A 28-Year-Old Man with Obsessive-Compulsive Disorder, Post-Traumatic Stress Disorder, and Dissociative Identity Disorder Responding to Aripiprazole Augmentation of Clomipramine Combined with Psychoeducation and Exposure and Response Prevention.

BACKGROUND We report the case of a 28-year-old man with comorbidity of OCD, PTSD, and DID responding to aripiprazole augmentation of clomipramine combined with psychoeducation and exposure and response prevention (ERP). CASE REPORT A 28-year-old, well-educated man presented with depression, obsessive thoughts, behavioral impulsivity, and suicidal thoughts/behavior. He was known to be stubborn and sensitive to criticism since childhood. The obsessive thoughts and compulsive behaviors also started at an early age. He had 4 past psychiatric hospitalizations, mostly for dissociative episodes and bizarre behaviors, complicated with significant anxiety and distress from traumatic experiences during doctoral study. He had no-to-minimal responses to various psychotropics and traditional Chinese medicine. A thorough assessment showed he met the diagnostic criteria for OCD, PTSD, and DID. He was then treated with clomipramine in combination with aripiprazole, plus psychoeducation and exposure and response prevention (ERP). His anxiety and irritability significantly improved within 2 months and his obsessive thoughts faded away. At 6-month follow-up, the patient achieved clinical remission. One year later, he remained stable and reported having a normal life. CONCLUSIONS The case illustrates both how impairing the comorbidity of OCD, PTSD, and DID can be and how concurrent use of tricyclic antidepressant (TCA) clomipramine and partial dopamine agonist aripiprazole, together with psychoeducation and ERP, can improve outcomes when other treatment choices fail to be effective.

Efficacy of transcutaneous electrical acupoint stimulation for patients with first-episode schizophrenia: An 8-week, preliminary, randomized controlled trial.

Combination therapy with antipsychotics has been investigated for treating schizophrenia, and has shown clear advantages among non-invasive therapies. Transcutaneous electrical acupoint stimulation (TEAS) is a novel non-invasive treatment with definite efficacy in treating mental disorders. The current study aimed to investigate the efficacy of TEAS in further improving the psychotic symptoms in patients with first-episode schizophrenia (FES) being treated with pharmacological drugs. This 8-week, preliminary, sham-controlled, randomized clinical trial was conducted in patients with FES to compare the efficacy of TEAS and sham TEAS in combination with aripiprazole treatment. The primary outcome was a change in the Positive and Negative Syndrome Scale (PANSS) score after ending the intervention (Week 8). A total of 49 participants completed the whole treatment cycle. The linear mixed-effects regression for PANSS indicated a significant time × group interaction (F(2, 116)=9.79, p <0.001). The PANSS score differed by 8.77 points (95% CI, -2.07 to -15.47 points; p=.01) between the TEAS group and the sham TEAS group after 8 weeks of treatment; this difference was significant. This study indicates that 8 weeks of TEAS combined with aripiprazole treatment can effectively treat FES. Thus, TEAS is an effective combination therapy to improve the psychiatric symptoms of FES.

Pharmacological treatment strategies for antipsychotic-induced hyperprolactinemia: a systematic review and network meta-analysis.

Antipsychotic-induced hyperprolactinemia (AP-induced HPRL) occurs overall in up to 70% of patients with schizophrenia, which is associated with hypogonadism and sexual dysfunction. We summarized the latest evidence for the benefits of prolactin-lowering drugs. We performed network meta-analyses to summarize the evidence and applied Grading of Recommendations Assessment, Development, and Evaluation frameworks (GRADE) to rate the certainty of evidence, categorize interventions, and present the findings. The search identified 3,022 citations, 31 studies of which with 1999 participants were included in network meta-analysis. All options were not significantly better than placebo among patients with prolactin (PRL) less than 50 ng/ml. However, adjunctive aripiprazole (ARI) (5 mg: MD = -64.26, 95% CI = -87.00 to -41.37; 10 mg: MD = -59.81, 95% CI = -90.10 to -29.76; more than 10 mg: MD = -68.01, 95% CI = -97.12 to -39.72), switching to ARI in titration (MD = -74.80, 95% CI = -134.22 to -15.99) and adjunctive vitamin B6 (MD = -91.84, 95% CI = -165.31 to -17.74) were associated with significant decrease in AP-induced PRL among patients with PRL more than 50 ng/ml with moderated (adjunctive vitamin B6) to high (adjunctive ARI) certainty of evidence. Pharmacological treatment strategies for AP-induced HPRL depends on initial PRL level. No effective strategy was found for patients with AP-induced HPRL less than 50 ng/ml, while adjunctive ARI, switching to ARI in titration and adjunctive high-dose vitamin B6 showed better PRL decrease effect on AP-induced HPRL more than 50 ng/ml.

Cannabidiol for the treatment of autism spectrum disorder: hope or hype?

