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)

Antipsychotic drugs are widely used to treat abnormal behaviour particularly that related to the functional psychoses such as schizophrenia. This review discusses the pharmacokinetics and pharmacology of antipsychotic drugs like chlorpromazine. Clinical use comprises the induction of tranquillization in disturbed psychiatric patients, the treatment of acute and chronic schizophrenic symptoms, and the postponement of relapse in such patients. Unwanted effects are multifarious, involving many systems of the body. Extrapyramidal signs and symptoms are particularly noticeable, and the chronic type, tardive dyskinesia, is a major problem.
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PMID:Clinical pharmacology of antipsychotic drugs. 256 64

Long-acting depot neuroleptics are likely to receive increasing consideration in the maintenance treatment of schizophrenia because of the growing recognition of noncompliance with daily oral medication in this patient population. The impending availability of haloperidol decanoate in the United States may also increase the use of long-acting neuroleptics. The long-term safety of these drugs, therefore, deserves close scrutiny. Based on experiences with other depot neuroleptics, the safety profile of haloperidol decanoate is unlikely to differ from short-acting formulations of haloperidol. In general, tardive dyskinesia remains the most troubling problem associated with long-term neuroleptic treatment. The available information indicates that all neuroleptics, including long-acting preparations, share the same propensity for causing tardive dyskinesia. Furthermore, the use of the lowest effective dose of a neuroleptic appears to minimize the severity of tardive dyskinesia should it develop. Extrapyramidal symptoms, notably akinesia and akathisia, are also potential concerns of maintenance treatment with oral and depot neuroleptics; however, the occurrence of these side effects appears dose related. Thus, the clinician can favorably influence the benefit-to-risk ratio of long-acting depot neuroleptics by minimizing potential side effects through the use of a low dose strategy.
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PMID:Depot neuroleptics: side effects and safety. 287 89

Extrapyramidal symptoms cause much misery, often go undiagnosed, and can interfere with treatment and rehabilitation. Akinesia is a behavioral state of diminished motoric and psychic spontaneity that is difficult to distinguish from the negative symptoms of schizophrenia. The most useful clinical correlates of akinesia are a subjective sense of sedation and excessive sleeping. Akinesia interferes with social adjustment and may manifest as "postpsychotic depression." The subjective restlessness of akathisia is usually accompanied by telltale foot movements: rocking from foot to foot while standing or walking on the spot. Akathisia is strongly associated with depression and dysphoric responses to neuroleptics and has even been linked to suicidal and homicidal behavior in extreme cases.
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PMID:Behavioral toxicity of antipsychotic drugs. 288 52

The following are key factors to consider in assessing a patient for long-term neuroleptics: 1. Who--accurate diagnosis of schizophrenia is of primary concern. There are no good prognostic indicators other than a history of repeated relapses and positive responses to neuroleptics. 2. When and for how long--should always be considered for the patient who has had more than two acute episodes. The first year post-acute episode back in the community is extremely critical. Consider maintaining patient on tapering dosage of medication for at least four to five years. 3. What benefits--symptoms of acute psychosis respond, those of chronic defect state do not. Medication also can act as buffer against stress. 4. Dosages--standard range is the equivalent of 300-800 mg. of Thorazine for most patients. Dose range for depot administration of Prolixin decanoate is 25-62.5 mg. 2-4 week intervals. Differences within this range may not be important. Data about very low doses (one-tenth standard dose) and megadoses (4-5 times standard dose) are inconsistent. 5. Risks--extrapyramidal symptoms, tardive dyskinesia, and akinetic depression are the most prevalent risks. Extrapyramidal symptoms can often be controlled effectively with dosage reduction. However, anticholinergic drugs are the treatment of choice during acute phases, and for the first 3-5 months post-acute phase. Tardive dyskinesia rarely occurs after a few weeks or months, but occurs most commonly beginning after two years of drug treatment. The usual form is persistent, but transient forms also occur. The earliest signs are reversible in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maintenance medication for chronic schizophrenics: risk/benefit assessment. 290 33

