clozapine and Depressive-Disorder

The high rates of co-morbidity of drug addiction with depression may be attributable to shared neurobiology. Here, we discuss shared neurobiological substrates in drug withdrawal and depression, with an emphasis on changes in brain reward circuitry that may underlie anhedonia, a core symptom of depression and drug withdrawal. We explored experimentally whether clinical antidepressant medications or other treatments would reverse the anhedonia observed in rats undergoing spontaneous nicotine or amphetamine withdrawal, defined operationally as elevated brain reward thresholds. The co-administration of selective serotonin reuptake inhibitors with a serotonin-1A receptor antagonist, or the tricyclic antidepressant desipramine, or the atypical antidepressant bupropion ameliorated nicotine or amphetamine withdrawal in rats. Thus, increases in monoaminergic neurotransmission, or neuroadaptations induced by increased monoaminergic neurotransmission, ameliorated depression-like aspects of drug withdrawal. Further, chronic pretreatment with the atypical antipsychotic clozapine, that has some efficacy in the treatment of the depression-like symptoms of schizophrenia, attenuated nicotine and amphetamine withdrawal. Finally, a metabotropic glutamate 2/3 receptor antagonist reversed threshold elevations associated with nicotine withdrawal. The effects of these pharmacological manipulations are consistent with the altered neurobiology observed in drug withdrawal and depression. Thus, these data support the hypothesis of common substrates mediating the depressive symptoms of drug withdrawal and those seen in psychiatric patients. Accordingly, the anhedonic state associated with drug withdrawal can be used to study the neurobiology of anhedonia, and thus contribute to the identification of novel targets for the treatment of depression-like symptoms seen in various psychiatric and neurological disorders.

Topics: Adrenergic Uptake Inhibitors; Animals; Antipsychotic Agents; Central Nervous System Stimulants; Clozapine; Depressive Disorder; Dopamine Agents; Glutamic Acid; Humans; Norepinephrine; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome; Substance-Related Disorders

Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.

Topics: Antipsychotic Agents; Anxiety Disorders; Cholinesterase Inhibitors; Clozapine; Dementia; Depressive Disorder; Humans; Mental Disorders; Parkinson Disease; Psychotic Disorders

Many people who attempt suicide or succeed at it visit their physicians shortly before the act; thus, primary care physicians have a key role in preventing suicide. The first step is to suspect that the patient might be at risk, and the second step is to ask about it. Nevertheless, one cannot predict whether any particular person will or will not attempt suicide.

Topics: Bipolar Disorder; Clozapine; Crisis Intervention; Depressive Disorder; Diagnosis, Differential; Hospitalization; Humans; Physician's Role; Risk Factors; Serotonin; Serotonin Antagonists; Suicide; Suicide Prevention

With dopaminergic systems, non dopaminergic neurotransmission probably plays a major role in parkinsonian syndromes (Multiple System Atrophy, Progressive Supranuclear Palsy, Pure Autonomic Failure, Cortical basal degeneration, Lewy Body Disease). A better understanding of the pathophysiology of these syndromes led to the development of molecules that interact with non dopaminergic systems. Thus, freezing, gait and balance disorders, dysautonomia and neuropsychiatric disorders are likely to benefit from specific treatments. However, due to methodological difficulties related to the evaluation of such molecules, controlled trials are rather rare and the results are often partial and sometimes unclear.

Topics: Anti-Dyskinesia Agents; Botulinum Toxins; Cholinesterase Inhibitors; Clozapine; Dementia; Depressive Disorder; Dopamine; Glutamic Acid; Humans; Movement Disorders; Parkinsonian Disorders; Selective Serotonin Reuptake Inhibitors; Serotonin; Synaptic Transmission; Treatment Outcome

Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders.. A comprehensive literature review.. Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer's disease.. There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

Topics: Aged; Alzheimer Disease; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder; Drug Administration Schedule; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Risperidone

Depressive symptoms and syndromal depression commonly occur in patients with schizophrenia. Schizophrenia is also associated with aggression directed at self and others. For this article, the available literature regarding the efficacy of clozapine, risperidone, olanzapine, quetiapine, and ziprasidone in the treatment of depression, hostility, and suicidality in patients with schizophrenia was reviewed. These studies suggest that atypical antipsychotics may exert therapeutic effects on depression and hostility as well as psychosis and that clozapine and olanzapine may reduce suicidality in patients with schizophrenia. These therapeutic actions appear to represent additional advantages of atypical antipsychotics compared with standard agents.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Depression; Depressive Disorder; Dibenzothiazepines; Hostility; Humans; Multicenter Studies as Topic; Olanzapine; Piperazines; Pirenzepine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Suicide; Thiazoles; Treatment Outcome

Olanzapine is a novel antipsychotic agent displaying a unique and pleotrophic pharmacology, which distinguishes it from other existing treatments. Clinical investigations employing olanzapine have demonstrated a number of potential therapeutic advantages in reference not only to placebo but also to contemporary drug standards in the management of psychosis. This paper reviews data on the pharmacokinetics, efficacy and safety of olanzapine, its benefits for quality of life, and economic aspects to assist clinicians in determining where they can usefully employ it.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder; Drug Resistance; Humans; Olanzapine; Pirenzepine; Prolactin; Psychotic Disorders; Quality of Life; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

Attempts to clarify the domains of schizophrenia gained importance when the atypical antipsychotics joined the armamentarium of schizophrenia treatments because of evidence that these agents are superior to conventional antipsychotics for the treatment of negative symptoms. Negative symptoms can be divided into 3 components: (1) deficit or primary enduring negative symptoms that may or may not respond to treatment, (2) primary nonenduring negative symptoms, and (3) secondary negative symptoms that are associated with positive symptoms, extrapyramidal symptoms, depression, and environmental deprivation. The atypical antipsychotics have generally been found to be more effective than conventional antipsychotics against the totality of negative symptoms, but their effects on specific components are still under study. Sophisticated statistical tools such as path analysis have been used in investigations of the direct and indirect effects of atypical antipsychotics on negative symptoms, but these tools have limitations. Future study is needed to identify specific components of negative symptoms that may respond preferentially to one or another of the atypical antipsychotics.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Clozapine; Delusions; Depressive Disorder; Hallucinations; Humans; Models, Statistical; Multivariate Analysis; Psychiatric Status Rating Scales; Regression Analysis; Risperidone; Schizophrenia; Schizophrenic Psychology

Depression in schizophrenia may be partially responsible for the increased suicide rate in schizophrenic patients, which is more than 20 times higher than that found in the general population. Affective disorders in patients with schizophrenia are associated with a poor outcome, an increased risk of relapse, and a high rate of suicide. There is evidence that atypical antipsychotics may contribute to a reduction in suicidality, and although the new drugs are marketed for the treatment of schizophrenia, their novel psychopharmacologic effects suggest the possibility of other therapeutic applications. Recent studies of the efficacy of the novel antipsychotics found that these agents may produce an antidepressant effect in schizophrenia and may be used as either an adjunctive medication or an alternative to mood stabilizers in patients with affective disorders.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Comorbidity; Depressive Disorder; Humans; Mood Disorders; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology; Suicide; Suicide Prevention