RATIONALE: Autism spectrum disorder (ASD) is defined as a group of neurodevelopmental disorders whose symptoms include impaired communication and social interaction, restricted and repetitive patterns of behavior, and varying levels of intellectual disability. ASD is observed in early childhood and is one of the most severe chronic childhood disorders in prevalence, morbidity, and impact on society. It is usually accompanied by attention deficit hyperactivity disorder, anxiety, depression, sleep disorders, and epilepsy. The treatment of ASD has low efficacy, possibly because it has a heterogeneous nature, and its neurobiological basis is not clearly understood. Drugs such as risperidone and aripiprazole are the only two drugs available that are recognized by the Food and Drug Administration, primarily for treating the behavioral symptoms of this disorder. These drugs have limited efficacy and a high potential for inducing undesirable effects, compromising treatment adherence. Therefore, there is great interest in exploring the endocannabinoid system, which modulates the activity of other neurotransmitters, has actions in social behavior and seems to be altered in patients with ASD. Thus, cannabidiol (CBD) emerges as a possible strategy for treating ASD symptoms since it has relevant pharmacological actions on the endocannabinoid system and shows promising results in studies related to disorders in the central nervous system. OBJECTIVES: Review the preclinical and clinical data supporting CBD's potential as a treatment for the symptoms and comorbidities associated with ASD, as well as discuss and provide information with the purpose of not trivializing the use of this drug.

Tratamiento del Síndrome Neuropsiquiátrico Diferido por intoxicación con monóxido de carbono con risperidona y oxígeno hiperbárico / Treatment of Delayed Post-Hypoxic Leukoencephalopathy as a complication of carbon monoxide poisoning with risperidone and hyperbaric oxygen therapy

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Update on the Pharmacological Treatment of Tics with Dopamine-Modulating Agents.

More than 40 years of research and clinical practice have proven the effectiveness of dopamine receptor antagonists in the pharmacological treatment of tics. A blockade of the striatal dopamine-D2 receptors is mainly responsible for their tic-reducing effect. A broad spectrum of dopamine-modulating agents, such as typical and atypical antipsychotics, but also dopamine receptor agonists are used with an immanent discord between experts about which of them should be considered as first choice. The present Review outlines the state of the art on pharmacological treatment of tics with dopamine-modulating agents by giving an systematic overview of studies on their effectiveness and a critical discussion of their specific adverse effects. It is considered as an update of a previous review of our research group published in 2013. The Review closes with a description of the current resulting treatment recommendations including the results of a first published revised survey on European expert's prescription preferences. Based on the enormously growing evidence on its effectiveness and safety, aripiprazole currently seems to be the most promising agent in the pharmacological treatment of tics. Furthermore, benzamides (especially tiapride), which are commonly used in Europe, have proven their excellent effectiveness-tolerability profile over decades in clinical practice and are therefore also highly recommended for the treatment of tics. Nevertheless, pharmacological treatment of tics remains an indiviual choice depending on each patient's own specific needs.

Long-Acting Injectable Atypical Antipsychotic Use in Adolescents: An Observational Study.

OBJECTIVES: Although second generation long-acting injectable antipsychotics (SG-LAIAs) have been approved and are widely used in adults, there is limited evidence for the use of long-acting formulations in children and adolescents. Thus, we systematically describe the off-label use of SG-LAIAs in clinical practice in adolescent inpatients. METHODS: All individuals admitted to our Children and Adolescent Inpatient Psychiatry Unit receiving treatment with SG-LAIAs between January 2013 and June 2016 were reviewed. A retrospective analysis of medical records was conducted. Clinical diagnoses were established using DSM-5 criteria. RESULTS: Thirty individuals (53.3% female) out of a total of 1,148 admitted patients (2.6%) were identified. The mean age was 16.3 (SD = 1.3; range: 12.5-17.9).The main diagnoses were psychosis (70%) and disruptive behavior disorders (DBDs) (30%), although comorbidity was frequent (96.6%), especially drug use (55.2%, mostly cannabis). SG-LAIAs used were aripiprazole (40%), risperidone (36.7%), and paliperidone palmitate (23.3%), and the main reasons were a history of low compliance (90%) and/or poor insight (73.3%). A mean improvement of 31.7 (SD = 8.7) between admission and discharge was registered in the Children's Global Assessment Scale (CGAS); no differences were observed between different SG-LAIAs. Although they were generally well tolerated, 23.3% of patients reported mild short-term side effects, which were more frequent with risperidone than with aripiprazole (p = .014). CONCLUSIONS: Our clinical experience suggests that SG-LAIAs may be a safe treatment option during adolescence in inpatients with psychotic disorders, as well as with DBD. No differences were found in CGAS improvement scores between the three SGA-LAIAs used, although patients on risperidone reported more side effects than those on aripiprazole. Further research is needed so as to evaluate safety and effectiveness of SG-LAIAs in this population.

Unbiased screen identifies aripiprazole as a modulator of abundance of the polyglutamine disease protein, ataxin-3.

