This study determined the effectiveness of the Tobacco Tactics intervention.This was a pragmatic, quasi-experimental study conducted from 2010 to 2013 and analyzed from 2014 to 2015 in five Michigan community hospitals; three received the Tobacco Tactics intervention, and two received usual care. Smokers (N=1,528) were identified during hospitalization, and sent surveys and cotinine tests after 6 months. Changes in pre- to post-intervention quit rates in the intervention sites were compared with usual care control sites.The toolkit for nurses included: (1) 1 continuing education unit contact hour for training; (2) a PowerPoint presentation on behavioral and pharmaceutical interventions; (3) a pocket card entitled "Helping Smokers Quit: A Guide for Clinicians"; (4) behavioral and pharmaceutical protocols; and (5) a computerized template for documentation. The toolkit for patients included: (1) a brochure; (2) a cessation DVD; (3) the Tobacco Tactics manual; (4) a 1-800-QUIT-NOW card; (5) nurse behavioral counseling and pharmaceuticals; (6) physician reminders to offer brief advice to quit coupled with medication sign-off; and (7) follow-up phone calls by trained hospital volunteers.The effectiveness of the intervention was measured by 6-month 30-day point prevalence; self-reported quit rates with NicAlert® urinary biochemical verification (48-hour detection period); and the use of electronic medical record data among non-responders.There were significant improvements in pre- to post-intervention self-reported quit rates (5.7% vs 16.5%, p<0.001) and cotinine-verified quit rates (4.3% vs 8.0%, p<0.05) in the intervention sites compared with no change in the control sites. Propensity-adjusted multivariable analyses showed a significant improvement in self-reported 6-month quit rates from the pre- to post-intervention time periods in the intervention sites compared to the control sites (p=0.044) and a non–statistically significant improvement in the cotinine-verified 6-month quit rate.The Tobacco Tactics intervention, which meets the Joint Commission standards for inpatient smoking, has the potential to significantly decrease smoking among inpatient smokers.This study is registered at www.clinicaltrial.gov NCT01309217.

Adolescents and young adults disproportionately abuse 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'); however, since most MDMA research has concentrated on adults, the effects of MDMA on the developing brain remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline) during late adolescence and assessed anxiety-like behavior and monoamine levels during abstinence. Rats were conditioned to associate 5 or 10mg/kg MDMA or saline with contextual cues over 4 twice-daily sessions. Five days after conditioning, anxiety-like behavior was examined with the open field test and brain tissue was collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus by high-pressure liquid chromatography (HPLC). In a separate group of rats, anxiety-like and avoidant behaviors were measured using the light-dark box test under similar experimental conditions. MDMA conditioning caused a place aversion at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the open field and avoidant behavior in light-dark box test at the same dose. Additionally, 10mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we show that repeated high (10mg/kg), but not low (5mg/kg), dose MDMA during late adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by region-specific alterations in 5-HT levels during abstinence. These results suggest that MDMA causes a region-specific dysregulation of the serotonin system during adolescence that may contribute to maladaptive behavior.

When psychiatric hospitalization is over-used, it represents a financial drain and failure of care. We evaluated implementation and cessation of transporting people medically certified for psychiatric hospitalization to a central psychiatric emergency service for management and re-evaluation of hospitalization need. After implementation, the hospitalization rate declined 89 % for 346 transported patients; only four of the nonhospitalized patients presented in crisis again in the next 30 days. Following cessation, the hospitalization rate jumped 59 % compared to the preceding year. Costs declined 78.7 % per diverted patient. The findings indicate that it is possible to reduce hospitalization and costs, and maintain quality care.

To examine and compare brain activation patterns of premenopausal women with normal sexual function and those with hypoactive sexual desire disorder (HSDD) during viewing of validated sexually explicit film clips.Cross-sectional pilot study.University-based clinical research center.Premenopausal women.None.Areas of brain activation during viewing of sexually explicit film clips.Women with normal sexual function showed significantly greater activation of the right thalamus, left insula, left precentral gyrus, and left parahippocampal gyrus in comparison with women with HSDD, who exhibited greater activation of the right medial frontal gyrus and left precuneus regions.Women with HSDD may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one's own physical state.

