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Background Dysmyelination could be part of the pathophysiology of schizophrenia spectrum (SCZ) and bipolar disorders (BPD), yet few studies have examined myelination of the cerebral cortex. The ratio of T1- and T2-weighted magnetic resonance images (MRI) correlates with intracortical myelin. We investigated the T1w/T2w-ratio and its age trajectories in patients and healthy controls (CTR) and explored associations with antipsychotic medication use and psychotic symptoms. Methods Patients with SCZ (n = 64; mean age = 30.4 years, s.d. = 9.8), BPD (n = 91; mean age 31.0 years, s.d. = 10.2), and CTR (n = 155; mean age = 31.9 years, s.d. = 9.1) who participated in the TOP study (NORMENT, University of Oslo, Norway) were clinically assessed and scanned using a General Electric 3 T MRI system. T1w/T2w-ratio images were computed using an optimized pipeline with intensity normalization and field inhomogeneity correction. Vertex-wise regression models were used to compare groups and examine group × age interactions. In regions showing significant differences, we explored associations with antipsychotic medication use and psychotic symptoms. Results No main effect of diagnosis was found. However, age slopes of the T1w/T2w-ratio differed significantly between SCZ and CTR, predominantly in frontal and temporal lobe regions: Lower T1w/T2w-ratio values with higher age were found in CTR, but not in SCZ. Follow-up analyses revealed a more positive age slope in patients who were using antipsychotics and patients using higher chlorpromazine-equivalent doses. Conclusions While we found no evidence of reduced intracortical myelin in SCZ or BPD relative to CTR, different regional age trajectories in SCZ may suggest a promyelinating effect of antipsychotic medication. [ABSTRACT FROM AUTHOR]

Background: Agitated patients constitute 10% of all emergency psychiatric treatment. Management guidelines, the preferred treatment of clinicians differ in opinion and practice. In Lebanon, the use of the triple therapy haloperidol plus promethazine plus chlorpromazine (HPC) is frequently used but no studies involving this combination exists. Method: A pragmatic randomised open trial (September 2018–July 2019) in the Lebanese Psychiatric Hospital of the Cross in Beirut Lebanon involving 100 people requiring urgent intramuscular sedation due to aggressive behaviour were given intramuscular chlorpromazine 100 mg plus haloperidol 5 mg plus promethazine 25 mg (HPC) or intramuscular haloperidol 5 mg plus promethazine 25 mg Results: Primary outcome data were available for 94 (94%) people. People allocated to the haloperidol plus promethazine (HP) group showed no clear difference at 20 min compared with patients allocated to the HPC group [relative risk (RR) 0.84, 95% confidence interval (CI) 0.47–1.50]. Conclusions: Neither intervention consistently impacted the outcome of 'calm', or 'asleep' and had no discernible effect on the use of restraints, use of additional drugs or recurrence. If clinicians are faced with uncertainty on which of the two intervention combinations to use, the simpler HP is much more widely tested and the addition of chlorpromazine adds no clear benefit with a risk of additional adverse effects. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function. Methods: The present study sought to fill this gap by examining healthy controls (N = 75), unmedicated (N = 48) and medicated (N = 148) individuals with schizophrenia. Participants were recruited across five sites as part of the CNTRaCS Consortium to complete tasks assessing processing speed, cognitive control, working memory, verbal learning, relational encoding and retrieval, visual integration and reinforcement learning. Results: Individuals with schizophrenia who were not taking antipsychotic medications, as well as those taking antipsychotic medications, showed pervasive deficits across cognitive domains including reinforcement learning, processing speed, cognitive control, working memory, verbal learning and relational encoding and retrieval. Further, we found that chlorpromazine equivalency rates were significantly related to processing speed and working memory, while there were no significant relationships between anticholinergic load and performance on other tasks. Conclusions: These findings add to a body of literature suggesting that cognitive deficits are an enduring aspect of schizophrenia, present in those off antipsychotic medications as well as those taking antipsychotic medications. [ABSTRACT FROM AUTHOR]

CPZ was soon applied by psychiatrists as a general sedative and marked the "beginning of the end" of asylums and the decrease in the number of those admitted to mental institutions (Lieberman, 2015; Sherman, 2016). Before the use of this neuroleptic and drugs such as imipramine and lithium, serious mental illness condemned the patients to a lifetime of confinement and reduced activity. This approach to the patients' productions emanated from the idea that the written, verbal and pictorial expression of patients directly reflected the proposed classification of their mental illnesses: their works did not belong to the world of art but were symptomatic for their disease. The fury and violence had given way to calmness and peace ... the results with CPZ could be measured in the psychiatric hospital in decibels... recorded before and after the drug. [Extracted from the article]

