Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Olanzapine is a potential new "atypical" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.
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PMID:Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. 2654 64

Anticholinergic treatment of neuroleptic extrapyramidal movement disorders (EPS) has been associated with induction of tardive dyskinesia. Also an increasing abuse of anticholinergics by schizophrenic patients is noted. Since as early as 1976, positive effects of amantadine (AMA) on neuroleptic EPS have been described, therefore a controlled study of these reports seemed worthwhile. Forty-two schizophrenic patients (of which 7 were dropouts) of three centers entered the study and were treated for EPS in a double-blind design: 18 (11 m, 7 f) with AMA and 17 (8 m, 9 f) with biperiden (BIP). Identical preparations of AMA 100 mg, tid) and BIP (2 mg, tid) were used in treatment of haloperidol-induced EPS (AMA, mean 22.4 mg haloperidol; BIP, mean 19.6 mg haloperidol). Effects of treatment and possible side effects were rated: EPS for the intensity of EPS, BPRS for quantification of psychotic symptoms, FSUCL for rating the side effects and KUSTA to document patients' mood. Ratings were recorded on days 0, 3, 7, 14, 28 and at discontinuation, respectively. All patients were treated with haloperidol and levomepromazine (for tranquilization/sleep induction) and the respective antiparkinsonian agent for 14 days. Patient characteristics did not differ significantly in either groups. In the AMA treatment group, 2 patients dropped out for noncompliance, in the BIP group, 5 (3 no effect, 1 noncompliance, 1 agitation). All results as recorded with the different rating instruments showed a significant (p < 0.01) overall improvement, whereas no significant differences between treatment groups could be determined, notably the treatment effect of both drugs on EPS was similar. Thus, the application of AMA in cases of neuroleptic EPS seems justified and is a useful alternative of anticholinergic drugs. Certain advantageous aspects of AMA treatment of EPS with regard to the glutamate hypothesis of schizophrenia and tardive dyskinesia are discussed.
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PMID:Amantadine versus biperiden: a double-blind study of treatment efficacy in neuroleptic extrapyramidal movement disorders. 892 33

Following the conduct of a 28-day inpatient bioequivalence study of clozapine in schizophrenia patients, withdrawal effects after abrupt discontinuation from clozapine were assessed. Thirty patients who met DSM-III-R criteria for schizophrenia, residual type, or schizophrenia in remission were enrolled in the study. Patients were evaluated for symptoms of withdrawal effects for 7 days after clozapine 200 mg/day was abruptly withdrawn. Of 28 patients who completed the study, 11 had no withdrawal symptoms; 12 had mild withdrawal adverse events of agitation, headache, or nausea; four patients experienced moderate withdrawal adverse events of nausea, vomiting, or diarrhea; and one patient experienced a rapid-onset psychotic episode requiring hospitalization. Cholinergic rebound is a likely explanation for the mild to moderate withdrawal symptoms and is easily treated with an anticholinergic agent. Mesolimbic supersensitivity, as well as specific properties of clozapine, are discussed as likely causes for rapidonset psychosis. Our findings are consistent with previous reports of withdrawal reactions associated with clozapine, further reminding clinicians to monitor patients closely following abrupt discontinuation of clozapine.
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PMID:Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal. 893 13

Functional alterations in the central serotonergic system, including presynaptic and postsynaptic function, have been reported in schizophrenia. Recently, there have been conflicting reports that the increase in plasma cortisol or prolactin concentrations induced by meta-chlorophenylpiperazine (mCPP) was significantly blunted in schizophrenic patients compared with normal volunteers. Studies of the behavioral effects of mCPP, a serotonin (5-HT) receptor partial agonist with high affinity for 5-HT1C binding sites, have also yielded conflicting results in schizophrenic patients. The purpose of this study was to examine plasma levels of prolactin and cortisol, body temperature, and behavioral responses to mCPP and placebo in a single-blind study in 25 schizophrenic and 15 normal men. No differences either between schizophrenic patients and normal volunteers or between paranoid and undifferentiated/residual subtypes of schizophrenia were found in mCPP-induced prolactin, cortisol, or temperature responses. Schizophrenic patients and normal volunteers reported significant increases in feeling calm and feeling strange of comparable magnitude following mCPP. No significant differences between normal volunteers and schizophrenic patients were found in post-mCPP behavioral ratings, such as anxiety, irritability, depression, restlessness, or arousal.
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PMID:Effects of meta-chlorophenylpiperazine on neuroendocrine and behavioral responses in male schizophrenic patients and normal volunteers. 894 93

