scholarly journals Clozapine and Constipation: A Review of Clinical Considerations and Treatment Options

2021 ◽  
Vol 2 (3) ◽  
pp. 344-352
Author(s):  
Amber N. Edinoff ◽  
Emily Sauce ◽  
Carolina O. Ochoa ◽  
Jordan Cross ◽  
Mark Cogburn ◽  
...  

Psychosis, a break in reality which is manifested as hallucinations, delusions or the disruption in thought process, is the hallmark of schizophrenia. Despite novel pharmacotherapy advancements of antipsychotic medications that have resulted in some patients having the ability to return to social settings and thereby decreasing psychotic symptoms and reducing hospital admissions, there is still a sub-population of patients who remain symptomatic. Treatment-resistant schizophrenia is defined as failure of treatment with at least two different antipsychotics with the proper length of treatment and titration. Clozapine has been heralded as a drug to resolve the puzzle of treatment-resistant schizophrenia. Clozapine has one side effect that is well known, being the development of agranulocytosis. However, there is another side effect that can limit clozapine’s use and can also be life-threatening. Recently, at the end of January 2020, the FDA issued a communications statement which “[strengthened] an existing warning that constipation caused by the schizophrenia medicine clozapine can, uncommonly, progress to serious bowel complications.” After identifying ten cases of constipation from between 2006 to 2016 that progressed to hospitalization, surgery, and even death, the FDA focused their attention on this often overlooked, common side effect, especially when considering the strong anticholinergic effects of clozapine. Although patients are screened by their physicians for agranulocytosis by weekly lab monitoring, constipation is also a complication that needs to be identified and treated. Much like opioid-induced constipation, constipation can also be reduced with the use of laxatives and reduction in the co-prescribing of anticholinergic therapies with clozapine.

Author(s):  
Kazuya Iwata

Psychotropic drugs are the main form of physical treatment in psychiatry and they exert their action by mainly acting on dopamine, noradrenaline, serotonin, and muscarinic receptors. Antipsychotics, which are the mainline treatment for psychotic ill­nesses, usually act by blocking dopamine receptors in the dopamine pathways of the brain, usually the mesolimbic system. The D2 receptors are the usual target of the antipsychotics, although clozapine, which is considered the gold standard antipsychotic, has a strong affinity for the D4 receptors. The underlying principle of antipsychotic treatment builds on the dopamine theory of schizophrenia, whereby an excess of dopa­mine is linked to the development of psychotic symptoms. Overactive dopamine receptors are thought to be involved in this, and thus block­age of the dopamine receptors through antipsychotics can provide relief from psychotic symptoms. Antipsychotics are divided into typical and atypical, and the defining feature of typicals is their propensity to cause EPSEs. This is thought to be due to the fact that typical antipsychotics are not specific for dopa­mine receptors in the mesolimbic pathways, but can also block those in mesocortical, tuberoinfundibular, and nigrostriatal pathways. Atypical antipsychotics can impact on a variety of receptor types, such as serotonin, and thus they are usually subclassified according to their pharmacological properties. Their heterogeneous pharmacodynamics in part explains their variable side-effect profile. One common side-effect of atypical antipsychotics is their tendency to trigger metabolic syndrome, which is a cluster of cardiovascular risk factors including dyslipidaemia, hypertension, central obesity, and impaired glucose tolerance. They also cause endocrine-related side-effects, such as hyperprolactinaemia. An important adverse effect seen with any antipsychotic is neuroleptic malignant syndrome (NMS), which is an idiosyncratic reaction to antipsy­chotics taken even at therapeutic doses. Patients can present with hyper­thermia, rigidity, autonomic disturbances, and altered mental state over 24–48 hours. It can be potentially life threatening, and thus, if suspected, urgent referral to a general hospital is required. Antidepressants also vary greatly with regards to their pharmacologi­cal properties, but the majority increase the concentration of neuro­transmitters in the synaptic cleft to alleviate depressive symptoms.


PEDIATRICS ◽  
1991 ◽  
Vol 88 (2) ◽  
pp. 419-419
Author(s):  
GERALD B. HICKSON

In Reply.— The purpose of our paper was to examine the question of safety concerning over-the-counter (OTC) release of promethazine.1 Our stated opinion, that the drug is not appropriate for OTC release, was based on more than a suggested relationship with SIDS, but also on the drug's common side effect of sedation, ability to act as a cerebral stimulant even in therapeutic doses inducing hallucinations, convulsions and encephalopathy in some children, case reports concerning promethazine use and apparent life-threatening events, the potential for families to misuse this drug due to its sedative and antiemetic properties, and most importantly, FDA standards of safety for OTC medications which require "a low potential for harm which may result from abuse under conditions of wide spread availability."2


Author(s):  
Rakesh Sharma ◽  
P. S. Dattatreya ◽  
A. V. S. Suresh ◽  
Ch Mohana Vamsy

Anaplastic Thyroid Carcinoma (ATC) is an aggressive rare form of caner with limited treatment options and short survival. In view of initial case reports have shown some good clinical response with lenvatinib, we used the same in our institute. We are presenting a retrospective series of 4 cases between 2018-2021. It showed very promising results with 75% showing clinically meaningful regression of tumor. Hypertension is the most common side effect, which should be aggressively managed. We feel that, lenvatinib remains a safe and effective option to explore in patients with refractory anaplastic thyroid carcinoma.


