Current Medicinal Chemistry - Volume 25, Issue 41, 2018

Background: Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). Since response is often inadequate, in recent years researchers investigated whether combining CBT and SRIs, either ab initio or sequentially, results in a greater reduction of obsessivecompulsive symptoms. Objective: The aims of the present paper are to assess if combination treatment seems adding benefits as compared to either monotherapy alone and if sequential strategies may be effective in converting partial or non responders to a first-line treatment into responders. Method: We reviewed available literature on pharmacological and CBT combination and sequential treatments for adult and pediatric OCD patients and then we conducted a separate analysis for studies concerning these two promising strategies. Search results included openlabel trials and randomized controlled trials (RCTs). Results: We identified ten controlled studies assessing the efficacy of combination treatments ab initio versus CBT alone and six evaluating combination strategies ab initio versus medications alone. Eleven studies, only two of which were RCTs, have been published on sequential treatments. The combination ab initio of CBT and SRIs has not been found to be clearly superior to either monotherapy alone in most studies conducted on this topic, except for patients with severe depression who might benefit more from the combination versus only CBT. A sequential administration of CBT after medications has been found useful in promoting remission in patients who partially responded to drugs and in promoting response in resistant patients. Conclusion: OCD patients with comorbid major depression should receive medication firstly, eventually associated with CBT; for all remaining patients there is clear evidence from the literature of no additive benefits of combining ab initio CBT and medication. Therefore, the routine use of a combination approach in all adult patients affected by OCD is not supported by the literature. The available evidence supports the effectiveness of the sequential addition of CBT to SRIs.

Background: Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients. Objective: The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD. Method: We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/ remission rates (according to the YBOCS). Results: We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin- dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies). Conclusion: Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).

Obsessive-compulsive disorder is a heterogeneous and debilitating condition, characterized by intrusive thoughts and compulsive repetition. Animal models of OCD are important tools that have the potential to contribute significantly to our understanding of the condition. Although there is consensus that pre-clinical models are valuable in elucidating the underlying neurobiology in psychiatric disorders, the current paper attempts to prompt ideas on how interpretation of animal behavior can be expanded upon to more effectively converge with the human disorder. Successful outcomes in psychopharmacology involve rational design and synthesis of novel compounds and their testing in well-designed animal models. As part of a special journal issue on OCD, this paper will 1) review the psychobehavioral aspects of OCD that are of importance on how the above ideas can be articulated, 2) briefly elaborate on general issues that are important for the development of animal models of OCD, with a particular focus on the role and importance of context, 3) propose why translational progress may often be less than ideal, 4) highlight some of the significant contributions afforded by animal models to advance understanding, and 5) conclude by identifying novel behavioral constructs for future investigations that may contribute to the face, predictive and construct validity of OCD animal models. We base these targets on an integrative approach to face and construct validity, and note that the issue of treatment-resistance in the clinical context should receive attention in current animal models of OCD.

Many patients with OCD respond partially or not at all to standard medications and cognitive behavioral therapy approaches, making alternate treatments necessary. We review the preliminary evidence that exists in support of the use of stimulants, high-dose caffeine, opiates, memantine, ondansetron, ketamine, and transcranial magnetic stimulation in some patients with OCD. Although limited by small or modest sample sizes, open-label study designs, and brief follow-up periods, studies suggest that each of these strategies can help some patients who have inadequately responded to first-line treatments. The existing data and the unmet needs of OCD patients justify research attention to further test these treatments' safety and efficacy. Previously untested drugs also deserve attention, especially as recent research has suggested new possible contributors to OCD pathophysiology. Similarly, psychotherapeutic interventions beyond CBT should be investigated, and treatments with preliminary evidence in OCD, including Acceptance Commitment Therapy, Danger Ideation Reduction Therapy, and technology-enabled interventions like computerized CBT and Virtual Reality Exposure Therapy, should be carefully tested.

Many of the currently available treatments for obsessive-compulsive and related disorders (OCRDs) such as pharmacotherapy augmentation strategies, partial hospitalization programs, deep brain stimulation, and neurosurgery are efficacious for individuals suffering from more severe forms of these conditions. Unfortunately, the application of these treatments in milder forms of illness and subclinical samples, which affect a substantial portion of the population, is not justifiable by their costs (e.g. cognitivebehavioral therapy) and/or potential for side effects (serotonin-reuptake inhibitors associated sexual side effects). As such, there is an urgent need to develop simple yet effective treatments, such as modifiable lifestyle interventions, that can be employed on a broader scale. Here, we review the current state of evidence that supports or refutes the efficacy of lifestyle approaches for OCRDs. We focus on dimensions of lifestyle that are deemed important for cardiovascular diseases; namely, physical activity, stress, sleep, diet and eating behaviors, alcohol consumption, and smoking. Despite the relative scarcity of welldesigned randomized controlled trials targeting unhealthy life styles in OCRDs, we found meditation-based therapies and interventions focusing on eliminating sedentarism to be promising approaches. In the future, these strategies may represent valid alternative for subjects with subthreshold symptoms or at risk for OCRDs or other “compulsive” disorders.

