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)

Insomnia is a significant public health concern that has prompted substantial efforts to develop treatment and management strategies. A significant proportion of complaints of insomnia are related to psychiatric conditions such as anxiety disorders and depression, and treatments for these disorders are known to exert both direct and indirect benefits on sleep as well as some negative effects on sleep and sleep physiology. Insomnia is also a prominent symptom of a number of other psychiatric disorders, including schizophrenia and bipolar disorder. The observed impact of a variety of psychiatric medications on insomnia has prompted an empirically derived practice of treating non-psychiatric disorder-related insomnia with psychiatric medications by clinicians searching for alternatives to established medication treatments for primary insomnia. This article aims to review the evidence of the impact of psychiatric medications on sleep physiology, sleep disorders in psychiatric conditions, and on primary sleep disorders. The potential for exploiting the relevant pharmacological mechanisms of action in drug development for primary insomnia will be addressed as well.
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PMID:Effects of psychiatric medications on sleep and sleep disorders. 1730 51

A long-acting depot formulation of olanzapine that sustains plasma olanzapine concentrations for over a month after a single injection is currently under development. This multicenter, open-label study explored D(2) receptor occupancy of a fixed dose of olanzapine pamoate (OP) depot given every 4 weeks. Patients (nine male, five female) with schizophrenia or schizoaffective disorder previously stabilized on oral olanzapine were switched to OP depot 300 mg by intramuscular injection every 4 weeks for 6 months. No visitwise within-group significant changes were found in Brief Psychiatric Rating Scale Total or Clinical Global Impressions-Severity of Illness scores, although seven patients received oral olanzapine supplementation during the first four injection cycles. To minimize impact on D(2) occupancy, positron emission tomography (PET) scans were not completed during injection cycles that required supplemental oral olanzapine. Two patients reported transient injection site adverse events, which did not result in discontinuation. The most frequently reported treatment-emergent adverse events were insomnia, aggravated psychosis, and anxiety. Mean striatal D(2) receptor occupancy, as measured by [(11)C]-raclopride PET, was 69% on oral olanzapine (5-20 mg/day) and 50% (trough) on OP depot at steady state. Following an initial decline, occupancy returned to 84% of baseline oral olanzapine occupancy after six injections. Over the study period, D(2) receptor occupancy and plasma olanzapine concentrations were significantly correlated (r=0.76, P</=0.001). OP depot resulted in mean D(2) receptor occupancy of approximately 60% or higher at the end of the 6-month study period, a level consistent with antipsychotic efficacy and found during treatment with oral olanzapine. However, supplemental oral olanzapine or another dosing strategy may be necessary to maintain adequate therapeutic response during the first few injection cycles.
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PMID:D2 receptor occupancy of olanzapine pamoate depot using positron emission tomography: an open-label study in patients with schizophrenia. 1744 31

AMPA-receptor-positive modulators (Ampakines) facilitate learning and memory in animal models and in preliminary trials in human subjects. CX516 is the first Ampakine to be studied for cognitive enhancement in schizophrenia. Stable schizophrenia patients treated with clozapine (n=52), olanzapine (n=40), or risperidone (n=13) were randomly assigned to add-on treatment with CX516 900 mg three times daily or placebo for 4 weeks. Subjects were assessed with a cognitive battery at baseline, week 4, and at 4-week follow-up. Clinical scales and safety monitoring were also performed. The primary endpoint was the change from baseline in a composite cognitive score at week 4 for the intent-to-treat sample. Additional analyses examined change in symptom rating scores and examined drug effects on patients treated with clozapine separately from patients treated with either olanzapine or risperidone. A total of 105 patients were randomized and 95 (90%) completed the 4-week trial. Patients treated with CX516 did not differ from placebo in change from baseline on the composite cognitive score, or on any cognitive test at weeks 4 or 8. The between groups effect size at week 4 for the cognitive composite score was -0.19 for clozapine-treated patients and 0.24 for patients treated with olanzapine or risperidone. The placebo group improved more on the PANSS total score than the CX516 group; no other clinical rating differed between treatment groups. CX516 was associated with fatigue, insomnia and epigastric discomfort compared to placebo, but was generally well tolerated. CX516 was not effective for cognition or for symptoms of schizophrenia when added to clozapine, olanzapine, or risperidone.
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PMID:A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. 1748 27

