Serotonergic Medications Research Articles

Management of Psychiatric Diagnoses in Reversible Cerebral Vasoconstriction Syndrome: The Dangers of Worsening Pathology with Serotonergic Medications: A Case Report and Literature Review.

Reversible cerebral vasoconstriction syndrome (RCVS) represents a group of conditions that show reversible multifocal narrowing or constriction of the cerebral arteries that supply blood to the brain. The initial manifestation of RCVS often includes a "thunderclap" headache that is sudden, severe, and often disabling. Stimulants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and antipsychotics with serotonergic activity can alter the cerebral arterial tone, trigger vasoconstriction, and place patients at risk of a cerebrovascular accident. Thus, psychiatric medications are commonly discontinued on admission for RCVS, and psychiatry is often consulted for input on acute medication management and longitudinal treatment options. Currently, there is a dearth of literature on managing psychiatric medications in RCVS, resulting in variable practice patterns that place patients at risk of withdrawal, decompensation, and relapse. In this article, we provide a case example and aim to consolidate the limited data surrounding the management of psychiatric illness with comorbid RCVS in our discussion. There is a clear concern about worsening and even potentially lethal consequences due to serotonin or stimulant-induced vasospasm both during an acute episode and in long-term management of RCVS. We discuss the underlying pathophysiologic mechanisms proposed for serotonergic-, noradrenergic-, and dopaminergic-induced cerebral vasospasm and how this correlates with the clinical management of patients on psychiatric medications. These data will then be organized to create a risks versus benefits outline to equip psychiatrists to make decisions about when to stop and when to restart psychiatric medications in the setting of RCVS.

Risk of stress cardiomyopathy associated with selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors: a real-world pharmacovigilance analysis

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are reported to cause stress cardiomyopathy (SC). This study evaluated the association between SSRI/SNRI use and the occurrence of cardiomyopathy in the publicly available U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionate analysis and likelihood ratio tests were used to identify risk associated with SSRIs or SNRIs and the incidence of SC, using data from between from 2012 to 2022 acquired from the FAERS database. The study identified 132 individual case safety reports (ICSRs) of SC associated with SSRIs or SNRIs. Venlafaxine (48%) and fluoxetine (27%) were the most common antidepressants of the ICSRs. Approximately 80% of SC cases were reported in females, with individuals aged 45–65 years identified as a high-risk population. Both venlafaxine (ratio-scale information component [RSIC] 2.54, 95% CI 2.06–3.04) and fluoxetine (RSIC 3.20, 95% CI 2.31–4.47) were associated with SC, with likelihood ratio estimates of 3.55 (p = 0.02) for venlafaxine and 4.82 (p = 0.008) for fluoxetine. The median time to cardiomyopathy onset was 20 days, with hospitalization reported in 48.33% of patients. Venlafaxine and fluoxetine were associated with SC risk, particularly in middle-aged women. Caution should be exercised when using SSRIs or SNRIs combined with other serotonergic medications.

Serotonin syndrome controversies: A need for consensus

Serotonin syndrome (SS) is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system. Although more than seven decades have passed since the first description of SS, it is still an enigma in terms of terminology, clinical features, etiology, pathophysiology, diagnostic criteria, and therapeutic measures. The majority of SS cases have previously been reported by toxicology or psychiatry centers, particularly in people with mental illness. However, serotonergic medications are used for a variety of conditions other than mental illness. Serotonergic properties have been discovered in several new drugs, including over-the-counter medications. These days, cases are reported in non-toxicology centers, such as perioperative settings, neurology clinics, cardiology settings, gynecology settings, and pediatric clinics. Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers. Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings. Patients may develop SS at therapeutic dosages. Moreover, these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons. Thus, the clinical presentation (onset, severity, and clinical features) in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings. They produce considerable diversity in many aspects of SS. However, other experts discount these new developments in SS. Since SS is a potentially lethal illness, consensus is required on several concerns related to SS.

