The aim of this study was to compare the clinical efficacy and the safety of venlafaxine and fluoxetine in the treatment of obsessive-compulsive disorder (OCD).

One hundred and Eight inpatients who met the Diagnostic and Statistical Manual of Mental Disorders, the Forth Edition(DSM-IV) for OCD were involved in this study. The subjects were randomly divided into venlafaxine group or fluoxetine group. Efficacy of venlafaxine and fluoxetine in treatment of OCD were assessed with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression-Severity(CGI-S), the side effects were evaluated with Treatment Emergent Symptom Scale (TESS).

The therapeutic efficacy in venlafaxine group was similar to that in fluoxetine (70.36%vs68.29%, P>0.05) after eight weeks’ therapy. The improve-rates of Y-BOCS after 2 weeks’ therapy of venlafaxine were significant higher than those of baseline, while the improve-rates of Y-BOCS after 4 weeks’ therapy of fluoxetine were significant higher than those of baseline(P< 0.05). The side effects of venlafaxine group were similar to fluoxetine group (P>0.05).

The results indicate that both venlafaxine and fluoxetine is effective in the treatment of OCD, but venlafaxine work faster than fluoxutine.

To describe and compare the demographic and clinical characteristics of adult patients with depression in the UK treated with duloxetine and venlafaxine XR.

Depressed adults treated with duloxetine or venlafaxine XR between 1/1/2006 and 9/30/2007 were identified using the General Practice Research Database (GPRD), which represents all primary care practices in the UK. Demographic (age and sex) and clinical characteristics (psychiatric and physical comorbid conditions and concomitant medication use) were examined and the characteristics of the two treatment groups were compared using chi-square or t tests, as appropriate.

Of 2,195 patients identified (mean age 47.2 years; 65.8% female), 41% were prescribed duloxetine and 59% were prescribed venlafaxine XR. On average, patients treated with duloxetine were older than patients treated with venlafaxine XR (49.6 years versus 45.5 years; p< 0.001). Compared to patients treated with venlafaxine XR, patients treated with duloxetine had higher prevalence of a variety of comorbid physical health conditions, including diseases of the circulatory, digestive, respiratory systems, as well as a higher prevalence of diabetes (p< 0.01 for all). Additionally, patients treated with duloxetine had higher prevalence of unexplained pain (p< 0.001). Greater proportions of patients treated with duloxetine had prescription utilization of medications in a variety of classes, including anticonvulsants, analgesics, migraine medications, as well as medications used to treat cardiovascular and gastrointestinal disorders (p< 0.01 for all).

Depressed patients treated with duloxetine in the UK are slightly older and appear to be in poorer health overall than patients treated with venlafaxine XR.

Poststroke depression (PD) occurs in approximately one third of the patients within first two years of a cerebrovascular event. However, no definite consensus has been reached on the best treatment option. The aim was to determine the efficacy and safety escitalopram, a selective serotonin reuptake inhibitor, in PSD treatment.

Patients with symptoms of depression within 6 months of a cerebrovascular event were included. Patients with Hamilton depression (HAM-D) score of < 13, mini mental standardized test score of < 23, schizophrenia, behavioral disorders, substance abuse, history of alcoholism, current use of antidepressants, and history of stroke or major depression within the last one year were excluded. Patients were administered escitalopram 10 mg/day for 3 months. HAM-D scores, stroke severity and extent of functional impairment were assessed and side effects were recorded; the relationship between HAM-D scores and sociodemographic variables and stroke localization was investigated.

Totaly,35 patients (60% female; mean age, 67± 6) were included. Depression was diagnosed 3±1.2 months after the stroke. HAM-D scores decreased significantly in all visits (days 15, 30, 45 and 90). The mean HAM-D score decreased from 27.5±4.7 to 4.65±2.47 at day 90 (p< 0.0001). No significant correlation was found between HAM-D scores and cerebrovascular event localization, sociodemographic variables and medical history (p>0.05). Escitalopram was well tolerated. A total of 9 patients reported nausea, anxiety, drowsiness and dyspepsia.

In this open-label study escitalopram was found to be safe and effective for use in poststroke depression patients.