To present a critical overview of the selected literature published in the past 7 years on the efficacy and safety of psychoactive agents in conduct disorder, schizophrenia, separation anxiety disorder, selective mutism, obsessive-compulsive disorder, panic disorder, major depressive disorder, bipolar disorder, and sleep and eating disorders.. Reports of double-blind and placebo-controlled trials and open studies were reviewed and selected studies presented.. Employment of larger samples of diagnostically homogeneous patients and a more sophisticated design and methodology led to progress in the treatment of most of these conditions. Data have been accumulated on dose range and safety of lithium in this age group, and there is supportive evidence that lithium is useful in reducing aggression.. For a rational treatment approach, further studies are needed, particularly in depression and conduct disorder; psychosocial-environment contributions and possible biological markers should be investigated in order to identify children who require psychopharmacological treatments and those who will respond to psychosocial interventions or the combination of both. Symptoms targeted to require pharmacotherapy and symptoms targeted to respond to psychosocial interventions have to be identified.

Topics: Adolescent; Alprazolam; Anticonvulsants; Antipsychotic Agents; Anxiety, Separation; Bipolar Disorder; Carbamazepine; Child; Child Behavior Disorders; Child, Preschool; Clonidine; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Feeding and Eating Disorders; Fluoxetine; Humans; Imipramine; Lithium; Mutism; Obsessive-Compulsive Disorder; Phenobarbital; Phenytoin; Phobic Disorders; Schizophrenia; Sleep Wake Disorders; Tranquilizing Agents

Lithium remains the mainstay of treatment for patients with bipolar affective disorder; however, nearly half of patients with bipolar disorder fail to respond to lithium. Recently, there have been an increasing number of preliminary clinical reports that clozapine, an atypical antipsychotic agent, has potential efficacy in patients with mood disorders. We review the available clinical data supporting the potential use of clozapine in these psychiatric disorders and report our preliminary data from a study that used clozapine in the acute treatment of mania in treatment-refractory patients. Twenty-five patients meeting the DSM-III-R criteria for the manic phase of either bipolar or schizoaffective disorder entered a 13-week open prospective trial of clozapine. These patients either had failed to respond to or had been intolerant to treatment with lithium, an anticonvulsant, and at least two typical neuroleptics. Eighteen of 25 patients demonstrated a greater than 50% decrease in the Young Mania Rating Scale score. These preliminary data as well as the clinical reports reviewed indicate that the efficacy of clozapine in treatment-resistant patients is not limited to patients with schizophrenia.

Topics: Affective Disorders, Psychotic; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Depressive Disorder; Humans; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies

Topics: Antidepressive Agents; Clozapine; Depressive Disorder; Dopamine; Electroconvulsive Therapy; Female; Homovanillic Acid; Humans; Levodopa; Male; Mental Disorders; Nomifensine; Nortriptyline; Parkinson Disease; Personality; Psychotic Disorders; Serotonin; Tryptophan

Recent data suggest that inhibitory pathways may be involved in the pathophysiology of depression and in the mode of action of some antidepressant interventions. The aim of the present study was to test whether vagus nerve stimulation (VNS) can affect motor cortex excitability. Measures of motor cortical excitability were probed by using single-pulse and paired-pulse transcranial magnetic stimulation at baseline, after 10 weeks of left VNS, and additionally, in an on-off paradigm in 10 patients with treatment-resistant unipolar depression. Ten weeks of VNS was associated with a selective and pronounced increase in intracortical inhibition, whereas no changes occurred in the on-off paradigm. These results suggest that VNS is capable of changing motor cortical excitability in patients with depression.

Topics: Adult; Benzodiazepines; Citalopram; Clomipramine; Clozapine; Depressive Disorder; Doxepin; Drug Therapy, Combination; Electric Stimulation; Female; Humans; Lamotrigine; Lithium Carbonate; Male; Mianserin; Middle Aged; Mirtazapine; Morpholines; Motor Cortex; Neural Conduction; Neural Inhibition; Olanzapine; Paroxetine; Psychiatric Status Rating Scales; Reboxetine; Tranylcypromine; Triazines; Vagus Nerve; Valproic Acid

There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year.

Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Depressive Disorder; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Schizophrenic Psychology

Schizophrenia is characterized by high suicide risk and low awareness of disorder. Although awareness has benefits for medication compliance and clinical outcome, it is unclear how it may relate to suicide risk in this population.. This multicenter investigation assessed awareness and suicide-related behavior in 980 patients with schizophrenia or schizoaffective disorder. Patients were followed over 2 years and assessed by blinded raters for suicide-related events.. Awareness of psychiatric condition at baseline was associated with increased risk of suicide events over the follow-up. This effect was mediated by depression and hopelessness levels. By contrast, changes in awareness associated with treatment decreased the risk of suicide.. Although some patients may become depressed after acknowledging the clinical handicaps of their disorder, treatment-related changes in awareness are generally associated with a positive outcome relative to suicide risk. The complex interactions and mediation effects of these clinical variables require careful monitoring.

Topics: Adult; Antipsychotic Agents; Awareness; Benzodiazepines; Clozapine; Comorbidity; Depressive Disorder; Female; Health Status; Humans; Male; Middle Aged; Olanzapine; Proportional Hazards Models; Risk Factors; Schizophrenia; Schizophrenic Psychology; Suicide; Suicide Prevention; Treatment Outcome

Fluvoxamine (FLUVOX) is an inhibitor of the cytochrome P450 isoenzyme 1 A2 and thereby inhibits clozapine (CLOZ) metabolism. We performed an open clinical study to gather experience in necessary dosages, plasma levels, side effects and clinical efficiency of the coadministration of the two drugs. Eighteen psychotic patients were studied. 50 mg FLUVOX were given throughout the study period, while the CLOZ dosage was increased individually (week 5: 96.9+/-37.2 mg). After 5 weeks the plasma concentrations were as follows: CLOZ 252+/-174 ng/ml, N-desmethylclozapine (DM-CLOZ) 143+/-74 ng/ml and clozapine N-oxide (CLOZ N-OX) 30+/-14 ng/ml. There were no differences in side effects, especially sedation, after 5 weeks compared to the pretreatment condition. Moreover, we found a significant improvement in measures of cognitive speed which might be regarded as a measure of vigilance. The BPRS scores dropped continuously until week 5 (pretreatment: 53.3+/-13.4; week 5: 33.2+/-12.9) and 5 patients were considered treatment responders (BPRS reduction > 50%). Ten patients continued the combination treatment after the study period and 9 of these patients were in clinical remission when discharged. Given strict therapeutic drug monitoring, coadministration of FLUVOX and CLOZ seems to be a safe and efficient treatment strategy with a low occurrence of the side effects associated with CLOZ treatment. This might be due to additive effects of the two drugs and/or metabolic interaction.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Clozapine; Depressive Disorder; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Psychotic Disorders; Schizophrenia; Schizophrenia, Paranoid