Recurrent Serotonin Syndrome After Ketamine-assisted Electroconvulsive Therapy: A Case Report and Review of the Literature.

Serotonin (5-HT) syndrome (SS) consists of changes in mental status as well as autonomic and neuromuscular changes. Though not well understood, serotonergic pathways have been implicated in the mechanism of action of electroconvulsive therapy (ECT). Ketamine has been used as an induction agent in ECT and as therapy for treatment-resistant depression. Utilizing a case report and literature review, we explored the underlying serotonergic mechanisms of ECT and ketamine by which a syndrome of serotonin toxicity may be precipitated. We describe the case of a 72-year-old woman who developed recurrent SS on 2 occasions in similar circumstances involving the administration of ketamine for ECT. In our literature review, we found 5 cases in which SS was associated with ECT and 1 case linking ketamine to SS. There is emerging evidence that the mechanism of ECT involves 5-HT1A and 5-HT2A receptors, the same receptors that are involved in SS. ECT can transiently increase the permeability of the blood-brain barrier, leading to increased levels of antidepressants in the brain. ECT can, therefore, enhance 5-HT transmission and the likelihood of SS in the presence of serotonergic agents. The effect of ketamine on 5-HT transmission is mediated by the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Ketamine increases α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid activity in the medial prefrontal cortex, which leads to downstream 5-HT release through glutamate. Through this mechanism, ketamine can increase 5-HT transmission, leading to SS. To our knowledge, this is the only case report of recurrent SS with concurrent use of ECT and ketamine. As ketamine is frequently used in ECT and many patients undergoing ECT are on serotonergic medications, it is important to recognize ketamine as a potential risk factor for SS. There is no evidence for added efficacy when combining ECT and ketamine. Thus, one should proceed with caution when combining these treatments. The burgeoning use of ketamine in ambulatory settings makes it necessary to elucidate the risks, which we discuss further. More research is needed into the mechanisms of ketamine and ECT, specifically how the combination of these treatments influence 5-HT levels.

Serotonin Syndrome Following Low-Dose Sertraline: A Case Report

IntroductionSerotonin syndrome is a potentially life-threatening condition that is precipitated by the use of serotonergic medications, Selective Serotonin Reuptake Inhibitors (SSRIs) and Monoamine Oxidase Inhibitors (MAOIs). It usually occurs when high doses of serotonergic drugs are prescribed. It is a medical emergency that requires prompt recognition, cessation of offending drugs and supportive therapy.ObjectivesWe present a case of serotonin syndrome that occurred in a patient who was prescribed a low dose of sertraline, and aim to highlight the importance of early detection of this severe condition.MethodsDetails of the case were described. Information was gathered based on medical records.Results Patient M was a 29-year-old Malay male with a history of major depressive disorder, who was previously trialed on fluvoxamine 100mg every night but subsequently switched to and maintained on sertraline 75mg every night in 2020. He then defaulted follow up appointments. In 2023, he presented to the emergency services for a suicide attempt and was diagnosed with major depressive disorder with psychotic features. He was restarted on sertraline 50mg every night and risperidone 0.5mg every night was newly started. Two days later, sertraline was increased to 100mg every night. Two days following this increase, he was noted to have altered mental state, fever of 39.3-degree celcius, tachycardia of 120 beats per minute, ocular clonus and generalized hyperreflexia. Sertraline and risperidone were immediately stopped. Blood tests including creatine kinase, lumbar puncture and magnetic resonance imaging (MRI) of the brain did not show any abnormalities. After stopping of the medications, the patient’s symptoms resolved within 24 hours. Based on clinical symptoms and a normal creatine kinase level, neuroleptic malignant syndrome (NMS) was ruled out. Subsequently, he was restarted on risperidone 0.5mg and mirtazapine 7.5mg every night. He developed symptoms of serotonin syndrome with a low dose of sertraline. Symptoms resolved after the discontinuation of the SSRI.Conclusions In this case, differential diagnoses of serotonin syndrome were also considered, such as NMS, encephalitis, meningitis and thyroid storm. NMS was less likely due to the rapid onset of onset and resolution of symptoms. Encephalitis and meningitis were unlikely in view of normal MRI brain and lumbar puncture findings.There have been case reports of serotonin syndrome developing with lower doses of an SSRI in the pediatric population. There is, however, a lack of literature describing serotonin syndrome with low doses of SSRI in the adult population. To avoid a missed diagnosis, clinicians should monitor closely for SSRI toxicity, including serotonin syndrome, even when low doses of serotonergic drugs are used.Disclosure of InterestNone Declared

