Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of olanzapine in treatment-resistant schizophrenia is still unresolved. This article presents an open-label, prospective, 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder selected for unambiguous resistance to either clozapine or risperidone and to typical antipsychotics. Forty-three inpatients (mean age, 41.6 years; mean duration of illness, 21.7 years) were enrolled and treated after cross-titration from their previous antipsychotic treatment with olanzapine 10 to 40 mg daily without any concomitant antipsychotic medication. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale, and the Extrapyramidal Symptom Rating Scale. The change with olanzapine treatment was associated with a PANSS total score improvement of 3.7 (SD = 15.6; not significant). There was a significant improvement for the PANSS cognitive and depression/anxiety factors, whereas the PANSS excitement factor worsened. The improvement rate was superior in patients receiving olanzapine doses higher than 20 mg. A total of 16.7% of patients reached response criteria set forth by a previous study. There was a significant decrease in extrapyramidal side effects (t = 2.04; p < 0.05) and statistically significant, yet modest, weight gain. These results indicate that olanzapine is only modestly effective in these severely treatment-resistant patients with schizophrenia. However, a trial with olanzapine can be recommended in these patients before moving to augmentation strategies, given the lack of proven alternatives and the observation that 16.7% of patients reached the response criteria.
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PMID:Olanzapine for schizophrenia refractory to typical and atypical antipsychotics: an open-label, prospective trial. 1147 31

A number of studies have demonstrated a strong relationship between quality of life in schizophrenia and general psychopathology measures, and moreover, that the positive, negative, and disorganized symptoms are less related to quality of life. The current investigation examined the relationship between quality of life and symptomatology in 63 stabilized outpatients diagnosed with schizophrenia or schizoaffective disorder. Consistent with other findings, more severe depression, as rated on the Brief Psychiatric Rating Scale (BPRS) was associated with lower general life satisfaction and lower satisfaction with daily living, finances, health, and social life. In addition, higher anxiety ratings on the BPRS were associated with less satisfaction with global quality of life, daily activities, family, health and social relationship, even when controlling for positive symptoms, negative symptoms, or depression. No other symptoms of schizophrenia were as strongly associated with subjective quality of life. Anxiety was also significantly correlated with a number of positive and negative symptoms while depression was substantially less related. These findings, suggest that more precise analyses of general psychopathology, and anxiety in particular, may be necessary to further clarify the factors involved in quality of life in schizophrenia. In addition, these findings suggest future directions for theories of affect and treatment in schizophrenia.
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PMID:Quality of life in schizophrenia: contributions of anxiety and depression. 1151 37

Suicidal patients often report problems with their sleep. Although sleep-related complaints and EEG (electroencephalographic) changes have been seen widely across the spectrum of psychiatric disorders, sleep complaints such as insomnia, hypersomnia, nightmares, and sleep panic attacks are more common in suicidal patients. The subjective quality of sleep as measured by self-rated questionnaires also appears to be more disturbed in suicidal depressive patients. Sleep studies have reported various polysomnographic findings including increased REM (rapid eye movement) time and REM activity in suicidal patients with depression, schizoaffective disorder, and schizophrenia. One mechanism responsible for this possible association between suicide and sleep could be the role of serotonin (5HT). Serotonergic function has been found to be low in patients who attempted and/or completed suicide, particularly those who used violent methods. Aggression dyscontrol appears to be an intervening factor between serotonin and suicide. Additionally, agents that enhance serotonergic transmission decrease suicidal behavior. Serotonin has also been documented to play an important role in onset and maintenance of slow wave sleep and in REM sleep. CSF 5-HIAA levels have been correlated with slow wave sleep in patients with depression as well as schizophrenia. Moreover, 5HT2 receptor antagonists have improved slow wave sleep. Further studies are needed to investigate the possible role of sleep disturbance in suicidal behavior.
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PMID:Sleep and suicide in psychiatric patients. 1153 31

