GABAb receptors are coupled to calcium channels. A role for GABA in the pathophysiology of depression has long been postulated, and several recent studies support this hypothesis.111,112 Preclinical studies have demonstrated decreased CNS GABA concentrations in animal models of depression.111 CSF and CI-1033 mouse plasma GABA concentrations have been reported to be decreased in depressed patients.111 Postmortem investigation of the hippocampus

in depressed patients suggested possible GABAergic Inhibitors,research,lifescience,medical dysfunction.113 GABAb receptors are found on most 5-HT-containing neurons in the dorsal raphe, and GABA release into the dorsal raphe decreases firing of 5-HT neurons.114 Modulating GABAb function has been shown to have important behavioral effects in animal models, with GABAb antagonists demonstrating certain antidepressantlike properties.112,114 Using magnetic resonance spectroscopy, Sanacora et al demonstrated decreased GABA concentrations in the

occipital cortex of depressed patients.100,115 Moreover, this group showed GABA concentrations increase in the occipital cortex Inhibitors,research,lifescience,medical after SSRI treatment and ECT,116,117 but not after Inhibitors,research,lifescience,medical CBT118 CNS GABA concentrations have also been shown to be normal in remitted depressed patients compared with controls.119 Neurokinins Neurokinins are neuropeptides widely distributed in the CNS and peripheral nervous system, and are believed to play a role in nociception. Substance P is the most abundant neurokinin in humans and is found in neurons in several brain regions implicated in the neurobiology of depression.120 Substance P is also colocalized in cells containing 5-HT and NE.121-124 Substance P binds to several receptor subtypes (NK-1, NK-2, NK-3, NKA, NKB), and appears to Inhibitors,research,lifescience,medical have an important role in modulating the mammalian stress response. In animal models, substance P results in behavioral and physiologic changes characteristics of a stress response.125,126 Inhibitors,research,lifescience,medical These changes can be attenuated by substance P antagonists.127,128 Supporting its role in depression, CSF substance P concentrations were reported to be elevated in depressed patients

compared with controls,129-131 and lower serum concentrations of substance P have been correlated with better antidepressant treatment response.130 Our group has reported elevations in CSF substance P concentrations in drug-free patients with major depression and PTSD.132 One placebo-controlled study using a neurokinin receptor (NK-1) antagonist (MK-869) suggested efficacy in treating depression,127 Tolmetin but several follow-up studies found no significant antidepressant effects for this agent.133 Two other selective NK-1 receptor antagonists (L-759274 and CP-122721) have shown potential efficacy in treating depression,134,135 although data are relatively limited. In general, these drugs appear to be well-tolerated. Neuroanatomical models Several lines of evidence support a neuroanatomical basis for depression.

The major weakness in this information is in its source. Recommendations were based on a survey of experts rather than scientifically collected data. In recent years, scientifically collected data from large multicenter trials began to emerge for the treatment of BPSD, especially psychosis. Hie first multicenter, randomized, double-blind, placebo-controlled trial of BPSD psychosis was recently published.36 The study evaluated the effects of risperidone versus placebo in 612 demented patients. The study revealed risperidone to be significantly better than placebo in improving symptoms of psychosis and aggressive

behavior when used in 1-mg and 2-mg doses.36 A similar randomized trial37 of risperidone, Inhibitors,research,lifescience,medical placebo, and haloperidol for BPSD demonstrated conventional neuroleptics to be modestly efficacious for treating aggression in demented patients, while risperidone Inhibitors,research,lifescience,medical was associated with a. greater reduction in both the severity and frequency of aggression than was either placebo or haloperidol. ‘Ihe antipsychotic

drug olanzapine was also recently utilized in a randomized, double-blind, placebocontrolled study Inhibitors,research,lifescience,medical with AD. This study included 206 patients. This study found olanzapine 5 mg and 10 mg to be superior to placebo in the treatment of both psychosis and aggression in BPSD patients.38 Until recently, cholinest.era.se inhibitors were untested in treating BPSD Inhibitors,research,lifescience,medical symptoms such as agitation, delusions, and hallucinations. In a previous study, it, was observed that, patients given tacrine at. 120 mg a day or higher were less likely to have entered a. nursing home than patients on lower doses.39 It was hypothesized that this decline was in part due to a decrease in the onset, of noncognitive symptoms in those patients. Inhibitors,research,lifescience,medical Furthermore, in a study evaluating

