ANTIDEPRESSANT MEDICATIONS ARE ASSOCIATED WITH INCREASED RISK OF HOSPITAL-ACQUIRED CLOSTRIDIOIDES DIFFICILE INFECTION: A POPULATION-BASED STUDY.

WHAT IS ALREADY KNOWN: •The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. •Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: •The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. •The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

Tardive Oromandibular Dystonia Induced by Trazodone: A Clinical Case and Management from the Perspective of the Dental Specialist.

BACKGROUND: Tardive Oromandibular Dystonia is an iatrogenic drug-induced movement form of extrapyramidal symptoms associated primarily with chronic consumption of dopamine receptor blocking agents. Tardive symptoms attributable to selective serotonin reuptake inhibitors antidepressants are far less prevalent. CLINICAL CASE: The authors will present a clinical case and management, from the dental specialist perspective, of a 55-year-old female patient who developed tardive oromandibular dystonia induced by Trazodone prescribed for sleep insomnia. CONCLUSIONS: Trazodone-induced oromandibular dystonia is extremely rare. Early identification and assessment of tardive symptoms are imperative for successful treatment. Trazodone should be prescribed with caution in patients taking other medications with the potential to cause tardive syndromes.

Alleviation of neuropathic pain by trazodone in rats

Abstract Neuropathic pain is generally characterised by an abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia). The present study was designed to investigate the effect of trazodone (5mg/kg and 10mg/kg) on peripheral neuropathic pain induced by partial sciatic nerve ligation in rats. Mechanical hyperalgesia, cold allodynia and thermal hyperalgesia were assessed by performing the pinprick, acetone, and hot plate tests, respectively. Biochemically, lipid peroxidation level and total calcium levels were measured. However, trazodone administration (5 and 10 mg/ kg i.p.) for 21days significantly diminished partial sciatic nerve ligation-induced neuropathic pain along with areduction in oxidative stress and calcium levels. The results of the present study suggest that trazodone is effective in attenuating partial sciatic nerve ligation-inducedpainful neuropathic states, which may be attributed to decreased oxidative stress and calcium levels.

Trazodone-induced delirium: case report / Delirio inducido por trazodona: reporte de caso

ABSTRACT Trazodone is used as an antidepressant in doses between 150 and 600 mg. At lower doses, it is commonly used to treat insomnia. There are few case reports about confusional symptoms as an undesirable side effect of this drug. We report a case of a patient who presented with delirium after prescription of trazodone 100 mg. She required hospitalisation but, shortly after discontinuation of trazodone, the symptoms disappeared without antipsychotic medication. Seven months after the episode, the patient remains asymptomatic.

RESUMEN La trazodona se usa como antidepresivo en dosis de 150-600 mg. En dosis más bajas, se usa comúnmente para tratar el insomnio. Hay pocos reportes de caso sobre síntomas confusionales como un efecto secundario indeseable de este medicamento. Se presenta el caso de una paciente que acudió con delirio después de la prescripción de trazodona 100 mg. La paciente requirió hospitalización pero, poco después de la interrupción de la trazodona, los síntomas desaparecieron sin medicación antipsicótica. A los 7 meses del episodio, la paciente permanecía asintomática.

Interventions to reduce bruxism in children and adolescents: a systematic scoping review and critical reflection.

The aim of the present study was to perform a critical reflection about intervention options for bruxism reduction in children and adolescents. Search was conducted based on the PICO-structured question: "What are the intervention options to reduce bruxism in children/adolescents?". No language, year, or study design restrictions were imposed. Studies reporting interventions to reduce bruxism in children (< 10) and adolescents (10 to 19 years old) were included. Reviews and letters to editors were not included. From 2723 records, 17 papers were included. Included studies were primarily randomized clinical trials performed in Brazil (35.3%) and using different criteria for the diagnosis of bruxism. Reduction in self-reported bruxism and headaches associated with bruxism were observed in studies that used medications (hydroxyzine/trazodone/flurazepam), occlusal splints, orthodontic interventions, and psychological and physical therapy interventions. Reduction in Rhythmic Masticatory Muscle Activity was observed with the use of the occlusal splint and in orthodontic interventions. Alternative treatments (medicinal extracts such as Melissa officinalis-L) have shown inconclusive results.Conclusions: Several intervention options are available to inhibit or reduce bruxism activity. The respective indication, contraindications, and side effects of each treatment option must be assessed individually and carefully, taking into account that bruxism is not considered a disorder in otherwise healthy individuals.What is known• Biological and psychological factors have been strongly correlated to the development of bruxism• Bruxism prevalence ranging from 6 to 50% in childrenWhat is new• Reduction in self-reported bruxism and headaches associated with bruxism were observed in studies that used medication (Hydroxyzine/ Trazodone/ Flurazepam), occlusal splints, orthodontic interventions, psychological, and physical therapy interventions• A reduction in Rhythmic Masticatory Muscle Activity was observed with the use of the occlusal splint and orthodontic interventions. Alternative treatments (medicinal extracts such as Melissa officinalis L) show inconclusive results in respect of the reduction in bruxism.