1. The aim of the study was to determine if a more rational therapeutic approach could be devised for neuroleptic resistant psychotic patients treated for months and years with clozapine. Clozapine is an atypical antipsychotic medication, but its therapeutic benefit has been limited by a high incidence of agranulocytosis and seizures. 2. The study has been performed in an open setting and included 12 patients. Some of them developed a secondary depression and were treated with fluoxetine. 3. Pharmacokinetic analysis were conducted at the same time as clinical evaluations, grading using the BPRS, the PDS, and QLS, and determinations of plasma and red blood cell clozapine and desmethylclozapine, plasma and RBC fluoxetine and norfluoxetine, whole blood serotonin and tryptophan. 4. A positive linear correlation was found only between RBC concentration and the evolution of the QLS. 5. Clozapine is efficacious both on positive and negative symptoms but its mechanism of action remains unclear. Positive symptoms disappear more quickly, sometimes followed by a post psychotic depression. Negative symptoms improve more slowly but regularly. They seem to be correlated with serotoninergic mechanisms. For whole blood 5HT, an important increase was seen about 4 weeks after Cloza administration, and then a decrease. 6. Therapeutic drug monitoring (on the same sample drawn for haematological monitoring providing) could play a useful role in the management of patients treated by clozapine: compliance, lowest dose, possible toxicity, drug interaction, lack of efficacy, relapse predictivity.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Depressive Disorder; Drug Monitoring; Female; Fluoxetine; Humans; Male; Middle Aged; Schizophrenia; Serotonin; Tryptophan

Antidepressants are frequently used in the treatment of depressive symptoms associated with schizophrenia. In patients taking clozapine, choice of antidepressant is complicated by additive pharmacodynamic effects and by pharmacokinetic interactions. We predicted that citalopram would not elevate plasma clozapine levels when the two drugs were co-administered because it does not inhibit the relevant enzyme systems. In this preliminary study of five patients given citalopram and clozapine there was no overall change in mean clozapine levels. Based on this limited evidence, citalopram might be the antidepressant of choice in patients taking clozapine.

Topics: Adolescent; Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Citalopram; Clozapine; Depressive Disorder; Drug Interactions; Drug Therapy, Combination; Humans; Middle Aged; Pilot Projects; Schizophrenia

Little is known about the comparative effectiveness of long-term pharmacological treatments for severe unipolar depression. We aimed to study the effectiveness of pharmacological treatments in relapse prevention in a nationwide cohort of patients who had been admitted to hospital at least once as a result of unipolar depression.. Our nationwide cohort study investigated the risk of readmission to hospital in 1996-2012 in all patients in Finland who had been admitted to hospital at least once for unipolar depression (without a diagnosis of schizophrenia or bipolar disorder) in Finland between Jan 1, 1987, and Dec 31, 2012. We used nationwide databases to obtain data for hospital admission, mortality, and dispensed medications. Exposure and non-exposure periods for medications were established using the PRE2DUP method. The primary analysis was within-individual analysis of readmission to hospital in the total cohort, in which each individual was used as his or her own control to eliminate selection bias. Putative survival and protopathic biases were controlled in sensitivity analyses. Since 33 independent statistical comparisons were done for specific medications, the level of statistical significance was set at p<0·0015.. Data from 123 712 patients were included in the total cohort, with a mean follow-up time of 7·9 years (SD 5·3). Lithium use was associated with a lower risk of re-admission to hospital for mental illness than was no lithium use (hazard ratio [HR] 0·47 [95% CI 0·40-0·55]; p<0·0001), whereas the groups of antidepressants (HR 1·10 [1·06-1·13]; p<0·0001) and antipsychotics (HR 1·16 [1·12-1·20]; p<0·0001) were not associated with a reduced risk of readmission to hospital. Risk of hospital readmission was lower during lithium therapy alone (HR 0·31 [0·21-0·47]; p<0·0001) than during use of lithium with antidepressants (HR 0·50 [0·43-0·59]; p<0·0001). After lithium, clozapine (HR 0·65 [0·46-0·90]; p=0·010) and amitriptyline (HR 0·75 [0·70-0·81]; p<0·0001) were the specific agents associated with the next lowest risk of readmission. In the sensitivity analyses controlling for survival and protopathic biases, all drugs were associated with lower rates of readmission to hospital than they were in the primary analysis, showing the same rank order in comparative effectiveness. The lowest mortality was observed during antidepressant use (HR 0·56 [0·54-0·58]; p<0·0001).. Our results indicate that lithium, especially without concomitant antidepressant use, is the pharmacological treatment associated with the lowest risk of hospital readmission for mental illness in patients with severe unipolar depression, and the outcomes for this measure related to antidepressants and antipsychotics are poorer than lithium. Lithium treatment should be considered for a wider population of severely depressed patients than those currently considered, taking into account its potential risks and side-effects.. The Finnish Ministry of Health.

Topics: Adult; Aged; Amitriptyline; Antidepressive Agents; Antipsychotic Agents; Clozapine; Cohort Studies; Depressive Disorder; Depressive Disorder, Major; Female; Finland; Humans; Incidence; Lithium; Male; Middle Aged; Outcome Assessment, Health Care; Patient Readmission; Risk; Secondary Prevention; Severity of Illness Index

Depression is one of the most common chronic mental disorders, which is a leading cause of morbidity and mortality in patients. Depression often leads to offensive and defensive behaviours but the underlying mechanisms are not known. We propose that the aggressive behaviours in depression can be modelled in animal experiments. In this study, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm and detected aggressive and social dominance behaviours in rodents by resident/intruder test and social dominance tube test (SDTT), respectively. The CUMS-exposed mice showed increased defensive, offensive and aggressive behaviours in the resident-intruder test. In the SDTT, these mice showed enhanced social dominance. These alterations were associated with reduced MAP-2 expression in the hippocampus while no difference in β-tubulin expression was detected. In addition, the treatment of anti-depressant fluoxetine reversed the aggressive behaviours without reducing the social dominance behaviour induced by CUMS. However, fluoxetine did effectively reverted the changes in MAP-2 expression in the hippocampus. In addition, the nonspecific tricyclic antipsychotic drug, clozapine, reversed all symptoms of CUMS-exposed mice including aggressive tendencies, impulsive violence, social dominance behaviour and MAP-2 expression in the hippocampus. The results suggests that social maladjustment such as competition and social dominance are likely related to the dopaminergic system rather than the serotonergic system and the hippocampal dendritic structure protein MAP-2. Thus, dominance can be separated from aggression. This study shows that aggression/hostility and social hierarchy/dominance are increased in the CUMS-exposed mice and thus provide an excellent model for further study in the diagnosis and the treatment of depression-associated aggression.

