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Journal of Alzheimer's Disease : JAD 2019Although Alzheimer's disease (AD) is the world's leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved... (Review)
Review
Although Alzheimer's disease (AD) is the world's leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved in more than a decade. Many clinical trials of single-agent therapies have failed to affect disease progression or symptoms compared with placebo. The complex pathophysiology of AD may necessitate combination treatments rather than monotherapy. The goal of this narrative literature review is to describe types of combination therapy, review the current clinical evidence for combination therapy regimens (both symptomatic and disease-modifying) in the treatment of AD, describe innovative clinical trial study designs that may be effective in testing combination therapy, and discuss the regulatory and drug development landscape for combination therapy. Successful combination therapies in other complex disorders, such as human immunodeficiency virus, may provide useful examples of a potential path forward for AD treatment.
Topics: Alzheimer Disease; Drug Therapy, Combination; Humans; Nootropic Agents
PubMed: 30689575
DOI: 10.3233/JAD-180766 -
The Psychiatric Clinics of North America Sep 2014Obsessive-compulsive disorder (OCD) affects up to 2.5% of the population of the course of a lifetime and produces substantial morbidity. Approximately 70% of patients... (Review)
Review
Obsessive-compulsive disorder (OCD) affects up to 2.5% of the population of the course of a lifetime and produces substantial morbidity. Approximately 70% of patients can experience significant symptomatic relief with appropriate pharmacotherapy. Selective serotonin reuptake inhibitors are the mainstay of pharmacological treatment. These drugs are typically used at higher doses and for longer periods than in depression. Proven second-line treatments include the tricyclic clomipramine and the addition of low-dose neuroleptic medications. OCD refractory to available treatments remains a profound clinical challenge.
Topics: Combined Modality Therapy; Drug Therapy, Combination; Humans; Nonprescription Drugs; Obsessive-Compulsive Disorder; Precision Medicine; Psychotherapy; Psychotropic Drugs
PubMed: 25150568
DOI: 10.1016/j.psc.2014.05.006 -
CNS Drugs Jan 2021The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure... (Review)
Review
The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics. A systematic search of the PubMed database was conducted to identify physical and formulation properties and pharmacokinetic data of commercially available LAI antipsychotics, including flupentixol decanoate, fluphenazine decanoate, haloperidol decanoate, zuclopenthixol decanoate, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate, risperidone microspheres, and risperidone polymeric microspheres. Additional information was obtained from package inserts and product monographs. Relevant data on drug properties, administration details, pharmacokinetic parameters, and oral dose equivalencies of LAI antipsychotics are summarized. Based on our analysis, formulation characteristics (e.g., vehicle medium) and administration characteristics (e.g., injection site) can affect rate of absorption and adverse effects and may factor into whether oral supplementation or an additional injection is needed. Dose adjustments may be necessary based on potential drug-drug interactions, and approximate dose equivalence with oral formulations can help inform titration when switching from oral to LAI formulations. Clinicians administering LAI antipsychotics should consider these formulation and pharmacokinetic factors to maximize clinical impact and to adjust to an individual patient's needs and treatment goals.
Topics: Administration, Oral; Antipsychotic Agents; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Injections; Schizophrenia
PubMed: 33507525
DOI: 10.1007/s40263-020-00779-5 -
Drug Delivery Dec 2022Chemotherapy drugs have been used for a long time in the treatment of cancer, but serious side effects are caused by the inability of the drug to be solely delivered to... (Review)
Review
Chemotherapy drugs have been used for a long time in the treatment of cancer, but serious side effects are caused by the inability of the drug to be solely delivered to the tumor when treating cancer with chemotherapy. Natural products have attracted more and more attention due to the antitumor effect in multiple ways, abundant resources and less side effects. Therefore, the combination of natural active ingredients and chemotherapy drugs may be an effective antitumor strategy, which can inhibit the growth of tumor and multidrug resistance, reduce side effects of chemotherapy drugs. Nano-drug co-delivery system (NDCDS) can play an important role in the combination of natural active ingredients and chemotherapy drugs. This review provides a comprehensive summary of the research status and application prospect of nano-delivery strategies for the combination of natural active ingredients and chemotherapy drugs, aiming to provide a basis for the development of anti-tumor drugs.
