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Next-generation antipsychotics- Trends and perspectives beyond dopaminergic and glutamatergic agents
- O. Vasiliu, A. G. Mangalagiu, B. M. Petrescu, C. A. Candea, C. Tudor, D. Ungureanu, M. Miclos, C. Florescu, A. I. Draghici, R. E. Bratu-Bizic, M. Dobre, A. F. Fainarea, M. C. Patrascu
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S558-S559
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Introduction
Three generations of antipsychotics, all of which are based on the dopaminergic hypothesis of schizophrenia, are available for clinical use. Still, more than 66% of the patients diagnosed with schizophrenia spectrum disorders (SSD) could not achieve remission. Also, the glutamatergic hypothesis of schizophrenia is supported by translational models of this disease, even if the antipsychotics derived from this conceptual framework are not yet available on the market. However, the need for new pathogenesis models for schizophrenia and new generations of antipsychotics is acute, therefore, an exploration of the antipsychotics in the pipeline could be helpful in understanding the current stage of research in schizophrenia.
ObjectivesTo assess the evidence supporting the potential benefits of new antipsychotics in the pipeline.
MethodsA literature review was performed through the main electronic databases PubMed, Cochrane, Clarivate/Web Of Science, and EMBASE) and clinical trials repositories (US National Library of Medicine and World Health Organization Clinical Trials Registry Platform) using the search paradigm “antipsychotics” AND “schizophrenia” AND “non-dopaminergic” AND “non-glutamatergic”. All papers published between January 2010 and September 2022 were included.
ResultsXanomeline/trospium (xanomeline is a muscarinic M1/M4 receptor agonist at the central nervous system, while trospium limits its peripheral effects) was efficient for schizophrenia in one phase III clinical trial. Pimavanserin (a selective 5HT2A inverse agonist and antagonist) was efficient in improving negative symptoms of schizophrenia in a phase II trial. Roluperidone (a 5HT2A and σ2 receptor antagonist) has been associated with favorable results in phase III clinical trials, mainly on negative symptoms of schizophrenia. SEP-363856 is a TAAR-1 agonist and 5HT1A agonist, currently explored in phase III clinical trials for schizophrenia. MK-8189 is a phosphodiesterase 10A inhibitor, investigated in phase III clinical trials for schizophrenia.
ConclusionsBased on the retrieved data in the literature, multiple mechanisms, other than glutamatergic and dopaminergic pathways, are currently being investigated, and many of the antipsychotics based on these mechanisms are in the advanced stage of research. This is important not only for the clinical need to find more efficient and tolerable drugs for patients with schizophrenia but also because they may shed new light on the pathogenesis of this disease.
Disclosure of InterestNone Declared
Depression in patients with coronary heart disease
- A. Baloescu, G. Grigorescu, M. Miclos, E. Badescu, M.D. Gheorghe
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- Journal:
- European Psychiatry / Volume 22 / Issue S1 / March 2007
- Published online by Cambridge University Press:
- 16 April 2020, p. S223
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Background:
Depression is a risk factor for coronary heart disease (CHD) and for other cardiovascular diseases. It cause high mortality in known patients. SSRIs are safe and have a negligible effect on the cardiovascular system, even in cases of overdose.
Objective:To examine the antidepressant effect of sertraline and paroxetine in patients with CHD after the incidence of an acute coronary event.
Method:46 patients (26 female, mean age 59,8; 20 male, mean age 57,8) diagnosed with CHD, after 1-3 months from an acute coronary syndrome, no depression in the past, met the criteria for major depressive disorder (MDD) according to ICD10. It was performed HAMD 17 items.
Results:Patients received either sertraline 75-150 mg/day (n=23; mean dose 104,3 mg/day) or paroxetine 20-30 mg/day (n=23; mean dose 22,6 mg/day). They were examined on baseline and days 7, 28, 56, 112, 168 using cardiologic evaluation, and depression rating scale HAMD. All treated patients had a significant improvement on HAMD score (from mean 21,8 to 10,6). Significant improvement was noted at 28 days of treatment. 12/46 (26,08%) were mildly improved and 34/46 (73,92%) were much or very much improved. No important side effects were recorded.
Conclusions:1) Patients with no recent history of depression suffering a cardiovascular event were more likely to be diagnosed with depression. 2) Diagnosis and treatment of depression should be incorporated into the clinical management of CHD 3) Sertraline and paroxetine are a safe and effective treatment in patients with CHD without other life-threatening medical conditions.