Agitation is a nonspecific constellation of symptoms seen in a variety of psychiatric disorders, ranging from psychotic exacerbations in patients with schizophrenia to behavioral disturbances associated with organic factors. Its treatment must be individualized and based on the etiology of the psychomotor disturbance. Certain categories of drugs are broadly effective. Sedation and control of disruptive and dangerous behavior are the initial goals in stabilizing acutely agitated patients. Sedation is necessary during the lag period before antipsychotic and mood-stabilizing drugs take effect. Barbiturates and chlorpromazine, initially given to control agitated behavior, are largely supplanted by higher-potency antipsychotics, benzodiazepines, and, recently, a combination of these two agents. Agitation is generally controlled within hours to days, whereas remission of affective or psychotic symptoms often requires weeks to months. Once remission is obtained, sedation is no longer desired and may be a barrier to optimal patient function and compliance. Thus, for long-term treatment, strategies are used to minimize sedation, such as reducing dosages, changing administration to bedtime, or adding antidepressants or stimulants where appropriate.
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PMID:Sedation in acute and chronic agitation. 894 99

Although there has been renewed interest in the serotonin (5-HT) system in schizophrenia, direct evidence for 5-HT dysfunction is limited. This study compares the responses of m-chlorophenyl-piperazine (mCPP), a 5-HT agonist, in first-episode schizophrenia and a known psychotogenic dopamine agonist, methylphenidate. Eighteen patients experiencing their first episode of psychosis and eight healthy controls received methylphenidate (0.5 mg/kg) and mCPP (0.1 mg/kg) intravenously. Behavioral assessments were done before and after the procedure, and a peak response to each agent was rated. Methylphenidate, but not mCPP, produced psychotic symptoms in patients. mCPP did decrease anxiety, hallucinations, and anger and increased agitation, somatic concern, and impaired understandability. Both agents had limited effects on controls. In conclusion, unlike methylphenidate, mCPP did not produce psychotic symptom activation in schizophrenic patients in, and its effects appeared to be nonspecific.
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PMID:The behavioral effect of m-chlorophenylpiperazine (mCPP) and methylphenidate in first-episode schizophrenia and normal controls. 898 89

Continuation and maintenance electroconvulsive therapy (ECT-C & ECT-M) has been used to control schizophrenic patients for more than 50 years. In spite of this, there has been no prospective study made of this treatment. Most of the information comprises naturalistic studies or case reports. As a result many unanswered questions concerning ECT-C & ECT-M remain, including its therapeutic efficacy. This pilot study was prospectively completed on 16 schizophrenic patients, suffering acute exacerbations in order to determine the merits of ECT-C. After acute treatment using only ECT, 12 patients were identified as ECT responders and enrolled in this study. No neuroleptic drugs were used. Diazepam was the only medication prescribed to control agitation on prn basis. The duration of the study was 6 months. Bilateral ECT was used throughout the study, after the acute treatment. Global Assessment of Functioning (GAF), Brief Psychiatric Rating Scale (BPRS) and the Thai Mental State Exam (TMSE) were used to measure the outcome. A total of 8 patients completed the study and 4 dropped out. There were no relapses and all measurements progressed satisfactorily. There were no serious side effects, in particular no cognitive impairment. This study supports the therapeutic efficacy of ECT-C in schizophrenia.
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PMID:Continuation electroconvulsive therapy in schizophrenia: a pilot study. 917 75

