Current Treatments for Psychotic Disorders

2017 ◽  
Author(s):  
Deepak K. Sarpal ◽  
Anil K. Malhotra
Keyword(s):  
First Generation ◽  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
Treatment Modalities ◽  
The Past ◽  
Novel Treatment ◽  
Nonpharmacologic Treatment ◽  
Second Generation Antipsychotic ◽  
Treatment Refractory ◽  
Considerable Work

Over the past several decades, considerable work has established our current repertoire of approaches to treatment of psychosis. This chapter provides an overview of current treatments for psychotic disorders with a focus on schizophrenia. Diagnostic considerations will be introduced, followed by discussions of first generation and second generation antipsychotic drugs, our current mainstay for treatment. Adverse effects of medications will be examined, as well as approaches to treatment refractory illness and nonpharmacologic treatment modalities. Finally, in light of recent advances in our understanding of the neurobiology of psychotic disorders, we will briefly discuss treatment-related biomarkers, and novel treatment targets under development.

Differential Impairments in Incentive Learning Caused by First‐ and Second‐ Generation Antipsychotic Drugs

2016 ◽  
Author(s):  
Matthew Florczynski
Keyword(s):  
Neural Control ◽  
First Generation ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Operant Chamber ◽  
Incentive Learning ◽  
Dopamine Receptor Antagonists ◽  
Natural Response ◽  
Second Generation Antipsychotic ◽  
First And Second Generation

Schizophrenia is a neuropsychiatric disorder characterized by increased function of dopamine in the brain.  Dopamine release is a natural response to reward.  It promotes incentive learning (IL), a process by which neutral stimuli acquire the ability to elicit approach and other responses.  A recent model characterizes dopamine‐mediated IL as a progressive process with early and late stages accompanied by a shift in neural control from the nucleus accumbens (NAc) to the dorsolateral striatum (DLS).  A parallel can be drawn to differences in regionally specific neural responses generated by first‐ and second‐generation antipsychotic drugs (APDs) used to treat schizophrenia.  APDs are dopamine receptor antagonists, but first‐generation APDs affect the NAc and DLS while second‐generation APDs affect primarily the NAc.  We compared the effects of APDs on IL. Rats (N = 48) were trained to press a lever forfood pellets in an operant chamber.  Intraperitoneal injections (1 hr before testing) of the first‐generation APD haloperidol (0,0.05,0.10,0.20 mg/kg) or of the second‐generation APD risperidone (0,0.20,0.40,0.80 mg/kg) induced dose‐dependent suppression of lever pressing on days 1‐4, with the highest dose groups failing to demonstrate any evidence of previous learning on day 5 when tested drug‐free.  On days 16‐20 haloperidol induced a day‐to‐day suppression not seen with risperidone.  The results suggest that the effects of first‐ and second‐generation APDs on learning processes putatively mediated by the NAc and DLS can be differentiated experimentally.  The findings imply that APDs may differentially affect IL inpatients with schizophrenia.  

4.  Differential Impairments in Incentive Learning Caused by First‐ and Second‐ Generation Antipsychotic Drugs

2016 ◽  
Author(s):  
Matthew Florczynski
Keyword(s):  
Neural Control ◽  
First Generation ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Operant Chamber ◽  
Incentive Learning ◽  
Dopamine Receptor Antagonists ◽  
Natural Response ◽  
Second Generation Antipsychotic ◽  
First And Second Generation