Mild cognitive impairment often occurs in depressive illness. But it is unknown whether the occurrence or severity of cognitive deficits has diagnostic specificity. It is of interest to investigate whether there are time-related differences in cognitive functions characteristic of different kinds of depressive diagnoses, and therefore whether such differences might help to distinguish between types of depressive disorder. Eighty inpatients with a DSM-IV depressive episode (unipolar, bipolar, dysthymic and schizoaffective disorder, depressive type) were assessed with a series of neuropsychological tests at the beginning and at the end of their hospital stays. A group of 62 matched healthy controls were assessed with the same series of tests at comparable intervals. The diagnostic sub-groups could not be distinguished by cognitive parameters in the time-course. At the time of admission the inpatient group had a worse performance than the control group. After a significant decrease of their mean depression score, the patients still continued to show an outcome worse than the controls. We conclude that the variation of cognitive dysfunction with time in depression seems to be a phenomenon which does not depend on the kind of depressive sub-diagnosis. The results indicate that cognitive deficits might persist longer than the period of illness, but this seems to be true for all depressive sub-diagnoses.
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PMID:Time-related cognitive deficiency in four different types of depression. 1154 11

We examined the relationships among changes in anxiety, depression, core symptoms of schizophrenia, and subjective quality of life (QL) longitudinally. Fifty-three stabilized outpatients diagnosed with schizophrenia or schizoaffective disorder were assessed for QL and symptoms every 3 months for a period of 1 year. Using mixed effects models, we found that changes in anxiety, as rated on the Brief Psychiatric Rating Scale, were inversely associated with general life satisfaction and satisfaction with many specific domains. These relationships were stronger than the relationships of QL and any other core symptoms of schizophrenia, including depression. Anxiety was also related to some positive and negative symptoms. These findings support the notion that more precise analysis of general psychopathology, and anxiety in particular, is important in clarifying the factors involved in QL in schizophrenia. We explain our findings in the context of current theories of affect and suggest implications for the treatment of schizophrenia.
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PMID:Longitudinal analysis of subjective quality of life in schizophrenia: anxiety as the best symptom predictor. 1170 67

Ziprasidone is a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. The initial evidence suggests an effective dosage range of 80-160 mg/day. Clinical trials suggest that the drug is an effective antipsychotic in schizophrenia and schizoaffective disorder with a beneficial effect on negative symptoms and symptoms of depression. The main adverse effects appear to be somnolence (14%) and nausea (10%). Ziprasidone has relatively fewer side-effects and yet has at least equivalent efficacy for florid 'positive' symptoms compared with conventional antipsychotics. The additional serotonergic actions deliver further efficacy against 'negative' and affective symptoms of schizophrenia. Reduced effects on cognitive abilities compared to conventional antipsychotics make ziprasidone more attractive still. Barring any unforeseen complications, it appears to a most valuable addition to the antipsychotic agents.
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PMID:Focus on ziprasidone. 1175 85

This study examined changes in the pharmacologic treatment of 70 patients who were hospitalized with a diagnosis of schizoaffective disorder at some time during a six-year period. An increasing use of divalproex sodium and atypical antipsychotics instead of lithium and conventional antipsychotics was observed. The use of a combination of an antipsychotic and a thymoleptic medication was more common than monotherapy, and physicians tended to continue antidepressants if patients had a history of depression. Patients with a new diagnosis of schizoaffective disorder were stabilized less quickly than those with a previous diagnosis. The use of divalproex sodium and newer antipsychotics did not reduce the time to stabilization in routine clinical practice.
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PMID:Pharmacologic treatment of hospitalized patients with schizoaffective disorder. 1177 57

