MDLinx UpDate July

 

Hippocampal Angiogenesis and Progenitor Cell Proliferation Are Increased with Antidepressant Use in Major Depression

Boldrini M et al. – Antidepressants increase human hippocampal neural progenitor cells and angiogenesis selectively in the anterior and mid dentate gyrus. These results raise the possibility of a causal relationship between angiogenesis and neurogenesis, as seen in other proliferating tissues, and support their possible role in the mechanism of action of antidepressants.

 

 

 

 

Role of aripiprazole in treatment-resistant schizophrenia Neuropsychiatric Disease and Treatment, 06/06/12

Mossaheb N et al. ? The most commonly found beneficial effects are better metabolic outcomes and indicators of the possibility of reducing the clozapine dose. However, other side effects, such as akathisia, are repeatedly reported. Further, none of the studies report longer?term outcomes. In the absence of alternatives, polypharmacy is a common strategy in clinical practice. Combining aripiprazole with clozapine in clozapine?resistant or clozapine?intolerant patients seems to be worthy of further investigation from the pharmacological and clinical points of view. About one third of patients with schizophrenia respond unsatisfactorily to antipsychotic treatment and are termed ?treatment-resistant?. Clozapine is still the gold standard in these cases. However, 40%?70% of patients do not improve sufficiently on clozapine either. In the search for more efficacious strategies for treatment-resistant schizophrenia, drugs with different pharmacological profiles seem to raise new hopes, but are they valid? The aim of this review was to evaluate the evidence for aripiprazole as a potential strategy in monotherapy or combination therapy for patients with treatment-resistant schizophrenia. The evidence for aripiprazole monotherapy and for the combination of aripiprazole with psychotropics other than clozapine is scant, and no recommendation can be made on the basis of the currently available data. More effort has been made in describing combinations of aripiprazole and clozapine. Most of the open-label and case studies as well as case reports have shown positive effects of this combination on overall psychopathology and to some extent on negative symptoms. Several reports describe the possibility of dose reduction for clozapine in combination with aripiprazole, a strategy that might help so-called ?treatment-intolerant? patients. The findings of four randomized controlled trials with respect to changes in psychopathology seem less conclusive.

 

 

 

Hippocampal Angiogenesis and Progenitor Cell Proliferation Are Increased with Antidepressant Use in Major Depression Biological Psychiatry, 06/06/12

Boldrini M et al. – Antidepressants increase human hippocampal neural progenitor cells and angiogenesis selectively in the anterior and mid dentate gyrus. These results raise the possibility of a causal relationship between angiogenesis and neurogenesis, as seen in other proliferating tissues, and support their possible role in the mechanism of action of antidepressants.

 

 

 

 

Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis : The Lancet The Lancet - Early Online Publication, 05/23/12

Leucht S et al. – Maintenance treatment with antipsychotic drugs benefits patients with schizophrenia. The advantages of these drugs must be weighed against their side–effects. Methods The authors searched the Cochrane Schizophrenia Group's specialised register for reports published before Nov 11, 2008; and PubMed, Embase, and ClinicalTrials.gov for those before June 8, 2011. They also contacted pharmaceutical companies and searched the reference lists of included studies and previous reviews. Randomised trials of patients with schizophrenia continued on or withdrawn from any antipsychotic drug regimen after stabilisation were eligible. The primary outcome was relapse between 7 and 12 months. The authors also examined safety and various functional outcomes. They used the random effects model and verified results for the primary outcome with a fixed effects model. Heterogeneity was investigated with subgroup and meta-regression analyses. Results The authors identified 116 suitable reports from 65 trials, with data for 6493 patients. Antipsychotic drugs significantly reduced relapse rates at 1 year (drugs 27% vs placebo 64%; risk ratio [RR] 0.40, 95% CI 0.33?0.49; number needed to treat to benefit [NNTB] 3, 95% CI 2?3). Fewer patients given antipsychotic drugs than placebo were readmitted (10% vs 26%; RR 0.38, 95% CI 0.27?0.55; NNTB 5, 4?9), but less than a third of relapsed patients had to be admitted. Limited evidence suggested better quality of life (standardised mean difference -0.62, 95% CI -1.15 to -0.09) and fewer aggressive acts (2% vs 12%; RR 0.27, 95% CI 0.15?0.52; NNTB 11, 6?100) with antipsychotic drugs than with placebo. Employment data were scarce and too few deaths were reported to allow significant differences to be identified. More patients given antipsychotic drugs than placebo gained weight (10% vs 6%; RR 2.07, 95% CI 2.31?3.25), had movement disorders (16% vs 9%; 1.55, 1.25?1.93), and experienced sedation (13% vs 9%; 1.50, 1.22?1.84). Substantial heterogeneity in size of effect was recorded. In subgroup analyses, number of episodes, whether patients were in remission, abrupt or gradual withdrawal of treatment, length of stability before trial entry, first-generation or second-generation drugs, and allocation concealment method did not significantly affect relapse risk. Depot preparations reduced relapse (RR 0.31, 95% CI 0.21?0.41) more than did oral drugs (0.46, 0.37?0.57; p=0.03); depot haloperidol (RR 0.14, 95% CI 0.04?0.55) and fluphenazine (0.23, 0.14?0.39) had the greatest effects. The effects of antipsychotic drugs were greater in two unblinded trials (0.26, 0.17?0.39) than in most blinded studies (0.42, 0.35?0.51; p= 0.03). In a meta-regression, the difference between drug and placebo decreased with study length.

 

 

 

 

 

Role of aripiprazole in treatment-resistant schizophrenia

Neuropsychiatric Disease and Treatment, 06/06/12

Mossaheb N et al. ? The most commonly found beneficial effects are better metabolic outcomes and indicators of the possibility of reducing the clozapine dose. However, other side effects, such as akathisia, are repeatedly reported. Further, none of the studies report longer?term outcomes. In the absence of alternatives, polypharmacy is a common strategy in clinical practice. Combining aripiprazole with clozapine in clozapine?resistant or clozapine?intolerant patients seems to be worthy of further investigation from the pharmacological and clinical points of view.

• About one third of patients with schizophrenia respond unsatisfactorily to antipsychotic treatment and are termed ?treatment-resistant?.
• Clozapine is still the gold standard in these cases.
• However, 40%?70% of patients do not improve sufficiently on clozapine either.
• In the search for more efficacious strategies for treatment-resistant schizophrenia, drugs with different pharmacological profiles seem to raise new hopes, but are they valid? The aim of this review was to evaluate the evidence for aripiprazole as a potential strategy in monotherapy or combination therapy for patients with treatment-resistant schizophrenia.
• The evidence for aripiprazole monotherapy and for the combination of aripiprazole with psychotropics other than clozapine is scant, and no recommendation can be made on the basis of the currently available data.
• More effort has been made in describing combinations of aripiprazole and clozapine.
• Most of the open-label and case studies as well as case reports have shown positive effects of this combination on overall psychopathology and to some extent on negative symptoms.
• Several reports describe the possibility of dose reduction for clozapine in combination with aripiprazole, a strategy that might help so-called ?treatment-intolerant? patients.
• The findings of four randomized controlled trials with respect to changes in psychopathology seem less conclusive