clozapine and Affective-Disorders--Psychotic

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

Treatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical maturation quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject's contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges's g = 2.09, P < .001) and a reduced clustering coefficient (Hedges's g = 1.07, P < .001) with increased length (Hedges's g = -2.17, P < .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Cerebral Cortex; Clozapine; Female; Follow-Up Studies; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Nerve Net; Psychotic Disorders; Schizophrenia; Young Adult

Topics: Affective Disorders, Psychotic; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Enuresis; Female; Humans; Psychotic Disorders

Ramadan is a religious month dedicated to prayer, fasting and feasting. Recently, there has been an increased interest among healthcare providers regarding possible health-related complications as a consequence of religious fasting such as that seen during Ramadan. In , a 34-year-old female patient with a diagnosis of schizoaffective disorder, depressive type, was admitted for inpatient hospitalization to an inpatient psychiatric hospital in Buffalo, New York. The earliest date of initial diagnosis is unclear; however, the patient reports an increase in symptoms during her early twenties. Upon admission, the patient was continued on haloperidol, lithium and fluphenazine decanoate which had been initiated prior to this admission. Medication administration and meal times were adjusted to accommodate her observance of Ramadan. Despite efforts to mitigate the potential impact, the patient complained of dizziness and weakness following initiation and titration of clozapine. Due to psychiatric exacerbation, inpatient hospitalization and continuous monitoring, clozapine titration occurred quickly. Upon admission, the patient's blood pressure was 137/85 mmHg, which decreased to a low of 87/58 mmHg as her clozapine dose was increased, leaving the patient requesting bedrest due to significant dizziness and weakness. On the 21st day of Ramadan, the patient broke her fast due to substantial adverse effects. Five days after breaking her fast, the patient's blood pressure increased and returned to baseline. Individuals participating in Ramadan tend to have disrupted sleep cycles, including nocturnal sleep reduction and broken sleep patterns, which can impact overall health. Additional health-related complications that have been reported include dehydration and changes in blood glucose, blood pressure, lipid panel, body weight and exacerbation of psychiatric symptoms. These adverse effects can result in serious complications in fasting individuals with acute medical and psychiatric illness. Clozapine was initiated and rapidly titrated during the patient's observance of Ramadan. She exhibited signs and symptoms of hypotension, which were also subjectively reported by the patient. The significant drop in blood pressure while fasting, and rapid increase once the fast was broken, confirm that medication changes implemented during religious fasting, such as that seen during Ramadan, can increase a patient's risk of serious adverse effects.

Topics: Adult; Affective Disorders, Psychotic; Blood Pressure; Body Weight; Clozapine; Fasting; Female; Humans; Polypharmacy

To explore the pattern of clozapine use in persons with severe mental illness and in persons with Parkinson's disease and the characteristics associated with early discontinuation in naturalistic conditions.. A historical fixed cohort study of persons newly treated with clozapine was performed on a representative community-based sample of persons affiliated to the French health insurance system (n = 611,393). Treatment for Parkinson's disease was used as a proxy for this condition and lack of such treatment as a proxy for severe mental illness (SMI).. The prevalences of antipsychotic and clozapine use were 4.4% and <0.1% respectively. Of the 237 persons with a new outpatient prescription of clozapine, 25% were prescribed an antiparkinsonian treatment. In persons with SMI, the median duration of the index episode of clozapine treatment was 4.9 months (Interquartile range 1.0-20.5). Longer duration was independently associated with coprescription of anxiolytics or antidepressant. Few new additions of antipsychotics were observed during the clozapine episode.. Efforts have to be made to optimize clozapine treatment in real-world conditions. Considering the high frequency of persons with Parkinson's disease among clozapine users, further studies have to be performed in this population.

Topics: Adult; Affective Disorders, Psychotic; Aged; Anti-Anxiety Agents; Antidepressive Agents; Antiparkinson Agents; Antipsychotic Agents; Bipolar Disorder; Case-Control Studies; Clozapine; Cohort Studies; Female; France; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders; Schizophrenia

This study examined the difference in the functional capacity of patients receiving clozapine, compared with those prescribed other antipsychotic medication, who attend the forensic psychiatry day hospital at Murray Royal Hospital, Perth. (This facility caters for 34 patients. It provides a number of advantages such as access to therapies and supervision of mental state and medication at this critical time in the care pathway.) This study was cross-sectional in nature and examined the patients' demographic details, diagnosis and medication. A functional assessment was carried out using the social behaviour schedule (SBS) for each patient. We discovered that there was a marked difference in the hostility scores between clozapine patients and non-clozapine patients. Only 10.5% of clozapine patients had a severe score (more than two) on the SBS whereas 61.5% of those not receiving clozapine had a severe score. The non-clozapine group had more socially unacceptable habits and were more destructive than patients receiving clozapine, as scored by the SBS. The slowness and under-activity items were more severe in the clozapine patients. The non-clozapine group scored higher in the category of other behaviours that might impede progress, particularly drug-taking.