Background: Previous literature supports antipsychotics' (AP) efficacy in acute first-episode psychosis (FEP) in terms of symptomatology and functioning but also a cognitive detrimental effect. However, regarding functional recovery in stabilised patients, these effects are not clear. Therefore, the main aim of this study is to investigate dopaminergic/anticholinergic burden of (AP) on psychosocial functioning in FEP. We also examined whether cognitive impairment may mediate these effects on functioning. Methods: A total of 157 FEP participants were assessed at study entry, and at 2 months and 2 years after remission of the acute episode. The primary outcomes were social functioning as measured by the functioning assessment short test (FAST). Cognitive domains were assessed as potential mediators. Dopaminergic and anticholinergic AP burden on 2-year psychosocial functioning [measured with chlorpromazine (CPZ) and drug burden index] were independent variables. Secondary outcomes were clinical and socio-demographic variables. Results: Mediation analysis found a statistical but not meaningful contribution of dopaminergic receptor blockade burden to worse functioning mediated by cognition (for every 600 CPZ equivalent points, 2-year FAST score increased 1.38 points). Regarding verbal memory and attention, there was an indirect effect of CPZ burden on FAST (b = 0.0045, 95% CI 0.0011–0.0091) and (b = 0.0026, 95% CI 0.0001–0.0006) respectively. However, only verbal memory post hoc analyses showed a significant indirect effect (b = 0.009, 95% CI 0.033–0.0151) adding premorbid IQ as covariate. We did not find significant results for anticholinergic burden. Conclusion: CPZ dose effect over functioning is mediated by verbal memory but this association appears barely relevant. [ABSTRACT FROM AUTHOR]

Introduction Quincke-edema has been specifically associated with using certain drugs including chlorpromazine as detailed through two clinical cases. Objectives Illustration of two clinical cases about angioedema induced by Chlorpromazine. Methods We reviewed clinical data from two patients who committed a suicide attempt and then transferred to the psychiatry department after their somatic stabilization: the first was 27-year-old followed in psychiatry since childhood for intellectual deficiency and admitted to the emergency department for the suicide attempt by taking 14 tablets of chlorpromazine 100 mg and the second was a 20-year-old patient, admitted to the emergency department for suicide attempt by Raticid. Results The first patient presented a delusional persecution-themed syndrome with auditory hallucinations. Therefore, he was initially put on injectable treatment with Haloperidol 15mg and Diazepam 30mg then oral relay after 48h by Risperidone 4 mg and Chlorpromazine 200 mg. On the fourthday of his hospitalization, he presented a Quincke edema without laryngeal impairment. We stopped chlorpromazine and eliminated the other causes of this edema, resulting in a gradual regression of symptomatology. The second patient was put on chlorpromazine. On the second day, the patient presented a Quincke edema without laryngeal impairment. Somatic examination and biological exploration did not reveal any abnormalities. We stopped chlorpromazine and put the patient on Dexamethasone 3 days in a row resulting in a good outcome. Conclusions These two cases identified a Quincke-edema reaction associated with the use of Chlorpromazine, this complication can lead to life-threatening manifestations and warrants greater awareness of the potential for recurrence.

Introduction: There is growing evidence of excitation / inhibition (E/I) balance abnormalities in schizophrenia, which might be associated with abnormal gamma frequency oscillations and glutamate concentrations. However, to the best of our knowledge, only one multimodal study have examined such associations between EEG and metabolite characteristics in patients at clinical-high risk of psychosis (CHR) so far. Objectives: We aimed to investigate potential associations between GLX (glutamate + glutamine) levels and resting-state gamma-band power in CHR individuals and healthy controls (HC). Methods: Twenty right-handed male patients (16-27 years, mean age 19.9 ± 2.7) fulfilling CHR criteria and 19 healthy male controls (16-27 years, mean age 21.6 ± 3.6) underwent resting-state EEG (16 leads; 10−20 system) and MR spectroscopy at 3T MRI scanner with voxels of 30×30×30mm located in left and right medial prefrontal cortex. Spectral analysis with estimation of gamma-band power (30-45 Hz) were conducted. MEGA-PRESS acquisitions were analyzed with jMRUi (ver. 5.1 Alpha), levels of GLX were calculated as a ratios to creatine + phosphocreatine (GLX/Cr). Gamma-band (30-45 Hz) spectral power and GLX/Cr were compared between groups. Correlations between EEG and metabolite data were analyzed with regression model including age and chlorpromazine equivalents as covariates. Results: Compared to healthy controls, patients showed reduced spectral gamma-band power in 6 leads (Table). No alterations in GLX/Cr were detected. Positive correlations between altered gamma-power in all leads (except Cz) and GLX/Cr in left medial prefrontal cortex were revealed in CHR (F3: r=0.51, p=0.006; F8: r=0. 54, p=0.004; C3: r=0.37, p=0.037; Pz: r=0.51, p=0.039; P4: r=0.56, p=0.009). No correlations in HC group were found. Chlorpromazine equivalents did not correlate with GLX/Cr of gamma power in CHR group. Table. Results of between-group comparisons corrected for multiple comparisons Lead CHR Mean±SD HC Mean±SD p -value F Cohen's d Cohen's d CI 95% F3 0.97±0.62 1.4±0.64 0.0097 7.2 -0.69 -1.22 -0.16 F8 0.84±0.61 1.45±1.03 0.0072 7.8 -0.71 -1.24 -0.19 C3 0.97±0.55 1.44±0.64 0.0026 9.9 -0.79 -1.32 -0.27 Cz 1.03±0.61 1.42±0.52 0.0074 7.7 -0.70 -1.22 -0.18 Pz 1.17±0.7 1.62±0.63 0.0098 7.1 -0.68 -1.2 -0.16 P4 1.04±0.66 1.53±0.66 0.0051 8.5 -0.74 -1.27 -0.22 Conclusions: The findings suggest that clinical-high risk of psychosis is associated with widespread alterations in resting-state gamma-band power. Positive correlations of such alterations with GLX/Cr and absence of such correlations in HC group are presumably indicative of disturbances in the excitation / inhibition balance in CHR individuals. This study was supported by RFBR grant 19-29-10040 Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