To examine and compare brain activation patterns of premenopausal women with normal sexual function and those with hypoactive sexual desire disorder (HSDD) during viewing of validated sexually explicit film clips.Cross-sectional pilot study.University-based clinical research center.Premenopausal women.None.Areas of brain activation during viewing of sexually explicit film clips.Women with normal sexual function showed significantly greater activation of the right thalamus, left insula, left precentral gyrus, and left parahippocampal gyrus in comparison with women with HSDD, who exhibited greater activation of the right medial frontal gyrus and left precuneus regions.Women with HSDD may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one's own physical state.

The presence and magnitude of information processing deviations associated with Post-Traumatic Stress Disorder (PTSD) are far from being well-characterized. In this study we assessed the auditory and visually evoked cerebral responses in a group of Iraqi refugees who were exposed to torture and developed PTSD (N = 20), Iraqi refugees who had been exposed to similar trauma but did not develop PTSD (N = 20), and non-traumatized controls matched for age, gender, and ethnicity (N = 20). We utilized two paired-stimulus paradigms in auditory and visual sensory modalities, respectively. We found significantly smaller amplitudes of both the auditory P50 and the visual N75 responses in PTSD patients compared to controls, reflecting decreased response to simple sensory input during a relatively early phase of information processing (interval 50-75 ms post stimulus). In addition, deficient suppression of the P50/N75 response to repeating stimuli at this early stage in both modalities is indicative of difficulty in filtering out irrelevant sensory input. Among associations between electrophysiological and clinical measures, a significant positive correlation was found between dissociation score and P50 S1 amplitudes (p = 0.024), as well as stronger auditory P50 gating correlated with higher quality-of-life index scores (p = 0.013). In addition, smaller amplitudes of N150 visual evoked response to Si showed a significant association with higher avoidance scores (p = 0.015). The results of this study highlight the importance of early automatic auditory and visual evoked responses in probing the information processing and neural mechanisms underlying symptomatology in PTSD. (C) 2013 Elsevier Ltd. All rights reserved.

OBJECTIVE:The aim of this study was to determine the effects of 10 and 20 mg/day of escitalopram on objectively recorded hot flashes and on the rectal temperature threshold for sweating. METHODS:Two studies were performed: 16 women received 10 mg/day and 26 women received 20 mg/day escitalopram for 8 weeks. They were randomly assigned in equal numbers to receive active drug or placebo in a double-blind fashion. Hot flash frequency was measured with an ambulatory recorder during the first 3 weeks and during the 8th week of the study. Rectal temperature threshold for sweating was measured during the 1st and 8th weeks of the study using published methods. RESULTS:In the first study, there were no significant effects whatsoever for any measure. In the second study, the escitalopram group showed an average decline in hot flash frequency of 14.4%, whereas the placebo group showed an average increase of 6.7% (P < 0.05). However, there were no significant effects across time for either group. There were no significant effects whatsoever for rectal temperature sweating thresholds. CONCLUSIONS:Escitalopram at 10 or 20 mg/day is not effective in the treatment of menopausal hot flashes.

