Depressive Signs and Symptoms in Schizophrenia

Tollefson, Gary D.; Sanger, T.M.; Lü, Yifei; Thieme, Martha E.

doi:10.1001/archpsyc.55.3.250

Cited by 232 publications

(38 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These symptoms are treated, to varying degrees, with antidepressant drugs [37,38], second-generation antipsychotics including clozapine and olanzapine [39,40,41], and muscarinic antagonists [42,43]. The same drugs have been used to reduce immobility times in the forced swimming test [20,44,45,46], and, as shown here, they significantly reduce immobility in C. elegans .…”

Section: Discussionmentioning

confidence: 97%

Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants

Dagenhardt¹,

Trinh²,

Sumner

et al. 2017

Complex Psychiatry

View full text Add to dashboard Cite

Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2) and syntaxin (unc-64) genes in Caenorhabditis elegans, brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults. The animals remain responsive to external stimuli; however, they fail to forage and will remain in place for >12 days or until they die. Their immobility can be prevented with drugs used to treat depression and schizophrenia and that reduce immobility in the forced swimming test. This includes amitriptyline, amoxapine, clozapine, and olanzapine, but not benzodiazepines and haloperidol. Recovery experiments confirm that immobility is induced and maintained by excessive signaling via serotonergic and muscarinic cholinergic pathways. The immobility response described here represents a potential protophenotype for avolition/anhedonia in man. This work may provide clues about why there is a significant increase in depression in patients with diabetes and suggest new therapeutic pathways for disorders featuring diminished motivation as a prominent symptom.

show abstract

Section: Discussionmentioning

confidence: 97%

Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants

Dagenhardt¹,

Trinh²,

Sumner

et al. 2017

Complex Psychiatry

View full text Add to dashboard Cite

show abstract

“…14–17 The American Psychiatric Association Clinical Practice Guidelines assigned a level II evidence for a recommendation on the use of SGAs for the treatment of depression in schizophrenia not associated with relapse. 12 While some studies suggest a specific antidepressant effect for SGAs, and for olanzapine in particular, mediated through 1 or more non-D 2 pathways, 15 others have suggested that the difference detected in some studies may have reflected akinesia due to a lack of prophylactic anticholinergic medication in the FGA arm of the studies involving moderate to high doses of the high-potency drug haloperidol. 18 It has also been suggested that in drug-naive patients, depression in schizophrenia is related to low presynaptic dopamine function.…”

mentioning

confidence: 99%

Impact of Second-Generation Antipsychotics and Perphenazine on Depressive Symptoms in a Randomized Trial of Treatment for Chronic Schizophrenia

Addington¹,

Mohamed²,

Rosenheck³

et al. 2010

J. Clin. Psychiatry

View full text Add to dashboard Cite

Background According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia, second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia. We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), conducted between January 2001 and December 2004. Method Patients with DSM-IV–defined schizophrenia (N = 1,460) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of 4 second-generation drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months (phase 1). Patients with tardive dyskinesia were excluded from the randomization that included perphenazine. Depression was assessed with the Calgary Depression Scale for Schizophrenia (CDSS). Mixed models were used to evaluate group differences during treatment with the initially assigned drug. An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of ≥ 6, indicative of a current major depressive episode (MDE). Results There were no significant differences between treatment groups on phase 1 analysis, although there was a significant improvement in depression across all treatments. A significant interaction was found between treatment and experiencing an MDE at baseline (P = .05), and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline (P = .0056). Conclusions We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for clinical practice recommendations, but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline.

show abstract

“…We found that clozapine demonstrated superior effect over quetiapine on the CDSS items of depression (p < .01), hopelessness (p = .01), self-depreciation (p = .01), guilty ideas of reference (p < .01), pathological guilt (p < .01), morning depression (p = .02), and observed depression (p = .01). Further, considering the likelihood that improvement in depressive symptoms may be influenced by that in positive or negative symptoms (Tollefson et al, 1998), we calculated Pearson product-moment correlation coefficients between changes in the CDSS and PANSS Positive or Negative score in the clozapine group, using the last observation carried forward (LOCF). However, no correlation was found between changes in the CDSS and PANSS Positive or Negative score (r = 0.04, p = .81; r = 0.15, p = .32, respectively).…”

Section: Resultsmentioning

confidence: 99%

Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: Analysis of the CATIE phase 2E data

Nakajima

Takeuchi

Fervaha

et al. 2015

Schizophrenia Research

View full text Add to dashboard Cite

Background The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Interventions Effectiveness phase 2E. Methods Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models. Results No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone. Conclusion The present findings suggest clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE.

show abstract

Depressive Signs and Symptoms in Schizophrenia

Cited by 232 publications

References 52 publications

Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants

Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants

Impact of Second-Generation Antipsychotics and Perphenazine on Depressive Symptoms in a Randomized Trial of Treatment for Chronic Schizophrenia

Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: Analysis of the CATIE phase 2E data

Contact Info

Product

Resources

About