clozapine and Sleep-Wake-Disorders

Topics: Aged; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Diagnosis, Differential; Female; Humans; Metabolic Syndrome; Middle Aged; Olanzapine; Pain; Patient Compliance; Peripheral Nervous System Diseases; Piperazines; Quinolones; Schizophrenia, Paranoid; Skin Diseases, Parasitic; Sleep Wake Disorders

The treatment of patients suffering from idiopathic Parkinson's disease has become more and more complex. From its beginning the treatment has to be tailored to the needs of each patient. Not only the individual symptomatology and its course have to be taken into consideration, but also the short- and longtime reaction to treatment.

Topics: Adult; Aged; Antidepressive Agents; Antiparkinson Agents; Antipsychotic Agents; Benserazide; Cholinesterase Inhibitors; Clozapine; Dementia; Depression; Diagnosis, Differential; Dopamine Agents; Dopamine Agonists; Drug Combinations; Humans; Levodopa; Parkinson Disease; Quality of Life; Sleep Wake Disorders; Time Factors

In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.

Topics: Animals; Antipsychotic Agents; Clozapine; Cytokines; Endotoxins; Fatigue; Fatigue Syndrome, Chronic; Fibromyalgia; Humans; Inflammation Mediators; Multiple Chemical Sensitivity; Neuroimmunomodulation; Receptors, Cytokine; Sleep; Sleep Stages; Sleep Wake Disorders

Since its introduction to the United States in 1990, the benefits of clozapine use have been repeatedly validated. Clozapine remains the only antipsychotic with proven efficacy in treatment-resistant schizophrenia. Because clozapine has been part of the psychiatric pharmacopeia for considerably less time than neuroleptics, which have dominated the field for over 4 decades, its underutilization may be partly attributed to a lack of experience in managing associated side effects. Most side effects associated with clozapine are typical of antipsychotics in general, and with clozapine, these side effects are typically benign, tolerable, and manageable. It is conceivable that there remains a concern over the risk of agranulocytosis. However, the mandatory blood monitoring carried out through the Clozaril National Registry has considerably reduced the incidence of fully developed cases of agranulocytosis from premarketing values of approximately 1% to 2% to current values of 0.38% and virtually prevented mortalities. These values are likely to decrease further with the application of cytokine augmentation therapy among patients developing blood dyscrasias. Many side effects of clozapine are observed early after treatment onset and are greatly reduced by dose adjustments. Appropriate management of side effects will facilitate a maximization of the benefits of clozapine treatment. Clearly, the benefits of clozapine therapy far outweigh its risks.

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Chemical and Drug Induced Liver Injury; Clozapine; Drug Administration Schedule; Drug Monitoring; Humans; Incidence; Risk Factors; Schizophrenia; Sleep Wake Disorders; Tachycardia; Urinary Incontinence; Weight Gain

Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System Diseases; Clozapine; Dibenzothiazepines; Drug Interactions; Dyskinesia, Drug-Induced; Health Status; Humans; Hypotension, Orthostatic; Olanzapine; Pirenzepine; Quality of Life; Quetiapine Fumarate; Receptors, Cholinergic; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Sleep Wake Disorders; Treatment Refusal; Weight Gain

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

Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Clozapine; Databases, Factual; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Polysomnography; Schizophrenia; Sleep Wake Disorders; Time Factors; Treatment Outcome; Young Adult

Sleep disturbances are strongly associated with mood disorders, although the majority of data have been obtained in patients with major depressive disorder. Studies reporting results in bipolar disorder are few, and results have not been consistent. Clozapine is a prototype of atypical antipsychotics, which is effective in improving symptoms of manic episodes in patients with bipolar disorder, or schizoaffective disorder, bipolar type and has been shown to influence sleep in other psychiatric disorders. The present study evaluated the sleep effects of clozapine in bipolar and schizoaffective disorders.. Participants were 11 women and 4 men (range:28-53 years of age, mean 40.9+/-8.6 years), all with a history of mania by DSM-IV criteria for either bipolar I disorder or schizoaffective disorder, bipolar type. They participated in a sleep study at baseline and again after 6 months initiation of clozapine add-on therapy.. Sleep latency was longer on clozapine and the number of awakenings were increased, whereas time in bed (TIB) and total sleep period (TSP) were increased (range: F=6.2-17.9; df=l,12; p<0.05). Although none of the individual sleep stage showed significant treatment changes, both Stage 2 and slow-wave sleep were increased and Stage 2 decreased on clozapine. Subjective sleep measures improved on clozapine with a small but significant improvement in how rested patients felt upon awakening (t=-2.1; df=26; p<0.05).. Clozapine prolonged sleep latency, improved restedness, and increased total sleep time. Although lack of a control group limits interpretation of these results, they are in general agreement with studies in other psychiatric populations, and support the view that clozapine is primarily a NREM sleep enhancer. The improvement in restedness may be of positive clinical consequence.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Polysomnography; Psychiatric Status Rating Scales; Psychotic Disorders; Sleep Stages; Sleep Wake Disorders