Byline: Vikram. Yeragani, Manuel. Tancer, Pratap. Chokka, Glen. Baker Arvid Carlsson was born in Uppsala, Sweden in 1923. Dr. Carlsson, a pharmacologist, is best known for his contributions on the neurotransmitter, dopamine, for which he won the Nobel Prize in 2000 for Medicine/Physiology. The co-recipients were Dr. Eric Kendel and Dr. Paul Greengard. Dr. Carlsson entered Medical School in 1941 and his education was interrupted by several years of service in the Swedish armed forces. In 1951, he finished the M.L. degree, now equivalent to M.D. in North America. Later, he became a Professor at the University of Lund. In 1959, he moved to Goteborg University. In 1957, Dr. Carlsson showed that dopamine was a neurotransmitter in the brain and not just a precursor of norepinephrine.[sup] [1] This was the prevailing view at that time. He also developed an assay to measure dopamine in the brain and found that the highest regional concentration existed in the basal ganglia. This finding led to his experiments on reserpine, which depleted dopamine and produced a loss of movement control. These symptoms were similar to the clinical symptoms seen in the neurological illness, Parkinsonism.[sup] [2],[3] He did not end his investigations there, and showed that L-dopa, a precursor of dopamine, was effective treat symptoms of Parkinsonism. L-dopa is still one of the mainstays of drug treatment in Parkinsonism. Dr. Carlsson was also instrumental in developing the 'dopamine theory of schizophrenia'[sup] [4],[5] and the role of dopamine in the development of extrapyramidal side-effects of antipsychotic medications. Inhibition of central dopamine function is a basic property common to many to antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets for the psychological and the extrapyramidal actions, respectively, of these drugs. The fact that dopaminergic hyperfunction induced by amphetamines or L-dopa may lead to a disturbance mimicking paranoid schizophrenia, further supporting the role of dopamine in mental function. Although a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems should be studied in more detail. The possible involvement of other amine, amino acid or peptide transmitters in schizophrenia cannot be disregarded. For example, there is now a large body of evidence supporting dysfunction of the glutamate receptors in schizophrenia. Dr. Carlsson was also among the first researchers of the antidepressant compound, zimeldine, which was the first selective serotonin re-uptake inhibitor. The precursor of this drug was brompheniramine. Here, one should note that he did substantial work on the synthesis and metabolism of 5-hydroxytryptamine (serotonin) in the central nervous system.[sup] [6] However, zimeldine produced a serious neuro logical side-effect, Guillian-Barre syndrome, in a few patients and thus was withdrawn from the market. Thirteen cases of the Guillain-Barre syndrome were reviewed in an article in which the authors showed that all occurred with a similar relationship to treatment with zimeldine. The risk of developing Guillain-Barre syndrome was increased about 25-fold among patients receiving zimeldine, as compared with the natural incidence of the disorder. These cases substantiate strong evidence that Guillain-Barre syndrome may occur as a specific, probably immunologically mediated, complication of drug therapy. …

We have previously shown that nonlinear measures of regularity and complexity are very useful as complimentary measures to the linear measures of time and frequency domain of beat-to-beat heart rate and QT intervals. In this study, we have applied Cross-ApEn, a nonlinear measure that can give an index of dissociation between two time series. We have shown that it can be superior to the linear measure of cross-coherence between the two signals. The practical implications of this finding have been further discussed in detail.

In natural cycles of attempted conception, stress has been shown to predict lower conception rates. The objective of this article is to determine whether stress affects the outcome of assisted reproductive technology (ART) as well. In addition, this article analyzes the effect that psychosocial interventions targeting the reduction of stress have on ART outcomes. This review examined available PubMed articles published in the past 15 years, and 28 articles were included. Looking specifically at numbers of women studied, stress appears to negatively affect ART outcome; interventions targeting stress reduction appear beneficial. Because stress appears to negatively affect ART outcome, and psychosocial interventions do not have detrimental effects, screening for stress should occur and some type of intervention considered during the ART process.

Previous studies have observed reduced vagal modulation in patients with acute schizophrenia and their first-degree relatives, thus suggesting a genetic predisposition. To investigate vagal modulation, we analyzed the coupling between heart rate and breathing as a putative measure of central autonomic function in 19 patients, 19 of their relatives and 19 matched control subjects. The interaction of heart rate and breathing was investigated in all groups applying the non-linear parameter cross-ApEn, indicating the asynchrony between both time series. In addition, measures of the time and frequency domain of heart rate variability (HRV) were obtained. The main finding of our study is a significantly increased cross-ApEn value, indicating reduced central vagal modulation both in relatives and patients suffering from schizophrenia. Non-linear measures of HRV proved to more sensitively differentiate relatives from control subjects. Furthermore, we observed a correlation between psychopathology and breathing, indicating that positive symptoms are associated with a higher degree of regularity in the breathing pattern. Our results suggest that autonomic dysfunction previously described for patients suffering from schizophrenia is also present in first-degree relatives. This might relate to changes of brainstem activity in patients and relatives, and a common genetic background in patients and their family members can be assumed.

