearance of psychiatric symptoms. Psychiatric symptoms may have been associated with activation of dopaniine by ZNS. MHPG levels were slightly increased in 2 cases. However, in thc other 2 cases, there were no changes in MHPG. The influence of ZNS on neurotransmitter metabolites should be further investigated in a larger nuniber of patients. [source] PRECLINICAL STUDY: Long-term haloperidol treatment (but not risperidone) enhances addiction-related behaviors in mice: role of dopamine D2 receptorsADDICTION BIOLOGY, Issue 3 2009Rita C. Carvalho ABSTRACT The high prevalence of psychostimulant abuse observed in schizophrenic patients may be related to the development of mesolimbic dopaminergic supersensitivity (MDS) or nigrostriatal dopaminergic supersensitivity (NDS) in response to the chronic blockade of dopamine receptors produced by typical neuroleptic treatment. We compared the effects of withdrawal from long-term administration of the typical neuroleptic haloperidol (Hal) and/or the atypical agent risperidone (Ris) on MDS and NDS, behaviorally evaluated by amphetamine-induced locomotor stimulation (AILS) and apomorphine-induced stereotypy (AIS) in mice, respectively. We further evaluated the duration of MDS and investigated the specific role of dopamine D2 receptors in this phenomenon by administering the D2 agonist quinpirole (Quin) to mice withdrawn from long-term treatment with these neuroleptics. Withdrawal (48 hours) from long-term (20 days) Hal (0.5 mg/kg i.p.) (but not 0.5 mg/kg Ris i.p.) treatment potentiated both AILS and AIS. Ris co-administration abolished the potentiation of AILS and AIS observed in Hal-withdrawn mice. Ten days after withdrawal from long-term treatment with Hal (but not with Ris or Ris + Hal), a potentiation in AILS was still observed. Only Hal-withdrawn mice presented an attenuation of locomotor inhibition produced by Quin. Our data suggest that the atypical neuroleptic Ris has a pharmacological property that counteracts the compensatory MDS and NDS developed in response to the chronic blockade of dopamine receptors imposed by Ris itself or by typical neuroleptics such as Hal. They also indicate that MDS may be long lasting and suggest that an upregulation of dopamine D2 receptors in response to long-term treatment with the typical neuroleptic is involved in this phenomenon. [source] Oxytocin injected into the ventral tegmental area induces penile erection and increases extracellular dopamine in the nucleus accumbens and paraventricular nucleus of the hypothalamus of male ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Maria Rosaria Melis Abstract The neuropeptide oxytocin (20,100 ng), induces penile erection when injected unilaterally into the caudal but not rostral mesencephalic ventral tegmental area (VTA) of male Sprague,Dawley rats. Such pro-erectile effect started 30 min after treatment and was abolished by the prior injection of d(CH2)5Tyr(Me)2 -Orn8 -vasotocin (1 µg), an oxytocin receptor antagonist injected into the same caudal ventral tegmental area or of haloperidol (1 µg), a dopamine receptor antagonist, injected either into the nucleus accumbens shell (NAs) or into the paraventricular nucleus of the hypothalamus (PVN) ipsilateral to the injected ventral tegmental area. Penile erection was seen 15 min after the occurrence of, or concomitantly to, an increase in extracellular dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the dialysate obtained from the nucleus accumbens or the paraventricular nucleus, which was also abolished by d(CH2)5Tyr(Me)2 -Orn8 -vasotocin (1 µg), injected into the ventral tegmental area before oxytocin. In the caudal ventral tegmental area oxytocin-containing axons/fibres (originating from the paraventricular nucleus) appeared to closely contact cell bodies of mesolimbic dopaminergic neurons retrogradely labelled with Fluorogold injected into the nucleus accumbens shell, suggesting that oxytocin effects are mediated by the activation of mesolimbic dopaminergic neurons, followed in turn by that of incerto-hypothalamic dopaminergic neurons impinging on oxytocinergic neurons mediating penile erection. As the stimulation of paraventricular dopamine receptors not only induces penile erection, but also increases mesolimbic dopamine neurotransmission by activating oxytocinergic neurons, these results provide further support for the existence of a neural circuit in which dopamine and oxytocin influence both the consummatory and motivational/rewarding aspects of sexual behaviour. [source] Dopaminergic regulation of orexin neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005Michael Bubser Abstract Orexin/hypocretin neurons in the lateral hypothalamus and adjacent perifornical area (LH/PFA) innervate midbrain dopamine (DA) neurons that project to corticolimbic sites and subserve psychostimulant-induced locomotor activity. However, it is not known whether dopamine neurons in turn regulate the activity of orexin cells. We examined the ability of dopamine agonists to activate orexin neurons in the rat, as reflected by induction of Fos. The mixed dopamine agonist apomorphine increased Fos expression