Flurazepam 15mg capsules

Background: The clinical decision-making to insomnia drugs should comprehensively weight its risks. Objective: To perform a systematic review and network meta-analysis of randomized controlled trials to compare the AEs associated with different insomnia drugs for adults with insomnia. Methods: We conducted Bayesian network meta-analyses and fixed-effects Mantel-Haenszel network meta-analyses to estimate the relative safety between treatments. Results: Compared with placebo, zolpidem (somnolence: relative risk [RR] 1.85; dizziness: RR 2.33; headache: RR 1.26), zopiclone (somnolence: RR 2.02; dizziness: RR 2.33; dysgeusia: RR 7.84), indiplon (somnolence: RR 3.46; dizziness: RR 2.30; headache: RR 1.63), gaboxadol (dizziness: RR 3.44), eszopiclone (somnolence: RR 2.00; dizziness: RR 3.18; dysgeusia: RR 10.54), estazolam (somnolence: RR 2.08), flunitrazepam (somnolence: RR 3.04), flurazepam (somnolence: RR 2.52), lemborexant (somnolence: RR 6.57), nitrazepam (somnolence: RR 3.80), Ramelteon (somnolence: RR 2.19), suvorexant (somnolence: RR 3.32), Temazepam (somnolence: RR 3.77), trazodone (somnolence: RR 2.86), triazolam (somnolence: RR 2.35), and esmirtazapine (somnolence: RR 4.63; dizziness: RR 2.87) had the most harmful profile in nervous system disorders. Additionally, compared to placebo, zolpidem was also found to be associated with dry mouth (RR 1.92) and anxiety (RR 3.32); gaboxadol was associated with nausea/vomiting (RR 3.49); and eszopiclone was associated with dry mouth (RR 4.39). Doxepin was associated with lower risk of headache and somnolence than placebo or/and most of other drugs, and had also a lower rate of AEs. We observed no associations between drugs and the risks of serious AEs including nasopharyngitis, respiratory problem, accidental injury, infection, upper respiratory tract infection, sinusitis, or hematuria. Conclusions: Most drugs were positive associated with nervous system disorders and gastrointestinal disorders. Data on some drugs like flurazepam, nitrazepam, triazolam, and zaleplon in some outcomes were mainly based on limited study with rare event and thus was highly uncertain and do not allow firm conclusions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022344981.

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Aim This network meta‐analysis of randomized controlled trials (RCTs) aimed to investigate which hypnotics are associated with the most favorable sleep architecture and respiratory outcomes in adults with obstructive sleep apnea. Methods Primary outcomes included total sleep time (TST) and apnea–hypopnea index (AHI) during TST. Other outcomes were rapid eye movement (REM) sleep time, latency to persistent sleep (LPS), wake after sleep onset (WASO), sleep efficiency (SE), AHI during non‐REM or REM sleep, mean peripheral oxygen saturation (SpO 2 ) during TST, mean SpO 2 nadir during TST, arousal index (AI), all‐cause discontinuation, adverse event‐related discontinuation, and incidence of individual adverse events. Effect sizes with 95% confidence intervals were calculated. Results This systematic review included 32 RCTs ( n = 1871, average age = 51.60 years, 62.52% male, mean AHI = 23.60). Our network meta‐analysis evaluated brotizolam, daridorexant, eszopiclone, flurazepam, lemborexant, nitrazepam, ramelteon, temazepam, triazolam, zaleplon, zolpidem, zopiclone, and placebo. Compared with placebo, lemborexant increased TST, REM sleep time, and SE and decreased LPS and WASO, whereas both daridorexant and zolpidem increased TST and SE and decreased WASO. These three medications demonstrated respiratory safety and discontinuation profiles similar to those of placebo. Eszopiclone increased TST and SE and decreased LPS, WASO, AHI during TST, and AI, but its effects on LPS, WASO, AHI during TST, and AI disappeared in the sensitivity analysis, excluding continuous positive airway pressure titration studies. Conclusion Our network meta‐analysis identified different effects of various hypnotics on sleep architecture and respiratory parameters; however, the lack of data prevented a formal synthesis of subjective outcomes. Therefore, these results should be interpreted with caution in clinical practice.