Development of a multivariate prediction model for antidepressant resistant depression using reward-related predictors.

Individuals with depression who do not respond to two or more courses of serotonergic antidepressants tend to have greater deficits in reward processing and greater internalizing symptoms, yet there is no validated self-report method to determine the likelihood of treatment resistance based on these symptom dimensions. This online case-control study leverages machine learning techniques to identify differences in self-reported anhedonia and internalizing symptom profiles of antidepressant non-responders compared to responders and healthy controls, as an initial proof-of-concept for relating these indicators to medication responsiveness. Random forest classifiers were used to identify a subset from a set of 24 reward predictors that distinguished among serotonergic medication resistant, non-resistant, and non-depressed individuals recruited online (N = 393). Feature selection was implemented to refine model prediction and improve interpretability. Accuracies for full predictor models ranged from .54 to .71, while feature selected models retained 3-5 predictors and generated accuracies of .42 to .70. Several models performed significantly above chance. Sensitivity for non-responders was greatest after feature selection when compared to only responders, reaching .82 with 3 predictors. The predictors retained from feature selection were then explored using factor analysis at the item level and cluster analysis of the full data to determine empirically driven data structures. Non-responders displayed 3 distinct symptom profiles along internalizing dimensions of anxiety, anhedonia, motivation, and cognitive function. Results should be replicated in a prospective cohort sample for predictive validity; however, this study demonstrates validity for using a limited anhedonia and internalizing self-report instrument for distinguishing between antidepressant resistant and responsive depression profiles.

(368) Real World Survey Study to Explore the Effects of Flibanserin in Men with Sexual Dysfunction

Abstract Introduction Low sexual desire (LSD) is a syndrome of symptoms including diminished sexual interest or desire and absence of sexual thoughts or fantasies. Hypoactive sexual desire disorder (HSDD) is a subtype of persistent LSD associated with marked distress with no known cause. LSD/HSDD in men frequently occurs with other sexual dysfunctions such as erectile dysfunction and delayed orgasms. Flibanserin is a centrally-acting serotonergic medication approved in the United States to treat acquired, generalized HSDD in certain premenopausal women. Improvement in symptoms following the initiation of flibanserin treatment may take up to eight weeks. Objective Given the paucity of research available on the off-label use of flibanserin in men, this survey study was conducted to capture general information on the safety and outcomes of flibanserin in men with LSD/HSDD. Methods Dispensing data from sexual health clinics were used to identify males older than 18 years prescribed flibanserin between July 1 to December 31, 2022. Invitational emails containing a secure survey link were sent to eligible males. Survey questions captured changes in sexual function and sleep quality during active treatment. Patients not currently on treatment were excluded from the survey after the first question. In addition, 10-minute physician interviews were conducted to capture general safety information and outcomes. Study results are summarized using descriptive statistics. Results Thirty-four of 75 eligible males (45%) from 5 centers responded to the survey. The mean age was 55 years (range 30 to 81 years). Among respondents actively taking flibanserin (n=20), 12 selected low sexual desire, and 8 selected difficulties in reaching orgasm as their primary indication. Eleven of 16 respondents (69%) with treatment durations longer than 2 months indicated treatment-related benefits since starting flibanserin (TABLE). For the sleep quality question, 53% reported no change, 31% reported some improvement, and 16% reported worsening sleep. The most common reasons cited by physicians for treatment discontinuation were lack of effect and insomnia, followed by somnolence and fatigue. Conclusions Select male patients at sexual health clinics may experience benefits in LSD/HSDD and the ability to reach orgasm following 2 months of flibanserin treatment. Physician interviews suggest flibanserin is well tolerated in men with a safety profile similar to women. It is important to acknowledge survey study limitations when interpreting these findings. These results suggest that more research on the use of flibanserin in men with sexual dysfunctions is warranted. Disclosure Yes, this is sponsored by industry/sponsor: Sprout Pharmaceuticals, Inc. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Sprout Pharmaceuticals, Inc.