Background: Somatic symptoms of the gastrointestinal tract occur frequently in major depressive disorder (MDD) and might be associated with the known autonomic imbalance in the disease. Hence, we have investigated gastric electrical activity in patients suffering from major depression before and after treatment by means of electrogastrography (EGG) to investigate a putative association with either the disease state and its symptoms or its relation to the treatment.Methods: EGG readings before and after ingestion of a test meal of 27 patients suffering from major depression were recorded before and after treatment with antidepressants and compared with age-matched controls. Abdominal symptoms were rated by a specific Autonomic Nervous Symptom-score.Results: We found a significantly increased amount of tachygastria before and after medication, indicating increased sympathetic modulation. A significant difference was observed for the instability coefficients before and after medication, indicating gastric dysmotility in our patients prior to treatment. The elevated approximate entropy measure points to increased complexity and dysregulation. Furthermore, we have observed a correlation between subjective sensation of sweating and dry mouth with the sympathetic parameter tachygastria.Discussion: Our results suggest that major depression is associated with gastric dysrhythmia possibly caused by increased sympathetic modulation. Linear and non-linear EGG measures emphasize a possible role of the autonomic nervous system in the development of gastric symptoms. The treatment with antidepressants seems to increase the activity of the sympathetic nervous system, without aggravating gastric symptoms. The association of increased sympathetic modulation with somatic symptoms was indicated by correlation analysis with these symptoms. (C) 2009 Elsevier Inc. All rights reserved.

Age has been identified as an independent risk factor for cardiovascular diseases. In addition, autonomic imbalance toward sympathetic preponderance has been shown to facilitate the occurrence of heart disease. Here, we aimed to assess autonomic modulation of cardiovascular parameters during normal ageing applying well-established linear and novel nonlinear parameters.Linear and nonlinear measures of heart rate variability and complexity as well as measures of QT interval variability and baroreflex sensitivity were obtained from a total of 131 healthy, medication-free participants from a continuous age range between 20 and 90 years, who were allocated to three different age groups.Heart rate variability and complexity significantly decreased with age, while regularity of heart rate time series increased. In addition, QT interval variability linearly increased with age, while baroreflex sensitivity showed a pronounced decrease. Overall, concerning effects of ageing, linear and nonlinear parameters showed equal differentiation between groups.These data indicate a shift of autonomic balance toward sympathetic predominance in higher age groups, limiting the reactiveness of the cardiovascular system to adjust to different demands and increasing the risk for developing tachyarrhythmias.

In patients with panic disorder, an anxiety disorder, isoproterenol increases beat-to-beat QRS amplitude variability much more than in normal controls. In this pilot study, we found that patients with panic disorder had significantly higher beat-to-beat QRS amplitude variability compared to controls in resting supine and standing postures. This may be partly due to myocardial electrical instability or irregular respiration in this patient group. These findings are important in view of the association between panic disorder and increased cardiovascular mortality.