Previous research has indicated that rats selectively bred for high and low saccharin preference exhibit differential drug-taking behavior within multiple phases of the animal model of human drug abuse. Namely, rats bred for high saccharin preference (HiS) show heightened vulnerability to addiction compared to rats bred for low saccharin preference (LoS). Prior research has also shown phenotypes that confer vulnerability to be more responsive to pharmacological interventions. For example, the GABA(B) agonist baclofen is more effective at blocking cocaine acquisition in female rats, who are typically more vulnerable to addiction, compared to males.

To examine the differential effects of baclofen on the escalation of cocaine-seeking behavior in female rats bred for high and low saccharin preference.

HiS and LoS female rats were trained to administer cocaine (0.4 mg/kg/infusion, i.v.) within daily 2-hr sessions under a fixed ratio (FR1) schedule until criteria for stability were met. Next, the escalation phase began in which daily session length was extended to 6-hrs for 21 days. Thirty minutes prior to session during this phase, one HiS and one LoS group of rats received baclofen injections (1.25 mg/kg) while one HiS and one LoS group received saline injections.

Baclofen potentiated escalation of cocaine infusions in HiS rats compared to HiS rats treated with saline. Conversely, baclofen attenuated escalation in LoS rats.

While these results do not support the original hypothesis of the present study, they underscore the importance of considering vulnerability factors while treating human drug addiction.

It is generally acknowledged that individuals with intellectual disabilities (ID) benefits from psychotropic treatment for mental disorders (MD) in the same way as people in the general population. It has also been shown that problem behavior (PB) does not respond to psychotropic treatment. Thus, we hypothesized that the presence of MD was assocated with psychotropic treatment, whereas PB (not MD) was not.

In a community sample of adults with ID (N=593), the presence of dementia, psychoses, depression, mania, obsessive-compulsive disorders, five anxiety disorders and eight problem behaviors were screened using the Psychopathology Checklists for Adults with Intellectual Disability (P-AID). Information regarding the use of psychotropic medicine (ACT-N) was collected. Staff members in group homes served as informants both for the screening and the use of drug.

Psychotropic medication was reported in 40% of the sample. Of the 23% that presented with MD only, 44% received psychotropic medication (p=.310). Of the 12% that presented with both MD and PB, 51% received such medication (p=.032). The strongest association was found between psychotropic treatment and having PB only. Among the 8% that showed PB only, 52% received psychotropic medication (p=.022).

Contrary to our expectations, the presence of PB rather than MD were associated with the use of psychotropic treatment. The present findings suggest that people with ID often receives no psychotropic treatment for MD, or they receives such treatment for the wrong reason, leaving the accuracy of psychotropic treatment to a minimum.

Present study focuses on metabolic and neuroendocrinologic effects of long-acting injectable risperidone (LAIR) treatment in a naturalistic sample of patients with schizophrenia spectrum disorders.

Twenty three outpatients with schizophrenia or schizoaffective disorder (ICD X) (age 32.3±6.5years, illness duration 8.7±5.1 years, PANSS 78.1±14.7) were included. At the time of evaluation the patients were treated with LAIR for 1.4±0.7 years, average dose 38.6±9.9mg. Total duration of antipsychotic therapy was 8.0±4.8 years. Control group (n=23) were healthy volunteers matched by age, sex and education.In the morning serum we measured leptin, prolactin, cortizol, IGF1, T4, FSH, LH, HbA1c, total cholesterol, HDL, LDL and triglicerides. Both groups were tested by oral glucose load (OGTT), with measuring insulin levels and anthropometric parameters.

In comparison to control group, the patients had higher BMI (p< .001), waist circumference (WC, p=.004), increased leptin (p=.013), prolactin (p< .001), triglycerides (p=.029) and fasting glucose (p=.004). After controlling for BMI, WC and sex, only prolactin (p< .001, ηp2= .50) and leptin (p=.040, ηp2=.13) were significantly increased in the patient group.

This is the first study of LRAI effects on metabolic and neuroendocrine parameters. Our cross-sectional study has shown that the most consistent side effects of LAIR were increased prolactin and leptin, while other deviations might be attributed to confounding covariates. Whether pharmacokinetic and pharmacodynamic advantages of LAIR over oral drug formulation are accompanied with favorable metabolic and neuroendocrine profile remains to be assessed by head to head studies.

This study was supported by a grant from the Ministry of Science, Republic of Serbia (Project 145019).

