Zinc Pharmacotherapy for Elderly Osteoporotic Patients with Zinc Deficiency in a Clinical Setting

Although there have been reported associations between zinc and bone mineral density (BMD), no reports exist on the effect of zinc treatment in osteoporotic patients. Therefore, we investigated the efficacy and safety of zinc pharmacotherapy in Japanese elderly patients. The present investigation included 122 osteoporotic patients with zinc deficiency, aged ≥65 years, who completed 12 months of follow-up. In addition to standard therapy for osteoporosis in a clinical setting, the subjects received oral administration of 25 mg zinc (NOBELZIN^®, an only approved drug for zinc deficiency in Japan) twice a day. BMD and laboratory data including bone turnover markers were collected at 0 (baseline), 6, and 12 months of zinc treatment. Neither serious adverse effects nor incident fractures were seen during the observation period. Serum zinc levels were successfully elevated by zinc administration. BMD increased significantly from baseline at 6 and 12 months of zinc treatment. Percentage changes of serum zinc showed significantly positive associations with those of BMD. Bone formation markers rose markedly from the baseline values, whereas bone resorption markers displayed moderate or no characteristic changes. Additive zinc supplementation may contribute to BMD augmentation ensuing the prevention of fracture occurrence in elderly osteoporotic patients with zinc deficiency.     

Marijuana Neurobiology and Treatment

ABSTRACT

Marijuana is the number one illicit drug of abuse worldwide and a major public health problem, especially in the younger population. The objective of this article is to update and review the state of the science and treatments available for marijuana dependence based on a pre-meeting workshop that was presented at ISAM 2006. At the workshop, several papers were presented addressing the neurobiology and pharmacology of marijuana and treatment approaches, both psychotherapy and medications, for marijuana withdrawal. Medicolegal and ethical issues concerning marijuana medical use were also discussed. Concise summaries of these presentations are incorporated in this article, which is meant to be an updated review of the state of the science. Major advances have been made in understanding the underpinning of marijuana dependence and the role of the CNS cannabinoid system, which is a major area for targeting medications to treat marijuana withdrawal and dependence, as well as other addictions.

Behavioral therapies are efficacious for facilitating abstinence from marijuana. Nefazadone, Marinol, and buspirone are showing early positive signals for efficacy in ameliorating marijuana withdrawal symptoms. Effective psychotherapeutic approaches are available and promising medications studies need to be confirmed in outpatient trials. The next few years looking promising for translational research efforts to make treatment widely accessible to patients with marijuana dependence.     

Nitric oxide in patients with schizophrenia: the relationship with the severity of illness and the antipsychotic treatment

Objectives: Past studies regarding the relationship between nitric oxide and schizophrenia have reported controversial results. Consequently, the aims of this study are i) to analyze the differences in nitric oxide concentration between patients with schizophrenia and healthy controls, ii) to investigate the influence of antipsychotic treatment on nitric oxide, iii) to correlate nitric oxide concentration with severity of illness, and iv) to investigate the relationship between nitric oxide and any personality disorder.

Research design and methods: We recruited 24 patients and 24 controls; the sample was divided into three groups of 8 patients, each according to the pharmacological treatment (haloperidol, olanzapine, or risperidone). The severity of illness was assessed by PANSS and personality traits were evaluated by SCID II. A blood sample was taken to assess the plasma concentration of nitrites and nitrates.

Results: Patients presented higher nitrate levels than controls (p < 0.05); subjects under olanzapine reported lower nitrate levels than those treated with risperidone (p < 0.05) or haloperidol (p < 0.001). Nitrate levels were correlated with PANSS total score (rho = 0.748; p < 0.001), but not with SCID II scores.

Conclusions: Despite the fact that this study found a correlation between PANSS score and nitrate levels, it is unclear whether nitric oxide is related to the severity of schizophrenia, because nitrate levels are also affected by antipsychotic treatment.     