Topics: Aggression; Animals; Antidepressive Agents, Second-Generation; Clozapine; Depressive Disorder; Disease Models, Animal; Fluoxetine; Hippocampus; Male; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins; RNA, Messenger; Social Dominance; Stress, Psychological

Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function.

Topics: Animals; Anxiety; Behavior, Animal; Cell Line; Clozapine; Depressive Disorder; Disease Models, Animal; Female; Male; Mice; Mice, Transgenic; Serotonergic Neurons; Serotonin; Swimming

Depression interferes with the human ability to make decisions. Multiple criteria have been adopted for the diagnosis of depression in humans, but no clear indicators are available in animal models to reflect the depressive mood, involving higher cognitive functions. The act of foraging is a species-specific behaviour which is believed to involve the decision-making and higher cognitive functions. We previously established a method to detect the foraging behaviour of rodents, in which our results demonstrated that NMDA and dopamine receptors were involved. Conversely, increased NMDA receptors and reduced dopamine have been reported in depression model rodents. However, we hypothesise that foraging activities may also be impaired in depression. To test the theory, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm. Most interestingly, the food foraging activity of mice after CUMS was significantly reduced. In addition, the treatment of anti-depressant fluoxetine reversed most depressive symptoms and reduced glial fibrillary associated protein (GFAP) expression in the hippocampus, but was less effective in the reduction of foraging activities. However, clozapine reversed all symptoms of CUMS-exposed mice including reduction of GFAP expression in the hippocampus and impaired foraging activity. Our findings of GFAP expression as a marker to validate the CUMS protocol provide further validation of our hypothesis, that the reduced food foraging is probably a new behavioural finding of depression in which the serotoninergic system could not be singly involved. Our study suggests that NMDA receptors, serotoninergic and dopaminergic systems are differentially involved in these food foraging behaviours. Our data suggest that the foraging test in rodents can be a useful tool to assess the ability of decision-making in depression.

Topics: Animals; Antidepressive Agents; Appetitive Behavior; Body Weight; Cerebral Cortex; Chronic Disease; Clozapine; Depressive Disorder; Disease Models, Animal; Exploratory Behavior; Feeding Behavior; Fluoxetine; Freezing Reaction, Cataleptic; Glial Fibrillary Acidic Protein; Hippocampus; Male; Mice; Mice, Inbred C57BL; RNA, Messenger; Stress, Psychological

Recently, second-generation antipsychotics (SGAs) have been widely used in the treatment of mood disorders. However, the mechanisms of the antidepressant effect of SGAs remain unclear. We proposed that Golf protein, a stimulant alpha-subunit of G protein coupled with the dopamine D1 receptor, might a play the key role in the antidepressive effect of antidepressants. To clarify the relationship between Golf protein and the antidepressive effects of antipsychotics, we examined the effects of chronic treatment with several antipsychotics on the level of Golf protein in the rat striatum.. Male Wistar rats were treated with one of several antipsychotics for 2 weeks: olanzapine (2, 5, or 10 mg/kg), sulpiride (5, 10, or 50 mg/kg), amisulpride (3, 10, or 20 mg/kg), risperidone (0.2 or 2 mg/kg), haloperidol (0.3 or 3 mg/kg), or clozapine (2 or 10 mg/kg).. Olanzapine (5 mg/kg), sulpiride (5, or 10 mg/kg), and amisulpride (10 mg/kg) treatments significantly increased the level of Golf protein, but there was no increase with administration of higher doses of these three antipsychotics. Risperidone, haloperidol, and clozapine treatment did not change the level of Golf protein at any dose. In this study, all antipsychotics that have antidepressive effects increased Golf protein. This suggests that an increase in Golf may play an important role in the antidepressive effect of antipsychotics.. We postulate that the increase in Golf protein levels result in an increase the proportion of D1 receptors in the high-affinity state and that augmentation of the dopaminergic system exerts the antidepressant effect.

Topics: Amisulpride; Animals; Antipsychotic Agents; Benzodiazepines; Blotting, Western; Clozapine; Corpus Striatum; Depressive Disorder; Dose-Response Relationship, Drug; GTP-Binding Protein alpha Subunits; Haloperidol; Injections, Intraperitoneal; Male; Olanzapine; Rats; Rats, Wistar; Risperidone; Sulpiride; Time Factors

Two patients with a psychotic depression showed insufficient response to pharmacotherapy and electroconvulsive therapy. The problem therefore was which alternative treatment options should be considered at this stage. On the bases of the available literature the most suitable options seemed to be clozapine, a monoamine oxidase inhibitor and lithium addition. Patient A responded well to clozapine and the condition of patient B improved during treatment with tranylcypromine, lithium and quetiapine.

Topics: Antipsychotic Agents; Clozapine; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Lithium Compounds; Middle Aged; Psychotic Disorders; Therapeutics; Tranylcypromine

The authors report an improvement in delusions and hallucinations after antidepressant treatment (Clomipramine) in a parkinsonian patient with psychosis and comorbid depression. Their findings, which support a previous case treated with Citalopram, highlight the possible effectiveness of antidepressant therapy on psychotic symptoms in parkinsonian patients.

Topics: Affect; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antiparkinson Agents; Antipsychotic Agents; Clomipramine; Clozapine; Delusions; Depressive Disorder; Hallucinations; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Pergolide; Psychiatric Status Rating Scales; Psychotic Disorders

No systematic study has focused on the characteristics and outcome of acute clozapine intoxication, although clozapine is the most widely used antipsychotic agent in China. The study reported herein examined the features of clozapine intoxication and the therapeutic effect of hemoperfusion (HP).. In a retrospective chart review, the notes of 47 patients who attempted suicide by ingesting large amounts of clozapine and were treated at the only psychiatric emergency service in Beijing were analyzed. Of the 20 unconscious patients with plasma clozapine concentrations of more than 2000 ng/mL, 14 received a combination of HP and symptomatic treatment, whereas the other 6 and the remaining 27 patients received only symptomatic treatment. Patients' psychiatric conditions and both plasma clozapine and norclozapine concentrations were closely monitored and registered.. One patient died of pulmonary edema and subsequent heart failure, but the rest of the patients recovered without any sequelae. Patients who received HP regained consciousness significantly faster than their counterparts with the same level of clozapine plasma concentration (>2000 ng/mL) who did not receive HP.. A combination of HP and symptomatic treatment is the best therapeutic option when plasma clozapine concentration is high.