the effectiveness of physostigmine slow release (SR),Thal et al40 reported a decrease in the onset, of psychosis and aggression as well as other psychiatric pathology in the physostigmine SR-treated groups. In addition, recent data on the cholinesterase inhibitor donepezil indicate that this compound else can also improve behavioral symptoms commonly associated with psychosis in AD, such as hallucination, apathy, and aberrant motor behavior.41 Furthermore, selleck chemicals another large multicenter trial using donepezil for AD treatment of nursing home (NH) populations revealed a statistically significant (P<0.05) difference (in favor of donepezil) in the individual agitation/aggression response of the NPI/NH assessment tool.41 Similar findings with rivastigmine and galantamine (both cholinesterase inhibitors) have recently been revealed.42 The common limitation of all these studies is that 65% or fewer of the patients were considered responders either for psychosis or aggression at doses with a benign side-effect profile.

14 Herbert Lepor, MD: Does nerve-sparing surgery improve outcomes? Jason Engel, MD: At this point, I do not think that anyone would argue that sparing the Epigenetics inhibitor erectile nerves does not improve outcome. There is abundant literature that shows improvement in erection rates after prostatectomy when both versus 1 versus neither

nerve Inhibitors,research,lifescience,medical bundle is spared. However, the quality of a nerve-sparing operation remains a subjective assessment, so there will always be inexactness to this claim. Robotic dissection and visualization allows surgeons to spare the nerve bundles in a more comprehensive and consistent manner. However, linearity between my subjective assessment of nerve sparing and whether erectile function returns cannot be proved. The importance of blood flow and the revascularization of the penis via collateralization are central to the recovery of erectile function after prostatectomy. Finding the best penile rehabilitation protocol is the highest priority in improving sexual Inhibitors,research,lifescience,medical outcomes after prostatectomy. In highly experienced hands, surgical technique cannot Inhibitors,research,lifescience,medical be refined much further in terms of nerve sparing. Herbert Lepor, MD: Does robotic prostatectomy improve outcomes? Jason D. Engel, MD: Dr. McCullough and I have just finished the MUSE RP-01 trial, which has provided some insight. As a multisite penile rehabilitation trial comparing daily MUSE®

(alprostadil urethral suppository; VIVUS, Inc, Mountain Inhibitors,research,lifescience,medical View, CA) versus daily

Viagra® (sildenafil citrate; Pfizer Inc., New York, NY) in both the open and robotic surgical setting, it has allowed a comparison of open versus robotic sexual outcomes within the same protocol. This makes MUSE Inhibitors,research,lifescience,medical RP-01 truly unique, particularly given the fact that nearly 200 patients were enrolled prospectively and randomized. We found no differences in International Index of Erectile Function (IIEF) scores between open and robotic surgery, although we did show some significant differences favoring robotic surgery when looking at stretched penile length and intercourse success. Whether stretched penile length is a surrogate for penile health and eventual return of erectile function mafosfamide has not been fully established, so we are not sure of the significance of this finding. Whether the observations are real or due to intersite variability is not clear. This significant finding warrants further study. Nevertheless, although certainly not definitive, MUSE RP-01 has strengthened my own personal belief that there are inherent advantages of the robotic approach that lead to improved sexual outcomes. Herbert Lepor, MD: As far as penile length, it is important to note that the difference in outcome may simply be due to the fact that the penis was stretched more vigorously at the robotic surgical site than at the open surgical site.

Diet is believed to play a major role in the development of gastric cancer. It is very well known that salt rich, smoked or poorly preserved foods, nitrates, nitrites have been associated with an increase in gastric cancer. Conversely,

diets high in raw vegetables, fresh fruits (containing vitamin C, antioxidants) are associated with decreased risk (7-9). Helicobacter pylori infection is associated with an approximately two-fold increased risk of developing gastric cancer (10-12). Pylori H have been categorized as a “Group-1 human carcinogen” by the International Agency for Inhibitors,research,lifescience,medical Research on Cancer (13). The role of tobacco in the occurrence of gastric cancers cannot be undermined (6). The state of Manipur, located in the north eastern region of