The author reflects on discoveries over the course of a century concerning histamine as a potent chemical signal and neurotransmitter, the development of antihistamines, including promethazine, and chlorpromazine from a common precursor, and the recognition of a major brain pathway involving histamine. Although chlorpromazine has been succeeded by numerous other antipsychotics, promethazine remains the antihistamine recommended for sedation in acutely disturbed patients, largely because it is potently anticholinergic at atropinic muscarinic receptors and therefore anti-Parkinsonian: this means it is also useful in combination with older antipsychotics such as haloperidol. [ABSTRACT FROM AUTHOR]

Twentieth-century psychiatry was transformed in the 1950s and 1960s by the introduction of powerful psychopharmaceuticals, particularly Chlorpromazine (Thorazine). This paper examines the reception of Chlorpromazine in the Soviet Union and its effect on the Soviet practice of psychiatry. The drug, known in the USSR by the name Aminazine, was first used in Moscow in 1954 and was officially approved in 1955. I argue that Soviet psychiatrists initially embraced it because Aminazine enabled them to successfully challenge the Stalin-era dogma in their field (Ivan Pavlov's 'theory of higher nervous activity'). Unlike in the West, however, the new psychopharmaceuticals did not lead to deinstitutionalisation. I argue that the new drugs did not disrupt the existing Soviet system because, unlike the system in the West, the Soviets were already dedicated, at least in theory, to a model which paired psychiatric hospitals with community-based 'neuropsychiatric dispensaries.' Chlorpromazine gave this system a new lease on life, encouraging Soviet psychiatrists to more rapidly move patients from in-patient treatment to 'supporting' treatment in the community. [ABSTRACT FROM AUTHOR]

Background: Cognitive deficits are a core feature of early stages in schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious effect on cognitive performance remains under debate. We aim to investigate whether anticholinergic loadings and dose of AP drugs in first episode of psychosis (FEP) in advanced phase of remission are associated with cognitive impairment and the differences between premorbid intellectual quotient (IQ) subgroups. Methods: Two hundred and sixty-six patients participated. The primary outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS), respectively]. Results: Impairments in processing speed, verbal memory and global cognition were significantly associated with high Eq-CPZ and verbal impairment with high ARS score. Moreover, this effect was higher in the low IQ subgroup. Conclusions: Clinicians should be aware of the potential cognitive impairment associated with AP in advanced remission FEP, particularly in lower premorbid IQ patients. [ABSTRACT FROM AUTHOR]

Background Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes. Methods The sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers. Results During the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319 mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score. Conclusions In our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes. [ABSTRACT FROM AUTHOR]

The so-called chemical revolution has produced a vast historiographical corpus. Yet the patient’s voice remains surprisingly absent from these stories. Based on the archives of the Institut de Psychiatrie (Brussels), this paper traces the introduction of Largactil as recounted in patient letters, physician records and nurse notes. The paper thus contributes to the history of therapies from below, but also participates in the historiographical debate about whether the introduction of neuroleptics can indeed be considered a revolution. [ABSTRACT FROM AUTHOR]

Background Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. Methods Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. Results Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate ( P = . 032) and earlier occurrence ( P = .043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. Conclusions Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample. [ABSTRACT FROM AUTHOR]