in orexin cells, with a greater effect on orexin neurons located medial to the fornix. Both the selective D1-like agonist, A-77636, and the D2-like agonist, quinpirole, also induced Fos in orexin cells, suggesting that stimulation of either receptor subtype is sufficient to activate orexin neurons. Consistent with this finding, combined SCH 23390 (D1 antagonist),haloperidol (D2 antagonist) pretreatment blocked apomorphine-induced activation of medial as well as lateral orexin neurons; in contrast, pretreatment with either the D1-like or D2-like antagonists alone did not attenuate apomorphine-induced activation of medial orexin cells. In situ hybridization histochemistry revealed that LH/PFA cells rarely express mRNAs encoding dopamine receptors, suggesting that orexin cells are transsynaptically activated by apomorphine. We therefore lesioned the nucleus accumbens, a site known to regulate orexin cells, but this treatment did not alter apomorphine-elicited activation of medial or lateral orexin neurons. Interestingly, apomorphine failed to activate orexin cells in isoflurane-anaesthetized animals. These data suggest that apomorphine-induced arousal but not accumbens-mediated hyperactivity is required for dopamine to transsynaptically activate orexin neurons. [source] D2 Dopamine receptor blockade results in sprouting of DA axons in the intact animal but prevents sprouting following nigral lesionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2003W. Tripanichkul Abstract Recently it was demonstrated that sprouting of dopaminergic neurons and a microglial and astrocyte response follows both partial lesions of the substantia nigra pars compacta and blockade of the D2 dopamine receptor. We therefore studied the effects of the combination of these two treatments (lesioning and D2 dopamine receptor blockade). Haloperidol administration caused a 57% increase in dopaminergic terminal tree size (measured as terminal density per substantia nigra pars compacta neuron) and an increase of glia in the striatum. Following small to medium nigral lesions (less than 60%), terminal tree size increased by 51% on average and returned density of dopaminergic terminals to normal. In contrast, administration of haloperidol for 16 weeks following lesioning resulted in reduced dopaminergic terminal density and terminal tree size (13%), consistent with absent or impaired sprouting. Glial cell numbers increased but were less than with lesions alone. When haloperidol was administered after the striatum had been reinnervated through sprouting (16,32 weeks after lesioning), terminal tree size increased up to 150%, similar to the effect of haloperidol in normal animals. By examining the effect of administering haloperidol at varying times following a lesion, we concluded that a switch in the effect of D2 dopamine receptor blockade occurred after dopaminergic synapses began to form in the striatum. We postulate that when synapses are present, D2 dopamine receptor blockade results in increased terminal density, whereas prior to synapse formation D2 dopamine receptor blockade causes attenuation of a sprouting response. We speculate that D2 dopamine receptors located on growth cones ,push' neurites toward their targets, and blockade of these receptors could lead to attenuation of sprouting. [source] Conditional involvement of striatal serotonin3 receptors in the control of in vivo dopamine outflow in the rat striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Grégory Porras Abstract Serotonin3 (5-HT3) receptors can affect motor control through an interaction with the nigrostriatal dopamine (DA) neurons, but the neurochemical basis for this interaction remains controversial. In this study, using in vivo microdialysis, we assessed the hypothesis that 5-HT3 receptor-dependent control of striatal DA release is conditioned by the degree of DA and/or 5-HT neuron activity and the means of DA release (impulse-dependent vs. impulse-independent). The different DA-releasing effects of morphine (1 and 10 mg/kg), haloperidol (0.01 mg/kg), amphetamine (1 and 2.5 mg/kg), and cocaine (10 and 20 mg/kg) were studied in the striatum of freely moving rats administered selective 5-HT3 antagonists ondansetron (0.1 mg/kg) or MDL 72222 (0.03 mg/kg). Neither of the 5-HT3 antagonists modified basal DA release by itself. Pretreatment with ondansetron or MDL 72222 reduced the increase in striatal DA release induced by 10 mg/kg morphine but not by 1 mg/kg morphine, haloperidol, amphetamine or cocaine. The effect of 10 mg/kg morphine was also prevented by intrastriatal ondansetron (1 µm) administration. Reverse dialysis with ondansetron also reduced the increase in DA release induced by the combination of haloperidol and the 5-HT reuptake inhibitor citalopram (1 mg/kg). Considering the different DA and 5-HT-releasing properties of the drugs used, our results demonstrate that striatal 5-HT3 receptors control selectively the depolarization-dependent exocytosis of DA only when central DA and 5-HT tones are increased concomitantly. [source] The functional properties of the human ether-ŕ-go-go -like (HELK2) K+ channelEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2002Andrea Becchetti Abstract The voltage-dependent K+ channels belonging to the ether-ŕ-go-go family (eag, erg, elk) are widely expressed in the mammalian CNS. Their neuronal function, however, is poorly understood. Among the elk clones, elk2 is the most abundantly expressed in the brain. We have characterized the human ELK2 channel (HELK2) expressed in mammalian cell lines. Moreover, we have detected helk2 mRNA and ELK2-like currents in freshly dissociated human astrocytoma cells. HELK2 was inhibited by Cs+ in a voltage-dependent way (Kd was 0.7 mm, at ,120 mV). It was not affected by Way 123398 (5 µm), dofetilide (10 µm), quinidine (10 µm), verapamil (20 µm), haloperidol (2 µm), astemizole (1 µm), terfenadine (1 µm) and hydroxyzine (30 µm), compounds known to inhibit the biophysically related HERG channel. The crossover of the activation and inactivation curves produced a steady state ,window' current with a peak around ,20 mV and considerably broader than it usually is in voltage-dependent channels, including HERG. Similar features were observed in the ELK2 clone from rat, in the same experimental conditions. Thus, ELK2 channels are active within a wide range of membrane potentials, both sub- and suprathreshold. Moreover, the kinetics of channel deactivation and removal of inactivation was about one order of magnitude quicker in HELK2, compared to HERG. Overall, these properties suggest that ELK2 channels are very effective at dampening the neuronal excitability, but less so at producing adaptation of action potential firing frequency. In addition, we suggest experimental ways to recognize HELK2 currents in vivo and raise the issue of the possible function of these channels in astrocytoma. [source] Effects of amphetamine on salivary secretionEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 3 2009Bengt Götrick Amphetamine induces xerogenic effects, but its mechanism of action and xerogenic potency are unknown. In the current in vivo study on the rat parotid gland, the effects of amphetamine on reflex-evoked and acetylcholine-evoked salivation were examined in the absence and presence of adrenergic and dopaminergic antagonists. Under anaesthesia, amphetamine increased the secretion of salivary fluid and the amount of protein therein in response to acetylcholine. Phentolamine abolished the increase in salivary flow and had no effect on the salivary protein concentration, whereas propranolol only reduced the salivary protein concentration. Reflex activation of the secretion evoked a well-maintained level of secretion that was reduced by amphetamine [50% inhibitory dose (ID50) 1.9 ± 0.1 mg kg,1 intravenously); the salivary protein concentration was increased in the presence of amphetamine. Phentolamine and haloperidol reduced the amphetamine-inhibitory effect on the reflex-evoked fluid response, whereas propranolol had no effect on the fluid response. The xerogenic effect of amphetamine is mainly exerted by central mechanisms involving ,-adrenoceptors, while, indirectly, amphetamine causes secretion of protein by inducing the release of noradrenaline from glandular nerve terminals. [source] Sigma receptors: from discovery to highlights of their implications in the cardiovascular systemFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2002Laurent Monassier Sigma receptors are the targets of many ligands, of which some (the haloperidol for instance) are psychoactive, and of substances known to have antiarrhythmic effects (amiodarone and clofilium). They are involved in a variety of cardiovascular functions, such as the regulation of cardiac contractility and rhythm and the regulation of coronary and peripheral arterial vasomotricity. This short review will focus on some aspects regarding the ligands, the binding sites, the intracellular coupling and the cardiovascular functions of these enigmatic receptors. [source] The effect of dopamine partial agonists on the nicotine dependency in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2010Se Hee Kim Abstract Objective We compared the effects of haloperidol and three atypical antipsychotics (risperidone, olanzapine, and aripiprazole) on nicotine dependence in schizophrenic patients. Methods One hundred and thirty nine schizophrenic patients, who began using antipsychotic medication, were assessed for severity of nicotine dependence and for cigarette craving at baseline and following 8 weeks of treatment using the Fagerström Tolerance Questionnaire (FTQ) and a Likert-style, seven point, visual-analogue rating scale. Results Nicotine dependence increased in the haloperidol group, but not in atypical antipsychotics groups. Patients treated with aripiprazole showed a reduction both in nicotine dependence and cigarette craving. Conclusions The effects of aripiprazole, a partial agonist of the dopamine D2 receptor, may reduce the severity of nicotine dependence in schizophrenic patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Efficacy and tolerability of quetiapine in patients with schizophrenia who switched from haloperidol, olanzapine or risperidoneHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2005Ilkka Larmo Abstract A post hoc analysis of the SPECTRUM trial was carried out to evaluate whether the improvements in efficacy and tolerability gained on switching to quetiapine occurred consistently for patients previously treated with either: haloperidol (n,=,43); olanzapine (n,=,66); or risperidone (n,=,55) monotherapy. Patients were initiated with quetiapine to 400,mg/day over 7 days, and then flexibly dosed (300,750,mg/day) for 11 weeks. The mean (SD) modal dose of quetiapine was 501 (138),mg/day in the haloperidol subgroup, 472 (147),mg/day in the olanzapine subgroup and 485 (141),mg/day in the risperidone subgroup at the study endpoint. Switching to quetiapine induced significant improvements from baseline in PANSS scores, with least square mean changes in total scores of ,32.5, ,15.4, and ,18.5 for patients previously treated with haloperidol, olanzapine and risperidone, respectively, (all p,<,0.001 vs baseline). Significant improvements were also noted in CDSS scores, particularly for patients clinically depressed at baseline (all p,<,0.001 vs baseline). There were significant reductions in EPS on the SAS and BAS for all subgroups (all p,<,0.001 vs baseline). Switching to quetiapine produced efficacy and tolerability benefits regardless of whether their previous antipsychotic was haloperidol, olanzapine or risperidone. Copyright © 2005 John Wiley & Sons, Ltd. [source] Which neuroreceptors mediate the subjective effects of MDMA in humans?HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2001A summary of mechanistic studies Abstract In preclinical studies, 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') has been shown to release serotonin (5-HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5-HT2 antagonist ketanserin (50 mg orally) in 14 subjects, and the D2 antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double-blind placebo-controlled within-subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self-confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier-mediated 5-HT release, while the more stimulant-like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D2 receptor stimulation. The mild hallucinogen-like perceptual effects of MDMA appear to be due to serotonergic 5-HT2 receptor stimulation. Copyright © 2001 John Wiley & Sons, Ltd. [source] Iloperidone for schizophrenia: a review of the efficacy and safety profile for this newly commercialised second-generation antipsychoticINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2009L. Citrome Summary Objective:, The aim of the study was to describe the efficacy and safety of iloperidone for the treatment of schizophrenia. Data sources:, The pivotal registration trials were accessed by querying http://www.pubmed.gov, http://www.fda.gov and http://www.clinicaltrials.gov for the search term ,iloperidone'. Study selection:, Four published primary reports of phase III studies were identified as well as preclinical animal and receptor affinity studies that describe potential mechanisms of action and pharmacogenomic studies that identify potential genetic biomarkers for efficacy and tolerability. Product labelling provided additional data. Data extraction:, Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis:, Iloperidone is a second-generation antipsychotic agent indicated for the acute treatment of schizophrenia in adults. Iloperidone has been evaluated in several double-blind placebo-controlled clinical trials. The oral formulation has demonstrated efficacy in reducing the symptoms of acute schizophrenia at fixed daily doses ranging from 12 to 24 mg. Data reported for categorical definitions of response using the Positive and Negative Syndrome Scale were limited to one study and specifically to rates of achieving a , 20% decrease in the positive subscale from baseline; significantly more patients receiving iloperidone 24 mg/day (72%) than placebo (52%) met this criterion, yielding a NNT of five. Iloperidone should be titrated slowly to avoid orthostatic hypotension, potentially delaying the achievement of a therapeutic dose level. There appears to be a dose relationship for adverse events such as dizziness, somnolence and dry mouth; for example NNH vs. placebo for somnolence was 25 for iloperidone 10,16 mg/day and 10 for 20,24 mg/day. There is a possibility of a therapeutic dose response as well. Iloperidone is essentially free of extra-pyramidal side effects. Iloperidone is associated with weight gain comparable with risperidone. Long-term double-blind maintenance studies have demonstrated iloperidone's non-inferiority to haloperidol for relapse prevention. Product labelling includes a warning about the potential for QT interval prolongation. At present there are no efficacy studies available that are powered to directly compare iloperidone with other second-generation antipsychotics. The development of a depot formulation of iloperidone as well as efforts to identify genetic biomarkers for prediction of both efficacy and tolerability are in progress. Conclusions:, Aside from paliperidone, iloperidone is the first