Topics: Acute Disease; Adult; Alprazolam; Antipsychotic Agents; China; Clonazepam; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Drug Overdose; Emergency Service, Hospital; Hemoperfusion; Humans; Medical History Taking; Middle Aged; Pulmonary Edema; Retrospective Studies; Schizophrenia; Stress Disorders, Post-Traumatic; Suicide, Attempted; Sulpiride; Unconsciousness; Wine

Topics: Antipsychotic Agents; Clozapine; Combined Modality Therapy; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Inpatients; Male; Severity of Illness Index; Treatment Failure

Topics: Adult; Cardiomyopathies; Clozapine; Depressive Disorder; Humans; Male; New South Wales

The present cross-sectional study examined the relationships of psychopathology, side effects, and sociodemographic factors with treatment outcomes in terms of patients' quality of life (QOL), functioning, and needs for care.. Sixty outpatients with chronic schizophrenia who had been treated with either clozapine or olanzapine for at least 6 months were investigated.. Most psychopathological symptoms as well as psychic side effects, weight gain, and female sex were associated with lower QOL, while cognitive symptoms correlated with better QOL. Female sex, cognitive symptoms, and parkinsonism negatively influenced occupational functioning, and negative symptoms determined a lesser likelihood of living independently. Age, education, depression/anxiety, negative symptoms, and psychic side effects were predictors of patients' needs for care.. Our results highlight the complex nature of patient outcomes in schizophrenia. They reemphasize the need of targeting effectiveness, i.e. both symptomatic improvement as well as drug safety, in such patients.

Topics: Adult; Age Factors; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Clozapine; Cognition; Comorbidity; Cross-Sectional Studies; Depressive Disorder; Educational Status; Female; Humans; Male; Olanzapine; Parkinsonian Disorders; Quality of Life; Schizophrenia; Schizophrenic Psychology; Sex Factors; Socioeconomic Factors; Treatment Outcome; Weight Gain

This study investigates the efficacy of clozapine in treatment-resistant abused adolescents detained in a secure environment who present with chronic posttraumatic stress disorder and psychotic symptoms. All participants had received at least 2 trials of conventional neuroleptic medication prior to starting clozapine. Efficacy was assessed by using single case methodology across 6 participants employing predependent and postdependent measures of psychiatric symptoms and behavioral observations. Subjective self-reports were also sought after treatment had been established. Evaluation of the data suggests that 4 of the participants demonstrated substantial improvements in psychiatric symptoms and behavioral presentation once a therapeutic dose of clozapine had been achieved. Questionnaire responses from 5 participants indicated that clozapine treatment was associated with a reduction in hallucinatory experiences. The most troubling side effects were those of excessive salivation, dizziness, and weight gain. These findings indicate that clozapine may be effective in decreasing psychiatric symptoms and risk behaviors in traumatized adolescents presenting with psychotic symptoms.

Topics: Adolescent; Aggression; Antipsychotic Agents; Clozapine; Depressive Disorder; Female; Humans; Inpatients; Male; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risk-Taking; Self-Injurious Behavior; Stress Disorders, Post-Traumatic

Topics: Adult; Antipsychotic Agents; Clozapine; Depressive Disorder; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome

This paper examines the effects of medical center budget stress on the use of expensive atypical antipsychotic medications for the treatment of schizophrenia in the Department of Veterans Affairs (VA). VA prescription drug records were collected for patients diagnosed with schizophrenia. Generalized estimation equations were used to identify patient and facility characteristics (especially fiscal stress) that are associated with the use of atypical antipsychotics. Of the 34,925 patients in the final sample, over half received an atypical antipsychotic, usually either olanzapine or risperidone. Unexpectedly, increased fiscal stress was associated with increased likelihood of receiving atypical antipsychotics. Among patients who receive atypicals, however, fiscal stress was associated with reduced likelihood of receiving the more expensive atypicals (clozapine and olanzapine) but positively associated with receiving the least expensive atypical (risperidone). Institutional fiscal pressure does not seem to reduce the broad availability of these medications overall but does affect which drug is prescribed.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Budgets; Clozapine; Comorbidity; Depressive Disorder; Drug Costs; Female; Health Care Costs; Health Facilities; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Practice Patterns, Physicians'; Regression Analysis; Risperidone; Schizophrenia; Treatment Outcome; United States; United States Department of Veterans Affairs

Topics: Antidepressive Agents; Antipsychotic Agents; Clozapine; Comorbidity; Depressive Disorder; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Fluoxetine; Humans; Schizophrenia; Schizophrenic Psychology; Secondary Prevention

Atypical anti-psychotic drugs (APDs) are widely used in psychotic disorders refractory to conventional neuroleptic agents.. Three cases of new-onset diabetes are reported in Caucasian men who were on clozapine (one) or olanzapine (two) for 3-6 months. They had a distinct presentation: weight loss, ketosis (one ketoacidosis), severe hyperglycaemia requiring insulin therapy, and relative insulin deficiency as reflected by glucagon stimulatory tests. In all cases, insulin was stopped within 1 month after the APD was discontinued.. Novel APDs not only induce diabetes as a result of weight gain in predisposed patients, but can also lead to a reversible state of insulin deficiency, and sometimes ketoacidosis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder; Diabetes Mellitus; Glyburide; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia

Topics: 1-Naphthylamine; Adult; Antipsychotic Agents; Clozapine; Cognition; Depressive Disorder; Drug Synergism; Drug Therapy, Combination; Fluoxetine; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Selective Serotonin Reuptake Inhibitors; Sertraline

Three hypotheses were tested: 1) schizophrenic patients would report more impairments on a self-rating scale for negative symptoms than normal subjects and attribute higher levels of distress to these impairments, 2) schizophrenic patients would report fewer impairments than patients with a depressive disorder and attribute lower levels of distress to these impairments, and 3) schizophrenic patients would attribute their impairments less often to mental illness than would patients with a depressive disorder.. A self-rating scale for negative symptoms was administered to 86 patients with schizophrenia, 20 patients with a depressive disorder, and 33 normal subjects. The scale items were derived from the Scale for the Assessment of Negative Symptoms (SANS). Two psychiatrists also rated all of the patients on the SANS.. The hypotheses were supported. The differences between the two groups of patients in the rates of reported impairments and the levels of reported distress remained statistically significant after control for differences in age, sex, length of current admission, length of illness, dose of neuroleptic medication, use of clozapine, and severity of negative symptoms.. The results suggest that a large number of schizophrenic patients are somewhat aware of negative symptoms but that they are less aware of these impairments and less concerned about them than are patients with a depressive disorder.