Two patients each developed a single, fixed somatic delusion complicating their existing bipolar disorder. Both failed to respond to a range of antidepressant and antipsychotic medications. They each showed a partial response to clozapine and to electroconvulsive therapy, with resolution of mood symptoms and diminution of their ongoing somatic preoccupation. A review of case reports suggests a possible relationship between somatic delusions and affective disorders.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Delusions; Diagnosis, Differential; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Mood Disorders; Mouth Diseases; Sleep Wake Disorders; Somatoform Disorders

The use of opioids for pain management is often associated with nausea and vomiting. Although conventional antipsychotics are often used to counter emesis, they can be associated with extrapyramidal symptoms. However, chronic pain can induce sleep disturbance. The authors investigated the effects of the atypical antipsychotic olanzapine on morphine-induced emesis and the sleep dysregulation associated with chronic pain.. A receptor binding assay was performed using mouse whole brain tissue. The emetic response in ferrets was evaluated by counting retching and vomiting behaviors. Catalepsy in mice was evaluated by placing both of their forepaws over a horizontal bar. Released dopamine was measured by an in vivo microdialysis study. Sleep disturbance in mice in a neuropathic pain-like state was assayed by electroencephalogram and electromyogram recordings.. Olanzapine showed high affinity for muscarinic M1 receptor in brain tissue. Olanzapine decreased morphine-induced nausea and vomiting in a dose-dependent manner. However, olanzapine at a dose that had an antiemetic effect (0.03 mg/kg) did not induce catalepsy or hyperglycemia. In addition, olanzapine at this dose had no effect on the morphine-induced release of dopamine or inhibition of gastrointestinal transit. Finally, olanzapine inhibited thermal hyperalgesia and completely alleviated the sleep disturbance induced by sciatic nerve ligation.. These findings suggest that olanzapine may be useful for the treatment of morphine-induced emesis and as an adjunct for the treatment of neuropathic pain associated with sleep disturbance.

Topics: Analgesics, Opioid; Animals; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Brain Chemistry; Catalepsy; Clozapine; Dopamine; Drug Therapy, Combination; Electroencephalography; Electromyography; Gastrointestinal Transit; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Microdialysis; Morphine; Neuralgia; Olanzapine; Pain Management; Receptors, Serotonin; Sciatica; Sleep Wake Disorders; Vomiting

Sleep disorders and hypnotic drug abuse in 112 opioid addicts were investigated. During intensive heroin use, regular or episodic benzodiazepines intake was found in 60.7% of the cases. The requirement for benzodiazepines in drug use may result from dissociated tolerance to opioids. Withdrawal insomnia was shown to develop in all the cases studied. The differentiation between objective and subjective requirements for hypnotics was carried out. The author suggests the term "hypnophilia". The interrelation between hypnophilia and higher anxiety is emphasized. Clozapine is a drug of choice in treatment of insomnia in opioid addicts.

Topics: Adolescent; Adult; Clozapine; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Prevalence; Serotonin Antagonists; Sleep Wake Disorders

Topics: Angiotensin-Converting Enzyme Inhibitors; Antipsychotic Agents; Clozapine; Comorbidity; Drug Administration Schedule; Drug Interactions; Humans; Hypertension; Lisinopril; Schizophrenia; Sleep Wake Disorders

Topics: Adult; Citalopram; Clozapine; Confusion; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Fatigue; Humans; Male; Psychotic Disorders; Sialorrhea; Sleep Wake Disorders

Topics: Clozapine; Disorders of Excessive Somnolence; Drug Monitoring; Humans; Male; Methylphenidate; Middle Aged; Psychotic Disorders; Sleep Wake Disorders

Topics: Adult; Airway Obstruction; Circadian Rhythm; Clozapine; Deglutition Disorders; Humans; Male; Psychotic Disorders; Sialorrhea; Sleep Wake Disorders

Topics: Adult; Clozapine; Death, Sudden; Drug Interactions; Drug Therapy, Combination; Humans; Injections, Intravenous; Lorazepam; Male; Respiratory Insufficiency; Schizophrenia, Paranoid; Sleep Wake Disorders

We present the results obtained using low doses of clozapine (mean dose 26.4 mg at bedtime) in the treatment of nocturnal akathisia in nine patients with Parkinson's disease for a mean period of 12.5 months. The results were excellent in all the patients. Furthermore, three patients experienced a remarkable improvement in rest tremor and in five patients the confusional state that accompanied the akathisia also disappeared. No serious side-effects were observed. We believe that clozapine is a very useful drug for the relief of nocturnal akathisia in parkinsonian subjects.

Topics: Adult; Aged; Aged, 80 and over; Benserazide; Carbidopa; Circadian Rhythm; Clozapine; Confusion; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Psychomotor Agitation; Sleep Wake Disorders

Topics: Cataplexy; Clozapine; Dibenzazepines; Fever; Humans; Sleep Wake Disorders; Sleep, REM

Topics: Adult; Anxiety Disorders; Clozapine; Dibenzazepines; Female; Humans; Male; Middle Aged; Neurotic Disorders; Psychopathology; Sleep Wake Disorders