In spite of apparent improvements in the pharmacotherapy of schizophrenia, many patients still demonstrate an incomplete therapeutic response to antipsychotic medication and/or intolerable adverse effects, necessitating a change in their medication regimen. The switch from one antipsychotic to another, however, is not without challenges and can be complicated by withdrawal-emergent adverse effects that prompt the patient or the clinician to abort the switch. The extent to which these adverse events can be predicted by comparing the effects of the old and new antipsychotic medications on various receptor systems, including dopaminergic, muscarinic, and histaminergic receptors, is of considerable clinical and research interest. For example, patients receiving a sedating antipsychotic with high affinity for histamine H(1) receptors could experience rebound insomnia if switched to a less sedating agent with a low affinity for H(1) receptors. An understanding of the differential receptor-binding profiles of the various antipsychotics can help clinicians anticipate and manage potential clinical issues that may be encountered when switching antipsychotic therapy.
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PMID:Receptor-binding profiles of antipsychotics: clinical strategies when switching between agents. 1765 53

The effects of paliperidone extended-release on sleep architecture in patients with schizophrenia-related insomnia were evaluated in this multicenter, double-blind, randomized, placebo-controlled study. Patients received paliperidone extended-release 9 mg/day or matching placebo during the 14-day double-blind phase. Sleep architecture and sleep continuity were evaluated using polysomnograms. Subjective sleep measures were evaluated daily using the Leeds Sleep Evaluation Questionnaire. Efficacy and safety were also assessed. Thirty-six patients (17 on paliperidone extended-release, 19 on placebo; mean age 32.2 years) completed the study. Paliperidone extended-release treatment vs. placebo resulted in clinically and statistically significant differences in sleep measurements from baseline to endpoint including a reduction in: persistent sleep latency (41 min), sleep onset latency (35 min), number of awakenings after sleep onset (7), time awake in bed (50 min), and stage 1 sleep duration (12 min); prolongation in: total sleep time (53 min), sleep period time (42 min), stage 2 sleep duration (51 min), and rapid eye movement sleep duration (18 min); and an increase in sleep efficiency index (11%). Paliperidone extended-release, compared with placebo, did not exacerbate daytime somnolence and improved symptoms of schizophrenia. Paliperidone extended-release was well tolerated and improved sleep architecture and sleep continuity in patients diagnosed with schizophrenia and concomitant insomnia.
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PMID:A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia. 1769 May 99

A retrospective study was conducted to examine aripiprazole's effectiveness and safety in a naturalistic treatment setting in both inpatients and outpatients affected by schizophrenia and other psychotic disorders. All patients with schizophrenia, schizoaffective and delusional disorders, and schizoid and schizotypal personality disorders treated with aripiprazole from March 1, 2005, to March 1, 2006, in the authors' community mental health service were divided into outpatient (n=26) and inpatient (n=17) groups; the average treatment periods were 204 days and 25 days, respectively. Effectiveness was evaluated by improvement of symptoms (a 25% reduction of Brief Psychiatric Rating Scale [BPRS] score from baseline) and functioning level (a 50% increase of Global Assessment of Functioning [GAF] scale score from baseline), as well as dropout rate. Adverse effects and their impact on treatment course were also evaluated. The final scores of the 2 scales showed a statistically significant difference from baseline (BPRS: p<.001 in the 2 groups; GAF: p<.005 in inpatients, p<.001 in outpatients). The average improvements in BPRS and GAF were 54% and 35%, respectively, in outpatients and 71% and 71% in inpatients. Side effects included anxiety, psychomotor agitation, insomnia, and psychotic symptom worsening. The dropout rate was 24% in inpatients and 23% in outpatients, largely because of the aforementioned side effects. The data, though limited by the small sample and naturalistic methodology, suggest that aripiprazole may be effective for both long- and short-term treatment, with a greater improvement among inpatients and a similar dropout rate between groups.
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PMID:Aripiprazole: effectiveness and safety under naturalistic conditions. 1817 10

