Janus kinase inhibitors and the changing landscape of vitiligo management: a scoping review.

Vitiligo is a chronic skin condition caused by an autoimmune response that results in the progressive loss of melanocytes and recent studies have suggested that Janus kinase inhibitors (JAKi) are emerging as a promising new treatment modality. Therefore, to assess and understand the extent of knowledge in the emerging field of JAKi use in vitiligo, a scoping review of the literature was undertaken. The reviewed articles explored a wide variety of JAKi administered either orally or topically for vitiligo. There were no injectable JAKi studied. Tofacitinib was the most commonly studied oral JAKi in 16 of the 35 studies selected for review, followed by baricitinib (n = 3), and one study each with ritlecitinib, ruxolitinib, and upadacitinib. Ruxolitinib (n = 6) and tofacitinib (n = 6) were the most often studied topical JAKi, followed by delgocitinib (n = 1). Potential benefits may vary between JAKi based on their receptor selectivity profile and coexistent autoimmune diseases. A topical JAKi would be advantageous in limited body area involvement and in adolescents. Concurrent use of JAKi with phototherapy or sun exposure appears beneficial. Most studies permitted the use of other topical agents. Acne-related events, though frequent yet mild, were reported with both oral and topical JAKi. Nasopharyngitis, upper respiratory tract infections, and headaches were the most common adverse effects seen in the larger trials with JAKi. No serious or clinically meaningful hematology or thromboembolic events were detected. Treatment of vitiligo with oral or topical JAKi seems to be promising and the growing evidence shows a favorable risk-benefit profile.

Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore.

BACKGROUND: Many individuals leave costly inpatient detoxification programs prematurely because of the severity of withdrawal symptoms experienced. In the absence of opioid-assisted detoxification in Singapore, diazepam is used to manage withdrawal. However since diazepam is addictive, there is a need to explore the effectiveness of alternative medications. DESIGN AND PROCEDURES: The study aimed to examine the safety and efficacy of lofexidine, a non-opiate, non-addictive, alpha 2-adrenergic agonist in assisting opioid detoxification in Singapore, using a randomized, double-blind, investigator-initiated placebo-controlled trial comparing lofexidine against diazepam. Opioid dependent patients (n = 111) were randomized to receive a 10-day course of lofexidine (n = 56) or diazepam (n = 55). The primary endpoint was the Objective Opioid Withdrawal Scale (OOWS) score on days 3 and 4 and secondary outcomes were the Short Opioid Withdrawal Scale (SOWS) score, program retention rate, and ratings of opiate craving. MAIN FINDINGS: The OOWS, SOWS and opiate craving scores were consistently lower in the lofexidine group relative to the diazepam group over the 14-day study period; however no statistically significant differences were found on days 3 and 4 (peak withdrawal). Changes in mean pupil size during peak withdrawal were significantly smaller in the lofexidine group and more participants in the lofexidine group remained in treatment and completed detoxification. CONCLUSIONS: Lofexidine was at least as effective as diazepam in reducing the opioid withdrawal syndrome and increased treatment retention. In addition to its non-addictive and non-abuse properties, lofexidine has several clinical advantages over diazepam. The use of lofexidine is recommended when opioid-assisted medications are not available.

A review of pharmacokinetic and pharmacodynamic interactions with antipsychotics.

INTRODUCTION: Antipsychotics are widely used and often in combination with other drugs, thereby frequently subjected to drug-drug interactions. This review will provide a summary of potential pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions associated with antipsychotic drugs. METHODS: A literature search was conducted for clinically significant drug interactions with antipsychotics. RESULTS: Most common PK drug interactions take place via the cytochrome P450 (CYP) system. PK profiles of first generation antipsychotics are inadequately studied; nevertheless most common drug interactions involve changes to their metabolic processes. Interactions with second generation antipsychotics are somewhat well-established, documented, and give some guidance for therapeutic treatment interventions. PD interactions occurring at the receptor level result in additive, synergistic, or antagonistic effects. DISCUSSION: This review summarizes a collection of relevant literature of significant PK and PD interactions occurring with antipsychotics. The involvement of multiple CYP enzymes makes it more difficult to predict the extent of the interaction and clinicians should take into consideration the timeline when evaluating potential interactions.

Atypical antipsychotics: A review on the prevalence, monitoring, and management of their metabolic and cardiovascular side effects.

INTRODUCTION: Excessive weight gain, glucose intolerance, and dyslipidemia are well-known physical side effects of the metabolic syndrome commonly associated with atypical antipsychotic (AAP) treatment. We review these side effects of AAPs and their monitoring and management strategies. METHODS: A literature search was conducted to identify articles published on the prevalence, monitoring, and management of cardiometabolic side effects of AAPs. RESULTS: Comparative risk of AAPs on weight gain, hyperlipidemia, glucose intolerance, and QT interval corrected for heart rate prolongation varies across the AAPs currently available. Likewise, pharmacologic and nonpharmacologic options investigated for management of these side effects, and monitoring those at appropriate intervals, differ based on the clinical condition and risk factors identified. DISCUSSION: Atypical antipsychotics in general have little difference among them in short-term efficacy; however, the prevalence of their physical side effects substantially distinguishes them. It is of importance that clinicians carefully select AAPs bearing in mind the presence of risk factors, initiating patients directly on AAPs with a low risk of cardiometabolic side effects, and monitoring and managing those side effects at appropriate intervals.

A review on mortality risks associated with antipsychotic use in behavioral and psychologic symptoms of dementia (BPSD).

INTRODUCTION: As the population ages, the prevalence rate of behavioral and psychologic symptoms of dementia (BPSD) rises, and there appears to be an increasing need for pharmacologic treatment where nonpharmacologic treatment would not suffice. Most clinicians are well aware of the increased risks of cerebrovascular event and mortality from antipsychotic use in older adults with dementia. Nevertheless, mortality risks reported in various publications still vary considerably and lack consistency to allow direct comparison between individual drugs. METHODS: A literature search was conducted for primary and secondary sources of evidence regarding the mortality risks associated with antipsychotic use in BPSD. RESULTS: Available evidence suggests that antipsychotics are indeed associated with elevated risks of cerebrovascular adverse events and mortality. There is also evidence suggestive of a varied risk among individual agents, and a dose-response as well as a time-response relationship. DISCUSSION: This review aims to provide an updated overview of the publications available on mortality data and risks associated with antipsychotic dose and duration of use. Confounders and limitations are discussed to allow clinicians to better make judgment calls on assessing risks and benefits when treating BPSD with an antipsychotic.