Distúrbio compulsivo em cadela da raça Border Collie / Compulsive disorder in Border Collie bitch

Background: Compulsive disorders are excessive and repetitive behaviors that jeopardize the quality of life of both animaland guardian. It generally affects dogs between 6 and 36 months of age and its etiology is associated to stress, anxiety andgenetic predisposition. Clinical manifestations are the usual behaviors of the dog, but overly and inappropriately done.Diagnosis is based on a history of repetitive behavior and on clinical and complementary exams to discard other diseases.The aim of this study is to report a case of compulsive disorder in a female Border Collie dog, including diagnostic andtherapeutic approaches.Case: A 5-month-old, female, Border Collie dog was presented to Uberabas Veterinary Hospital owing to a chasingshadows behavior that started as a playtime activity but intensified to the point of becoming a repetitive and excessive act,followed by self-trauma and excessive barking. Clinical examination showed lesions in nasal planum region. No alterationswere observed on neurological examination apart from the chasing of shadows that also happened in the consultation room.Therefore, since there were no other findings on clinical and neurological exams, and since the manifestation occurredas a response to environmental stimuli (presence of shadows), it was established a presumptive diagnosis of compulsivedisorder. Treatment with trazodone chlorhydrate was performed, and it was indicated ovariohysterectomy, a follow-upwith a professional behaviorist and trainer and environment modifications. After a fortnight, it was observed a discreetimprovement of the clinical signs, hence a second anxiolytic, clomipramine, was added to the treatment. Approximately3 months after the beggining of therapy, there was improvement of the animals clinical picture...(AU)

Mutagenicity and recombinogenicity evaluation of bupropion hydrochloride and trazodone hydrochloride in somatic cells of Drosophila melanogaster.

The aim of the present study was to appraise the mutagenic and recombinogenic potential of bupropion hydrochloride (BHc) and trazodone hydrochloride (THc). We used standard (ST) and the high bioactivation (HB) crossings from Drosophila melanogaster in the Somatic Mutation and Recombination Test. We treated third-instar larvae from both crossings with different concentrations of BHc and THc (0.9375 to 7.5 mg/mL). BHc significantly increased the frequency of mutant spots in both crossings, except for the lowest concentration in the ST crossing. ST had also the mostly recombinogenic result, and in the HB, BHc was highly mutagenic. On the other hand, THc significantly increased the frequency of mutant spots in both the ST and HB crossings at all concentrations. The three initial concentrations were recombinogenic and the highest concentration was mutagenic for the THc. BHc and THc at high concentrations were toxic, even though their mutagenicity was not dose-related. THc significantly increased the frequency of mutant spots when metabolized, probably as a result of the production of 1-(3'-chlorophenyl) piperazine. BHc was essentially recombinogenic and when metabolized, it became mutagenic. THc was recombinogenic in both crossings. Further studies are needed to clarify the action mechanisms from BHc and THc.

Distúrbio compulsivo em cadela da raça Border Collie / Compulsive disorder in Border Collie bitch

Background: Compulsive disorders are excessive and repetitive behaviors that jeopardize the quality of life of both animaland guardian. It generally affects dogs between 6 and 36 months of age and its etiology is associated to stress, anxiety andgenetic predisposition. Clinical manifestations are the usual behaviors of the dog, but overly and inappropriately done.Diagnosis is based on a history of repetitive behavior and on clinical and complementary exams to discard other diseases.The aim of this study is to report a case of compulsive disorder in a female Border Collie dog, including diagnostic andtherapeutic approaches.Case: A 5-month-old, female, Border Collie dog was presented to Uberaba’s Veterinary Hospital owing to a chasingshadows behavior that started as a playtime activity but intensified to the point of becoming a repetitive and excessive act,followed by self-trauma and excessive barking. Clinical examination showed lesions in nasal planum region. No alterationswere observed on neurological examination apart from the chasing of shadows that also happened in the consultation room.Therefore, since there were no other findings on clinical and neurological exams, and since the manifestation occurredas a response to environmental stimuli (presence of shadows), it was established a presumptive diagnosis of compulsivedisorder. Treatment with trazodone chlorhydrate was performed, and it was indicated ovariohysterectomy, a follow-upwith a professional behaviorist and trainer and environment modifications. After a fortnight, it was observed a discreetimprovement of the clinical signs, hence a second anxiolytic, clomipramine, was added to the treatment. Approximately3 months after the beggining of therapy, there was improvement of the animal’s clinical picture...