new second-generation antipsychotic to be commercialised in the USA since 2002. From the limited registration data, iloperidone appears to be relatively well tolerated once titrated to a therapeutic level and can be a useful option to consider. The development of a depot formulation and potential for genetic biomarkers may make this agent compelling. Further comparisons with other available agents among patients with schizophrenia in the ,real world' are needed. [source] Stopping antipsychotic drug therapy in demented nursing home patients: a randomized, placebo-controlled study,,The Bergen District Nursing Home Study (BEDNURS)INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 9 2008Sabine Ruths Abstract Background Despite modest efficacy, unpredictable individual utility, and a high rate of adverse effects, behavioural and psychological symptoms of dementia (BPSD) are common determinants for antipsychotic drug therapy in nursing home patients. Aims To explore the impact on BPSD of stopping long-term antipsychotic treatment in nursing home patients with dementia. Methods Fifty-five patients (43 women; mean age 84.1) taking haloperidol, risperidone, or olanzapine for BPSD were randomly assigned to cessation (intervention group, n,=,27) or continued treatment with antipsychotic drugs (reference group, n,=,28) for 4 consecutive weeks. The Neuropsychiatric Inventory (NPI) Questionnaire was used to examine changes in behavioural and psychological symptoms. Results By study completion, 23 of the 27 intervention group patients were still off antipsychotics. Symptom scores (NPI) remained stable or even improved in 42 patients (intervention group, 18 out of 27; reference group, 24 out of 28; p,=,0.18). As compared to patients with stable or improved symptom scores, patients with behavioural deterioration after antipsychotic cessation used higher daily drug doses at baseline (p,=,0.42). Conclusion A large share of elderly nursing home patients on long-term treatment with antipsychotics for BPSD, do well without this treatment. Standardized symptom evaluations and drug cessation attempts should therefore be undertaken at regular intervals. Copyright © 2008 John Wiley & Sons, Ltd. [source] Assertion that risperidone is superior to haloperidol for treatment of behavioural and psychological symptoms of dementiaINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2007Graham A. Jackson No abstract is available for this article. [source] Are All Commonly Prescribed Antipsychotics Associated with Greater Mortality in Elderly Male Veterans with Dementia?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2010Rebecca C. Rossom MD OBJECTIVES: To estimate mortality risk associated with individual commonly prescribed antipsychotics. DESIGN: Five-year retrospective study. SETTING: Veterans national healthcare data. PARTICIPANTS: Predominantly male, aged 65 and older, with a diagnosis of dementia and no other indication for an antipsychotic. Subjects who received an antipsychotic were compared with randomly selected controls who did not. Exposed and control cohorts were matched according to their date of dementia diagnosis and time elapsed from diagnosis to the start of antipsychotic therapy. MEASUREMENTS: Mortality during incident antipsychotic use. RESULTS: Cohorts who were exposed to haloperidol (n=2,217), olanzapine (n=3,384), quetiapine (n=4,277), or risperidone (n=8,249) had more comorbidities than their control cohorts. During the first 30 days, there was a significant increase in mortality in subgroups prescribed a daily dose of haloperidol greater than 1 mg (hazard ratio (HR)=3.2, 95% confidence interval (CI)=2.2,4.5, P<.001), olanzapine greater than 2.5 mg (HR=1.5, 95% CI=1.1,2.0, P=.01), or risperidone greater than 1 mg (HR=1.6, 95% CI=1.1,2.2, P=.01) adjusted for demographic characteristics, comorbidities, and medication history using Cox regression analyses. Greater mortality was not seen when a daily dose of quetiapine greater than 50 mg (HR=1.2, 95% CI=0.7,1.8, P=.50) was prescribed, and there was no greater mortality associated with a dose less than 50 mg (HR=0.7, 95% CI=0.5,1.0, P=.03). No antipsychotic was associated with greater mortality after the first 30 days. CONCLUSION: Commonly prescribed doses of haloperidol, olanzapine, and risperidone, but not quetiapine, were associated with a short-term increase in mortality. Further investigations are warranted to identify patient characteristics and antipsychotic dosage regimens that are not associated with a greater risk of mortality in elderly patients with dementia. [source] Treatment of Dementia in Community-Dwelling and Institutionalized Medicare BeneficiariesJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2007Ann L. Gruber-Baldini PhD OBJECTIVES: To establish nationally representative estimates of the use of agents to treat Alzheimer's disease and related dementias (ADRDs) and related behavioral symptoms in Medicare beneficiaries and to describe medication use according to residential status and other patient characteristics. DESIGN: Cross-sectional prevalence study. SETTING: Community and various