Topics: Adolescent; Adult; Animals; Antipsychotic Agents; Attitude to Health; Awareness; Clozapine; Depressive Disorder; Diagnosis, Differential; Female; Health Status; Humans; Length of Stay; Male; Mice; Middle Aged; Personality Inventory; Pregnancy; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder; Female; Humans; Olanzapine; Pirenzepine; Pregnancy; Pregnancy Complications; Schizophrenia; Schizophrenic Psychology; Sex Factors

Eosinophilia has been encountered from 0.2 to 61.7% in clozapine-treated patients, mostly with a transient course and spontaneous remission. There have been few reports, however, which have investigated a challenge with clozapine in patients previously showing eosinophilia. Two case reports are presented: the first with clozapine challenge after eosinophilia, the second under clozapine treatment and no previous haematological side effects. The challenge case showed eosinophilia with 1.2 10(9)/l (z = 1.79, p = 0.04) being followed by normalization despite clozapine continuation, whereas the maximum value reached 2.1 10(9)/l in the single episode case, with consecutive normalization and uninterrupted treatment. Eosinophilia caused by clozapine was observed in challenge, preceded by a faster neutrophil production and consecutive decrease (z = 2.27, p = 0.01). A challenge with clozapine was feasible and showed no clinical symptoms of eosinophilia.

Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Depressive Disorder; Eosinophilia; Humans; Male; Schizophrenia; Treatment Outcome

Recently, American authors pronounced the hypothesis that Clozapine-response may be considered as a predictor of response to atypical neuroleptic. We report the history of a schizoaffektive patient unresponsive to butyrophenone and phenothiazine neuroleptic who was first treated with Clozapine and then with Risperidone and who reacted very differently to these atypical neuroleptic.

Topics: Adult; Amitriptyline; Antipsychotic Agents; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Prognosis; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Treatment Outcome

A 53-year-old patient suffering from delusional disorder developed an anticholinergic syndrome 19 days after initiation of paroxetine in addition to a steady dose of clozapine. The clozapine plasma concentration had doubled and was in the toxic range. On re-exposition with a lower clozapine dosage the increase was significantly lower. The importance of a dose-dependent interaction of both drugs is emphasized and a possible pharmacological explanation described. With regard to interactions of SSRIs and clozapine, fluvoxamine, a potent inhibitor of cytochrome P450 1A2, gives rise to higher clozapine levels at an earlier time, compared to other SSRIs (paroxetine, fluoxetine and sertraline), which are potent cytochrome P450 2D6 inhibitors.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Blood Pressure; Central Nervous System Diseases; Clozapine; Cytochrome P-450 CYP2D6 Inhibitors; Depressive Disorder; Drug Interactions; Drug Therapy, Combination; Dysthymic Disorder; Humans; Male; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors

The purpose of this study was to test the hypothesis that minor EEG abnormalities predict a favorable response to clozapine. Eighty-six psychotic clozapine-treated psychiatric inpatients with EEG records before starting clozapine were included in the study. When all diagnostic groups were combined, there were no significant differences in clinical outcome between patients with abnormal EEGs and patients with normal EEGs. However, female patients with abnormal EEGs had a significantly greater improvement in Global Assessment of Functioning (GAF) scores compared to female patients with normal EEGs. In addition, patients with major depressive episodes (bipolar, schizoaffective, unipolar) and abnormal EEGs had a significantly greater improvement in GAF scores compared to the same subgroup of patients with normal EEGs. The results suggest that EEG abnormalities before clozapine treatment many predict a favorable clinical response in specific groups of patients.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Depressive Disorder; Electroencephalography; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Schizophrenia; Sex Factors; Single-Blind Method; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Clozapine; Depressive Disorder; Female; Humans; Suicide, Attempted

The treatment of refractory major depression, including the psychotic subtype, is a therapeutic challenge. Three cases of resistant psychotic depression were treated with clozapine monotherapy, an atypical antipsychotic drug effective in treatment-resistant schizophrenia and mania. Both psychotic and mood symptoms responded well to clozapine monotherapy, although response was delayed in one case. Tardive dyskinesia improved markedly, and tardive dystonia improved moderately in one patient. No patient relapsed during a follow-up period of 4-6 years of clozapine treatment. Clozapine was well-tolerated with few side effects. These observations suggest controlled trials of clozapine in the treatment of psychotic depression that fails to respond to electroconvulsive therapy or typical neuroleptics plus tricyclic antidepressants are indicated. The same is true for the use of clozapine in maintenance treatment for psychotic depression in those cases in which typical neuroleptic drugs are required, in order to reduce the risk of tardive dyskinesia and dystonia.

Topics: Adult; Clozapine; Depressive Disorder; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Time Factors

Twenty patients suffering from schizophrenia and 36 patients suffering from endogenous depression underwent a standardized heart rate analysis before drug therapy. The patient's parameters of heart rate variability (HRV), which are controlled by the parasympathetic nervous system and which are independent of heart rate, did not significantly differ from the HRV parameters of normal control subjects. Ten of the patients with schizophrenia were treated with 200-400 mg of clozapine/day as monotherapy, while the other ten patients received a combination of different psychotropic drugs. The depressed patients were either treated with 150 mg of amitriptyline/d (n = 24) or 20 mg of paroxetine/d (n = 12) as monotherapy, respectively. After treatment with an average of 300 mg of clozapine/d for 4 weeks or with 150 mg of amitriptyline/day for 2 weeks, all of the patients HRV parameters had significantly decreased (P < 0.001). At this time, about 90% of these patients fulfilled the criteria of cardiovascular autonomic neuropathy. However, treatment with 20 mg of paroxetine/day for 2 weeks had no impact on any of the heart rate parameters. Under amitriptyline treatment, HRV parameters were found to correlate significantly with the plasma levels of amitriptyline/nortriptyline in a group of 104 depressed patients. Thus, determination of decreased HRV parameters is suggested to be a useful tool for the detection of overdosage with amitriptyline. It has not yet been elucidated whether or not the observed HRV decrease, which is probably at least in part due to the anticholinergic side effects of clozapine and amitriptyline, has any impact on patient health.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amitriptyline; Arrhythmias, Cardiac; Autonomic Nervous System; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Overdose; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Psychotropic Drugs; Schizophrenia

Drug-induced psychosis is a serious late complication of Parkinson's disease (PD) that requires aggressive treatment. Recent studies have found clozapine a highly effective and ECT a possibly useful intervention. Two cases are presented that illustrate a possible treatment role for ECT. The cases demonstrate that ECT has significant but short-lived antipsychotic effects when used alone. However, patients who do not respond to clozapine monotherapy can be given adjunctive treatment with ECT. The combination therapy resulted in abrupt alleviation of psychotic symptoms in one of the cases, and maintenance with low-dose clozapine allowed for long-term efficacy. On the basis of these findings, a therapeutic approach to patients with drug-induced psychosis in PD is suggested.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Combined Modality Therapy; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced

Various types of movement disorder have been reported to occur rarely in patients treated with clozapine. This paper describes five cases in which these phenomena appeared to be clearly associated with clozapine medication and discusses possible pharmacologic mechanisms and treatment options.. Inpatients receiving clozapine were investigated for the presence of movement disorders. We present five patients with clozapine-induced myoclonus, describe their patterns, and compare clinical features.. Five patients treated with clozapine developed a similar pattern of movement disorder that can be described as myoclonus. The neurologic symptoms improved after the treatment was discontinued, the clozapine dose reduced, or concomitant carbamazepine administered.. Clozapine can induce dose-dependent myoclonus. However, these symptoms can be relieved by reducing the dose of clozapine or giving carbamazepine so that discontinuation of clozapine treatment can be avoided.