India bordering Myanmar, has different customs, food habits, life-style, diverse ethnic Brefeldin A groups, and the pattern of tobacco use as compared to the rest of Inhibitors,research,lifescience,medical the country. Majority of the people here consume dried salted fish, fermented, smoked and pickled meat and the use of tobacco is also widely prevalent. We undertook this study to analyse the demographic pattern, clinical presentations, pathological Inhibitors,research,lifescience,medical characteristics and stage at presentation of stomach cancer at Regional Cancer centre, Regional Institute of Medical Sciences (RIMS), situated in Imphal, Manipur state, is the biggest referral centre for the neighbouring North eastern states in India Inhibitors,research,lifescience,medical and bordering Myanmar. Materials and methods We conducted a retrospective study using the data base of 158 patients

of primary gastric cancer diagnosed in the Department of Surgery at Regional Cancer Centre, RIMS, Manipur, India from July 2009 to June 2013. All these patients were diagnosed on clinical, radiological and endoscopic examination. The diagnosis was confirmed pathologically after the histopathological examination of either the resected specimen or the endoscopic biopsy specimen. All the patients with a confirmed gastric carcinoma were included in the study. Inhibitors,research,lifescience,medical The cases with primary gastric lymphoma, gastro intestinal stromal tumours (GIST) and gastric melanoma were excluded. Restaging was performed according to AJCC staging system (7th edition) based on the available clinical and radiological findings. The compiled data included and demographic data, medical history of chronic gastritis, peptic ulcer disease, family history of gastric cancer, dietary habits (intake of fermented, smoked meat, red meat), drinking water source, smoking habits, consumption of alcohol, chief presenting complaints, histological grade, TNM staging and the site of metastasis. Descriptive statistics were used for analysing the data using SPSS version 20 and results were presented in percentage and simple frequency. Results This study included 158 patients with male to female ratio of 2.16:1, distribution of age varied from 28 to 91 years old. Majority of the men were in the age group of more than 60 years old (45.

10 Therefore, we aimed to evaluate the potential factors which may affect extubation time in Shiraz, southern Iran. Materials and Methods In a retrospective study, we conducted a review of the

records of 334 eligible patients who underwent elective coronary artery bypass grafting (CABG) in 2008 in Kowsar Hospital, affiliated to Shiraz University of Medical Sciences, Shiraz, southern Iran. The study was approved by the University’s Ethics Committee. The patients’ demographic data and operative variables were extracted from the records. All patients scheduled for CABG surgery Inhibitors,research,lifescience,medical were enrolled in the study. We excluded patients with difficult intubation, severe acid base disturbance, neurological Inhibitors,research,lifescience,medical problems, and cardiovascular instability, and those who used intra-aortic balloon pump, had underwent emergency operation, or had another concomitant surgery. The anesthesia technique had been the same for all the patients. Balanced anesthesia was induced with 0.1-0.2 mg/kg intravenous midazolam, 0.1-0.25 µ/kg sufentanil, 0.1-0.15 mg/kg morphine, 1-2 mg/kg sodium thiopental, plus 0.08-0.12 mg/kg intravenous pancuronium for muscle relaxation. Anesthesia was maintained with isoflurane. Standard CABG had been performed by the same groups of surgeons and anesthesiologists throughout. The Inhibitors,research,lifescience,medical patients had been transferred to the ICU and extubated after

hemodynamic and respiratory stability. To determine factors associated with the extubation period, the patients were selected regarding extubation time. One group had an extubation time of equal or less than 6 hours (early extubation group) and another group had experienced Apitolisib in vivo longer extubation time (delayed extubation group). The Inhibitors,research,lifescience,medical extubation criteria were adequate ventilation

according to arterial Inhibitors,research,lifescience,medical blood gas analysis and full consciousness of the patients. Also hemodynamic parameters of the patients should be within normal limit. Data were presented as mean (±SD) or ratios as appropriated and analyzed using SPSS software, version 13 (Chicago, IL, USA). P value of <0.05 was considered as statistically significant. In univariate analysis, the differences were analyzed using t test for continuous variables and chi-square test for discrete variables. for Consequently, in multivariable analysis, multiple logistic analyses of variance were conducted to reveal predicting factors of delayed extubation. The dependent variable was group indicator (early or delayed group), with the factors as independent variables. Results We selected 167 patients with early extubation and 167 patients with delayed extubation time. We found a significant difference in age (P<0.001) and sex (P=0.032) between the patients with early and delayed extubation (univariate analysis, table 1). There were not significant differences in baseline data including ejection fraction (P=0.21) and risk factors (P=0.27) between the two groups (table 1).

