- [Current and future pharmacotherapy of severe psychiatric disorders]. [Journal Article]
- CLCas Lek Cesk 2018; 157(2):96-100
- Despite of tremendous development in CNS research, current treatment is suboptimal especially in severe mental disorders. In medicine, there are two main methods of improving the healthcare provided:...
Despite of tremendous development in CNS research, current treatment is suboptimal especially in severe mental disorders. In medicine, there are two main methods of improving the healthcare provided: seeking new treatment procedures and perfecting (optimizing) the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring, but also implementation of general trends into the clinical practice. New pharmacological options include drugs aimed at other than monoaminergic systems and old drugs used before the psychopharmacological era. In pharmacoresistant depression promising options include switch to new multimodal/multifunctional antidepressants, augmentation with new atypical antipsychotics (cariprazine and brexpiprazole) and adjunctive treatment with anti-inflammatory and anti-apoptotic agents and nutraceuticals. Ketamine, opioids and psychedelics are in different phases of clinical testing. Recent advances in technology and emerging knowledge about the dysfunctional brain circuits and neuroplasticity have led to the development of different new neuromodulation techniques usually used as add-on therapy. In schizophrenia the cornerstone of the current treatment is still antipsychotic medications. In addition to aripiprazole two new partial dopamine agonists, brexpiprazole and cariprazine are now available. Especially the group of partial dopamine agonists is in the center of interest. Due to severe consequences of partial adherence, new formulations of long-acting injections of the second-generation antipsychotics with longer interval of application have been developed (3- month paliperidone palmitate). New treatment options not yet available include cannabidiol, glutamate modulators and nicotine receptors agonists.
- Novel Pharmacotherapeutic Approaches In Treatment Of Alcohol Addiction. [Journal Article]
- CDCurr Drug Targets 2018 May 22
- In the past two decades, the search for novel pharmacotherapies to treat alcohol addiction been a global endeavour. This has resulted in several drugs that have been approved and successfully markete...
In the past two decades, the search for novel pharmacotherapies to treat alcohol addiction been a global endeavour. This has resulted in several drugs that have been approved and successfully marketed for public use while some are still in the testing phase. These pharmacological agents, though effective for the treatment of alcoholism, are not without shortcomings; such as abuse potential, serious mental and physical adverse effects, interaction with alcohol and also poor metabolism and excretion. As more is being understood about the neurobiology of alcohol addiction as well as the unique pharmacological action of these drugs, new agents are evaluated for potential benefits when used as a adjunct in combination therapy. This review article summarizes the novel pharmacotherapeutic approaches in treatment of alcohol addiction by focusing on the drugs, which includes neramexane, gabapentin, baclofen, aripiprazole, nalmafene, and quetiapine.
- Pharmacogenetic testing of CYP2D6 in patients with aripiprazole-related extrapyramidal symptoms: a case-control study. [Journal Article]
- PMPer Med 2008; 5(4):361-365
- Aripiprazole is primarily metabolized by the polymorphic CYP2D6. We genotyped four children (aged 6-15 years) who had developed extrapyramidal symptoms within 1 week of aripiprazole initiation or dos...
Aripiprazole is primarily metabolized by the polymorphic CYP2D6. We genotyped four children (aged 6-15 years) who had developed extrapyramidal symptoms within 1 week of aripiprazole initiation or dose titration, and four matched children without extrapyramidal symptoms. All of the four children who developed extrapyramidal symptoms with aripiprazole had a dysfunctional CYP2D6 enzyme, based on genotype, and were categorized as either intermediate metabolizers (n = 2) or poor metabolizers (n = 2). By contrast, only two children from the control group had either of these phenotypes, and both were intermediate metabolizers. Children with CYP2D6 abnormalities may be at higher risk of aripiprazole-induced adverse drug reactions.
- Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions. [Journal Article]
- BCBreast Cancer Res 2018 May 19; 20(1):42
- CONCLUSIONS: Hyperprolactinemia-inducing antipsychotics instigate precancerous cells to progress to cancer via JAK/STAT5 to suppress the apoptosis anticancer barrier, and these cancer-promoting effects can be prevented by prophylactic anti-JAK/STAT5 treatment. This preclinical work exposes a potential breast cancer risk from hyperprolactinemia-inducing antipsychotics in certain patients and suggests a chemoprevention regime that is relatively easy to implement compared to the standard 5-year anti-estrogenic treatment in women who have or likely have already developed precancerous lesions while also requiring hyperprolactinemia-inducing antipsychotics.