The European Federation of Psychiatric Trainees (EFPT), a trainee-led organisation, encompassing official representatives from 24 countries, set up a research group to foster trainee-led collaborative research, emphasising training and clinical practice.

The first survey of the group assessed trainees’ treatment choices for patients and themselves, across psychiatric disorders, in addition to factors influencing decision-making and guideline use.

A web-based survey was piloted, and distributed to 16 European countries. For validity, a 50% response rate from a homogenous sample, with sample size 50 or more was required,

12 countries met inclusion criteria.

1. (a) Antipsychotic choice and factors influencing decision-making

93% (n=600) of respondents chose to prescribe 2nd Generation atypical antipsychotics for patients, and 89% (n=530) chose this treatment for themselves. 79% (n=458) of respondents felt efficacy was the most important factor influencing decision-making.

1. (b) Mood stabiliser choice and factors influencing decision-making 41% (n=263) of trainees chose to prescribe lithium to patients, with 35% (n=224) stating they would wish to receive this themselves. 66% (n=538) of respondents felt perceived efficacy was the most important factor influencing decision-making.

2. (c) Antidepressant choice and factors influencing decision-making 75% (n-461) of trainees would prescribe SSRIs to patients with a moderate depressive episode, 78% (n=438) wishing to receive SSRIs themselves. 67% (n=523) of respondents felt efficacy to be the most important determining facor.

Trainees are able to provide clinically-relevant research through trainee networks, and a number of decisions governing treatment do not appear to be based on current evidence.

Recent evidence has questioned modern psychiatric clinical practice, specifically the prescribing of “atypical” antipsychotics. Our Pan-European Research Group wished to ascertain clinical practice amongst European trainees, which treatments trainees would desire for themselves, and factors influencing this.

A semi-structured survey was constructed from prior literature, piloted, and a homogenous sample size of at least 50 was agreed upon from each country, with 50% minimum response rate. It was distributed via web-link, with questions on preference of antipsychotic for patients in given scenarios, and factors influencing choice. Physicians were asked for their preference should they develop psychosis.

1. i) Treatment choice of antipsychotic for patients

93% (n=600) of respondents chose to prescribe “atypical” antipsychotics (excluding Clozapine), 6% (n=42) choosing “typical” antipsychotics, 1% (n=6) choosing Clozapine as first-line therapy.

1. ii) Treatment choice if trainees developed psychosis

89% (n=530) of responders chose to prescribe “atypical” antipsychotics (excluding Clozapine), 7% (n=40) choosing “typical” antipsychotics, 4% (n=23) choosing Clozapine as first-line therapy.

1. iii) Factors influencing choice

These mapped onto three domains: cost, efficacy and side-effect profile (less than 5% other reasons). 79% (n=458) of those who responded felt efficacy most important, 46% (n=270) felt side-effect profile most important and 3% (n=16) considered cost of paramount importance.

38% (n=272) of those who responded to the survey stated that the CATIE trial had influenced their decision-making.

Psychiatry trainees’ choice of antipsychotic medication for both patients and themselves is based on perceived benefits, as opposed to evidence base and recent literature.

Twenty-five-year old man suffering from paranoid psychosis was given quetiapine for persisting symptoms. He also had myoclonic disorder which has become worse just after administering quetiapine. Physical, neurological and laboratory findings were normal. He once had a generalized seizure in our clinic. The electroencephalography (EEG) revealed an epileptic focus on frontal region. He has been diagnosed as frontal lobe epilepsy exacerbated by quetiapine. He has recovered and was doing well after withdrawn the drug.

Twenty-three-year old women who had bipolar disorder was hospitalized due to a manic episode. Physical examination and routine laboratory tests were normal. Lithium at 600mg/d and quetiapine at 300 mg/d were started. Quetiapine has been gradually increased up to 900 mg/d at which the myoclonic symptoms first noted. They were disappeared after quetiapin was tapered to 600 mg/d. To control manic symptoms, quetiapine dosage had to be increased up to 700 mg/d again, but myoclonus was reappeared. Quetiapin was replaced with risperidon and manic symptoms subsided. No myoclonic seizures were noted during follow-up.