We evaluated the effects of ICI 204,636 in 12 hospitalized patients with schizophrenia in a double-blind, placebo-controlled, parallel-group, rising-dose study. Patients met the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria for chronic or subchronic schizophrenia and had a total score > or = 30 on the 18-item Brief Psychiatric Rating Scale (BPRS) and a score > or = 3 on the Clinical Global Impression (CGI) Severity of Illness item. Patients received 21 days of double-blind treatment with increasing doses of ICI 204,636 (25 to 250 mg/d) or placebo. Efficacy was assessed using the BPRS and CGI. Response to treatment was defined as a > or = 30% decrease in the BPRS total score from baseline. Extrapyramidal symptoms and abnormal involuntary movements were assessed using the Simpson Scale and Abnormal Involuntary Movement Scale. Changes from baseline in the BPRS and CGI were significantly greater at end point for patients who received ICI 204,636 versus placebo (BPRS, -20.9 vs -4.8; CGI, -2.9 vs -1.0; P < 0.05, analysis of covariance; P < or = 0.06, Wilcoxon rank sum test). All patients in the ICI 204,636 group responded to treatment (P < 0.10) versus only two patients in the placebo group. Mild somnolence occurred in 50% of ICI 204,636-treated patients. No treatment-emergent extrapyramidal symptoms or dystonic reactions were observed. ICI 204,636 showed efficacy in the positive and negative symptoms of schizophrenia and was well tolerated.
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PMID:ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia. 758 41

Whereas the instability of positive symptoms over time is well recognized, the instability of negative symptoms is still debated. This controversy could be due to the fact that different negative symptoms have been studied in different phases of schizophrenia. We, therefore, hypothesized that some negative symptoms would improve whereas others would remain perfectly stable during the remission of the acute phase of illness. We further hypothesized that the changes in these negative symptoms would be linked to changes in other domains such as extrapyramidal, depressive and positive symptomatology. A broadly defined sample of schizophrenic patients was evaluated at admission and discharge of the hospital with the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS), the Montgomery and Asberg Depression Rating Scale (MADRS) and the Extrapyramidal Symptoms Rating Scale (ESRS). Doses of antipsychotic medications were converted into chlorpromazine-equivalents. Fifty-seven patients (mean age 40.3 years old) were included in the sample and followed-up during their hospitalization. All the sub-scores of the SANS-SAPS decreased significantly but 4 items of the SANS belonging to the affective flattening subscale (unchanging facial expression, decreased spontaneous movements, paucity of expressive gestures and lack of vocal inflections) and one item belonging to the alogia subscale (poverty of speech) did not vary significantly, showing the necessity of taking into account the individual items of the SANS rather than the subscale scores to evaluate the course of negative symptoms. Changes in all the SANS subscores except the alogia subscore were associated with variations in scores of other scales. The change in attentional subscores was positively correlated to the change in the positive formal thought disorder subscores, probably because both belong to the same syndrome. The change in affective flattening subscores was associated with changes in depressive and akinetic scores and 28% of the variance of the change in the affective flattening subscores was explained by the change in the MADRS scores. Changes in avolition-apathy and anhedonia subscores were also associated with changes in MADRS scores but not with the change in akinesia scores.
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PMID:Negative symptoms in schizophrenia: their evolution during an acute phase. 856 93

Six psychotic patients were included in a four-week study of the effects of the D1 selective antagonist SCH 39166 given as monotherapy. Four had a diagnosis of schizophrenia, and two suffered from a schizoaffective disorder. All presented with an acute psychotic exacerbation at the beginning of the trial. SCH 39166 was progressively increased from 50 mg/day to 600 mg/day. In the four schizophrenic patients, the BPRS worsened, and three out of the four failed to complete the study because of this. Three schizophrenic patients were aggressive or violent after abrupt discontinuation of treatment. In the two patients with schizoaffective disorder the BPRS improved during the trial, but they had an acute relapse immediately after treatment discontinuation. Extrapyramidal symptoms improved in three of the six patients, and worsened in one.
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PMID:An open trial of the D1 antagonist SCH 39166 in six cases of acute psychotic states. 858 13