Several drugs are apparently effective in treating pathologic anger and aggression. Because many of the studies on aggressive populations allowed the use of concomitant medications, it is unclear whether the efficacy of each drug in a particular population is dependent on the presence of other medications, such as antipsychotic agents. Finally, one needs to be circumspect in inferring efficacy of a particular drug in aggressive patients with neuropsychiatric conditions other than the ones in which some efficacy has been established. Lithium appears to be an effective treatment of aggression among nonepileptic prison inmates, mentally retarded and handicapped patients, and among conduct-disordered children with explosive behavior. Certainly, lithium would be the treatment of choice in bipolar patients with excessive irritability and anger outbursts, and it has been shown to be effective in this population. Anticonvulsant medications are the treatment of choice for patients with outbursts of rage and abnormal EEG findings. The efficacy of these drugs in patients without a seizure disorder, however, remains to be established, with the exception perhaps of valproate and carbamazepine. In fact, dyphenylhydantoin did not appear to be effective in treating aggressive behavior in children with temper tantrums and was found to be effective in only a prison population. There is some evidence for the efficacy of carbamazepine and valproate in treating pathologic aggression in patients with dementia, organic brain syndrome, psychosis, and personality disorders. As Yudofsky et al point out in their review of the literature, although traditional antipsychotic drugs have been used widely to treat aggression, there is little evidence for their effectiveness in treating aggression beyond their sedative effect in agitated patients or their antiaggressive effect among patients whose aggression is related to active psychosis. Antipsychotic agents appear to be effective in treating psychotic aggressive patients, conduct-disordered children, and mentally retarded patients, with only modest effects in the management of pathologic aggression in patients with dementia. Furthermore, at least in one study, these drugs were found to be associated with increased aggressiveness in mentally retarded subjects. On the other hand, atypical antipsychotic agents (i.e., clozapine, risperidone, and olanzapine) may be more effective than traditional antipsychotic drugs in aggressive and violent populations, as they have shown efficacy in patients with dementia, brain injury, mental retardation, and personality disorders. Similarly, benzodiazepines can reduce agitation and irritability in elderly and demented populations, but they also can induce behavioral disinhibition. Therefore, one should be careful in using this class of drugs in patients with pathologic aggression. Beta-blockers appear to be effective in many different neuropsychiatric conditions. These drugs seem effective in reducing violent and assaultive behavior in patients with dementia, brain injury, schizophrenia, mental retardation, and organic brain syndrome. As pointed out by Campbell et al in their review of the literature, however, systematic research is lacking, and little is known about the efficacy and safety of beta-blockers in children and adolescents with pathologic aggression. Although widely used in the management of pathologic aggression, the use of this class of drugs has been limited partially by marked hypotension and bradycardia, which are side effects common at the higher doses. The usefulness of the antihypertensive drug clonidine in the treatment of pathologic aggression has not been assessed adequately, and only marginal benefits were observed with this drug in irritable autistic and conduct disorder children. Psychostimulants seem to be effective in reducing aggressiveness in brain-injured patients as well as in violent adolescents with oppositional or conduct disorders, particu
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PMID:Psychopharmacologic treatment of pathologic aggression. 919 23

A suddenly occurring episode characterized by perceptual alteration (SEPA), mainly of visual and/or auditory modalities, which repeatedly occurred in three schizophrenic patients on long-term neuroleptic medication, is described. Perceptual alteration showed some distinct features that were different from acute symptoms of schizophrenia, and was accompanied by mood changes such as severe anxiety and agitation and, in one of the patients, also by extrapyramidal symptoms. Perceptual alteration, as well as mood changes and extrapyramidal symptoms, responded well to an anticholinergic drug, biperiden. Recent studies have shown that SEPA occurred not only in schizophrenic patients but also in patients on long-term neuroleptic medication for treating other mental disorders. These findings suggest that SEPA is associated with dopaminergic hypoactivity in the brain, which is induced by long-term neuroleptic medication.
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PMID:Recurrent paroxysmal episodes characterized by perceptual alteration in three schizophrenic patients on neuroleptic medication. 922 71

A series of 14 children and adolescents (ages 9-17 years, 10 males) were treated with risperidone for pervasive developmental disorder. The rationale for using an atypical neuroleptic agent is based on its ability to target both positive and negative symptoms of schizophrenia. It was postulated that symptoms similar to the positive and negative symptoms of schizophrenia may be observed in the pervasive developmental disorders and might respond favorably to risperidone. Twelve of the 14 youths had been treated previously with several psychotropic drugs, often concurrently. Risperidone was initiated at a starting dose of 0.25 mg twice daily and increased in 0.25 mg/day increments every 5-7 days. Optimal dosages ranged from 0.75 to 1.5 mg daily in divided doses. Thirteen of the 14 youths appeared to benefit from risperidone. Improvement in functionality on the Children's Global Assessment Scale was demonstrated in 13 of 14 cases. Disruptive behaviors, when present, markedly decreased on risperidone. Ten patients showed a marked reduction in agitation and anxiety. Social awareness improved markedly in 10 patients, moderately in 3, and only slightly in 1. All but 1 patient demonstrated a lessening in obsessional behaviors. Effects on attention were uniformly positive. Side effects were minimal at the dosages used in this study; 5 patients had initial sedation. Neither extrapyramidal side effects nor agitation was observed in any case. Ten of 14 youths could be managed with risperidone monotherapy. During the follow-up period (mean 7 months), none of the patients experienced a major relapse while taking risperidone. Positive and negative symptoms, as typically characterized in schizophrenia, were both found to improve equally well with risperidone treatment. Based on these findings, a prospective clinical trial with a randomized controlled design is warranted.
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PMID:Use of risperidone in pervasive developmental disorders: a case series. 923 11


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