The aim of this paper was to evaluate the efficacy of risperidone long-acting injectable (RLAI) for reducing negative symptoms of schizophrenia in patients with predominantly negative symptoms at baseline. A subanalysis was performed on data from the 6-month, open-label Switch to Risperidone Microspheres trial. Patients with Positive and Negative Syndrome Scale (PANSS) negative subscale score > or = 21, which was higher than their PANSS positive subscale score, were included in this subanalysis. Improvement in negative symptoms was measured by assessing change in the PANSS negative subscale and a negative factor score. Additional outcome variables included measures in general functioning, quality of life and patient satisfaction. A total of 842 patients were eligible for inclusion in this subanalysis. Six months of treatment was completed by 631 (74.9%) patients. Forty-three (5.1%) patients discontinued treatment due to an adverse event. Negative symptoms were significantly reduced by 6.1 +/- 6.3 points for the PANSS negative score and 6.1 +/- 6.4 points for the negative factor score (P < 0.0001 for both). Significant improvements were also noted for total PANSS and other PANSS subscale scores, general functioning, quality of life and patient satisfaction (P < 0.0001). The most common treatment-emergent adverse events (>5%) were: anxiety (6.8% of patients), exacerbation of disease (6.2%) and insomnia (5.7%). Overall, RLAI was well tolerated and associated with significant reductions in movement disorder severity. The treatment resulted in a significant improvement in negative symptom severity and was well tolerated in patients with predominantly negative symptoms, who switched from a stable antipsychotic regimen
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PMID:Long-acting risperidone improves negative symptoms in stable psychotic patients. 1830 4

Iloperidone, a mixed D2/5-HT2 antagonist, is currently in clinical development for the treatment of schizophrenia. This article assesses the short-term safety of iloperidone using a pooled analysis of 3 phase 2, short-term acute schizophrenia studies conducted between 1998 and 2002 (N = 1943). Patients exposed to 3 dose ranges of iloperidone, another antipsychotic, or placebo were compared on rates of serious adverse events (SAEs), adverse events (AEs), extrapyramidal symptoms, akathisia, prolactin, weight and metabolic parameters, QTc, and other standard safety parameters. The most common treatment-related AEs observed with iloperidone were dizziness, headache, dry mouth, nausea, and insomnia. Discontinuation due to AEs was 4.8% for iloperidone, 7.6% for haloperidol, 6.2% for risperidone, and 4.8% for placebo. Iloperidone groups showed better overall performance on the Extrapyramidal Symptom Rating Scale and Barnes Akathisia Scale than risperidone or haloperidol groups. Patients taking iloperidone experienced a mild weight increase (range, 1.5-2.1 kg) similar to that of risperidone (1.5 kg), whereas those on haloperidol and placebo showed mean weight loss (-0.1 kg and -0.3 kg, respectively). QTc interval significantly increased across all iloperidone groups (least squares mean change from baseline to end point, 2.9-9.1 msec) and for haloperidol (5.0 msec). No significant QTc changes occurred in the risperidone or placebo groups. Iloperidone was associated with no change from baseline in total cholesterol, mild elevation in serum glucose, and slight decrease in triglycerides. Prolactin levels decreased with iloperidone and increased significantly with risperidone and haloperidol. These short-term trials suggest that iloperidone has a reassuring safety profile in many of the areas that are of potential concern, including relatively low dropout rates because of AEs, low extrapyramidal symptoms, akathisia, and prolactin elevation, and a modest short-term effect on weight gain.
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PMID:Safety profile of iloperidone: a pooled analysis of 6-week acute-phase pivotal trials. 1833 8