Pharmacotherapy of fever control among hospitalized adult patients

Introduction: Fever is common and associated with increased mortality among hospitalized adults. This article will review the pharmacotherapy of commonly prescribed antipyretic drugs including the rationale for and against temperature control in febrile adults, as well as the evidence associated with fever control in specific patient populations.

Areas covered: Though fever is common, the molecular basis of pyrexia, and the interaction of these pathways with commonly prescribed antipyretic drugs are not fully understood. Furthermore, while experimental and clinical studies clearly demonstrate that pyrexia is harmful in select patients, available clinical trial data are unable to suggest an evidence-based approach to the treatment of fever. Interestingly, this also applies to patients with an acute neurologic injury wherein the treatment of fever with antipyretic therapy has become a common management strategy.

Expert opinion: Few adequately powered clinical trials have investigated temperature control strategies in febrile patients. Therefore, it is not possible to define an evidence-based approach to the control of fever in hospitalized adults. Further clinical and translational research is required to identify the patients most likely to benefit from a strategy of fever control versus permissive hyperthermia, and to determine the antipyretic therapies associated with the greatest improvement in outcome.     

Rationale for current therapies in Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disorder that affects an estimated 1 million people in the US and tens of millions worldwide. Medication therapy has made significant advances and improvements especially over the last 10 years. A number of new treatments and new strategies have emerged and the quality of life for the average sufferer has improved. This review will describe the rationale and strategies for current medical therapies in PD, with special emphasis on the use of antipsychotic agents. Levodopa remains the most efficacious medication for the management of PD. Long-term use of levodopa, however, is associated with the development of motor fluctuations including dyskinesia. Trials with dopamine agonists have demonstrated a delay in the onset of dyskinesia with the use of this therapy. There is also active, ongoing investigation to determine whether a neuroprotective effect may be present with agonist therapy. Anticholinergics have been successfully used to treat tremor as well as sialorrhoea and urinary urgency. Catechol-O-methyltransferase inhibitors increase ‘on time’, decrease ‘off time,’ and improve motor scores. Continuous stimulation of dopamine receptors may decrease the fluctations observed with pulsatile delivery of anti-Parkinsonian medications, but this will require more study. Monoamine oxidase-B inhibitors, specifically selegiline, may provide symptomatic improvement; the question as to whether a neuroprotective benefit is present remains unanswered. Amantadine has demonstrated both symptomatic benefit and dyskinesia benefit in some patients. Selective dopamine blockers such as clozaril and quetiapine, have been shown to be effective in the treatment of psychosis. This class of medications is particularly useful as an adjunctive to levodopa and dopamine agonists. Doses of dopaminergic drugs can be escalated to treat Parkinsonian symptoms, whereas selective dopamine blockers can be added to block psychosis. Old management strategies required a reduction in dopaminergic therapy and therefore worsened Parkinsonian symptoms. Even though there have been great advances in the medical options for symptomatic management of PD, there are still many unmet needs for this patient population.     

Pharmacotherapy for squamous-cell carcinoma of the head and neck

Introduction: Squamous-cell carcinoma of the head and neck (HNSCC) is one of the most common malignancies, the treatment of which constitutes a therapeutic challenge.

Areas covered: The purpose of this review is to provide an update on the pharmacotherapy for the treatment of HNSCC focusing mainly on molecular-targeted therapies. An overview of the different novel therapeutic agents that can selectively inhibit signaling pathways and receptors that are involved in the development and progression of cancer especially in HNSCC is presented.

Expert opinion: The treatment of HNSCC is traditionally based on surgery and radiotherapy for early-stage HNSCC; however, chemotherapy is no longer used only for palliation, and individualized patient treatment assisted by molecular-targeted therapies represents a future therapeutic challenge.     

Pharmacotherapy for treatment-refractory schizophrenia

Introduction: Despite advances in pharmacotherapy of schizophrenia-spectrum disorders, a large percentage of persons with schizophrenia remain at least partially nonresponsive to treatment, leading to increased morbidity/mortality, increased healthcare cost, and poor quality of life for affected individuals.