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A 39-year-old female patient, followed in outpatient care for bipolar I disorder, effectively treated with lithium since January 2022 (a dose of 18 mmol 2× per day and latest plasma concentrations around 0.85 mmol/L during the last months), and flurazepam (30 mg/j) for sleep onset difficulties, was referred to the emergency department for involuntary admission on August 13 by her psychiatrist for suspicion of a manic episode with mixed features. Upon arrival at the psychiatric emergency department, the patient was confused, with disorganized thinking, disoriented as far as the situation, the place and the time, a marked psychomotor slowing, bilateral miosis, spontaneous tremors, jaw dysarthria and muscle rigidity. She reported taking lithium as prescribed (18 mmol 2×/day), flurazepam (30 mg per day), and a weight-loss treatment which she had procured, without prescription, online (of a composition unknown to the patient). Biological tests revealed acute kidney injury (KDIGO III), with elevated lithium levels at 3.94 mmol/L, hypokalemia at 2.6 mmol/L, and hypophosphatemia at 0.22 mmol/L. A prolonged QTc of 570 ms was also noted. A brain CT scan ruled out any intracranial hemorrhage. The patient was transferred to intensive care for a lithium poisoning-associated toxic encephalopathy. All previously administered pharmacological treatment was suspended. Benzodiazepines (lorazepam 5 mg per day) were administered to manage the neurological symptoms with good effect. After two dialysis sessions, her condition improved, with a return to normal diuresis, creatinine levels within the normal range, and lithium levels below 1 mmol/L. Her clinical presentation improved as well. After her non-psychiatric condition was stabilized, the patient was transferred to a specialized inpatient mood disorders unit of our Hospital. She was euthymic. Lithium treatment was reinstated upon arrival in our unit, given that the non-psychiatric state had been stabilized and lithium serum concentration was below 1 mmol/L, to a final dose of 30 mmol/day, according to current clinical practice [1]. We conducted a toxicological screening using LC–MS/MS of the weight-loss treatment, which revealed that it contained fluoxetine, furosemide, hydrochlorothiazide, metformin, and sibutramine. These two diuretics likely contributed to the elevated lithium levels and the acute kidney injury. The patient has bipolar I disorder, diagnosed in 2016. She has had three psychiatric hospitalizations for manic episodes with behavioral disturbances, including hetero-aggressive behavior and persecutory delusions and two for major depressive episodes. She has been under outpatient care with a history of variable therapeutic compliance. She had been consequently treated with quetiapine up to 300 mg per day, aripiprazole (per os) up to 10 mg per day and intramuscular long-acting aripiprazole (400 mg per month). After two more hospital admissions for a manic episode following treatment discontinuation (the latest taking place in January 2022), lithium was introduced, and no new episode was reported since (Figure 1). In the end of July 2024, the patient started taking over-the-counter weight-loss pills ordered online from Brazil, without knowing their exact composition. According to her immediate family, since early August, she had experienced hand tremor, progressive psychomotor slowing and stiffness, culminating with a state of confusion over the last 3 days preceding her admission. She noted that she had developed tremors in her upper limbs, a metallic taste, and nausea after she started taking the weight-loss pills. The use of these weight-loss pills was not reported to her psychiatrist. Lithium treatment was continued as prescribed throughout the course of the weight-loss use. Lithium remains a cornerstone in managing bipolar disorder due to its efficacy in stabilizing mood fluctuations. However, its narrow therapeutic index necessitates rigorous monitoring, as interactions with other substances can precipitate toxicity. This case exemplifies the dangers associated with unregulated weight-loss supplements, which may contain undisclosed pharmacologically active ingredients [2]. The toxicological analysis of the patient's weight-loss product revealed the presence of fluoxetine, furosemide, hydrochlorothiazide, metformin, and sibutramine. The inclusion of diuretics such as furosemide and hydrochlorothiazide is particularly concerning, as they can reduce renal lithium clearance, leading to elevated serum lithium levels and potential toxicity. Additionally, sibutramine, an appetite suppressant withdrawn from the market due to cardiovascular risks, and fluoxetine, a selective serotonin reuptake inhibitor, can further complicate the clinical picture through their own side effect profiles and potential interactions. The prevalence of dietary supplements adulterated with pharmaceutical agents is a growing public health concern. A study assessing the US Food and Drug Administration's Tainted Supplements Database from 2007 through 2016 identified numerous products marketed for weight loss containing undeclared substances, including sibutramine and various diuretics [3]. These adulterated supplements pose significant health risks, especially when consumed without medical supervision. According to research, nonprescription weight-loss product use remains common, despite the potential for severe adverse effects [4]. Additionally, a systematic review identified a high prevalence of adolescent use of nonprescription weight-loss products, further emphasizing the necessity of stricter regulations and public awareness campaigns [5]. Patients with bipolar disorder may seek over-the-counter weight-loss products to address medication-associated weight gain, often without disclosing this to their healthcare providers. This behavior underscores the necessity for clinicians to proactively inquire about all substances patients are taking, including non-prescription products. Failure to do so can result in a confirmation bias, where new or worsening symptoms are misattributed solely to psychiatric causes, potentially overlooking underlying non-psychiatric issues such as medication interactions or toxicities. Beyond the pharmacological interaction with diuretics, rapid weight loss and associated volume depletion may have further reduced renal lithium clearance, thereby promoting lithium accumulation. Psychoeducation plays a pivotal role in preventing such adverse events. Educating patients on the potential risks of unapproved supplements and the importance of reporting all ingested substances can aid in early identification of toxicity. Moreover, informing patients about the early signs of lithium overdose—including gastrointestinal disturbances, tremors, confusion, and neuromuscular excitability—can facilitate prompt medical attention and intervention. In conclusion, this case highlights the imperative for comprehensive medication reconciliation and patient education in those receiving lithium therapy. Clinicians must maintain a high index of suspicion for potential interactions with over-the-counter products and provide thorough education on the risks associated with unregulated supplements and the early manifestations of lithium toxicity. Open access publishing facilitated by Universite de Geneve, as part of the Wiley - Universite de Geneve agreement via the Consortium Of Swiss Academic Libraries. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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