This research compared the long-term efficacy and safety of iloperidone with those of haloperidol in individuals with schizophrenia. Data were pooled from 3 prospective multicenter studies, each with 6-week stabilization followed by 46-week double-blind maintenance phases. Patients were randomized to iloperidone 4 to 16 mg/d or haloperidol 5 to 20 mg/d. Patients included in this analysis completed the initial 6-week phase with at least 20% reduction in Positive and Negative Syndrome Scale (PANSS) total score at weeks 4 and 6, had 7-item Clinical Global Impressions of Change (CGI-C) scores less than 4, received 1 or more doses of long-term phase medication, and had 1 or more efficacy/safety assessments during the long-term phase. The primary efficacy variable was time to relapse, defined as a 25% or more increase in PANSS total score, including at least a 10-point change; discontinuation because of lack of efficacy; aggravated psychosis with hospitalization; or 2-point increase in the 7-item CGI-C after week 6. Of 1644 patients randomized and 1326 completing the 6-week phase, 473 (iloperidone, n = 359; haloperidol, n = 114) were included in the long-term efficacy analysis, and 489 (iloperidone, n = 371; haloperidol, n = 118) in the safety analysis. Iloperidone was equivalent to haloperidol in time to relapse. The most common adverse events were insomnia (18.1%), anxiety (10.8%), and schizophrenia aggravated (8.9%) with iloperidone, and insomnia (16.9%), akathisia (14.4%), tremor (12.7%), and muscle rigidity (12.7%) with haloperidol. The Extrapyramidal Symptoms Rating Scale scores improved with iloperidone and worsened with haloperidol. Metabolic changes were minimal for both groups. Mean changes in Fridericia's QT interval correction were 10.3 msec (iloperidone) and 9.4 msec (haloperidol) at end point. Iloperidone demonstrated long-term efficacy equivalent to haloperidol and a favorable long-term safety profile, potentially making this agent a suitable option as maintenance therapy for schizophrenia.
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PMID:Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia. 1833 10

When taking antipsychotic medications, children and adolescents seem to have a higher risk than adults for experiencing adverse events such as extrapyramidal symptoms, prolactin elevation, sedation, weight gain, and metabolic effects. Side effects may be predicted by the pharmacologic binding profiles of antipsychotics to certain neuroreceptors. Data from 7 recently completed randomized placebo-controlled trials in adolescent schizophrenia and pediatric bipolar disorder that included a total of 1480 patients extend prior results and provide numbers-needed-to-harm as a clinically useful measure of risk. Results from these pediatric studies indicate that adverse effect profiles differ among commonly used antipsychotics. However, more detailed data are needed, as information is lacking regarding carryover or withdrawal effects from prior medications and regarding the masking of effects by adjunctive treatments used to treat agitation, insomnia, or extrapyramidal symptoms and akathisia in these studies. Moreover, randomized head-to-head trials and large-scale studies that investigate predictors of adverse effects as well as the safety and efficacy of interventions aimed at preventing and reversing negative effects of antipsychotics with relevant impact on psychological, psychiatric, and physical functioning are lacking. When choosing an antipsychotic treatment, patients and their families should be included in a careful risk-benefit assessment. Consideration of adverse effects, as well as dietary and lifestyle counseling, should be part of any antipsychotic treatment initiation and continuation. Routine, proactive monitoring of side effects is essential to optimize patient outcomes. In all treatment decisions, the benefits of improving often severe and debilitating manic, psychotic, and aggressive symptomatology must be balanced against the varying risks of adverse effects associated with specific antipsychotic agents in child and adolescent patients.
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PMID:Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. 1853 66


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