Background.Functional imaging studies in relatives of schizophrenic patients have had inconsistent findings, particularly with respect to altered dorsolateral prefrontal cortex activation. Some recent studies have also suggested that failure of deactivation may be seen.Method.A total of 28 patients with schizophrenia, 28 of their siblings and 56 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance was fitted to individual whole-brain maps from each set of patient–relative–matched pair of controls. Clusters of significant difference among the groups were then used as regions of interest to compare mean activations and deactivations among the groups.Results.In all, five clusters of significant differences were found. The schizophrenic patients, but not the relatives, showed reduced activation compared with the controls in the lateral frontal cortex bilaterally, the left basal ganglia and the cerebellum. In contrast, both the patients and the relatives showed significant failure of deactivation compared with the healthy controls in the medial frontal cortex, with the relatives also showing less failure than the patients. Failure of deactivation was not associated with schizotypy scores or presence of psychotic-like experiences in the relatives.Conclusions.Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontal cortex. This in turn suggests that default mode network dysfunction may function as a trait marker for schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Despite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability.Aims: To compare indices of obesity, glucose, lipids and prolactin between antipsychotic-treated and antipsychotic-naive individuals with intellectual disability and also between participants with intellectual disability and controls from the general population.Method: Observational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls.Results: Antipsychotic treatment comprised: risperidone 48%,olanzapine 18%, thioxanthenes 10%, other 24%; monotherapy 95% of participants; mean treatment duration 8 years;median daily chlorpromazine equivalent dose 108 mg(range 16–667). Metabolic indices were the same or more favourable in the intellectual disability group than the general population control group but overweight/obesity and type 2 diabetes were more prevalent in the women in the intellectual disability group than the control group. Metabolic indices were similar, statistically or clinically, between the antipsychotic-treated and the antipsychotic-naive groups but there was a non-significant trend towards a higher rate of type 2 diabetes in the antipsychotic group. A total of 100%and 70% of participants on amisulpride/sulpiride and risperidone respectively had hyperprolactinaemia, with secondary hypogonadism in 77% and 4% of affected women and men.Conclusions: Antipsychotics, on average, did not increase metabolic risk,although the existence of a susceptible subgroup at risk of diabetes cannot be excluded. Some antipsychotics induced hyperprolactinaemic hypogonadism, requiring active management. However, our findings suggest that antipsychotics at the low doses routinely prescribed for people with intellectual disability are generally safe in relation to metabolic adverse effects, even if efficacy remains poorly defined. [ABSTRACT FROM AUTHOR]

Background: The differential effects of so-called 'first- and second generation' antipsychotic medications, when given in the first episode, on the long-term outcome of schizophrenia remain to be elucidated.Aims: We compared the 9-year outcomes of individuals initially randomised to clozapine or chlorpromazine.Method: One-hundred and sixty individuals with treatment-naive, first episode schizophrenia or schizophreniform disorder in a mental health centre in Beijing, China were randomised to clozapine or chlorpromazine treatment for up to 2 years,followed by up to an additional 7 years of naturalistic treatment. The primary outcome was remission status for individuals in each group.Results: Individuals in both groups spent essentially equal amounts of time in each clinical state over the follow-up time period(remission, 78%; intermediate, 8%; relapse, 14%). There were no significant differences on other measures of illness severity. The clozapine group was more likely than the chlorpromazine group to remain on the medication to which they were originally assigned (26% v. 10%, P = 0.01). There were no significant differences between the two groups on other secondary efficacy outcomes.Conclusions: These findings support the comparability in effectiveness between antipsychotic medications but with slightly greater tolerability of clozapine in the treatment of first-episode psychosis. [ABSTRACT FROM AUTHOR]

Background: Substantial weight gain is common with many atypical antipsychotics.Aims: To evaluate the extent, time course and predictors of weight gain and its effect on study retention among people with first-episode psychosis treated with olanzapine or haloperidol.Method: Survival analysis assessed time to potentially clinically significant weight gain (> or =7%) and the effect of weight gain on study retention. Weight gain during the 2-year study was summarised using last-observation-carried-forward (LOCF), observed cases and study completion approaches.Results: After 2 years of treatment, LOCF mean weight gain was 10.2 kg (s.d.=10.1) for olanzapine (n=131) and 4.0 kg (s.d.=7.3) for haloperidol (n=132); observed cases mean weight gain was 15.4 kg (s.d.=10.0) for olanzapine and 7.5 kg (s.d.=9.2) for haloperidol. Change in body mass index was significantly predicted only by treatment group (P < 0.0001).Conclusions: Olanzapine was associated with significantly greater weight gain than haloperidol, with both leading to greater weight gain than previously described. [ABSTRACT FROM AUTHOR]