Topics: Adult; Antipsychotic Agents; Carbamazepine; Clozapine; Depressive Disorder; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Hospitalization; Humans; Male; Middle Aged; Myoclonus; Schizophrenia

Based on five case studies, the suggestion is that, if physiological myoclonus can be excluded, antidepressant - or neuroleptic-induced myoclonus must as a rule be presumed to be a most subtle indication of increased cerebral exitability, an epileptic fragment or, in some instances, a myoclonus epilepsy. In each of the reported cases EEG recordings reflected epilepsy-specific potentials. Whether, however, the scope of differences in the EEG recordings and the N1/P1 amplitude increase of the SSEP may be used as an additional diagnostic criterion to determine the risk of epileptic seizures, should depend on the type of myoclonus chiefly induced. This would require more extensive neurophysiological examinations which should mainly include the back-averaging to permit, beside the EEG, a better evaluation of the relatively easily obtainable SSEP findings.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents; Antipsychotic Agents; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Electroencephalography; Epilepsies, Myoclonic; Evoked Potentials; Female; Humans; Male; Maprotiline; Middle Aged; Psychotic Disorders; Trimipramine

A patient receiving electroconvulsive therapy (ECT), clozapine, and intravenous caffeine sodium benzoate developed supraventricular tachycardia. This was rapidly treated with intravenous verapamil. Subsequent maintenance ECT given without caffeine was well tolerated. We believe the combination of clozapine and caffeine at the time of ECT was responsible for the arrhythmia.

Topics: Affective Disorders, Psychotic; Aged; Caffeine; Clozapine; Combined Modality Therapy; Depressive Disorder; Drug Therapy, Combination; Electrocardiography; Electroconvulsive Therapy; Female; Humans; Recurrence; Tachycardia, Supraventricular

Longitudinal assessments (every six weeks for one year) were made of plasma norepinephrine, dopamine, epinephrine and 3-methoxy-4-hydroxyphenylglycol (MHPG) in 40 adolescents with schizophrenia, 20 on clozapine therapy and 20 on conventional medication. In addition to the plasma catecholamine determinations, serum levels of 5-HT were determined as a measure of serotoninergic status. All analyses were performed by HPLC-ECD (high-performance liquid chromatography with electrochemical detection). Clinical ratings of symptomatology were obtained with the Brief Psychiatric Rating Scale (BPRS) and the Andreasen scales for negative and positive symptoms (SANS and SAPS). Compared with the typical neuroleptic medication, clozapine administration was accompanied by a significant increase in plasma norepinephrine and MPHG and serum serotonin levels. The fluctuations in the biogenic amines were closely associated with the observed symptomatology. Plasma MHPG was linked to depressive symptoms (BPRS), and negative symptoms (SANS) were related to changes in the serum serotonin levels. The pathophysiological implications and clinical consequences of these findings are discussed.

Topics: Adolescent; Adult; Antipsychotic Agents; Chronic Disease; Clozapine; Depressive Disorder; Dopamine; Epinephrine; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Methoxyhydroxyphenylglycol; Neurotransmitter Agents; Norepinephrine; Prospective Studies; Psychiatric Status Rating Scales; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Serotonin; Treatment Outcome

To determine the efficacy and tolerance of long-term clozapine therapy in refractory affective illness.. Hospital records were reviewed for 193 treatment-resistant patients with a discharge diagnosis of bipolar disorder (N = 52), schizoaffective disorder (N = 81), unipolar depression (N = 14), schizophrenia (N = 40), or other disorders (N = 6) started on clozapine therapy as inpatients at McLean Hospital. An independent "best-estimate" diagnosis, based on DSM-III-R criteria, was established for each patient. Patients were contacted at least 6 months after clozapine initiation for structured follow-up interviews by raters blind to diagnosis. Patients were stratified by diagnosis, and a variety of patient characteristics and outcome measures were compared.. Subjects were followed up a mean of 18.7 months after clozapine initiation. Bipolar manic and schizoaffective bipolar subjects had significantly better outcomes than unipolar, bipolar, and schizoaffective depressed patients on a variety of measures. One or more episodes of depression prior to clozapine predicted clozapine discontinuation (p = .01). Affective and schizoaffective subjects had baseline measures of social functioning similar to that of the schizophrenics but had significantly greater improvement in scores at follow-up.. Clozapine is an efficacious and well-tolerated therapy for refractory affective illness. Manic symptomatology predicts a more favorable response than depression.

Topics: Adult; Affective Disorders, Psychotic; Bipolar Disorder; Clozapine; Depressive Disorder; Female; Follow-Up Studies; Humans; Male; Probability; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Treatment Outcome

Topics: Amitriptyline; Anti-Anxiety Agents; Benzodiazepines; Clozapine; Depressive Disorder; Humans; Leukocytosis; Male; Middle Aged; Neutrophils; Smoking; Stress, Psychological

Eosinophilia associated with clozapine treatment has been reported in some studies and limited case reports. Because little is known regarding incidence, course, and relevance of this finding, clozapine therapy has been terminated prematurely in some patients with elevated eosinophil counts.. Records were reviewed on 118 consecutively hospitalized, acutely psychotic patients treated over a 1-year period with clozapine for at least 3 weeks. Demographic data were obtained on those patients, and white blood cell counts were analyzed. We reviewed the data for predisposing factors, associated medical findings, or clinical sequelae, and performed a two-sided Fisher's exact test to determine if sex or diagnosis was associated with a higher risk of developing eosinophilia. The literature pertaining to this blood dyscrasia and its relationship to clozapine was reviewed.. In our population, the cumulative incidence of eosinophilia among women was 23% (13/57), a statistically significant higher risk (p < .01) than that in men (7% [4/61]). In all cases, the eosinophilia was noted between Weeks 3 and 5 of treatment and resolved without medical or psychiatric complications.. Eosinophilia should be added to the list of commonly observed side effects of clozapine treatment. Women appear to be at significant risk. Eosinophilia usually occurs early in therapy, spontaneously resolves, and is not associated with any known complications. An otherwise healthy person with this blood dyscrasia may continue with treatment but should be monitored closely. Further investigation into this finding may provide insight into the mechanism of neutropenia and other adverse reactions to clozapine.