Schizophrenia is a neuropsychiatric disorder characterized by increased function of dopamine in the brain.  Dopamine release is a natural response to reward.  It promotes incentive learning (IL), a process by which neutral stimuli acquire the ability to elicit approach and other responses.  A recent model characterizes dopamine‐mediated IL as a progressive process with early and late stages accompanied by a shift in neural control from the nucleus accumbens (NAc) to the dorsolateral striatum (DLS).  A parallel can be drawn to differences in regionally specific neural responses generated by first‐ and second‐generation antipsychotic drugs (APDs) used to treat schizophrenia.  APDs are dopamine receptor antagonists, but first‐generation APDs affect the NAc and DLS while second‐generation APDs affect primarily the NAc.  We compared the effects of APDs on IL. Rats (N = 48) were trained to press a lever for food pellets in an operant chamber.  Intraperitoneal injections (1 hr before testing) of the first‐generation APD haloperidol (0,0.05,0.10,0.20 mg/kg) or of the second‐generation APD risperidone (0,0.20,0.40,0.80 mg/kg) induced dose‐dependent suppression of lever pressing on days 1‐4, with the highest dose groups failing to demonstrate any evidence of previous learning on day 5 when tested drug‐free.  On days 16‐20, haloperidol induced a day‐to‐day suppression not seen with risperidone.  The results suggest that the effects of first‐ and second‐generation APDs on learning processes putatively mediated by the NAc and DLS can be differentiated experimentally.  The findings imply that APDs may differentially affect IL inpatients with schizophrenia.

Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies

2005 ◽  
Vol 20 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Anissa Abi-Dargham ◽  
Marc Laruelle
Keyword(s):  
First Generation ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Dopaminergic System ◽  
Therapeutic Strategies ◽  
Therapeutic Action ◽  
Imaging Studies ◽  
High Incidence ◽  
Second Generation Antipsychotic ◽  
Clinically Significant

AbstractMultiple lines of evidence including recent imaging studies suggest that schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyperstimulation of striatal dopamine (DA) D2 receptors and understimulation of cortical DA D1 receptors. This DA endophenotype presumably emerges from the background of a more general synaptic dysconnectivity, involving alterations in N-methyl-d-aspartate (NMDA) and glutamatergic (GLU) functions. Equally important is the fact that this DA dysregulation might further impair NMDA transmission. The first generation antipsychotic (FGA) drugs are characterized by high affinity to and generally high occupancy of D2 receptors. The efficacy of FGAs is limited by a high incidence of extrapyramidal side-effects (EPS). Second generation antipsychotic (SGA) drugs display reduced EPS liability and modest but clinically significant enhanced therapeutic efficacy. Compared to FGAs, the improved therapeutic action of SGAs probably derives from a more moderate D2 receptor blockade. We will review the effects of SGAs on other neurotransmitter systems and conclude by highlighting the importance of therapeutic strategies aimed at directly increasing prefrontal DA, D1 receptor transmission or NMDA transmission to enhance the therapeutic effect of moderate D2 receptor antagonism.

scholarly journals Differential Effects of Acute Treatment With Antipsychotic Drugs on Peripheral Catecholamines

2020 ◽  
Vol 11 ◽  
Author(s):  
Heidi N. Boyda ◽  
Amanzo A. Ho ◽  
Lurdes Tse ◽  
Ric M. Procyshyn ◽  
Jessica W. Y. Yuen ◽  
...  
Keyword(s):  
Side Effects ◽  
Acute Treatment ◽  
First Generation ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Psychotic Disorders ◽  
Female Rats ◽  
Maximum Increase ◽  
Sympathetic Nervous ◽  
Dose Dependent

Antipsychotic drugs represent the most effective treatment for chronic psychotic disorders. The newer second generation drugs offer the advantage of fewer neurological side-effects compared to prior drugs, but many cause serious metabolic side-effects. The underlying physiology of these side-effects is not well-understood, but evidence exists to indicate that the sympathetic nervous system may play an important role. In order to examine this possibility further, we treated separate groups of adult female rats acutely with either the first generation antipsychotic drug haloperidol (0.1 or 1 mg/kg) or the second generation drugs risperidone (0.25 or 2.5 mg/kg), clozapine (2 or 20 mg/kg), olanzapine (3 or 15 mg/kg) or vehicle by intraperitoneal injection. Blood samples were collected prior to drug and then 30, 60, 120, and 180 mins after treatment. Plasma samples were assayed by HPLC-ED for levels of norepinephrine, epinephrine, and dopamine. Results confirmed that all antipsychotics increased peripheral catecholamines, although this was drug and dose dependent. For norepinephrine, haloperidol caused the smallest maximum increase (+158%], followed by risperidone (+793%), olanzapine (+952%) and clozapine (+1,684%). A similar pattern was observed for increases in epinephrine levels by haloperidol (+143%], olanzapine (+529%), risperidone (+617%) then clozapine (+806%). Dopamine levels increased moderately with olanzapine [+174%], risperidone [+271%], and clozapine [+430%]. Interestingly, levels of the catecholamines did not correlate strongly with each other prior to treatment at baseline, but were increasingly correlated after treatment as time proceeded. The results demonstrate antipsychotics can potently regulate peripheral catecholamines, in a manner consistent with their metabolic liability.