Background. There is a well-recognized association between substance use and psychotic disorders, sometimes described as 'dual diagnosis'. The use of substances by people with psychosis has a negative impact in terms of symptoms, longitudinal course of illness and psychosocial adjustment. There are few validated treatments for such individuals, and those that do exist are usually impracticable in routine clinical settings. The present study employs a randomized controlled experimental design to examine the effectiveness of a manualized group-based intervention in helping patients with dual diagnosis reduce their substance use. Method. The active intervention consisted of weekly 90-min sessions over 6 weeks. The manualized intervention was tailored to participants' stage of change and motivations for drug use. The control condition was a single educational session. Results. Sixty-three subjects participated, of whom 58 (92%) completed a 3-month follow-up assessment of psychopathology, medication and substance use. Significant reductions in favour of the treatment condition were observed for psychopathology, chlorpromazine equivalent dose of antipsychotics, alcohol and illicit substance use, severity of dependence and hospitalization. Conclusions. It is possible to reduce substance use in individuals with psychotic disorders, using a targeted group-based approach. This has important implications for clinicians who wish to improve the long-term outcome of their patients. [ABSTRACT FROM AUTHOR]

Background: The dopamine hypothesis proposes that antipsychotic drugs act primarily through limbic cortical D2/D2-like dopamine receptor blockade.Aim: To evaluate this hypothesis with the D2/D3-selective SPET probe [123I]-epidepride.Method: [123I]-epidepride SPET scans were performed on 12 patients with schizophrenia treated with antipsychotics and II age-matched healthy controls. [123I]-epidepride 'specific binding' to D2/D3 dopamine receptors was estimated, and relative percentage D2/D3 receptor occupancy by typical antipsychotic drugs determined.Results: Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equivalents. Mean percentage D2/D3 receptor occupancy was 81.6 (8.1) and 73.2 (13.9) in the temporal cortex and striatum respectively.Conclusions: Typical antipsychotic drug treatment is associated with substantial temporal cortical D2/D3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia. [ABSTRACT FROM AUTHOR]

Nineteen patients with acute psychoses, the majority schizophrenics, were studied in the course of chlorpromazine (CPZ) treatment. Plasma levels of the drug, plasma prolactin (PRL), extrapyramidal side-effects (EPS) and changes in mental state were monitored weekly, as in our earlier study. The results confirm some of our previous findings: (a) plasma CPZ levels vary widely among patients and correlate poorly with daily doses of CPZ; (b) increased plasma PRL is associated with higher plasma CPZ levels and is more common among the patients who develop EPS; and (c) none of these three variables differ between groups of patients with good and poor treatment outcome. However we did not confirm our previous finding of a significant association between EPS and higher plasma CPZ, nor did we find that the ratio of CPZ-sulphoxide to CPZ differed between the improved patients and the rest. [ABSTRACT FROM AUTHOR]

A therapeutic trial with chlorpromazine was conducted with a homogeneous (for age and sex) group of recently admitted schizophrenic patients. Extrapyramidal effects were measured through quantitative analysis of digital tremor, after four days of fixed-dose treatment. Assessment of treatment efficacy was based on Brief Psychiatric Rating Scale ratings, done at the end of four weeks' treatment. Those patients whose tremor was least affected by drug were most likely to benefit from the treatment. Implications of this negative correlation for our understanding of the neuroleptic hypothesis and the closely associated dopamine hypothesis of schizophrenia are discussed. [ABSTRACT FROM AUTHOR]

Two drug trials in schizoaffective patients are reported. Nineteen "schizomanic" patients were treated for one month, on a double blind basis, with chlorpromazine or lithium and 41 "schizodepressive" patients with amitriptyline, chlorpromazine or both. In the schizodepressive patients there was a trend to a better response to chlorpromazine, but drug response generally was poor, only 20 per cent of patients recovering within the month. In the schizomanic patients lithium seemed as effective as chlorpromazine, which supports the view that these patients were suffering from a variant of mania. [ABSTRACT FROM AUTHOR]

In a double blind chlorpromazine-controlled trial, high dosage haloperidol (100 mg daily) given for three months, appreciably improved the mental state of male chronic 'drug resistant' schizophrenic inpatients in the rehabilitation/long-stay unit of one psychiatric hospital. The results of a three-month follow-up suggested that the improvement could be maintained in some patients on lower doses of the drug. Serious extrapyramidal side effects were not seen at high doses. However, the majority of patients on haloperidol showed a deterioration in ward behaviour, possibly related to drowsiness, and developed raised serum alkaline phosphatase levels. These side effects disappeared in the follow-up period when either the drug was discontinued or the dose of haloperidol reduced. [ABSTRACT FROM AUTHOR]