EEG abnormalities particularly likely with clozapine and olanzapine, moderate with risperidone, and the lowest with quetiapine. The risk of quetiapine-induced epilepsy was estimated as 0.75%. Evaluating of patients for the epileptic background is important in selecting proper antipsychotic medication.

Recent studies suggest that such neuroactive steroids as dehydroepiandrosterone-sulfate (DHEAS) and cortisol play an important part in conditioning psychiatric disorders in combatants. Cortisol may have a neurotoxic effect whereas DHEAS can produce a neuroprotective impact.

We have investigated the morning plasma level of DHEAS and cortisol as well as DHEAS/cortisol ratio in the group of forty combat veterans in the remote period of combat stress and the same parameters - in the control group consisting of 30 healthy males (N=30).

In comparison with the control group, the combatants reliably showed considerably higher level of cortisol (p< 0,05), lower level of DHEAS (p< 0,001) and lower DHEAS/cortisol ratio (p< 0,001). Then the veterans were divided into two groups with the help of the “Mississippi Scale for Combat-Related Posttraumatic Stress Disorder”: those having post-traumatic stress disorder (PTSD) and those without this diagnosis. As a result, no trustworthy difference between levels of DHEAS, cortisol and their proportion was found in PTSD-positive and PTSD-negative veterans. Each of these groups displayed the reliable reduction of DHEAS level as compared to the control group.

The results of our investigation demonstrate that the veterans differed significantly from the control group in the level of neurosteroids. This fact apparently cannot be linked to PTSD symptoms. Thus there is an urgent need for further examination of clinical and psychological components correlated with altered levels of DHEAS and cortisol in combat veterans.

To explore maintenance of effect with OROS MPH in adults with ADHD.

Multicenter study randomizing adult subjects with ADHD who completed open-label (OL) treatment with OROS MPH (18-90mg/day) for at least 52-week and consented to a 4-week, randomized, double-blind (DB), placebo-controlled (PLC) withdrawal period. Efficacy measures included total CAARS score, CAARS-S:S, GAE, CGI-S and CGI-C. Endpoint analyses were performed using LOCF.

99/155 patients completed the OL OROS MPH treatment phase, only 45/99 patients consented to double-blind randomization. At DB baseline, mean ± SD TCS was 12.1±5.34 (n=23) in the continued OROS MPH group and 16.5±7.49 (n=22) in the placebo group. CAARS changed from DB baseline to DB endpoint by 4.0±7.61 and 6.5±7.82, respectively (p = 0.2586 between groups). CGI-C scores indicated more worsening of symptoms in the placebo group compared to the continued PR OROS MPH (p = 0.0422). Median (range) GAE scores at endpoint were 2.0 (0-3) and 0.5 (0-3), respectively (p=0.0254). Other efficacy endpoints were numerically in favor of OROS MPH. The randomized withdrawal phase may have been underpowered to show statistical significance between treatment groups for the primary outcome. The incidence of treatment-emergent AEs during the DB phase was comparable between groups.

The results indicate that treatment discontinuation after long-term exposure of adults with ADHD to OROS MPH is associated with worsening of clinical symptoms. Statistical significance for several outcomes was not reached, possibly due to study limitations.

To explore functionality and quality of life outcomes in children and adolescents with ADHD transitioning from IR MPH, ER MPH or ATX onto OROS MPH.

Pooled analyses of two similar 12 week open label, flexibly dosed studies including children (6-18 yrs) diagnosed with ADHD (ICD-10) transitioning from shorter acting stimulants or Atomoxetine onto OROS MPH. Connor's parents rating scale, children's global assessment scale and quality of life (ILC, LQ-0-28) were applied.

822 patients (84.9% boys; median age 10 yrs) were analyzed. 81% of patients concluded the study. Starting and final dose was based on physician's judgment. Median dose at baseline and endpoint was 36mg/day. On average, C-GAS ratings improved by 12 points (p< 0.001). The percentage of children showing “variable functioning with sporadic difficulties” at baseline or worse decreased from 57,2% to 43,3% at endpoint. 61% of patients improved by at least 30% on CPRS. The percentage of children meeting educational demands at school at least “rather good” increased from 26,6% to 47,4% at endpoint. Results were similar for “social interaction with other children”, “emotional status”, “occupying with him or herself”. Burden of disease (patients or care givers) decreased (p< 0.001). Improved C-GAS and LQ 0-28 correlated with decreased CPRS. Treatment emergent AEs occurred in 35.6%. AEs ≥ 4%: insomnia (8%), muscle twitches (5%) and anorexia (4%).