Areas covered: This paper comprises a review of recent research in drug therapy for schizophrenia, particularly treatment-refractory schizophrenia, with a focus on research conducted between 2005 and June 2010. Databases that were searched include: Pubmed, CINAHL, Science Direct, Medline and Clinical Trials.gov. Primary search terms were ‘treatment-refractory schizophrenia’ and ‘treatment-resistant schizophrenia’, with cross reference to specific agents covered in this article. An objective perspective on current trends in pharmacotherapy for treatment-refractory schizophrenia. We review the available evidence and discuss the strengths and weaknesses of published data in this field.

Expert opinion: Although there have been many advances in pharmacotherapy for schizophrenia, more well-designed trials are required to establish true efficacy and safety of current prescribing trends in clinical practice.     

Pharmacotherapy for acute pain in children: current practice and recent advances

Introduction: Acute pain in children may be undertreated. Improved understanding of developmental neurobiology and paediatric pharmacokinetics should facilitate better management of pharmacotherapy. The objective of this review is to discuss current paediatric practice and recent advances with these analgesic agents by using an evidence-based approach.

Areas covered: Using PubMed an extensive literature review was conducted on the commonly used analgesic agents in children from 2000 to April 2010.

Expert opinion: A multimodal analgesic regimen provides better pain control and functional outcome in children. The choice of pharmacological treatment is determined by the severity and type of pain. However, more research and evidence is required to determine the optimal drug combinations.     

New approaches to combining pharmacotherapy and psychotherapy for posttraumatic stress disorder

Introduction: Posttraumatic stress disorder (PTSD) is a complex disorder associated with an intricate biological and psychological symptom profile and various common comorbidities. Despite an existing myriad of evidence-based and experimental treatments, PTSD is often difficult to treat. This reality necessitates a discussion of the potential of emerging treatments.

Areas covered: A literature search using PubMed and PsychInfo was done using the following keywords: randomized clinical trials, treatment guidelines, pharmacotherapy and psychotherapy, all in addition to PTSD. A comprehensive treatment review establishes that early intervention approaches have not yet been found to prevent PTSD in trauma survivors. However, psychotherapy research provides substantial support for cognitive behavioral therapies and eye movement desensitization and reprocessing for chronic PTSD, and psychopharmacological approaches are myriad – although at present there is FDA approval only for sertraline and paroxetine. However, the efficacy of these treatments varies and, unfortunately, not everyone will achieve remission.

Expert opinion: So far, the mental health field has tended to focus on either biological or psychological targets. We propose that maximizing treatment success may require an integrated approach that does not dichotomize biological and psychological aspects. Exciting new developments reflecting this perspective include psychopharmacologic augmentation strategies that enhance the mechanisms of psychotherapy.     

Pharmacological treatment of generalized anxiety disorder

Introduction: Generalized anxiety disorder (GAD) is a chronic, relapsing, debilitating disorder, associated with markedly impaired social and occupational functioning. Pharmacological treatment is considered standard care and several drug classes are now FDA approved for the treatment of GAD. While there are clear data for the efficacy of short-term acute treatment, long-term treatment and treatment-resistant GAD remain challenging.

Areas covered: This article describes current pharmacological treatment options for GAD, with focus on benzodiazepines, azapirones, antidepressants and anticonvulsant and antipsychotic drugs. Recent findings from placebo-controlled clinical trials are reviewed and evidence-based clinical implications are discussed. A PubMed search was completed using the terms: ‘generalized anxiety disorder AND treatment’ and ‘generalized anxiety disorder AND therapy’. Additional pivotal trials were included for a historical perspective (older landmark trials that established efficacy and safety for older drug classes in the treatment of GAD).

Expert opinion: Efficacy for treatment of GAD has been established for several different drug classes. At present, based on clear efficacy and good tolerability, first-line treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) is indicated. If an initial, at least moderate, clinical response is achieved under antidepressant therapy, treatment should be at least continued for 12 months.