Topics: Antineoplastic Agents; Drug Delivery Systems; Humans; Nanoparticle Drug Delivery System; Nanoparticles; Neoplasms
PubMed: 35815678
DOI: 10.1080/10717544.2022.2094498 -
JAMA Network Open Jun 2020Substance use disorders (SUDs) represent a pressing public health concern. Combined behavioral and pharmacological interventions are considered best practices for... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Substance use disorders (SUDs) represent a pressing public health concern. Combined behavioral and pharmacological interventions are considered best practices for addiction. Cognitive behavioral therapy (CBT) is a first-line intervention, yet the superiority of CBT compared with other behavioral treatments when combined with pharmacotherapy remains unclear. An understanding of the effects of combined CBT and pharmacotherapy will inform best-practice guidelines for treatment of SUD.
OBJECTIVE
To conduct a meta-analysis of the published literature on combined CBT and pharmacotherapy for adult alcohol use disorder (AUD) or other SUDs.
DATA SOURCES
PubMed, Cochrane Register, MEDLINE, PsychINFO, and Embase databases from January 1, 1990, through July 31, 2019, were searched. Keywords were specified in 3 categories: treatment type, outcome type, and study design. Collected data were analyzed through September 30, 2019.
STUDY SELECTION
Two independent raters reviewed abstracts and full-text articles. English language articles describing randomized clinical trials examining CBT in combination with pharmacotherapy for AUD and SUD were included.
DATA EXTRACTION AND SYNTHESIS
Inverse-variance weighted, random-effects estimates of effect size were pooled into 3 clinically informative subgroups: (1) CBT plus pharmacotherapy compared with usual care plus pharmacotherapy, (2) CBT plus pharmacotherapy compared with another specific therapy plus pharmacotherapy, and (3) CBT added to usual care and pharmacotherapy compared with usual care and pharmacotherapy alone. Sensitivity analyses included assessment of study quality, pooled effect size heterogeneity, publication bias, and primary substance moderator effects.
MAIN OUTCOMES AND MEASURES
Substance use frequency and quantity outcomes after treatment and during follow-up were examined.
RESULTS
The sample included 62 effect sizes from 30 unique randomized clinical trials that examined CBT in combination with some form of pharmacotherapy for AUD and SUD. The primary substances targeted in the clinical trial sample were alcohol (15 [50%]), followed by cocaine (7 [23%]) and opioids (6 [20%]). The mean (SD) age of the patient sample was 39 (6) years, with a mean (SD) of 28% (12%) female participants per study. The following pharmacotherapies were used: naltrexone hydrochloride and/or acamprosate calcium (26 of 62 effect sizes [42%]), methadone hydrochloride or combined buprenorphine hydrochloride and naltrexone (11 of 62 [18%]), disulfiram (5 of 62 [8%]), and another pharmacotherapy or mixture of pharmacotherapies (20 of 62 [32%]). Random-effects pooled estimates showed a benefit associated with combined CBT and pharmacotherapy over usual care (g range,â0.18-0.28; kâ=â9). However, CBT did not perform better than another specific therapy, and evidence for the addition of CBT as an add-on to combined usual care and pharmacotherapy was mixed. Moderator analysis showed variability in effect direction and magnitude by primary drug target.
CONCLUSIONS AND RELEVANCE
The present study supports the efficacy of combined CBT and pharmacotherapy compared with usual care and pharmacotherapy. Cognitive behavioral therapy did not perform better than another evidence-based modality (eg, motivational enhancement therapy, contingency management) in this context or as an add-on to combined usual care and pharmacotherapy. These findings suggest that best practices in addiction treatment should include pharmacotherapy plus CBT or another evidence-based therapy, rather than usual clinical management or nonspecific counseling services.
Topics: Adult; Cognitive Behavioral Therapy; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Substance-Related Disorders; Treatment Outcome
PubMed: 32558914
DOI: 10.1001/jamanetworkopen.2020.8279 -
Deutsches Arzteblatt International Jun 2020Asthma is a chronic inflammatory airway disease that usually causes variable airway obstruction. It affects 5-10% of the German population. (Review)
Review
BACKGROUND
Asthma is a chronic inflammatory airway disease that usually causes variable airway obstruction. It affects 5-10% of the German population.
METHODS
This review is based on relevant publications retrieved by a selective search, as well as on national and international guidelines on the treatment of mild and moderate asthma in adults.
