Serotonin syndrome is a mild to potentially life-threatening syndrome associated with excessive serotonergic activity within the central nervous system. Serotonin syndrome is associated with ...medication use, drug interactions, and overdose. While serotonin syndrome is often associated with the use of selective serotonin inhibitors (SSRI), an increasing number of reports are being presented involving the use of tramadol.
This review article contains an overview of serotonin syndrome while specifically looking at tramadol's pharmacology and risk factors for serotonin syndrome. With tramadol's increasing popularity, the goal of this article is to make physicians more alert and aware of this potential side effect associated with tramadol.
In conclusion, with the increasing incidence of serotonin syndrome, prescribing physicians should be aware of and educate their patients on the potential side effects of tramadol. It is important that the prescribing physician reviews patient medications for concurrent serotonergic drugs and monitors for potential abuse.
Owing to the low therapeutic index of barbiturates, benzodiazepines (BZDs) became popular in this country and worldwide many decades ago for a wide range of conditions. Because of an increased ...understanding of pharmacology and physiology, the mechanisms of action of many BZDs are now largely understood, and BZDs of varying potency and duration of action have been developed and marketed. Although BZDs have many therapeutic roles and BZD-mediated effects are typically well tolerated in the general population, side effects and toxicity can result in morbidity and mortality for some patients. The elderly; certain subpopulations of patients with lung, liver, or kidney dysfunction; and patients on other classes of medication are especially prone to toxicity.
This review details the present knowledge about BZD mechanisms of action, drug profiles, clinical actions, and potential side effects. In addition, this review describes numerous types of BZD-mediated central nervous system effects.
For any patient taking a BZD, the prescribing physician must carefully evaluate the risks and benefits, and higher-risk patients require careful considerations. Clinically appropriate use of BZDs requires prudence and the understanding of pharmacology.
Depression is the most prevalent psychiatric disorder in the world, affecting 4.4% of the global population. Despite an array of treatment modalities, depressive disorders remain difficult to manage ...due to many factors. Beginning with the introduction of fluoxetine to the United States in 1988, selective serotonin reuptake inhibitors (SSRIs) quickly became a mainstay of treatment for a variety of psychiatric disorders. The primary mechanism of action of SSRIs is to inhibit presynaptic reuptake of serotonin at the serotonin transporter, subsequently increasing serotonin at the postsynaptic membrane in the serotonergic synapse. The six major SSRIs that are marketed in the USA today, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine, are a group of structurally unrelated molecules that share a similar mechanism of action. While their primary mechanism of action is similar, each SSRI has unique pharmacokinetics, pharmacodynamics, and side effect profile. One of the more controversial adverse effects of SSRIs is the black box warning for increased risk of suicidality in children and young adults aged 18–24. There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression. Adults, who do not have certain risk factors, which could be confounding factors, do not seem to carry this increased risk of suicidality. Ultimately, when prescribing SSRIs to any patient, a risk–benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated. The aim of this review is to educate clinicians on potential adverse effects of SSRIs.
Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous ...system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States.
Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous ...system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing-remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.