Prevalence and Correlates of Serotonin Syndrome in Real-World Inpatients.

Serotonin syndrome (SS) is a potentially life-threatening adverse drug reaction due to an increased central and peripheral serotonin activity, which usually presents as a triad of behavioral changes, neuromuscular excitability, and autonomic instability. Probably SS is often misdiagnosed, and its symptoms are mistaken for psychiatric symptoms or general medical issues: the true incidence of SS is not clear, and literature concerning potential risk factors is scarce. Our aims were to examine the prevalence of SS in a naturalistic sample of hospitalized patients and to evaluate potential factors related to the risk of developing the condition. The sample included 133 patients being treated with serotonergic medications admitted to the psychiatric inpatient unit of the San Luigi Gonzaga Hospital. All patients received a medical examination (including a neurological examination) within 24 hours of admission. Serotonin syndrome was diagnosed according to Hunter Criteria. Sixteen patients (12%) were diagnosed with SS. In the subgroup of subjects with SS, we found a higher rate of male patients when compared with subjects with no SS (62.5% vs 33.3%, P = 0.023). SS probably is an underestimated condition, which should be carefully assessed in patients on serotonergic medications. Male gender was the only factor found to be significantly related to a higher risk of developing SS. Further studies on larger samples are needed, to gain more information on possible risk factors and to identify subjects more prone to developing SS, given the potential risk for patients' health.

Fentanyl-Induced Serotonin Syndrome 5 Days After Cessation of Serotonergic Agents: A Case Report.

A 21-year-old patient with intellectual disability was admitted for gastroenteritis due to serotonergic medication overdose, and subsequently developed serotonin syndrome. Her symptoms initially improved after the cessation of serotonergic medications, but worsened 5 days later after fentanyl administration during general anesthesia. On emergence, she had convulsions and was nonresponsive. Subsequent imaging and electroencephalography did not demonstrate intracranial pathology or seizure activity. We suspect she had an exacerbation of her serotonin syndrome. She recovered successfully after supportive care. This case demonstrates that common medications used during anesthesia such as fentanyl can provoke serotonin syndrome, even several days after serotonergic drug discontinuation.

Association of Gabapentinoids With Opioid-Related Overdose in the Inpatient Setting: A Single Center Retrospective Case-Control Study.

Objectives: Recent data suggest concomitant gabapentinoid use increases opioid-related overdose (ORO) risk; however, this association has not been well studied in the hospital setting. The primary objective of this study was to compare ORO risk, indicated by naloxone administration, in patients receiving opioids plus gabapentinoids versus opioids alone. Methods: In this retrospective case-control study of adults admitted to a large community hospital from 1/1/20 to 12/31/21, all cases (defined as patients who received naloxone more than 24 hours after admission) identified were matched 1:1 to randomly selected controls (defined as patients on opioids who did not receive naloxone). The primary outcome was the percentage of cases and controls with concomitant inpatient gabapentinoid use. Logistic regression was performed to determine the independent association between gabapentinoids and ORO (as evidenced by inpatient naloxone administration). Results: Baseline characteristics were similar between the 144 cases and 144 controls. Gabapentinoid exposure was greater for cases than controls (34.0%vs 20.8%, P = .0118). Median hospital length of stay (11vs 4 days, P < .0001) and mortality (19%vs 5%; P = .0018) were also higher for cases. In logistic regression analysis, ORO (adjusted OR 4.91; 95% CI 1.86-12.96) and serotonergic medication exposure (adjusted OR 4.31; 95% CI 1.50-12.38) were significantly associated with gabapentinoid use. Conclusions: Concomitant gabapentinoid use with opioids was associated with increased ORO risk in the inpatient setting. When considering prescribing gabapentinoids in conjunction with opioids in the hospital setting, potential benefits should be weighed against increased overdose risk.

Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric disorder that affects ∼2%-3% of the population globally. Studying spontaneous OCD-like behaviors in non-human primates may improve our understanding of the disorder. In large rhesus monkey colonies, we found 10 monkeys spontaneously exhibiting persistent sequential motor behaviors (SMBs) in individual-specific sequences that were repetitive, time-consuming and stable over prolonged periods. Genetic analysis revealed severely damaging mutations in genes associated with OCD risk in humans. Brain imaging showed that monkeys with SMBs had larger gray matter (GM) volumes in the left caudate nucleus and lower fractional anisotropy of the corpus callosum. The GM volume of the left caudate nucleus correlated positively with the daily duration of SMBs. Notably, exposure to a stressor (human presence) significantly increased SMBs. In addition, fluoxetine, a serotonergic medication commonly used for OCD, decreased SMBs in these monkeys. These findings provide a novel foundation for developing better understanding and treatment of OCD.

Serotonin syndrome: A case report

Serotonin syndrome or serotonin toxicity is defined as an iatrogenic drug-induced toxidrome associated with increased intrasynaptic serotonin concentration in the central nervous system. Most cases are provoked by therapeutic doses of a combination of two or more serotonergic agents. The incidence of serotonin syndrome is on the rise, because of increased use of serotonergic medications in current clinical practice. However, the actual incidence of perioperative serotonin syndrome and its morbidity are likely unknown. The diagnosis is difficult in the perioperative period, as clinical features may mimic other conditions commonly seen in the perioperative period or may be masked by the use of anaesthetic medications. Therefore, anaesthetists must be proactive in preventing, identifying and managing serotonin syndrome in the perioperative period.

Perseveration and Shifting in Obsessive-Compulsive Disorder as a Function of Uncertainty, Punishment, and Serotonergic Medication

BackgroundThe nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks, remains elusive. Here, a novel deterministic reversal task and inclusion of unmedicated patients in the study sample illuminated the role of fixed versus uncertain rules/contingencies and of serotonergic medication. Additionally, our understanding of probabilistic reversal was enhanced through theoretical computational modeling of cognitive flexibility in OCD. MethodsWe recruited 49 patients with OCD, 21 of whom were unmedicated, and 43 healthy control participants matched for age, IQ, and gender. Participants were tested on 2 tasks: a novel visuomotor deterministic reversal learning task with 3 reversals (feedback rewarding/punishing/neutral) measuring accuracy/perseveration and a 2-choice visual probabilistic reversal learning task with uncertain feedback and a single reversal measuring win-stay and lose-shift. Bayesian computational modeling provided measures of learning rate, reinforcement sensitivity, and stimulus stickiness. ResultsUnmedicated patients with OCD were impaired on the deterministic reversal task under punishment only at the first and third reversals compared with both control participants and medicated patients with OCD, who had no deficit. Perseverative errors were correlated with OCD severity. On the probabilistic reversal task, unmedicated patients were only impaired at reversal, whereas medicated patients were impaired at both the learning and reversal stages. Computational modeling showed that the overall change was reduced feedback sensitivity in both OCD groups. ConclusionsBoth perseveration and increased shifting can be observed in OCD, depending on test conditions including the predictability of reinforcement. Perseveration was related to clinical severity and remediated by serotonergic medication.