A new anticonvulsant drug lamotrigine (LTG) has recently been reported to be effective in treating patients with bipolar affective disorder, depression and schizoaffective disorder, suggesting that it is a mood stabilizer. However, the mechanism of action underlying its efficacy in mood disorders is not understood. This study examined the in vivo effect of LTG on 5-HT(1A) receptor-mediated adenylyl cyclase (AC) response in regions of rat brain, as this pathway has been implicated in the therapeutic action of various classes of mood stabilizers. The density of 5-HT(1A) receptors was measured by radioligand binding assay using [(3)H]8-OH-DPAT (0.05-0.8nM) in frontal cortex and hippocampus of rats treated orally with LTG (5mg/kg) for 7 days. AC activity was assayed using [(3)H]ATP. The oral administration of LTG significantly decreased the density of cortical (50%, P<0.001) but not hippocampal 5-HT(1A) receptors, without significant change in the affinity of [(3)H]8-OH-DPAT to 5-HT(1A) receptor in these regions. There was no significant alteration in basal or forskolin-stimulated AC activity in either of regions. However, a significant decrease (P<0.01) in the inhibition of forskolin-stimulated AC activity by 8-OH-DPAT was observed only in cortical membranes of LTG treated rats when compared to control. These results suggest that one mode of action of LTG may be by the downregulation of cortical 5-HT(1A) receptor-mediated AC response.
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PMID:Lamotrigine induced selective changes in 5-HT(1A) receptor mediated response in rat brain. 1179 61

Suicide is a major contributor to the morbidity and mortality of schizophrenia, accounting for approximately 10% of deaths in these patients. The known risk factors for suicide in schizophrenia include prior suicide attempts, substance abuse, male sex, onset during first decade of illness, social isolation, depression, and feelings of hopelessness. There is significant evidence suggesting that clozapine reduces the suicide rate in patients with schizophrenia and schizoaffective disorder. Possible factors that lead to a decrease in suicidality with clozapine include the following: a direct antidepressant action, improved cognitive function and insight, diminished negative symptoms, reduced substance abuse, and improved compliance. These effects may converge or lessen feelings of hopelessness and more of its converse optimism. The International Suicide Prevention Trial (InterSePT) is a large prospective, 2-year randomized trial of the comparative effects of clozapine and olanzapine involving 980 patients at high risk for suicide in 11 countries in 56 sites. The study included complete freedom to augment these treatments if needed, blinded ratings, a blinded Suicide Monitoring Board, and equivalent clinical contact. The results support the superiority of clozapine over olanzapine to reduce the risk of suicidality and suggest its use should be considered for all patients with schizophrenia with high risk for suicide.
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PMID:Suicidality in schizophrenia: a review of the evidence for risk factors and treatment options. 1212 96

The effect of fluoxetine on the steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was evaluated in 10 patients with schizophrenia or schizoaffective disorder. Patients stabilized on risperidone (4-6 mg/day) received additional fluoxetine (20 mg/day) to treat concomitant depression. One patient dropped out after 1 week due to the occurrence of akathisia associated with markedly increased plasma risperidone concentrations. In the other subjects, mean plasma concentrations of risperidone increased during fluoxetine administration from 12 +/- 9 ng/mL at baseline to 56 +/- 31 at week 4 (p < 0.001), while the levels of 9-OH-risperidone were not significantly affected. After 4 weeks of combined treatment, the levels of the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) increased by 75% (range, 9-204%, p < 0.01) compared with baseline. The mean plasma risperidone/9-OH-risperidone ratio also increased significantly. During the second week of adjunctive therapy, two patients developed Parkinsonian symptoms, which were controlled with anticholinergic medication. These findings indicate that fluoxetine, a potent inhibitor of the cytochrome P450 enzyme CYP2D6 and a less potent inhibitor of CYP3A4, reduces the clearance of risperidone by inhibiting its 9-hydroxylation or alternative metabolic pathways. This interaction may lead to toxic plasma risperidone concentrations. In addition to careful clinical observation, monitoring plasma risperidone levels may be of value in patients given adjunctive therapy with fluoxetine.
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PMID:Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia: a clinically relevant pharmacokinetic drug interaction. 1217 43


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