TeleCondutas: avaliação e manejo da insônia / TeleGuides: evaluation and management of insomnia

A insônia é o mais prevalente dos transtornos do sono. É definida como a insatisfação com a qualidade ou a quantidade de sono, que ocorre a despeito de adequada oportunidade para dormir e que impõe ao indivíduo algum tipo de prejuízo durante o dia. A prevalência da insônia crônica em sociedades industrializadas é de 5 a 10%. Entre pessoas portadoras de doença crônica (psiquiátricas ou não) e idosos, a prevalência é significativamente maior. Trata-se de queixa frequente na Atenção Primária à Saúde (APS). Este material contempla as situações mais comumente associadas a insônia na APS, assim como o manejo inicial desta queixa. Está baseado em extensa revisão das evidências disponíveis na literatura, em boas práticas clínicas e adaptado à realidade brasileira, considerando as intervenções terapêuticas disponíveis. Esta guia apresenta informação que orienta a conduta para casos de avaliação e manejo da insônia no contexto da Atenção Primária à Saúde, incluindo: Avaliação Geral, Avaliação Objetiva, Avaliação e Manejo em situações específicas, Intervenções Não-Farmacológicas, Manejo Farmacológico na APS, Retirada de benzodiazepínico, Preocupações com uso de amitriptilina, Fármacos não recomendados na APS, Avaliação longitudinal da insônia, Fluxograma para avaliação e manejo da insônia.

Chronic dosing with mirtazapine does not produce sedation in rats

Objective: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. Methods: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. Results: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. Conclusion: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

Fatal Cerebral Edema, Seizures, and Hyponatremia After Trazodone Overdose.

Trazodone is a serotonin antagonist and reuptake inhibitor that is widely used for the treatment of depression and insomnia. Fatal overdose is rare and usually occurs when combined with other drugs or alcohol. Only a few lethal cases of pure trazodone overdose have been reported, all attributed to cardiotoxicity. We reported a 37-year-old woman who presented after ingesting 6.45 g of trazodone in a suicidal attempt. She was hyponatremic because of the syndrome of inappropriate antidiuretic hormone secretion and, shortly after, had a seizure and developed fatal cerebral edema. Others have described seizures and hyponatremia after pure trazodone overdose, but this is the first report of cerebral edema and death from a neurological complication. Careful monitoring and correction of sodium levels may be necessary in these patients.

Chronic dosing with mirtazapine does not produce sedation in rats.

OBJECTIVE:: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. METHODS:: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. RESULTS:: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. CONCLUSION:: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

Non-tricyclic and Non-selective Serotonin Reuptake Inhibitor Antidepressants and Recurrent Falls in Frail Older Women.

OBJECTIVE: To determine the risk of recurrent falls associated with antidepressants other than tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs) among frail older women. METHODS: This is a secondary analysis of the Zoledronic acid in frail Elders to STrengthen bone, or ZEST, trial data treated as a longitudinal cohort in 181 frail, osteoporotic women aged ≥65 years in long-term care. The primary exposure was individual non-TCA/non-SSRI antidepressants (i.e., serotonin norepinephrine reuptake inhibitors, mirtazapine, trazodone, and bupropion) at baseline and 6 months. The main outcome was recurrent (at least two) falls within 6 months after antidepressant exposure. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were derived using a generalized estimating equations model. RESULTS: At least 15% of women experienced recurrent falls between 0-6 and 6-12 months. At baseline and 6 months, 18.2% and 6.9% had a non-TCA/non-SSRI antidepressant, respectively. Adjusting for demographics, health status, and other drugs that increase risk of falls, non-TCA/non-SSRI antidepressant exposure significantly increased the risk of recurrent falls (AOR: 2.14; 95% CI: 1.01-4.54). Fall risk further increased after removing bupropion from the non-TCA/non-SSRI antidepressant group in sensitivity analyses (AOR: 2.73; 95% CI: 1.24-6.01). CONCLUSIONS: Other antidepressant classes may not be safer than TCAs/SSRIs with respect to recurrent falls in frail older women.