long-term care (LTC) settings. PARTICIPANTS: Twelve thousand six hundred ninety-seven beneficiaries from the 2002 Medicare Current Beneficiary Survey (MCBS), of whom 11,593 were community dwelling and 1,104 resided in various LTC settings. MEASUREMENTS: ADRDs were identified according to International Classification of Diseases, Ninth Revision, codes in Medicare claims and self- and proxy reports. Medication use was derived from self-reports (community) and extracts of facility medication administration records (LTC). RESULTS: In 2002, an estimated 3.4 million Medicare beneficiaries were diagnosed with ADRDs (8.1%), of whom 58.9% resided in the community (prevalence rate=5.1%) and 41.1% resided in LTC facilities (prevalence rate=57.2%). Use of antidementia drugs was similar across settings, with 24.7% of subjects with dementia in the community and 26.3% of those in LTC receiving prescriptions for donepezil, galantamine, or rivastigmine. Use of haloperidol was comparable (and low) in both settings. Use of atypical antipsychotics, especially risperidone, olanzapine, and quetiapine, was much higher in LTC residents (21.0%, 11.9%, and 7.1%, respectively) than in the community (5.1%, 4.0%, and 2.3%). CONCLUSION: The prevalence of ADRDs in LTC settings is much larger than in the community, but there is little difference in the proportions receiving antidementia drugs, although LTC residents are more likely to be treated with atypical antipsychotics (risperidone, olanzapine, and quetiapine), presumably for behavioral symptoms. [source] Haloperidol Prophylaxis for Elderly Hip-Surgery Patients at Risk for Delirium: A Randomized Placebo-Controlled StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2005Kees J. Kalisvaart MD Objectives: To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium. Design: Randomized, double-blind, placebo-controlled trial. Setting: Large medical school,affiliated general hospital in Alkmaar, the Netherlands. Participants: A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium. Intervention: Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients. Measurements: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay. Results: The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6,1.3); the mean highest DRS-R-98 score±standard deviation was 14.4±3.4 and 18.4±4.3, respectively (mean difference 4.0, 95% CI=2.0,5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0,8.0; P<.001); and the mean number of days in the hospital was 17.1±11.1 and 22.6±16.7, respectively (mean difference 5.5 days, 95% CI=1.4,2.3; P<.001). No haloperidol-related side effects were noted. Conclusion: Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated. [source] Effect of Antipsychotic Withdrawal on Behavior and Sleep/Wake Activity in Nursing Home Residents with Dementia: A Randomized, Placebo-Controlled, Double-Blinded Study The Bergen District Nursing Home StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004Sabine Ruths MD Objectives: To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia. Design: Randomized, placebo-controlled, double-blind trial. Setting: NHs in Bergen, Norway. Participants: Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms. Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks. Measurements: Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and actigraphy. Results: After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24-hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI-Q. One patient was restarted on antipsychotics. Conclusion: Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long-term effect of these changes is not known. The NPI-Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies. [source] Interindividual variation of serum haloperidol concentrations in Japanese patients , clinical considerations on steady-state serum level,dose ratiosJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2003E. Yukawa Summary Objective:, Marked interpatient variability in haloperidol (HAL) level,dose (L/D) ratios makes it difficult to use the administered dose for predicting serum concentrations. Objective:, To investigate the effect of dose, age, total body weight and co-medication on steady-state HAL L/D ratios. Method:, Retrospective analysis of dose and HAL blood level data from 168 patients. Results:, The HAL L/D ratio decreased curvilinearly with increasing daily dose of HAL. The patients treated with concomitant antiparkinsonian drugs showed a mean HAL L/D ratio that was 24·9% higher than those without antiparkinsonian drugs. The patients treated with concomitant antiepileptic drugs showed a mean HAL L/D ratio that was 27·2% lower than those without antiepileptic drugs. The mean HAL L/D ratio of patients treated with concomitant CYP2D6 substrates was not significantly different from those without CYP2D6 substrates. Conclusion:, There is a wide interindividual variability in blood levels of HAL in patients given the same dose. Routine monitoring of HAL serum level is useful, especially in patients who require associated antiepileptic and/or antiparkinsonian medication. [source] | ||||||||||||||||||||||||||||||||||