No disease-modifying treatment exists for the fatal neurodegenerative polyglutamine disease known both as Machado-Joseph disease and spinocerebellar ataxia type 3. As a potential route to therapy, we identified small molecules that reduce levels of the mutant disease protein, ATXN3. Screens of a small molecule collection, including 1250 Food and Drug Administration-approved drugs, in a novel cell-based assay, followed by secondary screens in brain slice cultures from transgenic mice expressing the human disease gene, identified the atypical antipsychotic aripiprazole as one of the hits. Aripiprazole increased longevity in a Drosophila model of Machado-Joseph disease and effectively reduced aggregated ATXN3 species in flies and in brains of transgenic mice treated for 10 days. The aripiprazole-mediated decrease in ATXN3 abundance may reflect a complex response culminating in the modulation of specific components of cellular protein homeostasis. Aripiprazole represents a potentially promising therapeutic drug for Machado-Joseph disease and possibly other neurological proteinopathies.

Agonistas parciales, moduladores bioquímicos con múltiples aplicaciones / Partial agonists: biochemical modulators with multiple applications

En general, los diferentes tratados de farmacología se organizan en torno a una clasificación anatómica-terapéutica-química. Los tratados de «química farmacéutica» suelen organizarse, además, poniendo énfasis en la naturaleza química de los fármacos, así como en los procesos bioquímicos involucrados en su acción. En otras ocasiones, cuando se contempla la fitoterapia desde un punto de vista botánico, como hace la «botánica medicinal», la exposición se realiza mediante un viaje a través de los diferentes taxones que contienen especies con relevancia terapéutica. En cambio, en este artículo de revisión se va a hablar de un grupo de fármacos que, desde los enfoques expositivos anteriores, no tienen mucho que ver pero que, sin embargo, poseen mecanismos farmacodinámicos muy similares, a pesar de que actúen sobre diferentes receptores. Se trata de los agonistas (y antagonistas) parciales. Lógicamente no se revisarán todos en este artículo, sino aquellos que al autor le han parecido más curiosos e interesantes para ilustrar su relación mutua en cuanto al funcionamiento farmacodinámico: vareniclina, buprenorfina, diazepinonas, aripiprazol, memantina. Este es el objetivo de este artículo: la revisión de un grupo de fármacos desde un punto de vista novedoso, como es su mecanismo de acción farmacodinámico común. Entre las conclusiones, está la indicación de este tipo de fármacos cuando se va a intervenir en sistemas bioquímicos y fisiológicos tan complicados que las funciones a tratar no deben ni inhibirse ni potenciarse desmedidamente, sino simplemente modularse. Este es el caso de muchas dolencias que afectan al sistema nervioso (AU)

In general the different treatises of pharmacology are organised around an anatomical-therapeutic-chemical classification. Treatises about «medicinal chemistry» are organised, not only around this, but also emphasise the chemical nature of the drugs, as well as the biochemical processes involved in their action. Furthermore, when herbal medicine is contemplated from a botanical point of view, as does the «medical botany», exposure is performed by a journey through the different taxa containing species with therapeutic relevance. Nevertheless, in this review article a group of drugs is discussed that, from the previous points of view, do not have anything to do with each other. However, they have very similar pharmacodynamic mechanisms, despite acting on different receptors. These are partial agonists (and antagonists). Obviously not all of these will be reviewed in this article, but those more interesting to illustrate their relationship in terms of pharmacodynamic performance: varenicline, buprenorphine, diazepinones, aripiprazole, memantine. This is the purpose of this article: A review of a group of drugs from a novel point of view, such as their common pharmacodynamic mechanism of action. Among the conclusions, is the indication of these drugs to intervene in such complicated biochemical and physiological systems that functions to be treated should neither be inhibited nor enhanced, but simply modulated. This is the case of many diseases that affect the nervous system (AU)

Catatonia secondary to synthetic cannabinoid use in two patients with no previous psychosis.

BACKGROUND AND OBJECTIVES: Synthetic cannabinoids (SC) have become widely abused as recreational drugs, and are now known to carry risk of severe mental and physical health effects. Catatonia, spanning the gamut from motor retardation to agitation, can constitute a psychiatric emergency for which benzodiazepines are the mainstay of treatment. The purpose of this paper is to report on an unusual occurrence of catatonia in the context of synthetic cannabinoid use, and a discussion of treatment options that have been helpful as adjuncts to benzodiazepines. METHODS: We present two cases of catatonia occurring in context of SC use. The first patient was using SC quasi-daily for 18 months. The second patient used a large quantity over a two-week period. Both patients were admitted to our emergency center with catatonia and no overt psychosis or mood symptoms. RESULTS: The absence of pre-existing mood or psychotic disorder and the severity of catatonic symptoms separates these cases from other cases reported in the literature. Additionally, pharmacological management targeting gamma-aminobutyric acid (GABA) and serotonin neurotransmitter systems were used, specifically aripiprazole and valproic acid, supplementing benzodiazepine administration; these were needed for optimal symptom control. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The above-reported cases are highly significant because of the severity of catatonic symptoms requiring inpatient hospitalization, the potential for rapid and severe decompensation with catatonia, and the atypical/unexpected development of catatonia with SC use.