[Trazodone in REM sleep behavior disorder]. / Trazodona en el trastorno del comportamiento del sueño MOR.

This case concerns an elderly man with a REM sleep behavior disorder, who was initially offered a pharmacological treatment with clonazepam, recommended by other articles, but with poor adherence due to its adverse reactions and persistence of symptoms. He was then offered a treatment with Trazodone was offered, achieving a complete remission of symptoms, with no reported side effects. It is clear that Trazodone has no known indication for this type of disorder; nevertheless, it was considered in this case because of its pharmacological profile, obtaining satisfactory results. Further research is needed in order to document thoroughly the mechanisms of action, efficacy and utility of this molecule in cases such as the one presented.

Trazodona en el trastorno del comportamiento del sueño MOR / Trazodone in REM sleep behavior disorder

A un varón adulto mayor, con un cuadro clínico documentado de trastorno comportamental del sueño MOR, inicialmente se le ofreció tratamiento farmacológico con clonazepam, recomendado por la literatura, pero se obtuvo mala adherencia por intolerancia a los efectos secundarios y la persistencia sintomática. Por ese motivo, se propuso el tratamiento con trazodona y se logró control sintomático completo, sin efectos adversos reportados por el paciente. Es claro que la trazodona no tiene indicación conocida para este tipo de trastornos, pero se consideró en este caso por su perfil farmacológico y se obtuvo un resultado clínico satisfactorio. Se plantea la necesidad de realizar mayores estudios que permitan documentar de manera suficiente la acción, la eficacia y la utilidad de esta molécula en casos como el ilustrado.

This case concerns an elderly man with a REM sleep behavior disorder, who was initially offered a pharmacological treatment with clonazepam, recommended by other articles, but with poor adherence due to its adverse reactions and persistence of symptoms. He was then offered a treatment with Trazodone was offered, achieving a complete remission of symptoms, with no reported side effects. It is clear that Trazodone has no known indication for this type of disorder; nevertheless, it was considered in this case because of its pharmacological profile, obtaining satisfactory results. Further research is needed in order to document thoroughly the mechanisms of action, efficacy and utility of this molecule in cases such as the one presented.

Circadian rhythm in Alzheimer disease after trazodone use.

A circadian rhythm is a cycle of approximately 24 h, responsible for many physiological adjustments, and ageing of the circadian clock contributes to cognitive decline. Rhythmicity is severely impaired in Alzheimer disease (AD) and few therapeutic attempts succeeded in improving sleep disorders in such context. This study evaluated sleep parameters by actigraphy in 30 AD patients before and after trazodone use for 2 weeks, and we show a significant improvement in relative rhythm amplitude (RRA), compatible with a more stable daytime behavioral pattern. So, trazodone appears to produce a stabilization of the circadian rhythms in individuals with AD.

Outpatient treatment of sleep disorders in Alzheimer patients / Tratamento ambulatorial dos transtornos do sono em pacientes com doença de Alzheimer

Sleep disorders are common in patients with Alzheimer dementia and affect the quality of life of patients and of their caregivers. Despite the rising number of studies in the area, almost all of them are about non-pharmacological treatment. Our objective was to review the literature concerning pharmacological and non-pharmacological approaches to treat sleep disorders of elderly patients with Alzheimer dementia in the ambulatory setting. The treatments revised consisted of sleep hygiene and/or use of intense light coupled or not with use of melatonin, cholinesterase inhibitors, antipsychotics, hypnotics or antidepressants. In addition to the non-pharmacological measures, there is evidence that the use of trazodone may aid the treatment of sleep disorders of older individuals with Alzheimer dementia. More studies are necessary to examine the non-pharmacological and pharmacological treatments revised herein.

Os transtornos do sono são comuns nos pacientes com doença de Alzheimer e interferem na qualidade de vida do paciente e de seu cuidador. Apesar da alta prevalência desses transtornos, existe pouca evidência em relação ao seu tratamento. Nosso objetivo foi revisar a literatura em relação ao tratamento não farmacológico e farmacológico dos transtornos do sono nos idosos com doença de Alzheimer em comunidade. Os tratamentos incluídos consistiram na higiene do sono e/ou no uso da luz intensa, combinados ou não com o uso da melatonina, nos inibidores de acetilcolinesterases, antipsicóticos, hipnóticos ou antidepressivos. Para além das medidas não farmacológicas, há evidência de que o uso da trazodona é efetivo no tratamento dos transtornos do sono de pacientes com doença de Alzheimer. Mais estudos sobre as estratégias farmacológicas e não farmacológicas aqui revisadas ou outras são desejáveis.