The role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder

Despite extensive research efforts, the pathophysiology of obsessive-compulsive disorder (OCD) is still largely unknown. The dorsal anterior cingulate cortex (dACC) plays an important role in cognitive control and is therefore hypothesized to contribute to the pathogenesis of OCD. In this review, we aim to gain a wider understanding of the specific functions of the dACC and its role in the pathophysiology of OCD. The dACC is part of the cortico-basal ganglia-thalamo-cortical loop, where it forms connections between sensory input streams, cognitive and affective processing regions, and structures that regulate behaviour. This position facilitates a broad function for the dACC in multiple domains, which center on goal-directed behaviour and reward-based learning. When presented with a certain threatening stimulus, the dACC instructs downstream structures to select actions to respond to this particular stimulus, based on previous experiences We hypothesize that hyperactivity of the dACC may impair goal-directed behaviour in OCD patients which in turn may lead to obsessive-compulsive symptoms by creating an over-reliance on threatening stimuli and inadequate selection of neutralizing actions. The working mechanisms of cognitive behavioural therapy, serotonergic medication, repetitive transcranial magnetic stimulation and deep brain stimulation in OCD may be in part explained by the normalization of the activity of the dACC within the cortico-basal ganglia-thalamo-cortical (CBGTC) loop.

Tramadol utilization among patients with higher risk of adverse drug events: A claims analysis of commercially insured and Medicare Advantage members.

To assess prescribing of tramadol among patients with contraindications and higher risks of adverse events in a large population of commercially insured and Medicare Advantage members. We performed a cross-sectional analysis evaluating tramadol utilization in patients with higher risk of adverse outcomes. This study utilized 2016-2017 data from the Optum Clinformatics Data Mart. Patients with at least one tramadol prescription without a cancer or sickle cell diagnosis during the study period. We first determined if tramadol was prescribed among patients with contraindications or risk factors for adverse outcomes. We then determined if patient demographic or clinical factors were associated with the use of tramadol in these higher-risk scenarios using multivariable logistic regression models. Among patients with at least one prescription for tramadol, 19.66 percent (99 percent CI: 19.57-19.75) concurrently received an interacting cytochrome P450 isoenzyme medication, 19.24 percent (99 percent CI: 19.15-19.33) concurrently received a serotonergic medication, and 7.93 percent (99 percent CI: 7.88-8.00) concurrently received a benzodiazepine. Additionally, 1.59 percent (99 percent CI: 1.56-1.61) of patients who received tramadol also had a seizure disorder, while 0.55 percent (99 percent CI: 0.53-0.56) of patients were under the age of 18. Overall, nearly one in three patients (31.17 percent) received tramadol in the presence of at least one of these risks (99 percent CI: 31.06-31.27). Almost one in three patients prescribed tramadol had a clinically significant drug interaction or contraindication for use, suggesting that prescribers often disregard these concerns. Real-world studies are needed to better understand the likelihood of harms associated with the use of tramadol in these contexts.

Utilization patterns, cardiovascular risk, and concomitant serotoninergic medications among triptan users between 2008 and 2018: A gender analysis in one Italian region, Tuscany.

To describe the pattern of triptan use by gender in Tuscany, Italy, focusing on special user populations in which evidence on triptan safety is still not conclusive. Growing evidence supports the role of gender differences in migraine pathophysiology and treatment. However, gender impact on triptan real-word utilization has been poorly investigated. A retrospective, descriptive, cohort study was performed using the population-based Administrative Healthcare Database of Tuscany region (Italy). Subjects registered in the database on the January 1 of each year between 2008 and 2018 were identified. New users (NU) of triptans (ATC:N02CC*) were patients with one or more triptan dispensation during the year of interest and none in the past. Age, cardiovascular comorbidities representing an absolute or a possible contraindication to triptan utilization, concomitant serotonergic medications, and pattern of triptan use during 1-year follow-up were described by gender. A total of 86,109 patients who received one or more triptan dispensing were identified. Of 64,672 NU (men=17,039; women=47,633), 10.2% (6823/64,672) were aged >65 years, who were mostly women (n=4613). Among NU, men and women with absolute cardiovascular contraindications were 4.3% (740/17,039) and 2.1% (1022/47,633), respectively, while those concomitantly taking serotonergic medications were 17.2% (267/1549) and 21.9% (949/4330), respectively (949/4330). Regular users (two or more dispensing with ≥3 months between first and last observed dispensing) accounted for 26.4% of women (12,597/47,633) and 19.11% of men (3250/17,039); frequent users (≥15 dosage units/month during ≥3 consecutive months) were overall 0.1% (94/64,672) and 62.0% (58/94) of them concomitantly received serotonergic medications. Considering gender differences in triptan use highlighted here, large scale observational studies are warranted to better define what populations are safe to use triptans and whether it is appropriate to tighten or relax certain recommendations on triptan use. In the meantime, any suspected adverse drug reaction observed in the special user populations highlighted in this study should be promptly reported.