Nine patients diagnosed as having acute schizophrenic psychosis were treated with chlorpromazine. Their clinical response to drug treatment was measured by the use of a clinical rating scale developed from the Present State Examination, and a nurses rating scale. Plasma levels of chlorpromazine (CPZ), 7-hydroxychlorpromazine (7OHCPZ), monodesmethylchlorpromazine (NOR1CPZ) and chlorpromazine sulphoxide (SOCPZ), were monitored during the period of hospital treatment. Correlations were made between the increase in plasma levels of drug or metabolites and improvement in the different PSE scores. These showed that the most significant correlations occurred when symptoms with high diagnostic significance for schizophrenia (Group 1) and symptoms rating perceptual disorders (P) were correlated with plasma 7OHCPZ levels in plasma samples taken before the first morning dose of CPZ. The ration of 7OHCPZ to CPZ in these samples increased significantly as clinical ratings improved, this correlation being most highly significant against the Group 1 and P scores. The ratio of 7OHPCZ to SOCPZ increased significantly only in the case of Group 1 and P scores. This indicates a preferential shift of CPZ metabolism towards the formation of the active 7OHCPZ during the period of clinical improvement. [ABSTRACT FROM AUTHOR]

A group of 33 schizophrenic patients were typed for HLA-SD antigens and their qualitative clinical responses to chlorpromazine therapy determined. A highly significant positive correlation was found between response to chlorpromazine and HLA-AI positive, while HLA-A2 positive subjects showed a significant negative correlation to chlorpromazine treatment. In a second group of 17 patients the clinical response to chlorpromazine were evaluated quantitatively, by WPRS, in HLA-AI positive and HLA-AI negative patients. There were no pre-treatment differences in the scores. After treatment the scores of positive patients were significantly lower, indicating that they responded to a greater degree. Since the frequency of HLA-AI in hebephrenic patients is higher than that in other schizophrenics this may explain our earlier finding that hebephrenics, as a group, respond better to chlorpromazine than do other schizophrenics. [ABSTRACT FROM AUTHOR]

Phenothiazine drugs were withdrawn from 17 chronic schizophrenic in-patients, with a control group of 14 patients remaining on active medication. The trial was conducted under double blind conditions over a period of 42 weeks with weekly assessment of the patients by ward nurses. Of the placebo group 35% relapsed, relapse being related to the level of previous active medication. [ABSTRACT FROM AUTHOR]

Plasma prolactin has been estimated in 69 psychiatric in-patients receiving either thioridazine (20-300 mg./day) or chiorpromazine (50-200 mg./day) or other phenothiazines. A homologous radioimmuno-assay was used which depends on an antiserum to human amniotic prolactin. Prolactin levels were significantly increased in these patients compared with control patients, and were dose related. Simultaneous estimation of growth hormone revealed normal levels. [ABSTRACT FROM AUTHOR]

The article cites a study that assesses the effects of cyproterone acetate and ethinyl oestradiol on sexual behavior of sexual offenders by applying a combination of behavioral, attitudinal, and physiological measures including sexual interest score, sexual activity score, and sexual attitude score. The subjects were 12 patients at Broadmoor Hospital who volunteered to enter the trial. A balanced design was applied using three drug conditions which include placebo, chlorpromazine, and beneperidol. No significant difference between the drugs on any measure was found. These drugs were discovered to be equally effective to reduce the frequency of sexual thoughts and sexual activity. Only cyproterone acetate had a weak effect in reducing erectile and subjective responses to erotic stimuli.

The article discusses the risks and benefits of using lithium in psychiatry. Studies of lithium showed the phenomenon of lithium withdrawal mania and the recognition of permanent neurological sequelae after lithium toxicity. According to the article, adherence to treatment with lithium is low because of side-effects. It describes several situations that call for the immediate cessation of lithium. Trials showed that non-sedative selective dopamine-blocker pimozide improves mania. Also, studies comparing lithium with chlorpromazine are complicated by the non-specific sedative effects of chlorpromazine.

We report the efficacy of combined chlorpromazine and electroconvulsive therapy (ECT) in the treatment of mania. Two groups of 15 manic patients received eight ECT sessions either actual or simulated, in a double-blind, controlled study. All patients also received 600 mg of chlorpromazine daily until the sixth session. Results indicate that the group receiving the combination of chlorpromazine and ECT did significantly better than the other group. [ABSTRACT FROM AUTHOR]

An investigation in a large mental handicap hospital revealed that 24% of the in-patients were receiving antipsychotic drugs. Chlorpromazine and thioridazine prescriptions accounted for 62% of the total while 10% of patients received depot preparations. Fifty-five per cent of the patients receiving these drugs had no established psychiatric diagnosis; most of these could be categorised as having a behaviour disorder. Patients aged 30-50 received higher doses, and female patients received a significantly higher mean dosage than male ones. In the patients receiving neuroleptic drugs who had also been taking them four years previously, there was a significant reduction in the dosage of the drugs received and the extent of polypharmacy of these agents. A mandatory requirement to review all prescriptions annually, implemented in 1984, may be a reason for this. [ABSTRACT FROM AUTHOR]