Emergence of Ad-Mediated Combination Therapy Against Cancer: What to Expect?

2018 ◽  
Vol 18 (2) ◽  
pp. 139-152 ◽  
Author(s):  
JinWoo Hong ◽  
Chae-Ok Yun
Keyword(s):  
Combination Therapy ◽  
Malignant Tumors ◽  
Treatment Modalities ◽  
Preclinical Models ◽  
Promising Alternative ◽  
The Past ◽  
Novel Treatment ◽  
Viral Particles ◽  
Rapid Clearance ◽  
Therapeutic Profile

Novel treatment modalities are rapidly advancing toward clinical use as many malignant cancers still remain incurable. Adenovirus (Ad) in particular has been extensively researched as a promising alternative to conventional cancer therapy in the past decades. Although Ad has demonstrated promising therapeutic outcome and cancer specificity in preclinical models, its therapeutic efficacy in clinical trials is still insufficient due to several drawbacks such as rapid clearance of viral particles by host immune response, induction of acute inflammatory response, and hepatotoxicity. In this regard, combination of Ad with other cancer treatment modalities, such as chemotherapy, radiotherapy, or immunotherapy, can be an effective strategy to overcome the limitations of Ad. Cancerspecific and effective expression of multifunctional therapeutic genes by Ad can enhance the therapeutic profile of other treatment modalities, making it a logical candidate for combination therapy to combat malignant tumors.

Psychotic Disorders: Neurochemistry and Pharmacotherapy

2013 ◽  
pp. 346-354
Author(s):  
Carol A. Tamminga ◽  
Elena I. Ivleva
Keyword(s):  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
Structure And Function ◽  
Intermediate Phenotype ◽  
Treatment Development ◽  
Biological Basis ◽  
Novel Treatment ◽  
Experimental Treatments ◽  
And Function

This paper starts with the conceptualization of psychosis as an intermediate phenotype and argues for its usefulness. The goal of such a re-conceptualization includes the possibility of advantaging the molecular, cellular and systems understanding(s) of psychosis and promoting novel treatment development. Molecular hypotheses of schizophrenia exist but have not heretofore been correct. Although current understandings of the biological basis of psychosis remain hypothetical, it is clear that current hypotheses are more directly based on brain biochemistry, structure and function. In this context the use of traditional and experimental treatments for schizophrenia are reviewed, drugs which might enhance cognition in schizophrenia as well as antipsychotic drugs.

Novel treatment opportunities in Graves’ orbitopathy

2014 ◽  
Vol 155 (33) ◽  
pp. 1295-1300
Author(s):  
Annamária Erdei ◽  
Annamária Gazdag ◽  
Miklós Bodor ◽  
Eszter Berta ◽  
Mónika Katkó ◽  
...  
Keyword(s):  
Clinical Experience ◽  
Clinical Course ◽  
Treatment Protocol ◽  
Treatment Modalities ◽  
Graves Disease ◽  
Novel Treatment ◽  
Graves Orbitopathy ◽  
Cd20 Antibody ◽  
Anti Cd20 ◽  
Novel Therapeutic

Graves’ orbitopathy is the most common extrathyroidal manifestation of Graves’ disease. Up to now, curative treatment modalities for the most severe sight-threatening cases have not been developed. Here the authors summarize the treatment protocol of Graves’ orbitopathy and review novel therapeutic options. They review the literature on this topic and present their own clinical experience. The authors point out that anti-CD20 antibody could positively influence the clinical course of Graves’ orbitopathy. Selenium is efficient in mild cases. Further prospective investigations are warranted. Orv. Hetil., 2014, 155(33), 1295–1300.

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