2019 ◽  
pp. 38-43
Author(s):  
Jose A. Rey ◽  
Huy Pham ◽  
Lauren Blue ◽  
Carolina Liriano

Myotonia congenita is a rare non-dystrophic skeletal muscle disease characterized by an inability to relax skeletal muscles after abrupt voluntary movements. Patients with this condition have stiff muscles and difficulty with mobility, especially when initiating movement after periods of rest. It is well known that movement disorders are a common side effect of antipsychotics due to their ability to antagonize dopamine 2 receptors in the extrapyramidal part of the basal ganglia. The purpose of this case is to describe the effects antipsychotics had on a 59-year-old Caucasian male with comorbid myotonia congenita and schizophrenia in an inpatient psychiatric hospital setting. Medication trials of ziprasidone, haloperidol and clozapine exacerbated his myotonic symptoms leading to falls and complaints of severe muscle stiffness, which were relieved upon discontinuation of all antipsychotic medications. This suggests that patients with myotonia congenita may have an increased sensitivity to the extrapyramidal side effect profile of antipsychotics. Treatment options for this patient case are discussed with an emphasis on lamotrigine. Keywords: Myotonia congenita; Schizophrenia; Myopathy; Antipsychotics; Extrapyramidal symptoms


2021 ◽  
Author(s):  
Jia Ming Low ◽  
Le Ye Lee ◽  
Yvonne Peng Mei Ng ◽  
Youjia Zhong ◽  
Zubair Amin

This is a prospective cohort study of 88 lactating women in Singapore who received two doses of BNT162b2 vaccination (Pfizer/BioNTech), whereby outcomes of mother-child dyads within 28 days after the second vaccine dose were determined through a structured questionnaire. Minimal effects related to breastfeeding were reported in this cohort; 3 of 88 (3.4%) women had mastitis with 1 of 88 (1.1%) women experiencing breast engorgement. We report an incidence of lymphadenopathy in our cohort at 5 of 88 (5.7%). Reassuringly, there was no change in reported breastmilk supply after vaccination. The most common side effect was pain/redness/swelling at the injection site, which was experienced by 57 of 88 (64.8%) women. There were no serious adverse events of anaphylaxis and hospital admissions. No adverse symptoms were reported in 67 of 88 (76.1%) breastfed children.


2003 ◽  
Vol 20 (4) ◽  
pp. 132-134 ◽  
Author(s):  
Sarah E Prasad ◽  
Harry G Kennedy

AbstractWe describe a 44 year old man with treatment resistant schizophrenia who developed pseudophaeochromocytoma on clozapine with high blood pressure, tachycardia and elevated 24 hour urinary catecholamines. All resolved on discontinuing clozapine. We reviewed the literature and found five other cases. We suggest that this is a common side effect, transient in some patients. Elevated plasma noradrenaline does not appear to be relevant to the unique benefits of clozapine.


2021 ◽  
Vol 11 ◽  
Author(s):  
Umair Majeed ◽  
Tudor Puiu ◽  
Jason Sluzevich ◽  
Gina Reynolds ◽  
Marites Acampora ◽  
...  

Alpelisib is a PIK3a inhibitor approved for the treatment of metastatic ER+ breast cancer in combination with fulvestrant. Although rash is a common side effect of this medication, we present the first case of drug reaction with eosinophilia and systemic symptoms (DRESS) upon initial exposure to alpelisib. Here we describe the clinical-pathological findings and management of our patient with alpelisib-induced life-threatening DRESS syndrome. The goal of this case report is to highlight association of alpelisib with DRESS syndrome, in clinical practice, so that alpelisib can be immediately stopped and treatment for this serious condition promptly initiated.


2012 ◽  
Vol 21 (3) ◽  
pp. 75-84
Author(s):  
Venkata Vijaya K. Dalai ◽  
Jason E. Childress ◽  
Paul E Schulz

Dementia is a major public health concern that afflicts an estimated 24.3 million people worldwide. Great strides are being made in order to better diagnose, prevent, and treat these disorders. Dementia is associated with multiple complications, some of which can be life-threatening, such as dysphagia. There is great variability between dementias in terms of when dysphagia and other swallowing disorders occur. In order to prepare the reader for the other articles in this publication discussing swallowing issues in depth, the authors of this article will provide a brief overview of the prevalence, risk factors, pathogenesis, clinical presentation, diagnosis, current treatment options, and implications for eating for the common forms of neurodegenerative dementias.


2019 ◽  
Vol 14 (1) ◽  
pp. 80-83 ◽  
Author(s):  
Asma H. Almaghrebi

Background: The clozapine-derivative quetiapine has been shown in some cases to cause leukopenia and neutropenia. Case Presentation: We reported on a case of a young female diagnosed with treatment-resistant schizophrenia. After failed trials of three antipsychotic medications and despite a history of quetiapineinduced leukopenia, clozapine treatment was introduced due to the severity of the patient’s symptoms, the limited effective treatment options, and a lack of guidelines on this issue. Result: Over a ten-week period of clozapine treatment at 700 mg per day, the patient developed agranulocytosis. Her white blood cell count sharply dropped to 1.6 &#215; 10<sup>9</sup> L, and her neutrophils decreased to 0.1 &#215; 10<sup>9</sup> L. There had been no similar reaction to her previous medications (carbamazepine, risperidone, and haloperidol). Conclusion: The safety of clozapine in a patient who has previously experienced leukopenia and neutropenia with quetiapine requires further investigation. Increased attention should be paid to such cases. Careful monitoring and slow titration are advisable.


2019 ◽  
Vol 14 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Kerasia-Maria Plachouri ◽  
Eleftheria Vryzaki ◽  
Sophia Georgiou

Background:The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.Objective:To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.Method:English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.Results:The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.Conclusion:Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.


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