Topics: Affective Disorders, Psychotic; Antipsychotic Agents; Clozapine; Cross-Sectional Studies; Forensic Psychiatry; Hospitals, Psychiatric; Hostility; Humans; Outpatient Clinics, Hospital; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Social Behavior

The effectiveness of clozapine treatment in a treatment-refractory sample of older adult veterans with primary psychosis was examined.. Data were collected over a five-year period for patients age 55 and older who were given clozapine because of a history of treatment-refractory or treatment-intolerant psychosis. At initiation of clozapine therapy, baseline demographic, clinical, and psychopathology data were collected. At baseline and quarterly, patients' psychopathology was rated with the Brief Psychiatric Rating Scale (BPRS), and involuntary movements were rated with the Abnormal Involuntary Movement Scale (AIMS).. The 329 patients age 55 or older who received clozapine during the study period represented 10 percent of all patients on clozapine therapy in the VA system. Of the 312 patients for whom demographic information was available, 294 were men and 18 were women. Overall, patients improved on clozapine therapy, although wide variation in drug response was observed. Complete BPRS and AIMS data were available for 97 patients. The 55- to 64-year-old group had a mean improvement in total BPRS score of 19.8 percent, with 42.6 percent showing more than a 20 percent improvement; those age 65 and older had a mean improvement of 5.7 percent, with 17.2 percent showing an improvement greater than 20 percent. The 97 patients with complete AIMS data showed a mean improvement of 16.6 percent in total score.. Clozapine is an important therapeutic agent for older adults with treatment-refractory psychosis. Patients between the ages of 55 and 64 may have a better response than those age 65 and older.

Topics: Adult; Affective Disorders, Psychotic; Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Veterans

The selective serotonin reuptake inhibitor (SSRI) fluoxetine can increase serum levels of clozapine and norclozapine, but effects of other SSRIs are unknown. Thus, the authors evaluated interactions of clozapine with fluoxetine, paroxetine, and sertraline.. Serum clozapine and norclozapine concentrations were assayed in 80 psychiatric patients, matched for age and clozapine dose, given clozapine (mean dose = 279 mg/day) alone or with fluoxetine (mean dose = 39.3 mg/day), paroxetine (mean = 31.2 mg/day), or sertraline (mean = 92.5 mg/ day). Each patient's dose of clozapine was stable for at least a month before serum sampling.. Concentrations of clozapine plus norclozapine averaged 43% higher, and the risk of levels higher than 1000 ng/ml was 10-fold greater (25%), in the patients taking SSRIs, with minor differences between patients taking the individual SSRIs.. SSRIs can increase circulating concentrations of clozapine and norclozapine, sometimes to potentially toxic levels.

Topics: 1-Naphthylamine; Adult; Affective Disorders, Psychotic; Aged; Ambulatory Care; Clozapine; Drug Interactions; Drug Therapy, Combination; Fluoxetine; Humans; Middle Aged; Paroxetine; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Sertraline; Stimulation, Chemical

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

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

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

Clozapine, an effective but expensive drug treatment for patients with severe, chronic schizophrenia who are unresponsive to conventional antipsychotics, is associated with a high risk of agranulocytosis, which is sometimes fatal. Weekly blood tests to detect evidence of this side effect are required. To estimate the number of potential candidates for this treatment and the national cost of administering the drug to this population, the authors used data from three recent patient surveys conducted in New York State. Depending on the criteria used to exclude unsuitable candidates, between 133,000 and 189,000 individuals will be eligible for treatment with clozapine nationally at a cost of $1.2 to $1.7 billion annually.

Topics: Adult; Affective Disorders, Psychotic; Aftercare; Agranulocytosis; Chronic Disease; Clozapine; Community Mental Health Services; Cost Control; Cost-Benefit Analysis; Dibenzazepines; Female; Humans; Length of Stay; Male; Middle Aged; New York; Psychiatric Status Rating Scales; Risk Factors; Schizophrenia; Schizophrenic Psychology