A 27-year-old woman with a post-partum psychosis developed NMS which proved difficult to diagnose because of the organic features of the presenting illness. Possible contributory factors to the development of NMS included exhaustion, a non-specific viral illness, and rapid loading with haloperidol. [ABSTRACT FROM AUTHOR]

Skin conductance level (SCL) and skin conductance responses (SCR) to a random series of tones were measured in 25 drug-free schizophrenic patients, 15 males and 10 female, before and after standard chlorpromazine treatment. The DSM-III diagnostic criteria were used for selecting subjects. Psychopathology was measured with the Brief Psychiatric Rating Scale. After treatment, patients showed an improved psychopathology and decreased SCL. There was a transition of patients to lower response categories: the number of responders decreased twice and the number of non-responders increased three times. Responders exhibited significantly higher SCL than non-responders and fast habituators were between the two groups. [ABSTRACT FROM AUTHOR]

Procyclidine was administered to 25 chronic psychotic inpatients, stabilised on chlorpromazine, haloperidol or fluphenazine decanoate injection. We observed a significant reduction in mean serum levels of all three neuroleptic drugs which was reversed on stopping procyclidine and was inversely correlated with mean serum procyclidine levels. No significant alterations occurred on the BPRS scores or in serum prolactin levels throughout the study in any of the three groups. Possible mechanisms of this interaction and its clinical relevance are discussed. [ABSTRACT FROM AUTHOR]

The presence of tardive dyskinesia in a sample of 43 patients with schizophrenia and 37 psychopaths who had been hospitalised for many years and exposed to large amounts of medication was assessed while testing their cognitive function. Subjects who showed no evidence of abnormal movements performed significantly better on the test of delayed recall, but there were no differences in performance on any of the other tests of cognitive function used. Multiple regression analysis revealed that age and the total lifetime dose of neuroleptic medication received (in chlorpromazine equivalents) were the only variables to predict the Abnormal Involuntary Movement Scale score, although a large amount of variance in this variable was unaccounted for. The duration of treatment with neuroleptics did not predict AIMS score. [ABSTRACT FROM AUTHOR]

Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness, 120 entered a randomised placebo-controlled trial of maintenance neuroleptic medication on discharge; they were followed to relapse or loss to follow-up, for two years or to the end of the study. Of those on active medication, 46% relapsed, as did 62% of those on placebo; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication. This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis, or because susceptibility to relapse is reduced by early institution of treatment. The study provides no data on which a decision between these alternative explanations can be based. [ABSTRACT FROM AUTHOR]

Ten hospitalized chronic schizophrenic patients were given chlorpromazine alone and chlorpromazine plus high dose propranolol in two 7-week treatment periods according to a randomized crossover design. In the six patients who completed the whole study, plasma levels of chlorpromazine and chlorpromazine sulphoxide, total serum levels of neuroleptic and serum levels of prolactin were consistently and significantly elevated during treatment with chlorpromazine plus propranolol relative to levels during treatment with chlorpromazine alone. These effects are sufficient to explain previously reported clinical improvement in schizophrenic patients given propranolol in addition to neuroleptics. [ABSTRACT FROM AUTHOR]

Fifty-three hospitalized chronic schizophrenic patients were treated with either propranolol, chlorpromazine or placebo in a double-blind randomized trials for up to three months. Propranolol in a usual dose of 640 mg/day, produced marked cardiovascular effects but no improvement in schizophrenic symptomatology relative to placebo. The effects of chlorpromazine were small and inconsistent. [ABSTRACT FROM AUTHOR]

Platelet MAO activity was assessed in 35 schizophrenics during a trial of the isomers of flupenthixol. Enzyme activity was unrelated to severity of symptoms, the presence of delusions, hallucinations or thought disorder or to negative symptoms. In a few patients MAO activity fluctuated widely with time, but in the group of patients on medication there was a slow decrease in enzyme activity which was significant after 28 days of treatment. Enzyme activity after 14 days' drug treatment was still correlated with activity before treatment, but after 28 days this significant correlation disappeared. Slow effects of neuroleptic drugs on platelet MAO activity may explain previous findings of reduced activity of the enzyme in schizophrenia. [ABSTRACT FROM AUTHOR]

Measurements of spontaneous fluctuations in skin conductance in 20 acutely ill schizophrenic patients were made in a video-tape studio. Recordings were made initially with the patient talking to an interviewer, then during a video-taped interview conducted with the patient's key relative. The Expressed Emotion (EE) of the patient's key relative had been measured previously. Significant differences in the type of spontaneous fluctuation activity between patients who had low EE and high EE relatives were demonstrated when the relative was present, but not when the relative was absent. The findings were not related to phenothiazine medication. [ABSTRACT FROM AUTHOR]