The major goals of IPT are achieved by ascertaining with the patient which of these four problems was associated with the onset of the current episode of depression and, subsequently, by working with the patient to renegotiate interpersonal difficulties associated with the primary problem area. IPT strategies include role-play, communication analysis, and direct suggestion. Inhibitors,research,lifescience,medical Although maintenance

interpersonal psychotherapy (IPT-M) preserves the four distinctive problem areas and employs the strategies and techniques of IPT, it differs in that its primary goal is prevention of recurrence and it is conceptualized as a long-term rather than an acute intervention. Because of the length of maintenance treatment, Inhibitors,research,lifescience,medical a number of problem areas are typically addressed and the therapist often focuses on long-standing patterns of interpersonal behavior that appear nonadaptive for the patient.23 Cognitive behavioral analysis system of psychotherapy CBASP is a manualized psychotherapy specifically designed to help severely and chronically depressed individuals build new problem-solving and relationship skills.6 Hirschfeld et al30

explain that CBASP is similar to IPT, inasmuch as treatment focuses on interpersonal interactions, but is substantially more directive and structured than IPT, and frequently focuses on the therapist-patient Inhibitors,research,lifescience,medical interactions. CBASP is an acute treatment that is scheduled twice weekly for the first 4 weeks, and weekly thereafter until week 12, with a maximum session allowance of 20 sessions.6 CBASP evolved from McCullough’s view of the specific cognitive Inhibitors,research,lifescience,medical correlates of dysthymia or chronic depression.6 He argued that individuals with dysthymia tend to have a series of dysfunctional attitudes, particularly Inhibitors,research,lifescience,medical with respect to dependence, competence, and trust. They also tend to have an attributional style that views these problems as internal, global, and

irreversible. Their sense of self-efficacy relative to that of the general population is low and they tend to have a highly reactive response to problems and stressors consistent with MTMR9 Eysenck’s concept of neuroticlsm. The primary goal of CBASP is to teach patients to understand the Belinostat research buy consequences of their situational behavior and address the interpersonal difficulties and cognitive correlates of dysthymia through situational analysis, interpersonal discrimination exercises, and behavioral skill training and rehearsal. Problem-solving treatment Problem-solving treatment (PST) was developed at Oxford University by Gath, Mynors-Wallis, and colleagues as a very brief form of psychotherapy to be used in the treatment of major depressive disorders in primary care settings.7,31 They developed PST with an eye toward reducing emotional symptoms by addressing “problems with living.

VC is beneficial for following conversations with multiple participants [24]. Thus, audio-only speakerphones AZD9291 solubility dmso between multiple participants used in a time-critical setting, may cause more interruptions than VC for the rural hospital team. Also, specialists

found discussions easier when observing, and the availability of video has been shown to dramatically Inhibitors,research,lifescience,medical influence the use of a team’s conferencing system [25]. Therefore, it is reasonable to believe that speakerphones are less likely to be used, and would have several drawbacks when compared to VC. Specialists had to leave their own working environment for participation in VC. This is usually more interruptive to their work than phone calls from a remote hospital doctor. The added benefit of more information through VC, working in a team with other specialists contributing to the case, and the cooperation with the EMD for planning of patient transportation may outweigh Inhibitors,research,lifescience,medical this disadvantage. We found VC to cause misunderstandings, Inhibitors,research,lifescience,medical when vital signs were not displayed at both hospitals. Similarly, important information can be missed when microphones are muted, or cameras inadequately focused. These issues can be solved by forcing a different setup of computer

screens, different user interfaces or by improved training. VC has been used and studied in various settings for decades. Video has been shown to support interactions within teams, but important design issues need to be met or VC systems are not used [24-26]. The overhead of setting up Inhibitors,research,lifescience,medical and planning VC meetings should not be added to the tasks of a small rural hospital team in a time critical situation. In our setup this is the responsibility of the university hospital, whose team also remotely controls all cameras. Synergies between technology and work processes are important for Inhibitors,research,lifescience,medical successful implementations of technology in health care [27]. Methodological

issues We did not tell participants to work in any particular way with either technology. This may all have limited the use of technology to it’s full potential. For example, doctors at LYB usually left the patient room to make telephone calls. This was mentioned as a drawback with telephones, but was due to tradition rather than technical limitations. Participants received very little pre-training and had hardly any time to familiarize themselves with the VC system prior to this study. Compared with years of experience of telephone communication, the comparison between the use of the two technologies is less valid. However, not all potential team members in large hospitals can have extensive training in virtual emergency teams, and we believe our study reports typical experiences of new members in such teams.