RESULTS
The goal of treatment is to attain optimal asthma control with a minimal risk of exacerbations and mortality, loss of pulmonary function, and drug side effects. This can be achieved with a combination of pharmacotherapy and non-drug treatment including patient education, exercise, smoking cessation, and rehabilitation. Pharmacohterapy is based on inhaled corticosteroids (ICS) and bronchodilators. It is recommended that mild asthma should be treated only when needed, either with a fixed combination of ICS and formoterol or with short-acting bronchodilators. For moderate asthma, maintenance treatment is recommended, with an inhaled fixed combinations of ICS and long-acting beta-mimetics, possibly supplemented with longacting anticholinergic agents. Allergen immunotherapy, i.e., desensitization treatment, should be considered if the allergic component of asthma is well documented and the patient is not suffering from uncontrolled asthma. Asthma control should be monitored at regular intervals, and the treatment should be adapted accordingly.
CONCLUSION
The treatment of asthma in adults should be individually tailored, with anti-inflammatory treatment as its main component.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Drug Therapy, Combination; Formoterol Fumarate; Humans
PubMed: 32885783
DOI: 10.3238/arztebl.2020.0434 -
Therapeutic Delivery Jul 2017Pulmonary drug delivery is relatively complex because the respiratory tract has evolved defense mechanisms to keep inhaled drug particles out of the lungs and to remove... (Review)
Review
Pulmonary drug delivery is relatively complex because the respiratory tract has evolved defense mechanisms to keep inhaled drug particles out of the lungs and to remove or inactivate them once deposited. In addition to these mechanical, chemical and immunological barriers, pulmonary drug delivery is adversely affected by the behavioral barriers of poor adherence and poor inhaler technique. Strategies to mitigate the effects of these barriers include use of inhaler devices and formulations that deliver drug to the lungs efficiently, appropriate inhaler technique and improved education of patients. Owing to the advantages offered by the pulmonary route, the challenges that the route poses are worth addressing, and if successfully addressed, the pulmonary route offers huge opportunities, often fulfilling unmet clinical needs.
Topics: Administration, Inhalation; Drug Delivery Systems; Humans; Lung; Nebulizers and Vaporizers; Respiratory Tract Diseases
PubMed: 28730933
DOI: 10.4155/tde-2017-0037 -
Molecules (Basel, Switzerland) Mar 2018The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain,... (Review)
Review
The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients' age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non-steroidal anti-inflammatory drugs (NSAIDs) applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti-inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline) act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.
Topics: Administration, Cutaneous; Administration, Topical; Analgesics; Analgesics, Opioid; Animals; Humans; Pain
PubMed: 29562618
DOI: 10.3390/molecules23030681 -
Journal of Child and Adolescent... Jun 2019In the last 15 years, there has been a marked increase in the number of available stimulant formulations with the emphasis on long-acting formulations, and the... (Review)
Review
In the last 15 years, there has been a marked increase in the number of available stimulant formulations with the emphasis on long-acting formulations, and the introduction of several novel delivery systems such as orally dissolving tablets, chewable tablets, extended-release liquid formulations, transdermal patches, and novel "beaded" technology. All of these formulations involve changes to the pharmaceutical delivery systems of the two existing compounds most commonly employed to treat attention-deficit/hyperactivity disorder (ADHD), amphetamine (AMP) and methylphenidate (MPH). In addition to these new formulations, our knowledge about the individual differences in response has advanced and contributes to a more nuanced approach to treatment. The clinician can now make increasingly informed choices about these formulations and more effectively individualize treatment in a way that had not been possible before. In the absence of reliable biomarkers that can predict individualized response to ADHD treatment, clinical knowledge about differences in MPH and AMP pharmacodynamics, pharmacokinetics, and metabolism can be utilized to personalize treatment and optimize response. Different properties of these new formulations (delivery modality, onset of action, duration of response, safety, and tolerability) will most likely weigh heavily into the clinician's choice of formulation. To manage the broad range of options that are now available, clinicians should familiarize themselves in each of these categories for both stimulant compounds. This review is meant to serve as an update and a guide to newer stimulant formulations and includes a brief review of ADHD and stimulant properties.
Topics: Amphetamine; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Drug Administration Schedule; Humans; Methylphenidate; Tablets
PubMed: 31038360
DOI: 10.1089/cap.2019.0043 -
Drug Delivery Dec 2022Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g.... (Review)
Review
Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.
Topics: Administration, Oral; Alginates; Chitosan; Colitis, Ulcerative; Drug Carriers; Drug Delivery Systems; Humans; Nanoparticles; Pharmaceutical Preparations
PubMed: 35384787
DOI: 10.1080/10717544.2022.2058646