Transitioning onto OROS MPH was associated with clinically relevant improvements in daily functioning, aspects of quality of life and decreased burden of disease in patients and their cares.

This study aims to investigate synaptic degeneration as a possible underlying mechanism for depression and whether antidepressants could alleviate the stated pathology.

Primary rodent hippocampal neurons treated with corticosterone were used as an in vitro model of depression. Toxicity of corticosterone was determined through the lactate dehydrogenase and caspase-3 activity assays. Immunocytochemical analysis of synaptic proteins was employed to investigate effects of corticosterone on synapses.

Neurotoxicity was observed in hippocampal neurons after treatment with corticosterone (10μM) for 24 hours. Aggregations of synaptotagmin and synaptophysin were observed 24 hours after treatment with corticosterone (10μM). Similar effects were observed after sub-lethal treatments with corticosterone (0.5μM and 1μM) for 48 and 72 hours. Pre-treatment for 1 hour with imipramine and escitalopram (20μM and 40μM for both agents) were able to alleviate these toxic effects.

These results suggest the involvement of synaptic degeneration in corticosterone-induced toxicity and that commonly used antidepressants are able to alleviate synaptic derangements. Taken together, synaptic degeneration could be a common pathway for neuronal demise occurring in AD and depression, which can be attenuated by antidepressant administration. Future research to elucidate the precise mechanism for the synaptic protective effect of antidepressants is warranted.

Generalized anxiety disorders (GAD) are characterized by persistent excessive worrying about minor hassles. GAD patients are high utilizers of medical services and medication.

According to an analysis of 21 double-blind placebo-controlled trials by of Hidalgo et al. (2007) highest effect sizes are reproted for pregabalin (0.50), hydroxyzine (0.45), venlafaxine XR (0.42), benzodiazepines (0.38), SSRIs (0.36), buspirone (0.17) and herbal medicines (-0.31). The question is how GAD is treated under conditions of routine treatment. This was studied in patients were admitted to inpatient treatment.

Psychotropic premedication and changes in medication during the inpatient treatment were analyzed in 107 patients.

Before admission, 27,1% of GAD patients got tricyclic antidepressants, 25,2% SSRI, 8,4% benzodiazepines, 7,4% atypical antidepressants, 1,9% anticonvulsants/pregabaline, 1,9% herbal drugs. Furthermore, 20,6% got betablocker, preferably because of hypertension.

During the inpatient stay changes in medication were made according to the clinical discretion of the therapist. At discharge 41,1% of GAD patients received SSRI, 23,4% tricyclic antidepressants, 22,4% pregabaline, 9,4% atypical antidepressants.

SSRI and tricyclic antidepressants play the major role in the drug treatment of GAD. Under clinical conditions there has been an optimization of treatment by increasing preferably the rate of SSRI treatments and of pregabaline treatment, while reducing benzodiazepine treatment and to some degree tricyclic antidepressants.

Hidalgo RB, Tupler LA, Davidson JRT (2007): An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol 21(8):864-872.

In Spain, consumption of psychotropic drugs is high and benzodiazepines represent 74% of the total. His prescription in primary care is very common and their use continues to grow. They are safe and effective drugs, but patients with prolonged use are elaborating the most adverse effects, particularly the dependency.

Descriptive ans cross-sectional.

Primary Health Care.

We seleted 202 patients treated with benzodiazepines, consecutive sample, belonging to the health center Los Barrio who were seen in consultation during 2009.

We conducted through a questionnaire that cointained the treatment and demographic characteristics.

We detect a frequency of use of benzodiazepines 9% (95% CI 4,7-12,1%). The profile of the consumer responds to middle-aged woman, with primary and housewives. Somatic diseases were associated in 72.6% (CI 67,2-77,5%) and had mental pathology at 59.7% (CI 53,9-65,3%). 35% (95% 29,6-40,6%) of prescribed benzodiazepines were clorazape dipotassium. Consumption was constant for over a year. The prescription from primary care represents 81% (95% 76,3-85,4%) and in 65% (CI 59,3-70,3%) is associated with other psychoactive drug.