Neurological disorders, including Parkinson's disease (PD), have increased in prevalence and are expected to further increase in the coming decades. In this regard, PD affects around 3% of the ...population by age 65 and up to 5% of people over the age of 85. PD is a widely described, physically and mentally disabling neurodegenerative disorder. One symptom often poorly recognized and under-treated by health care providers despite being reported as the most common non-motor symptom is the finding of chronic pain. Compared to the general population of similar age, PD patients suffer from a significantly higher level and prevalence of pain. The most common form of pain reported by Parkinson's patients is of musculoskeletal origin. One of the most used combination drugs for PD is Levodopa-Carbidopa, a dopamine precursor that is converted to dopamine by the action of a naturally occurring enzyme called DOPA decarboxylase. Pramipexole, a D2 dopamine agonist, and apomorphine, a dopamine agonist, and Rotigotine, a dopamine receptor agonist, have showed efficacy on PD-associated pain. Other treatments that have shown efficacy in treating pain of diverse etiologies are acetaminophen, Nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors. Opioids and opioid-like medications such as oxycodone, morphine, tramadol, and codeine are also commonly employed in treatment of chronic pain in PD. Other opioid related medications such as Tapentadol, a central-acting oral analgesic with combined opioid and noradrenergic properties, and Targinact, a combination of the opioid agonist oxycodone and the opioid antagonist naloxone have shown improvement in pain. Anticonvulsants such as gabapentin, pregabalin, lamotrigine, carbamazepine and tricyclic antidepressants (TCAs) can be trialed when attempting to manage chronic pain in PD. The selective serotonin and noradrenaline reuptake inhibitors (SNRIs) also possess pain relieving and antidepressant properties, but carry less of the risk of anticholinergic side effects seen in TCAs. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown in multiple studies to be effective against various types of PD associated pain symptoms. Massage therapy (MT) is one of the most common forms of complementary and alternative medicine. Studies have shown that pressure applied during MT may stimulate vagal activity, promoting reduced anxiety and pain, as well as increasing levels of serotonin. In a survey study of PD patients, rehabilitative therapy and physical therapy were rated as the most effective for pain reduction, though with only temporary relief but these studies were uncontrolled. Yoga has been studied for patients with a wide array of neurological disorders. In summary, PD pathology is thought to have a modulating effect on pain sensation, which could amplify pain. This could help explain a portion of the higher incidence of chronic pain felt by PD patients. A treatment plan can be devised that may include dopaminergic agents, acetaminophen, NSAIDs, opioids, antidepressants, physical therapies, DBS and other options discussed in this review. A thorough assessment of patient history and physical examination should be made in patients with PD so chronic pain may be managed effectively.
Chronic pain and prescription opioid abuse are extremely prevalent both in this country and worldwide. Consequences of opioid misuse can be life-threatening with significant morbidity and mortality, ...exacting a heavy toll on patients, physicians, and society. Individuals with chronic pain and co-occurring substance use disorders and/or mental health disorders, are at a higher risk for misuse of prescribed opioids. Opioid abuse and misuse occurs for a variety of reasons, including self-medication, use for reward, compulsive use because of addiction, and diversion for profit. There is a significant need for treatment approaches that balance treating chronic pain; while minimizing risks for opioid abuse, misuse, and diversion. The use of chronic opioid therapy for chronic non-cancer pain has increased dramatically in the past 2 decades in conjunction with associated increases in the abuse of prescribed opioids and accidental opioid overdoses. Consequently, a validated screening instrument which provides an effective and rational method of selecting patients for opioid therapy, predicting risk, and identifying problems once they arise could be of enormous benefit in clinical practice. Such an instrument could potentially curb the risk of iatrogenic addiction. Although several screening instruments and strategies have been introduced in recent years, there is no single test or instrument which can reliably and accurately predict those patients not suitable for opioid therapy or identify those who need increased vigilance or monitoring during therapy. At present, screening for opioid abuse includes assessment of premorbid and comorbid substance abuse; assessment of aberrant drug-related behaviors; risk factor stratification; and utilization of opioid assessment screening tools. Multiple opioid assessment screening tools and instruments have been developed by various authors. In addition, urine drug testing, monitoring of prescribing practices, prescription monitoring programs, opioid treatment agreements, and utilization of universal precautions are essential. Presently, a combination of strategies is recommended to stratify risk, to identify and understand aberrant drug related behaviors, and to tailor treatments accordingly. This manuscript builds on the 2012 opioid guidelines published in Pain Physician and the 2016 guidelines released by the Centers for Disease Control and Prevention. It reviews the current state of knowledge regarding the growing problem of opioid abuse and misuse; known risk factors; and methods of predicting, assessing, monitoring, and addressing opioid abuse and misuse in patients with chronic non-cancer pain.Key words: Opioids, misuse, abuse, chronic pain, prevalence, risk assessment, risk management, drug monitoring, aberrant drug-related behavior.
Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. Schizophrenia and other psychiatric ...disorders such as mania and depression are known to be associated with catatonia; however, several case reports have been published of certain medical conditions inducing catatonia, including hyponatremia, cerebral venous sinus thrombosis, and liver transplantation. Neuroleptic Malignant Syndrome and anti-NMDA receptor encephalitis are also prominent causes of catatonia. Patients taking benzodiazepines or clozapine are also at risk of developing catatonia following the withdrawal of these medications—it is speculated that the prolonged use of these medications increases gamma-aminobutyric acid (GABA) activity and that discontinuation may increase excitatory neurotransmission, leading to catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT). Aberrant neuronal activity in different motor pathways, defective neurotransmitter regulation, and impaired oligodendrocyte function have all been proposed as the pathophysiology behind catatonia. There are many clinical challenges that come with catatonia and, as early treatment is associated with better outcomes, it becomes imperative to understand these challenges. The purpose of this manuscript is to provide an overview of these challenges and to look at clinical studies regarding the pathophysiology, diagnosis, and treatment of as well as the complications and risk factors associated with catatonia.
Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to ...assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public presentation and promises as well as in its use.
To provide guidance for the responsible, safe, and effective use of biologic therapy in the lumbar spine. To present a template on which to build standardized therapies using biologics. To ground potential administrators of biologics in the knowledge of the current outcome statistics and to stimulate those interested in providing biologic therapy to participate in high quality research that will ultimately promote and further advance this area of medicine.
The methodology used has included the development of objectives and key questions. A panel of experts from various medical specialties and subspecialties as well as differing regions collaborated in the formation of these guidelines and submitted (if any) their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these guidelines. The literature pertaining to regenerative medicine, its effectiveness, and adverse consequences was thoroughly reviewed using a best evidence synthesis of the available literature. The grading for recommendation was provided as described by the Agency for Healthcare Research and Quality (AHRQ).
Lumbar Disc Injections: Based on the available evidence regarding the use of platelet-rich plasma (PRP), including one high-quality randomized controlled trial (RCT), multiple moderate-quality observational studies, a single-arm meta-analysis and evidence from a systematic review, the qualitative evidence has been assessed as Level III (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best-evidence synthesis. Based on the available evidence regarding the use of medicinal signaling/ mesenchymal stem cell (MSCs) with a high-quality RCT, multiple moderate-quality observational studies, a single-arm meta-analysis, and 2 systematic reviews, the qualitative evidence has been assessed as Level III (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Lumbar Epidural Injections Based on one high-quality RCT, multiple relevant moderate-quality observational studies and a single-arm meta-analysis, the qualitative evidence has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Lumbar Facet Joint Injections Based on one high-quality RCT and 2 moderate-quality observational studies, the qualitative evidence for facet joint injections with PRP has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Sacroiliac Joint Injection Based on one high-quality RCT, one moderate-quality observational study, and one low-quality case report, the qualitative evidence has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis.
Based on the evidence synthesis summarized above, there is Level III evidence for intradiscal injections of PRP and MSCs, whereas the evidence is considered Level IV for lumbar facet joint, lumbar epidural, and sacroiliac joint injections of PRP, (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis.Regenerative therapy should be provided to patients following diagnostic evidence of a need for biologic therapy, following a thorough discussion of the patient's needs and expectations, after properly educating the patient on the use and administration of biologics and in full light of the patient's medical history. Regenerative therapy may be provided independently or in conjunction with other modalities of treatment including a structured exercise program, physical therapy, behavioral therapy, and along with the appropriate conventional medical therapy as necessary. Appropriate precautions should be taken into consideration and followed prior to performing biologic therapy. Multiple guidelines from the Food and Drug Administration (FDA), potential limitations in the use of biologic therapy and the appropriate requirements for compliance with the FDA have been detailed in these guidelines.
Regenerative medicine, platelet-rich plasma, medicinal signaling cells, mesenchymal stem cells, stromal vascular fraction, bone marrow concentrate, chronic low back pain, discogenic pain, facet joint pain, Food and Drug Administration, minimal manipulation, evidence synthesis.
Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the ...complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed.
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