Topics: Acute Disease; Adult; Clozapine; Depressive Disorder; Eosinophilia; Female; Hospitalization; Humans; Incidence; Leukocyte Count; Male; Middle Aged; Psychotic Disorders; Risk Factors; Schizophrenia; Sex Factors

Neuroleptic therapy frequently induces undesirable extrapyramidal side effects. The Pisa syndrome is a rare extrapyramidal side effect caused by neuroleptic treatment. Twisting and bending to one side of the upper thorax, the neck and the head are its typical symptoms. These symptoms mainly develop in elderly patients with a history of neuroleptic treatment. To our knowledge there have been no reports of Pisa syndrome occurring during therapy with clozapine--an atypical neuroleptic drug with no major extrapyramidal side effects. We report on 4 female patients suffering from a chronic schizophrenic and/or depressive condition and having been on a long-term neuroleptic treatment. These patients developed a dystonia equivalent to the Pisa syndrome during an acute clozapine therapy. All four women had signs of marked brain atrophy, two of them also showing tardive dyskinesia already prior to the treatment with clozapine. The etiology of the Pisa syndrome is discussed with respect to discontinuation of treatment with classic neuroleptics, coinciding with the beginning of the clozapine therapy, clinical phenomenology, history of medication, course of treatment, and results of cranial computer tomography.

Topics: Adult; Affective Disorders, Psychotic; Aged; Basal Ganglia Diseases; Clozapine; Depressive Disorder; Drug Therapy, Combination; Female; Humans; Long-Term Care; Middle Aged; Neurologic Examination; Schizophrenia, Paranoid

A 40-year-old woman suffering from major depression with psychotic features was unresponsive to conventional therapy. After the administration of a wide range of drug treatments and ECT, she received clozapine. Depressive symptoms improved and psychotic features disappeared. It is suggested that clozapine could be efficient in psychotic refractory depression.

Topics: Adult; Clozapine; Combined Modality Therapy; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Psychotic Disorders; Recurrence

Topics: Arousal; Clozapine; Depressive Disorder; Humans; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Patients with multiple system atrophy, a neurodegenerative disease entity, have a high incidence of associated mental disturbances such as a mood disorder with or without psychotic features. Treatment of the psychiatric symptoms, without compromising neurological status, is often complicated and unsuccessful. This article describes a patient with olivo-ponto-cerebellar atrophy and treatment-resistant psychotic depression whose psychiatric symptoms were successfully treated with clozapine without aggravating the neurological disabilities.

Topics: Clozapine; Comorbidity; Depressive Disorder; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Neurocognitive Disorders; Olivopontocerebellar Atrophies

Seven patients with bipolar disorder, characterized by dysphoric mania with psychotic features and chronic disability, refractory to standard treatments and anticonvulsants, all showed marked symptomatic and functional improvement when given the atypical antipsychotic clozapine. During follow-up over 3-5 years, most of the patients sustained substantial gains in psychosocial function; and of the six patients remaining on clozapine, no further hospitalizations were needed. This remarkable improvement in a severely ill group of patients suggests that clozapine may have utility in the treatment of bipolar disorder as well as schizophrenia.

Topics: Adult; Bipolar Disorder; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Risk Factors

Topics: Bulimia; Bupropion; Clinical Trials as Topic; Clozapine; Depressive Disorder; Humans; Nomifensine; Product Surveillance, Postmarketing; Schizophrenia

Topics: Aged; Chlorpromazine; Chronic Disease; Clonazepam; Clozapine; Depressive Disorder; Desipramine; Diphenhydramine; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Neurologic Examination

Topics: Clozapine; Depressive Disorder; Female; Humans; Middle Aged; Neurocognitive Disorders; Parkinson Disease

Topics: Chemistry, Physical; Clozapine; Depressive Disorder; Dibenzazepines; Europe; History, 20th Century; Humans; Models, Molecular; United States

On the basis of clinical self-assessment scales (von Zerssen) and the Frankfurt questionnaire of complaints, it is demonstrated by the comparison of three groups of schizophrenic patients with one control group which is not undergoing therapy with neuroplegics that within the "genuine" groups the psychopathological factors investigated recede, sometimes quite significantly. Cross-over design treatment involving the control group has not revealed any significance. We conclude that when treating schizophrenic psychoses, psychosocial measures must accompany biological measures.

Topics: Clozapine; Depressive Disorder; Dibenzazepines; Dyskinesia, Drug-Induced; Haloperidol; Humans; Psychiatric Status Rating Scales; Psychometrics; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology

The results of a standardized examination of 135 schizophrenics shows that the "depressive factor" is less pronounced during differential neuroleptic therapy (Clozapin, Haloperidol) and in the control group of schizophrenics receiving no drug treatment. This suggests that the depressive syndrome among schizophrenics is not manifested as a result of pharmaceutical action. The author proposes that neuroleptic therapy tailored to the patient can ameliorate the depressive syndrome observed in schizophrenics. Both psychoreactive and disease specific factors may play a role in the pathogenesis of depression among patients with this disease.

Topics: Clozapine; Depressive Disorder; Haloperidol; Humans; Risk; Schizophrenia; Schizophrenic Psychology

A 7-day treatment with 20 mg/kg/day desipramine reduced the immobility time in the behavioral "despair" test in rats. The effect of DMI was antagonized by sulpiride (100 mg/kg i.p.), metoclopramide (20 mg/kg i.p.) and clopazine (20 mg/kg i.p.) but not by haloperidol (0.5 mg/kg i.p.) or chlorpromazine (5 mg/kg i.p.). Alpha-adrenoreceptor blockers (prazosin 3 mg/kg s.c.; aceperone 10 mg/kg i.p.; azapetine 24 mg/kg s.c.; phentolamine 20 mg/kg i.p.), dl-propranolol (5 mg/kg i.p.) and clonidine (0.1 mg/kg i.p.) failed to modify the anti-immobility effect of DMI. The data suggest that a particular subtype of dopamine receptors is involved in the anti-immobility effect of a 7-day treatment with DMI in the behavioral "despair" test in rats.

Topics: Adrenergic alpha-Antagonists; Animals; Antipsychotic Agents; Butyrophenones; Chlorpromazine; Clonidine; Clozapine; Depressive Disorder; Desipramine; Dibenzazepines; Haloperidol; Humans; Male; Metoclopramide; Phentolamine; Prazosin; Propranolol; Rats; Sulpiride

The manifestation of depersonalisation, its relationship with anxiety and depression, as well as its influence on the course of endogenous psychoses were investigated. Forty patients with severe depersonalisation were treated with the benzodiazepine, phenazepam, and 14 with clozapine. The data indicate that depersonalisation results from anxiety; it follows an anxiety attack and is successfully treated with anxiolytic drugs. In the case of endogenous depression, depersonalisation leads to lingering depressive phase, increasing the patients' resistance to antidepressive therapy. The protective and the harmful role of depersonalisation is discussed.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Benzodiazepinones; Bipolar Disorder; Clozapine; Depersonalization; Depressive Disorder; Diagnosis, Differential; Dibenzazepines; Female; Humans; Hypochondriasis; Male; Middle Aged