Obsessive-Compulsive Disorder (OCD) is a highly disabling condition with early onset and chronic course in most of the affected patients. In addition, OCD may show high comorbidity and suicide attempt rates, which worsen the overall burden of the disease for patients and their caregivers. First-line treatments for OCD consist of pro-serotonergic compounds and cognitive-behavioral therapy. Nonetheless, many patients show only limited benefit from such interventions and require additional “next-step” interventions, including augmentative antipsychotics and glutamate-modulating agents. Based on the knowledge about altered neurocircuitry in OCD, brain stimulation techniques, including transcranial magnetic and electrical stimulations (TMS and tDCS) and deep brain stimulation (DBS), have been increasingly investigated over the last decade, revealing positive results for otherwise intractable and treatment-refractory patients. Available evidence in the field is in continuous evolution and professionals actively involved in the management of OCD patients, psychiatrists in particular, need to be updated about latest developments. Through the analysis of controlled studies, meta-analyses, and International treatment guidelines, the present article is aimed at providing the state of the art on the use of brain stimulation techniques for the treatment of OCD.

Background: Obsessive-compulsive disorder (OCD) symptoms within the context of a bipolar disorder (BD) have been described since the 19th century. Interestingly, the existence of a relevant overlap between the aforementioned psychiatric syndromes has been confirmed by a number of recent epidemiological and family studies. Aims: The aim of the present paper is to review the clinical features and the therapeutic implications of the OCD-BD comorbidity. Discussion: In the last two decades, the frequent association between OCD and BD has been earning a growing interest given its relevant nosological and therapeutic implications. Usually patients suffering from OCD-BD comorbidity show a peculiar clinical course, characterized by a larger number of concomitant depressive episodes and episodic course. In these cases, the treatment with antidepressants is more likely to elicit hypomanic or manic switches, while mood stabilizers significantly improve the overall clinical picture. Moreover, OCD-BD patients are frequently comorbid with a number of other psychiatric disorders, in particular anxiety disorders, social phobia, and different substance abuses, such as alcohol, nicotine, caffeine and sedatives. Conclusions: BD-OCD comorbidity needs further investigations in order to provide more solid evidences to give patients a more precise clinical diagnosis and a more targeted therapeutic approach.

Background: In the last decades the pharmacological treatment of obsessivecompulsive disorder (OCD) has been significantly promoted by the effectiveness of selective serotonin (5-HT) reuptake inhibitors (SSRIs) and the subsequent development of the 5-HT hypothesis of OCD. However, since a large majority of patients (between 40% and 60 %) do not respond to SSRIs or strategies based on the modulation of the 5-HT system, it is now essential to search for other possible therapeutic targets. Aims: The aim of this paper was to review current literature through a PubMed and Google Scholar search of novel hypotheses and related compounds for the treatment of OCD, with a special focus on the glutammate and the immune systems. Discussion: The literature indicates that glutamate, the main excitatory neurotransmitter, might play an important role in the pathophysiology of OCD. In addition, a series of clinical studies also supports the potential efficacy of drugs modulating the glutamate system. The role of the immune system alterations in OCD in both children and adults needs to be more deeply elucidated. In children, a subtype of OCD has been widely described resulting from infections driven by group A streptococcus β-hemolitic and belonging to the so-called "pediatric autoimmune neuropsychiatric disorders associated with streptococcus" (PANDAS). In adults, available findings are meager and controversial, although interesting. Conclusion: The glutamate and the immune systems represent two intriguing topics of research that hold promise for the development of open novel treatment strategies in OCD.