The subjects were 62 patients hospitalized for acute exacerbations of schizophrenia and were randomly assigned to receive risperidone (mean dose, 7.4 mg/day), haloperidol (7.6 mg/day), or methotrimeprazine (100 mg/day) for 4 weeks. Clinical improvement, defined a priori as a 20% reduction in total Positive and Negative Syndrome Scale (PANSS) scores at end point, was attained by 81% of the risperidone patients, 60% of the haloperidol patients, and 52% of the methotrimeprazine patients (p < 0.05). The reductions in total PANSS and Clinical Global Impression Scale severity scores from baseline to end point were significantly greater in the risperidone patients than in the other two groups. Reductions in scores on the Psychotic Anxiety Scale were significantly greater in the risperidone patients than the methotrimeprazine patients; the difference between haloperidol and methotrimeprazine was not significant. Extrapyramidal symptoms (scores on the Extrapyramidal Symptom Rating Scale) were more severe in the haloperidol patients than in the other two groups, but few differences were apparent between risperidone and methotrimeprazine patients. It is concluded that risperidone is an effective antipsychotic and anxiolytic agent in schizophrenic patients.
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PMID:Antipsychotic and anxiolytic properties of risperidone, haloperidol, and methotrimeprazine in schizophrenic patients. 883 17

We conducted a non-randomized, rater-blind study to safely determine the lowest effective neuroleptic dosage in older psychotic patients and to evaluate the clinical, neuropsychological, and psychosocial effects of neuroleptic dosage reduction. Twenty-seven carefully selected patients with schizophrenia and related psychotic disorders over the age of 45 had their dosage tapered by 25% each month to determine their lowest effective dosage. These patients were compared with patients similar in age, gender, and education who were currently off neuroleptics (n = 19) or maintained on neuroleptics (n = 22). All groups were followed for 11 months. Over the follow-up period, 29% of patients in the taper group, 8% of neuroleptic-free patients, and 0% of patients in the maintenance group experienced some increase in psychopathology, although there was no significant change in mean PANSS score in any group, and no patient required hospitalization. Patients in the taper group were maintained on approximately 60% of their original neuroleptic dosage after restabilization. Extrapyramidal symptoms continued to improve over time in the taper group. Neuropsychological testing did not change significantly over time except for those in the taper group who experienced a decrease in memory-retention on the Hopkins Verbal Learning Test and a significant improvement in digit vigilance and Stroop Interference Index. Carefully selected middle-aged and elderly psychotic patients can have their neuroleptic medications reduced without a significant change in psychopathology. Extrapyramidal symptoms may continue to improve gradually over time. The impact on cognition functioning needs further investigation.
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PMID:Neuroleptic dose reduction in older psychotic patients. 941 53

The purpose of this study was to assess the effects of an anticholinergic (trihexyphenidyl) antiparkinsonian medication on the Mini-Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG) scores in long-term institutionalized elderly patients with schizophrenia. Seventeen schizophrenic (DSM-III-R) inpatients on long-term medication who had received trihexyphenidyl for at least 6 consecutive months were compared for MMSE scores, CAMCOG scores, and other demographic and clinical variables with 14 patients not receiving any anticholinergic agent for the same time period. Results showed that age, years of education, illness duration, length of current hospital stay, the Manchester Scale scores, and chlorpromazine daily equivalent dose in mg were not different in the two groups compared. Extrapyramidal signs such as tremor, rigidity, and bradykinesia were more frequent in trihexyphenidyl receivers. The scores of MMSE (p < .007) and CAMCOG (p < .005) and CAMCOG subscales of orientation (p < .03), language (p < .01), and memory (p < .002) were significantly lower among trihexyphenidyl receivers, as was the Social and Occupational Functioning Assessment Scale score (p < .05). In addition, the MMSE and CAMCOG scores were significantly lower for patients receiving 10 mg of trihexyphenidyl a day compared with those receiving 5 mg/day and nonusers. It is suggested that trihexyphenidyl in usual clinical doses may impair total MMSE and CAMCOG scores as well as some of the CAMCOG subscales in this patient population. However, only a prospective study, preferably double-blind and controlled, with measures of change will validate this conclusion.
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PMID:Effects of trihexyphenidyl on MMSE and CAMCOG scores of medicated elderly patients with schizophrenia. 962 29


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