Serotonin Syndrome in Critical Care

Serotonin syndrome is a life-threatening syndrome that can occur when medications or drugs that cause serotonergic activity are taken. Frequently this syndrome is caused using 2 serotonergic medications at once or switching from 1 serotonergic medication to another without tapering appropriately. The classic triad of serotonin syndrome is neuromuscular excitability, autonomic dysfunction, and altered mental status. Patients can have symptoms ranging from tachycardia, diaphoresis, fever, and hypertension to severe swings in blood pressure, tremors, hyperreflexia, muscle rigidity, and even death. Most patients admitted to the hospital with fevers, tachycardia with hypertension, or hypotension will have blood cultures drawn as infection can easily explain these symptoms. If these symptoms persist, however, other options should be explored, including serotonin syndrome.

Persistent Postural-Perceptual Dizziness (PPPD) - A clinical case and essentials for the primary care medicine

Persistent Postural-Perceptual Dizziness (PPPD) is a chronic functional disorder that manifests with symptoms of dizziness, unsteadiness or non-spinning vertigo that lasts for at least three months. These symptoms are exacerbated by upright posture, active or passive motion, and exposure to complex or moving visual stimuli. This -pathology has been known for a long time ago. Still, after an expert's consensus in 2017, this term was born, and some precise diagnostic criteria have been defined based on identifying key symptoms in the patient's clinical history. Treatment is multimodal, incorporating -vestibular rehabilitation, cognitive-behavior therapy, and serotonergic medication.

Two failed trials of repetitive transcranial magnetic stimulation (rTMS) in obsessive-compulsive disorder (OCD): Is this rTMS-resistant OCD?

Abstract Treatment options for obsessive-compulsive disorder (OCD) includes serotonergic medications and cognitive-behavioral therapy, however, many patients show poor response to treatment. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive intervention which has shown some efficacy in OCD, and newer treatment protocols are being studied. We report a case of treatment-resistant OCD which did not improve with 20 sessions of high-frequency primed low frequency rTMS over supplementary motor area, and 15 sessions of accelerated continuous theta burst stimulation of the right frontal pole, raising the possibility of TMS-resistant OCD.

Serotoninski sindrom kod pacijentkinje sa dualnom dijagnozom - prikaz slučaja

Introduction: Serotonin syndrome is a rare but potentially life-threatening condition. In most cases, this complication is caused by taking two serotonergic medications simultaneously, leading to excessive serotonin concentration in the body. Selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SNRIs), as well as irreversible monoamine oxidase inhibitors (MAOIs) and their combination with other serotonergic substances, are associated with symptoms of serotonin syndrome. Case study: A patient who was prescribed sertraline (an SSRI) for a depressive episode suffered fractures in a traffic accident during the treatment, and tramadol was prescribed for her pain. Since both drugs tend to increase serotonin levels in the body, a complication in the form of serotonin syndrome developed. With timely recognition and treatment, the symptoms of serotonin syndrome resolved without lasting consequences. Conclusion: Numerous drugs and substances can induce serotonin syndrome, often in combination with antidepressants. Therefore, it is of great importance that doctors are aware of comorbid conditions that necessitate the use of the mentioned drugs in order to prevent serotonin syndrome. If it does occur, adequate and successful treatment is crucial.