- Safety and efficacy from a 6-week double-blind study and a 52-week open-label extension of aripiprazole in adolescents with schizophrenia in Japan. [Journal Article]
- PCPsychiatry Clin Neurosci 2018 May 18
- CONCLUSIONS: These study results suggested that aripiprazole would be safe and well tolerated in both short- and long-term treatment for adolescents with schizophrenia in Japan. This article is protected by copyright. All rights reserved.
- Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate. [Journal Article]
- HPHum Psychopharmacol 2018 May 15; :e2658
- CONCLUSIONS: Early administration and longer duration of ARI or PAL treatments could play a significant role in improving global functioning of patients with schizophrenia and schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations.
- Influences of the T102C polymorphism in the 5-HT2A receptor gene on the five-factor model of Positive and Negative Syndrome Scale and treatment response to aripiprazole in patients with acute schizophrenia. [Letter]
- PRPsychiatry Res 2018 May 08; 265:244-245
- Movement Disorders Associated With Antipsychotic Medication in People With Schizophrenia: An Overview of Cochrane Reviews and Meta-Analysis. [Journal Article]
- CJCan J Psychiatry 2018 Jan 01; :706743718777392
- Movement disorders associated with antipsychotic medications are relatively common, stigmatising, and potentially disabling. Their prevalence in people with psychosis who are prescribed second-genera...
Movement disorders associated with antipsychotic medications are relatively common, stigmatising, and potentially disabling. Their prevalence in people with psychosis who are prescribed second-generation antipsychotics (SGAs) is uncertain, as is their level of recognition by clinicinas. We conducted meta-analyses of randomised controlled trials included in the Cochrane Database of Systematic Reviews on schizophrenia and schizophrenia-like psychoses to estimate the prevalence of new-onset dystonia, akathisia, parkinsonism, and tremor with SGAs (amisulpride, asenapine, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, L-sulpiride, and ziprasidone) approved in Canada and the UK, comparing them with haloperidol and chlorpromazine. We used a random effects model because of the heterogeneity between-studies in drug dosage and method of ascertainment of movement disorders. Our systematic search yielded 37 Cochrane systematic reviews (28 for SGAs), which generated 316 informative randomised controlled trials (243 for SGAs). With respect to SGAs, prevalence estimates ranged from 1.4% (quetiapine) to 15.3% (L-sulpiride) for dystonia, 3.3% (paliperidone) to 16.4% (L-sulpiride) for akathisia, 2.4% (asenapine) to 29.3% (L-sulpiride) for parkinsonism, and 0.2% (clozapine) to 28.2% (L-sulpiride) for tremor. Prevalence estimates were not influenced by treatment duration, the use of a flexible or fixed dosing scheme, or whether studies used validated instruments for the screening/rating of movement disorders. Overall, we found high overlap on the prevalence of new-onset movement disorders across different SGAs precribed for established psychoses. Variations in prevalence figures across antipsychotic medications were observed for the different movement disorders. Differences in pharmacological properties, such as for the dopamine D2 R association rate and serotonin 5-HT2A antagonism, could contribute to this variation.
- Mixed states in bipolar and major depressive disorders: systematic review and quality appraisal of guidelines. [Review]
- APActa Psychiatr Scand 2018 May 13
- CONCLUSIONS: The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.
New Search Next
- Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands. [Journal Article]
- CCChem Cent J 2018 May 11; 12(1):55
- A series of azinesulfonamide derivatives of long-chain arylpiperazines with variable-length alkylene spacers between sulfonamide and 4-arylpiperazine moiety is designed, synthesized, and biologically...
A series of azinesulfonamide derivatives of long-chain arylpiperazines with variable-length alkylene spacers between sulfonamide and 4-arylpiperazine moiety is designed, synthesized, and biologically evaluated. In vitro methods are used to determine their affinity for serotonin 5-HT1A, 5-HT6, 5-HT7, and dopamine D2 receptors. X-ray analysis, two-dimensional NMR conformational studies, and docking into the 5-HT1A and 5-HT7 receptor models are then conducted to investigate the conformational preferences of selected serotonin receptor ligands in different environments. The bent conformation of tetramethylene derivatives is found in a solid state, in dimethyl sulfoxide, and as a global energy minimum during conformational analysis in a simulated water environment. Furthermore, ligand geometry in top-scored complexes is also bent, with one torsion angle in the spacer (τ2) in synclinal conformation. Molecular docking studies indicate the role of halogen bonding in complexes of the most potent ligands and target receptors.