STUDY OBJECTIVE 3,4-Methylenedioxymethamphetamine (MDMA) affects monoamine neurotransmitters that play a critical role in sleep and daytime alertness. However, the acute effects of MDMA on sleep and daytime sleepiness have not been studied under placebo-controlled conditions. This study was designed to establish the effects of acute MDMA or placebo administration and sleep restriction on sleep and daytime sleepiness. DESIGN Participants with a history of MDMA use were studied on 3 sessions of 3 nights (baseline, treatment, and recovery) and 2 days (following night 2 and 3) per session. On treatment nights (night 2), participants received placebo or 2 mg/kg of MDMA or underwent a restricted bed schedule with placebo. Sleep restriction was a positive control to compare sleep loss and consequent sleepiness associated with MDMA use. The scheduled sleep period was 8 hours long on nonrestricted nights, and standard sleep recordings and daytime sleepiness tests were conducted. Age-matched controls received 1 night and day of standard sleep and daytime sleepiness testing. SETTING Sleep laboratory. PARTICIPANTS Seven recreational MDMA-users and 13 matched control subjects. MEASUREMENTS AND RESULTS Acute MDMA shortened sleep primarily by increasing sleep latency, and it reduced stage 3/4 sleep and suppressed rapid eye movement (REM) sleep. The MDMA-reduced sleep time was not associated with increased daytime sleepiness the following day, as was seen in the sleep-restriction condition. Compared with control subjects, the MDMA users on the first night in the laboratory had shorter total sleep times and less stage 3/4 sleep. Average daily sleep latency on daytime sleepiness tests the day after nighttime placebo administration was increased in MDMA users compared with the control subjects, and MDMA users had an elevated number of sleep-onset REM periods on these tests, compared with control subjects. CONCLUSIONS Acute MDMA administration disrupts sleep and REM sleep, specifically, without producing daytime sleepiness such as sleep restriction does. Compared with control subjects, recreational MDMA users showed evidence of hyperarousal and impaired REM function. The mechanism behind these effects is likely due to the deleterious effects of MDMA on catecholamines.