In our area, highlights the prescription of benzodiazepines from primary care on demand and consumption during prolonged time. Interventions should be conducted on the prescription of benzodiazepines in medical and other interventions for patient support.

The prodromal syndrome in schizophrenia can be correlated with a series of neurobiological risk factors, the obstetrical traumas having an important role. The antipsychotic therapy at the male patients with obstetrical traumas in personal medical history can amplify the risk of cerebral structural changes.

We have studied 12 male patients (age 18-20 years), with prodromal schizophrenia syndrome or ARMS, negative symptoms, cognitive disabilities and poor social cognition. All the studied patients present obstetrical traumas in medical personal history, soft extrapyramidal symptoms, facial immobility and facial incapacity to express emotions (behavioral marker for poor social cognition and frontal-amygdala disconectivity). We administered aripiprazole (5mg/day) for 12 months associated with psychokinetotherapy technics, a series of facial mobility standard exercises.

These patients were evaluated at 6 and 12 months with PANSS, GAF, BARNES scales. The final results are: on the PANSS scale the evolution of negative and cognitive symptoms was ameliorated. The facial mobility and the capacity of emotional expression are also significantly ameliorated. The cognitive abilities and the level of social cognition are evaluated as very good. The extrapyramidal symptoms evaluated on the BARNES scale are not amplifying during the treatment.

The facial imobility and the facial incapacity to expressed emotions may be a clinical marker for neurodevelopmental abnormalities in the schizophrenia prodrome. Aripiprazole associated with the psychokinetotherapy technics improve in a significantly way the prodromal symptoms of schizophrenia at the male with obstetrical traumas in medical personal history.

The hypofrontaliety syndrome and the hippocampal alterations are correlated with the dopamine deficit secondary to D2 receptors blockade by the antipsychotic substances. The dopamine deficit amplifies the cognitive deficit, which is an important predictor for poor outcome in schizophrenia. The psychopharmacological action of aripiprazole is a dopamine modulator compared to haloperidole which is a highly potent D2 receptors blocker.

We have studied 3 groups, each consisted of 5 male adults Winstar rats each (200-250g), held through the study in temperature, humidity, food and ambient stressless conditions: N1 - control group; N2 - intraperitoneal administration of haloperidol (equivalent of 3mg); N3 - administration of aripiprazole (equivalent of 10mg). After 14 days, the rats were sacrificed and sections of their frontal cortex and hippocampus. The sample brain was histopathologically processed.

Compared with control group N1, the rats of group N2 (haloperidol) have shown significant alterations in frontal cortex (neuronal loss, pinocytosis and neuronal depopulation in III, IV and VI layers) and hippocampal areas (neuronal loss). The rats of group N3 (aripiprazole) have shown minimal, non-significant changes in frontal cortex and minimal loss in hippocampal areas.

The decrease of neuroprotection realised by haloperidole in frontal cortex and hippocampal areas suggest the aggravation of the structural cerebral abnormalities comparative to the aripiprazole action which presented a high level of neuroprotection.

After initial psychological treatment patients with Obsessive Compulsive Disorder are treated with selective serotonin re-uptake inhibitors (SSRIs). Treatment may later be augmented with clomipramine and/or an antipsychotic. This study focuses on the biological treatment received after, or in parallel to, the psychological.

To collate and evaluate the levels of biological treatment currently received by OCD outpatients in the Bedford east catchment of Bedfordshire and Luton mental health and social care partnership NHS trust.

In particular we wished to establish how many of the patients were receiving an atypical antipsychotic as well as maximal SSRIs.

An anonymised database of 45 outpatients with symptoms of OCD was prepared. Treatment groups were identified and the percentage of the cohort occupied by these groups was calculated. The possibilities for increased medication were noted.

Only 7% of patients had one SSRI, at maximum dose, plus clomipramine, plus an antipsychotic, even here the dosing was not maximal. Another 7% had a second SSRI instead of the tricyclic and may benefit from a trial of clomipramine. In the remaining 86% there was further scope for increasing biological therapy.

Relatively few of our patients were having maximal SSRI treatment and an antipsychotic, despite guideline recommendations.

There is plenty of leeway for the escalation of patients’ biological therapy. Given the number of patients currently receiving secondary care, an escalation of their treatment should result in better patient health and a subsequent increase in discharges.