The article presents a review of literature which aimed to provide a guide to current knowledge on the psychiatric aspects of diabetes mellitus. J. M. Dynes found that diabetes has an adverse effect upon the course and management of schizophrenia, while E. Thonnard-Neuman reported that patients developed hyperglycemia and glycosuria when treated with chlorpromazine. C. D. Van der Velde and M. W. Gordon, who studied the relationship between diabetes and affective disorder by looking at glucose tolerance and the response to lithium in manic-depressive patients, found that spontaneous fluctuations in glucose tolerance were not correlated significantly with mood swings.

The article focuses on a study designed to investigate the efficacy of the operant conditioning regime in the treatment of anorexia nervosa. Anorexoa nervosa is a disorder characterized by appetite loss, amenorrhoea, and weight loss in the absence of any primary psychiatric or physical illness. The treatment of anorexia nervosa is generally divided into two phases, including the restoration of weight loss and then the correction of pathological attitudes regarding eating. The most successful of the medically oriented approaches devised to achieve weight gain was treatment with chlorpromazine and insulin, which achieved a weekly gain of 2.1 kilograms as compared to bed rest and high calorie diet alone. Further results of the study are discussed.

The article presents eleven cases of patients who developed a syndrome comprising mutism and other neurological features while being treated with phenothiazine derivatives. Majority of the patients demonstrate complete speech loss, while some exhibit one or more neurological toxic phenomena, such as akathisia, buccal dyskinesias, dystonias, tremor and parkinsonism. The changes observed in patients after the commencing treatment of phenothiazine include disturbance of vocalization that results to aphonia, persistent stereotyped activities and difficulty in rising from the seated position, disintegration of mental functions and loss of mental alertness. The case history of each patient is discussed.

The article presents a study that demonstrates the rate of using creatinine as a basis of urinary excretion studies in chronically hospitalized psychiatric patients. In this study, patients were instructed to note the exact time of the first morning urine, empty the bladder completely and discard the specimen. Three different methods of computing the value of excretion of drug metabolites in milligram per hour using creatinine as the basis were described. Results concluded that urinary output of creatinine in normal and schizophrenic patients was found to be used as a basis for drug excretion rates.

The article presents a study that attempted to determine whether the resistance to chlorpromazine therapy is some schizophrenic patients is associated with the difference in drug metabolism. The rate of urinary excretion of chlorpromazine metabolites in 15 chronic schizophrenic patients in both sexes was investigated. A fluorometric micromethod was developed. The metabolites of chlorpromazine vanished after four week of withdrawal of medication, which coincided with the reoccurrence of clinical symptoms. Findings suggested that resistance to chlorpromazine is not associated with a difference in peripheral metabolism or the receptive sites for chlorpromazine.

The article presents a study which investigates the effect of lithium on the schizophrenic process by comparing lithium and chlorpromazine in newly hospitalized acute schizophrenics, irrespective of diagnostic sub-type or affective coloring. It was designed to avoid toxicity in those patients receiving lithium, so that any potential neuroleptic effect of this ion would not be masked. The results indicate that chlorpromazine is clearly more effective than lithium, either in reducing symptom severity or in bringing about remission in schizophrenic patients.

The article cites a study which examines the comparative impact of lithium and chlorpromazine in the treatment of acute manic conditions. Samples chosen were the patients with symptoms of acute mania. Analysis of the results shows the effect of lithium in the manic-depressive patient with no significant impact on schizoaffective patients. In addition, lithium produced the greater change in the manic-depressives, whereas chlorpromazine produced more change than lithium in the schizoaffective group.

The article presents a study on the serum vitamin-B12 levels in psychiatric patients. A total of 46 patients who had been exposed to long-term psychotropic drug therapy were investigated and compared with a control group of 96 individuals who matched the age, sex and psychiatric diagnosis of the 46 patients. The individual drugs, mean drug intake and serum vitamin-B12 levels of each population were analyzed. It was found that the intake of drugs was much greater in the long-term group and their serum vitamin B-12 levels were lower for most drugs but no individual value was low enough to lead to further investigation. It was concluded that none of the psychotropic drugs affected the vitamin-B12 level of one specimen of serum.

The article examines the effect of lithium carbonate on the electroencephalogram (EEG) of patients with affective disorders. EEG changes are apparently unnecessary for the effective therapeutic action of lithium. It is possible that the production of abnormal slow waves in conjunction with the reputed changes in sodium, catecholamines and steroids provides clues to the mechanism of action of lithium. There was no difference in the number of abnormal EEG patterns in the manic, depressed, and normal states.