In this review, we report the functionalization of textiles composed of nanoscale reactive materials in the treatment of wounds and skin diseases such as acne. In view of the growing demand for high-quality textiles, much research is focused on the creation of antimicrobial finishings for fabrics, in order to protect customers from pathogenic or odorgenerating microorganisms. We present coatings from inorganic, organic and biochemical nanoparticles (NPs) on surfaces that impart the ability to kill bacteria, avoid biofilm formation and speed up the recovery of wounds. In all three cases, sonochemistry is used for immobilizing the nanoparticles on the surfaces. The Introduction broadly covers the progress of nanotechnology in the fields of wound and skin care. The first section of this review outlines the mechanism of the ultrasound-assisted deposition of nanoparticles on textiles. The coating can be performed by an in-situ process in which the nanoparticles are formed and subsequently thrown onto the surface of the fabrics at a very high speed. This approach was used in depositing metal-oxide NPs such as ZnO, CuO and Zn-CuO or the organic NPs of tannic acid, chitosan, etc. on textiles. In addition, the sonochemical process can be used as a "throwing stone" technique, namely, previously synthesized or commercially purchased NPs can be placed in the sonication bath and sonicated in the presence of the fabric. The collapse of the acoustic bubble in the solution causes the throwing of the immersed commercial NPs onto the textiles. This section will also outline why sonochemical deposition on textiles is considered the best coating technique. The second section will discuss new applications of the sonochemically- coated textiles in killing bacteria, avoiding biofilm formation and more. Two points should be noted: 1) the review will primarily report results obtained at Bar-Ilan University and 2) since for all textiles tested in our experiments (cotton, polyester, nylon, nonwoven) similar results were obtained, the type of textile used in a specific experiment will not be mentioned - textiles will be discussed in general. It is also worth emphasizing that this review concentrates only on the sonochemical coating of textiles, ignoring other deposition techniques.

Alzheimer's and Parkinson's diseases are the most common neurodegenerative diseases worldwide and their incidence is increasing due to the aging population. At the moment, the available therapies are not disease modifying and have several limitations, some of which are discussed in this review. One of the main limitations of these treatments is the low concentration that drugs reach in the central nervous system after systemic administration. Indeed, the presence of biological barriers, particularly the blood-brain barrier (BBB), hinders the effective drug delivery to the brain, reducing the potential benefit coming from the administration of the medication. In this review, the mechanisms of transport across the BBB and new methods to improve drug passage across the BBB are discussed. These methods include non-invasive solutions such as intranasal and intravitreal administration, and the use of nanotechnology solutions based on polymeric carriers when the drug is intravenously injected, orally taken for intestine adsorption or delivered through the dermal mucosa. Also, it provides an analysis of more invasive solutions that include intracranially injected hydrogels and implanted devices for local drug delivery. Efforts in finding new therapeutic drugs blocking neurodegenerative disease progression or reverting their course should be coupled with efforts addressed to efficient drug delivery systems. Hence, new pharmacology discoveries together with advancements in nanotechnologies and biomaterials for regenerative medicine are required to effectively counteract neurodegenerative diseases.

Background: A major global health issue is the existence of chronic wounds. Appropriate diagnosis and treatment is essential to promote wound healing and prevent further complications. Traditional methods for treatment and diagnosis of chronic wounds have shown to be of limited effectiveness. Therefore, there is a need for the development of diagnostic and therapeutic innovations in chronic wound care. Objective: This mini-review aims to provide insight in the current knowledge of the wound healing process and the deficiencies encountered in chronic wounds, which provides a basis for the development of innovations in chronic wound care. Furthermore, promising diagnostic and therapeutic innovations will be highlighted. Methods: Literature was searched for recent articles (=<10 years) describing the current knowledge about the wound healing process and chronic wounds. The most promising diagnostic and therapeutic innovations were gathered from articles published in the past 5 years. Results/Conclusion: Wound healing is a well-organized process consisting of four phases: coagulation, inflammation, proliferation and wound remodelling. Chronic wounds often stagnate in the inflammatory phase and/or experience an impaired proliferative phase. This mini-review has demonstrated that increased knowledge about the processes involved in wound healing has paved the way for the development of new diagnostic tools and treatments for chronic wounds. Increased knowledge about bacterial invasion and infection in has encouraged researchers to develop diagnostic tools to help clinicians detect these phenomena appropriately and in time. Other researchers have shown that they are able to design/extract biochemical compounds that intervene in the disrupted healing processes in chronic wounds.

Background: Composed in a large extent of water and due to their nonadhesiveness, hydrogels found their way to the wound dressing market as materials that provide a moisture environment for healing while being comfortable to the patient. Hydrogels' exploitation is constantly increasing after evidences of their even broader therapeutic potential due to resemblance to dermal tissue and ability to induce partial skin regeneration. The innovation in advanced wound care is further directed to the development of so-called active dressings, where hydrogels are combined with components that enhance the primary purpose of providing a beneficial environment for wound healing. Objective: The objective of this review is to concisely describe the relevance of hydrogel dressings as platforms for delivery of active molecules for improved management of difficult- to-treat wounds. The emphasis is on the most recent advances in development of stimuli- responsive hydrogels, which allow for control over wound healing efficiency in response to different external modalities. Novel strategies for monitoring of the wound status and healing progress based on incorporation of sensor molecules into the hydrogel platforms are also discussed.