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)

Akathisia and tardive dyskinesia (TD) are disorders of movement that are often associated with administration of antipsychotic medication. We surveyed 196 outpatients in a schizophrenia clinic, all receiving antipsychotic medication, for the presence of these disorders. Clinical global ratings of akathisia were reliable. Akathisia was found in 36% of patients, and TD in 23.5%. Akathisia was disproportionately common in patients receiving high-potency neuroleptics. The data affirmed recent revisions in the dose-equivalence formulas used with fluphenazine decanoate. Akathisia and TD did not seem to be interrelated. Because akathisia is common and often limits medication dose and contributes to noncompliance, psychiatrists must take this into account when prescribing antipsychotic medication.
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PMID:Akathisia: clinical phenomenology and relationship to tardive dyskinesia. 135 16

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

In a sample of 120 long-stay in-patients who fulfilled DSM-III-R criteria for schizophrenia, chronic akathisia and pseudoakathisia were relatively common, with prevalence figures of 24% and 18%, respectively. Compared with patients without evidence of chronic akathisia, those patients with the condition were significantly younger, were receiving significantly higher doses of antipsychotic medication, and were more likely to be receiving a depot antipsychotic. Patients who experienced the characteristic inner restlessness and compulsion to move of akathisia also reported marked symptoms of dysphoria, namely tension, panic, irritability and impatience. The findings support the suggestion that dysphoric mood is an important feature of akathisia. Male patients appeared to be at an increased risk of pseudoakathisia. No significant relation was found between chronic akathisia and tardive dyskinesia, although there was a trend for trunk and limb dyskinesia to be commonest in patients with chronic akathisia while orofacial dyskinesia was most frequently observed in those with pseudoakathisia. Akathisia may mask the movements of tardive dyskinesia in the lower limb. There was no evidence that akathisia was associated with positive or negative symptoms of schizophrenia nor with depression.
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PMID:Akathisia: prevalence and associated dysphoria in an in-patient population with chronic schizophrenia. 790 11

In the present open study the effects of the D1-dopamine antagonist SCH 39166 on positive and negative symptoms of schizophrenia (DSM-IIIR) were investigated. SCH 39166 was given orally according to a fixed dosage schedule (day 1: 25 mg b.i.d; day 4: 50 mg b.i.d.; day 7: 100 mg b.i.d.; day 18: 200 mg b.i.d.; day 21: 225 mg b.i.d.). Seven patients completed 2 weeks, and five patients completed the study. The reason for premature withdrawal was lack of efficacy or refusal to take SCH 39166. In none of the patients a reduction of the BPRS or CGI score was found. As measured with the PANSS, a significant reduction was observed in the score of the negative subscale, whereas the positive symptoms scale and general psychopathology score remained unaffected. Akathisia, rigidity and hypokinesia were reported occasionally, although only mild in severity. The results of the present study do not support the hypothesis that D1-dopamine antagonists are clinically effective antipsychotics in schizophrenia, considering the fact that SCH 39166 had no effect on positive symptoms. The present study provides circumstantial evidence for an effect of SCH 39166 on negative symptoms.
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PMID:Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia. 858 12

The utility of quality of life (QOL) as an evaluative tool in clinical psychiatric research and drug trials could be enhanced by developing appropriate conceptual models of QOL, specific for psychiatric disorders. In our proposed model, QOL of individuals maintained on antipsychotic drug therapy for schizophrenia, is viewed as the subject's perception of the outcome of an interaction between severity of psychotic symptoms, side-effects including subjective responses to antipsychotic drugs, and the level of psychosocial performance. In order to test the validity of the model in clinical setting, we selected a sample of 62 schizophrenic patients clinically stabilized on antipsychotic drug therapy, and measured their subjective QOL and other potentially relevant clinical and psychosocial factors. Standardized scales including the positive and negative syndromes scale (PANSS), abnormal involuntary movements scale (AIMS), Hillside Akathisia scale (HAI), and the social performance schedule (SPS) were used for this purpose. Results of a multiple regression analysis using subjective quality of life as the outcome variable, indicated that severity of schizophrenic symptoms (partial R2 = 0.32, p < 0.0001) and subjective distress caused by akathisia (partial R2 = 0.11, p < 0.01) and neuroleptic dysphoria (partial R2 = 0.06, p < 0.05), accounted for nearly half of the variance, while the contribution from the psychosocial indicators was negligible. These results broadly endorse key aspects of the proposed model, and suggest further studies in this direction. These results experiences during antipsychotic therapy can enhance patients' QOL. This conceptual model has been developed with particular focus on the impact of antipsychotic medications on the QOL of persons with schizophrenia. As such, it is more applicable to clinical trials of new antipsychotic medications but may not be broad enough to be applicable for other social or vocational interventions.
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PMID:A conceptual model of quality of life in schizophrenia: description and preliminary clinical validation. 906 38