Antipsychotics have been broadly classified into classical/typical, which includes phenothiazines and butyrophenones, and atypical antipsychotics, which includes benzamides. The psychiatric effects of all the progeners of these groups were discovered serendipitously. Chlorpromazine, belonging to phenothiazines, heralded the “psychopharmacological era” and replaced biological therapies such as electroconvulsive therapy, insulin coma, frontal lobotomy and simple sedation, causing an important revolution in psychiatric practice. Derivatives of phenothiazines, such as methylene blue, had been used since the nineteenth century in the dyeing industry (textile as well as histopathological preparations) and pharmaceuticals such as antiseptics and antihelmenthics. A group of phenothiazine derivatives with an aminate chain were synthesized by a team led by Paul Charpentier to exploit the antihistaminic properties as pre-anesthetic medication. In 1949, Henri-Marie Laborit, a French army surgeon, used promethazine, a phenothiazine derivative, along with barbiturates, to prevent surgical shock and called this “lytic cocktail.” He also noticed that the patients who were extremely anxious were made calm, relaxed and indifferent to the surroundings. Agitated patients got subdued and co-operative as if they had a “pharmacological lobotomy.” The research on phenothiazines continued until 1950, when a chlorinated derivative of promazine was developed: RP-4560, later named chlorpromazine, which not only had antihistaminic properties but was also adrenolytic, gangliolytic and antiemetic among many other effects. Laborit tried to convince psychiatrists about the therapeutic uses of the drug in psychiatry, in line of his hypothesis and observations, especially in sleep disorders. No one in the scientific community was enthused about it. Finally, Joseph Hammon tried it for the first time in 1952 on a manic patient. The patient not only calmed down but was also able to maintain this state. He was eventually discharged after 3 weeks. Researchers almost disregarded this effect because the patient was on other medication, such as barbiturates, opiates and electro-convulsive therapy. In the same year, Jean Delay and Deniker conducted a study using chlorpromazine alone and observed a group of symptoms with decreased motor activity and affective indifference. They named the constellation of symptoms as “neuroleptic syndrome.” The word neuroleptic was suggested by Jean Delay in 1955, which meant “that take the nerve.” The duo further went on to present six clinical reports on 38 patients with mania and psychosis and confirmed the effectiveness of chlorpromazine. Heinz Lehmann, a psychiatrist from Berlin and a refugee residing in Canada, published similar articles on the use of chlorpromazine exhaustively over several years. He used the drug in different psychiatric conditions with psychomotor agitation (acute and chronic mania, schizophrenia, senile psychosis, post lobotomy and mentally challenged). He obtained positive results in 66%, but the response was the best in patients with manic depression, who were manageable within 24 hours, subsequently, having fewer relapses. He also cautioned that, in patients with chronic schizophrenia who were nonresponders, the possible toxic effects of the drug prevailed. In 1954, Elkes and Elkes conducted a historic study on psychotic patients, which was randomized and placebo-controlled, showing the effectiveness of chlorpromazine. Eventually chlorpromazine started being accepted by psychiatrists all over the world, although a slow start. Thus, it paved the way for the “neuro-biological” basis of psychiatric illnesses.[1] Haloperidol belongs to butyrophenones and was synthesized in 1958 at a Belgian laboratory by Paul Janssen. Janssen laboratories were then trying to develop a more powerful analgesic than dextromoramide. They used pethidine, the byproducts of which were named butyrophenones and haloperidol was the 45th of the series, R-1625. They observed that it was poorer an analgesic compared with opioids. However, the experimental mice were sedated and went into a cataleptic state similar to that produced by chlorpromazine, after an initial state of excitation. First clinical studies were conducted by Bloch on patients with delirium tremens. It resulted in no significant sedation except for hypotension. After a few weeks of its synthesis, the drug was used intravenously on a psychiatric patient with an emotional crisis by a resident physician Pinchard. The patient became considerably calm and later went into a state of sedation. Studies conducted all over Belgium with this drug showed outstanding results in agitated patients but its hallucinolytic effects surpassed the others. Delay and Deniker conducted studies in France on this drug as well and obtained similar results. However, they warned of its extrapyramidal side-effects similar to the effects of chlorpromazine. Haloperidol has also been considered very efficient in paranoid states.[2] After the advent of chlorpromazine, other drugs such as haloperidol, trifluperazine, thioridazine and fluphenazine came into use. All were found to have comparable efficacy, but had serious neurological side-effects such as neuroleptic malignant syndrome. The search continued for a neuroleptic with lesser side-effects. In 1958, a group of tricyclic compounds was synthesized, based on the antidepressant imipramine in a Swiss laboratory. Some of these compounds were found to have neuroleptic properties. One of them was clozapine. The initial studies by Wander in 1959 obtained mixed results, but one of them was significant; clozapine did not cause catalepsy in animal studies. In 1962, Gross and Langner conducted trials with human subjects and found the drug to be ineffective for psychosis. In 1966, Hanns Hippius, a German researcher, was asked to continue the trials on humans by Wander. The results confirmed that clozapine was an effective antipsychotic with no disabling neurological side-effects. The psychiatric community remained sceptical because the drug lacked side-effects. They believed that if there are no Parkinsonian symptoms, the drug is not a true antipsychotic. The more pronounced the extrapyramidal symptoms were, the more effective the drug was. Despite this belief, there were many patients with schizophrenia that were placed on clozapine. Finally, after several large trials summarized by Stille and Hippius, clozapine was launched into the market in several European countries. In 1973, Gilbert Honigfeld, a clinical psychologist, started open-label phase-2 trials on prison inmates in the USA. The inmates experienced increased heart rate and syncope due to orthostatic hypotension even with lower doses (25-75 mg). This finding was never mentioned in the earlier literature. The solution was to titrate the dose slowly up to a tolerable level, starting from a smaller dose. In 1974, open-label studies were conducted on schizophrenic patients by Simpson and Varga and double-blind clinical trials by Shopsin, Klein, Aaronson and Collora. Later, many multicentered trials of clozapine vs. chlorpromazine were conducted. When clozapine was gradually being accepted as a promising antipsychotic, an adversity befell upon it. In 1975, the Journal, Lancet, reported that 18 patients had developed severe blood dyscrasia. Sixteen of them had agranulocytosis with nine deaths. This was reported from Finland by Idanpaan- Heikkila, Alhava, Olkinvoura and Palva. The government agencies then ordered clozapine to be removed from the market in Finland as well as the other European countries. Later studies all over the world showed that agranulocytosis was 20-times higher in south-western Finland compared with the rest of the world. The exact causes for this Finnish “epidemic” were not known. In the meanwhile, agranulocytosis and sudden death with chlorpromazine and other phenothiazines were also reported. Shopsin et al. reported that the worldwide incidence of agranulocytosis with clozapine (0.3%) was similar to chlorpromazine (0.1-1.0%). However, there were controversial findings in some of the later studies. Amsler, Teerenhovi, Barth, Harjula and Vuopio did a thorough analysis and found that agranulocytosis occurred within the first 3 months, whether fatal or not, and deaths were due to secondary infection and delays in the detection or lack of preventive measures. This fact led to the mandatory weekly checks of white cell counts in the blood for the first 18 weeks. Until then, clozapine was restricted to compassionate use for treatment-resistant cases of schizophrenia. Later on, the worldwide support for clozapine grew and was also reported to be used in children with Tourette's syndrome successfully by Caine, Polinsky, Kartzinel and Ebert. In 1984, a 6-week double-blind study was conducted at 16 sites in the USA comparing clozapine with chlorpromazine. Clozapine was shown to have a definite superiority over chlorpromazine. The improvement not only continued even after 6 weeks, but the drug worked for positive as well as negative symptoms in schizophrenia. Kane, Henigfeld, Singer and Meltzer, finally, were able to show clozapine to be an effective antipsychotic without extrapyramidal symptoms and hence named it “atypical.” Although it had other benign side-effects, such as drowsiness, hypersalivation, hypotension and a propensity to decrease seizure threshold, clozapine continues to be the drug of choice for treatment refractory schizophrenia.[3] Although the process of scientific drug development is slow and tedious, clozapine still emerged victorious. The 1990s was the decade that witnessed the advent of several other atypical antipsychotics, such as risperidone, olanzapine, quetiapine, ziprasidone and similar drugs. These were considered as effective as the other antipsychotics and had the least propensity to cause extrapyramidal side-effects, but had other side-effects innate to the group, such as metabolic syndrome. While we compare the typical antipsychotics with the atypicals in terms of their effectiveness and side-effect profile, none seems to be more superior compared with the other. We have come a long way from insulin therapy and prefrontal lobotomies to compounds that not only are effective antipsychotics but also help patients to lead a better life, despite some of the side-effects. The search continues to develop drugs that address all aspects of the illness, the positive, the negative and the cognitive symptoms, and for that “ideal” antipsychotic.