Therefore, humans need methods that can help them to deal with their anxiety. Traditional methods, like for example, the cognitive-behavioral therapy (CBT), have been established as empirically supported treatments for anxiety disorders (e.g., Chambless and Ollendick 2001), GW4064 in vitro However, they often require relative long periods of treatment: “The large majority of people who suffer from an anxiety disorder are able to reduce or eliminate their anxiety symptoms and return to normal functioning after several months of appropriate psychotherapy” Inhibitors,research,lifescience,medical (APA 2013). Hence, researchers are always looking for new methods

which can also be successful in reducing anxiety symptoms using shorter periods of time. The purpose of this paper was to investigate an advanced version of the technique of Eye movement desensitization and reprocessing (EMDR; Shapiro 1989) for the treatment of anxiety, the so-called wingwave method (Besser-Siegmund Inhibitors,research,lifescience,medical and Siegmund 2010, 2013). The inventors of this method affirm that the wingwave method is appropriate in reducing anxiety symptoms in only a few hours of intervention. Inhibitors,research,lifescience,medical The wingwave method utilizes the technique of EMDR (Shapiro 1989) as main intervention tool. EMDR was developed by Shapiro (1989)

for the treatment of patients with posttraumatic stress disorder (PTSD) and has been empirically validated (Carlson et al. 1998; Marcus et al. 1997; Rothbaum 1997; Shapiro 1999). In EMDR treatment, Inhibitors,research,lifescience,medical the patient recalls trauma-related memories and while simultaneously attending to inner thoughts and sensory stimulation from a rhythmic, bilateral source. The sensory stimulus is most typically visual (hence “eye movement”), but can be auditory, tactile, or proprioceptive (Shapiro 2001). Furthermore, EMDR is not only used in the treatment of PTSD but also in the treatment of anxiety. There are several Inhibitors,research,lifescience,medical studies which could show that eye movements (EMDR) can decrease the emotional intensity Rebamipide of anxiety

(Muris and Merckelbach 1997; De Jongh et al. 2002; Graham and Robinson 2007; Smeets et al. 2012). De Jongh and ten Broeke (2009) found that there is randomized outcome research for panic disorders (PD) and specific (i.e., spider) phobia, but not for other anxiety disorders (i.e., social phobia, obsessive-compulsive disorder, and general anxiety disorders [GAD]). However, in addition to the intervention with EMDR, the wingwave method uses for the diagnosis of stress triggers and for evaluating the success of the treatment a muscle test named the Bi-Digital-O-Ring-Test (BDORT) originally developed by Omura (1985). The relationship between treatments for anxiety and muscle tension is until now poorly understood (Pluess et al. 2009). Barlow et al.

Huge individual variations in the activities of these enzymes have long been demonstrated, much of which have been accounted for with specific allelic variations in the genes encoding these enzymes. For example, CYP2D6 allelic profiles determine whether a particular individual is a poor metabolizer (those with defective genes encoding no enzyme; approximately 2% in Han Chinese and 7% in Caucasians), intermediate metabolizer (those with “less effective” gene; approximately

50% in East Asians), extensive metabolizer (those with “wildtype” alleles; approximately 47% in #Protein Tyrosine Kinase inhibitor keyword# East Asians) and ultrarapid metabolizer (those with gene duplication or multiplication; about 1% in East Asians and Northern Europeans, but up to 7% in Spaniards and up to 30% in Arabs and Ethiopians).10 Studies involving desipramine and venlafaxine clearly indicate that these CYP2D6 polymorphisms are mainly responsible for the pharmacokinetics, dosing, and side-effect profiles of these CYP2D6 substrates.11,12 Similarly, specific allelic alterations Inhibitors,research,lifescience,medical also have been demonstrated to determine CYP2C19 enzyme activities, and consequently

the dosing and side effect profiles of medications metabolized by this enzyme. In addition, the activity of some of these CYPs also could be significantly altered by exposure to environmental agents, whose mechanisms also have been elucidated. For example, the induction Inhibitors,research,lifescience,medical effect of St John’s wort (and other natural substances) on CYP3A4 is now known to be mediated via the steroid and xenobiotic receptor fSXR], and Inhibitors,research,lifescience,medical the induction of CYP1A2 by constituents of cigarettes is mediated through the activation of the Ah receptor.13