A prospective, open-label study in a 400-bed state psychiatric hospital evaluated change in therapeutic response among ten patients with treatment-resistant schizophrenia who were switched from clozapine to risperidone. Drug effects were examined before discontinuation of clozapine and at three, six, nine, and 12 weeks of risperidone treatment. No patients improved, and five discontinued treatment due to exacerbation of psychosis or adverse effects. Changes in scores on the Positive and Negative Syndrome Scale, the Brief Psychiatric Rating Scale, and the Barnes Akathisia Scale indicated clinically significant worsening of symptoms. The findings do not support replacing clozapine with risperidone for patients with treatment-resistant schizophrenia.
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PMID:Effects of switching inpatients with treatment-resistant schizophrenia from clozapine to risperidone. 911 79

A 6-week acute phase of an international 1-year double-blind study was conducted comparing three dose ranges of olanzapine (5 +/- 2.5 mg/day, 10 +/- 2.5 mg/day, and 15 +/- 2.5 mg/day) with a fixed dose of olanzapine (1.0 mg/day) and with a dose range of haloperidol (15 +/- 5 mg/day) in the treatment of 431 patients with schizophrenia. The purpose was to determine whether olanzapine demonstrated a dose-related ability to decrease overall psychopathology with minimal associated extrapyramidal symptoms in patients with schizophrenia. The high-dose olanzapine group showed statistically significantly greater improvement in overall psychopathology based on mean change in the CGI Severity score and statistically significantly greater improvement in positive psychotic symptoms based on mean change in both the BPRS positive score and the PANSS positive score compared with the 1.0-mg/day olanzapine group. Analyses indicated that an increasing dose-response curve was observed across the range of all olanzapine dose groups. Acute extrapyramidal syndromes were reported less frequently among all olanzapine groups compared with the haloperidol group. Endpoint mean change on both the Simpson-Angus Scale and the Barnes Akathisia Scale reflected improvement for all olanzapine treatment groups compared with worsening for the haloperidol group. Olanzapine was associated with weight gain but did not appear to have any clinically meaningful effect on vital signs. Although olanzapine was associated with some increase in prolactin concentrations, increases were transient, occurred less often, and were of lesser magnitude than those observed with haloperidol.
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PMID:Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial. 916

The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability.
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PMID:Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology -- a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group. 968 99

Olanzapine is a newly developed atypical neuroleptic with a marked affinity to the 5-HT2, D2 and D4 dopamine receptors. Like other atypical neuroleptics olanzapine is considered to show a reduced prevalence of extrapyramidal side effects when compared to classical neuroleptic drugs. We report on three patients with acute schizophrenia, who developed severe akathisia during treatment with olanzapine (20-25 mg/d). In two of these cases akathisia resolved after withdrawal of olanzapine and substitution by a classical or an atypical neuroleptic agent, respectively. In one of these patients olanzapine was well tolerated when reintroduced in combination with lorazepam after complete remission of akathisia. In the third patient akathisia was sufficiently controlled by dose reduction. Akathisia is generally considered to result from D2 dopamine receptor antagonism. In the case of atypical neuroleptics such as olanzapine a low but still considerable D2 dopamine receptor occupancy may be compensated by the 5-HT2 antagonism. However, this mechanism may fail under certain circumstances, in particular if D2 dopamine antagonism exceeds a certain threshold. One should therefore be aware of possible extrapyramidal side effects with olanzapine that are reduced compared to classical neuroleptic drugs but not completely eliminated.
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PMID:Severe akathisia during olanzapine treatment of acute schizophrenia. 975 50

A double-blind, placebo-controlled, multicenter study, was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Patients were randomized to receive ziprasidone 40 mg/day, 120 mg/day or placebo for 28 days. Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total, CGI-S. BPRS depression cluster and BPRS anergia cluster scores (all P < 0.05). Similarly, the percentages of patients classified as responders on the BPRS (> or = 30% reduction) and the CGI improvement (score < or = 2) were significantly greater with ziprasidone 120 mg/day compared with placebo (P < 0.05). The number of patients who experienced an adverse event was similar in all three treatment groups, and discontinuation due to adverse events was rare (five of 91 ziprasidone-treated patients). The most frequently reported adverse events, that were more common in either ziprasidone group than in the placebo group, were dyspepsia, constipation, nausea and abdominal pain. There was a notably low incidence extrapyramidal side-effects (including akathisia) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain. Ziprasidone-treated patients were not clinically different from placebo-treated patients on the Simpson-Angus Rating scale, Barnes Akathisia scale and AIMS assessments. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive, negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden.
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PMID:Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial. 986 Jan 8


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