Cardiac autonomic dysfunction has been reported in patients suffering from schizophrenia. The aim of the present study was to evaluate gastric electrical activity in unmedicated patients suffering from acute schizophrenia in relation to their symptoms. Electrogastrography was performed before and after test meal ingestion in 26 patients suffering from schizophrenia and 26 matched controls. The non-linear measure approximate entropy (ApEn) was calculated for the first time from the obtained signal in addition to standardized measures. Results were correlated with the scales for the assessment of positive symptoms and negative symptoms. In addition, autonomic and abdominal symptoms were assessed by the autonomic symptom score. We found a significantly increased amount of tachygastria and arrhythmia within the signal of the activity of the gastric pacemaker before and after test meal digestion in patients compared to controls, indicating increased sympathetic modulation within the enteric nervous system. A significant difference was observed for slow wave, which represents the dominant frequency of gastric pacemaker activity, indicating gastric dysmotility in our patients. The elevated ApEn measure points to increased complexity and dysregulation. In addition, we have observed a correlation between delusions and tachygastria. Sympathetic function seems to be altered in the enteric nervous system of patients suffering from schizophrenia. Future studies need to explore the influence of the disease on different branches of the autonomic nervous system and clinical consequences of enteric dysfunction. Our findings point to a possible systemic autonomic imbalance that needs to be studied in respect to the neurobiology of schizophrenia.