Although less well documented, a number of genes other than the CYPs also influence the process of pharmacokinetics, and thus are likely to also affect the dosing and side-effect profiles of ADs. These include genes encoding transferases, such as glutathione-S-transf erase (GST) and UDP-glucurunosyltransferases (UGTs), which are responsible for drug conjugation; multldrug-resistance Inhibitors,research,lifescience,medical gene (MDR1) encoding the P-glycoprotein responsible for exporting lipophilic compounds to the extracellular space (and thus reducing drug absorption in the gut as well as inhibiting their crossing the blood-brain barrier)14,15; and, the orosomucoid 1 and 2 (ORM1 and ORM2) encoding the alpha-1-acid glycoproteins responsible for most of the often extensive binding of psychotropics to plasma proteins.16,17 (Table I) Table I. Candidate genes and corresponding single nucleotide polymorphism (SNP) densities (pharmacokinetics). Genes encoding therapeutic targets of ADs (pharmacodynamics) A number of monoamine neurotransmitter systems, including serotonin (5-HT), norepinephrine (NE), and dopamine (DA), may all play crucial roles in mediating vulnerability to depressive disorders.

There exist reports of NMS occurring in patients prescribed venlafaxine in isolation [Lu et al. 2006]. NMS has generally been associated with high doses of antipsychotic medication as opposed to the low dose in this case although Lazarus and colleagues did conclude that NMS appeared not to be dose dependent [Viejo et al. 2003; Lazarus et al. 1989]. We considered the potential impacts of both hepatitis infection and methadone in the

development of NMS in this case but were unable to find any clear associations for either. It does not seem unreasonable to suggest that as a serotonergic enhancer, methadone may be involved in central dopaminergic inhibition similar to that seen with antidepressants Inhibitors,research,lifescience,medical and may therefore Inhibitors,research,lifescience,medical have played some role in the development of NMS in the above case. Footnotes Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of interest statement: GW has accepted transport and accommodation payments to attend

educational meetings sponsored by both AstraZeneca and Bristol-Myers Squibb. RB has accepted transport and accommodation Inhibitors,research,lifescience,medical payments to attend an educational meeting sponsored by Pfizer. Contributor Information Gary Woods, Ards Community Hospital, South Eastern Health and Social Care Trust, Newtownards, UK. Catherine Taggart, Windsor House, Belfast City Hospital, Belfast Health and Social Care Trust, Lisburn Road, Belfast BT9 7AB, UK. Robert Boggs, Substitute Prescribing Service, Belfast Health and Social Care Trust, Belfast, UK. Ian Cadden, Royal Victoria

Hospital, Belfast Health and Social Care Trust, Belfast, UK.
AZD8931 molecular weight clozapine is an antipsychotic drug that was first manufactured in 1959 and introduced into clinical practice in the 1970s. It has Inhibitors,research,lifescience,medical been shown to be more effective in the treatment of schizophrenia than typical antipsychotics [Wahlbeck et al. 2000]. It is the drug of choice for treating treatment refractory Inhibitors,research,lifescience,medical schizophrenia. It is the most effective antipsychotic for severe, refractory schizophrenia [Barnes, 2011]. Clozapine is a widely used atypical antipsychotic, and it has a complex and not entirely understood mechanism of action. It has a pharmacological profile and side effects that are different to those of other typical and atypical antipsychotic drugs; in fact, it interacts with several subtypes of dopaminergic (D1, D2, D3, D4), serotonergic (5-HT1A, 5-HT2A, 5-HT2C, 5- HT3, 5-HT6, 5-HT7), adrenergic isothipendyl (1, 2), histamine (H1) and muscarinic (M1) receptors [Raggi et al. 2004]. It has been hypothesized that this high affinity of clozapine for dopamine D4 receptors, rather than the D2 receptors, is the origin of its superiority. There is a 2.8% risk of granulocytopenia when taking clozapine and a 0.6% risk of agranuloctosis [Loebel et al. 1992]. Other well-known side effects concern sedation in 39% of patients [Safferman et al. 1991], and precipitation of seizures.