aripiprazole induced rosacea. case report and literature review

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Aripiprazole-induced rosacea. case report and literature review.

Published online by Cambridge University Press:  13 August 2021

Skin and subcutaneus tissue disorders are common type of adverse drug reactions reported with a wide variety of both typical and atypical antipsychotics. Aripiprazole is a quinolinone antipsychotic that is a partial agonist at the D2 and 5-HT1A receptors and antagonist at the 5-HT2A receptors. We report a case of rosacea that developed after starting aripiprazole in a patient with schizophrenia and which remitted after the drug was stopped.

To present a case of rosacea that developed in a schizophrenic patient after starting aripiprazole. Review of literature and search for the total number of cases reported in the european database of suspected adverse drug reactions (EudraVigilance).

We carried out a literature review in Pubmed electing those articles focused on skin ad subcutaneous skin disorders in those patients that have been taking aripiprazole. Review number of cases of skin reactions reported by the European database of suspected adverse drug reactions.

A 43-year-old man previously diagnosed with schizophrenia with low adherence to different treatments. He came to our service seeking for help in order to decrease delusions with a treatment with minimun adverse reactions. We started aripirazole 10 mg every day and, after 7 days appeared signs of rosacea in his face. After discontinuation of aripiprazol, after 5 days, rosacea remitted.

Rosacea in our case posibly point aripiprazole as the agent that produced the skin reaction. After stopping the treatment the signs disapeared. Awareness of skins manifestations produced by aripiprazole is essential to prevents worse skin reactions.

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• Volume 64, Special Issue S1
• T. Gutiérrez Higueras (a1) , B. Hernandez Gajate (a1) , F. Calera Cortés (a1) , S. Vicent Forés (a1) and S. Sainz De La Cuesta Alonso (a1)
• DOI: https://doi.org/10.1192/j.eurpsy.2021.1295

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Aripiprazole-induced rosacea. Case report and literature review

T. G. Higueras , B. H. Gajate , F. Cortés +2 more  ·  Apr 1, 2021

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European Psychiatry

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Aripiprazole may cause rosacea in schizophrenia patients, but discontinuing the drug after 5 days remitted the symptoms..

Introduction Skin and subcutaneus tissue disorders are common type of adverse drug reactions reported with a wide variety of both typical and atypical antipsychotics. Aripiprazole is a quinolinone antipsychotic that is a partial agonist at the D2 and 5-HT1A receptors and antagonist at the 5-HT2A receptors. We report a case of rosacea that developed after starting aripiprazole in a patient with schizophrenia and which remitted after the drug was stopped. Objectives To present a case of rosacea that developed in a schizophrenic patient after starting aripiprazole. Review of literature and search for the total number of cases reported in the european database of suspected adverse drug reactions (EudraVigilance). Methods We carried out a literature review in Pubmed electing those articles focused on skin ad subcutaneous skin disorders in those patients that have been taking aripiprazole. Review number of cases of skin reactions reported by the European database of suspected adverse drug reactions. Results A 43-year-old man previously diagnosed with schizophrenia with low adherence to different treatments. He came to our service seeking for help in order to decrease delusions with a treatment with minimun adverse reactions. We started aripirazole 10 mg every day and, after 7 days appeared signs of rosacea in his face. After discontinuation of aripiprazol, after 5 days, rosacea remitted. Conclusions Rosacea in our case posibly point aripiprazole as the agent that produced the skin reaction. After stopping the treatment the signs disapeared. Awareness of skins manifestations produced by aripiprazole is essential to prevents worse skin reactions.

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Aripiprazole-induced rosacea. Case report and literature review

Introduction Skin and subcutaneus tissue disorders are common type of adverse drug reactions reported with a wide variety of both typical and atypical antipsychotics. Aripiprazole is a quinolinone antipsychotic that is a partial agonist at the D2 and 5-HT1A receptors and antagonist at the 5-HT2A rec...

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• Published: 16 September 2024

Ocular effects of Rho kinase (ROCK) inhibition: a systematic review

• Jonathan B. Lin 1 ,
• James M. Harris 1 ,
• George Baldwin 1 ,
• Deborah Goss 1 &
• Milica A. Margeta   ORCID: orcid.org/0000-0002-5902-4168 1  

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• Optic nerve diseases

Topical therapies targeting Rho-associated protein kinase (ROCK) signalling, including netarsudil (Rhopressa®) and ripasudil (Glanatec®), have become widely adopted as part of standard clinical practice to lower intraocular pressure (IOP) in patients with ocular hypertension or glaucoma. Given the pleiotropic roles of ROCK signalling, ROCK inhibition has the potential to cause unintended ocular side effects beyond IOP lowering in other substructures of the eye, both beneficial and deleterious. Additional experience and observation of patients treated with this class of medications have uncovered both new side effects not reported in the initial clinical trials, as well as potential benefits that have inspired off-label uses and that have been the topic of numerous clinical studies, case series, case reports, and translational studies. Here, we performed a comprehensive systematic review and identified 170 studies describing ocular effects of ROCK inhibition. In addition to describing well-established ocular effects associated with inhibition of ROCK signalling, such as conjunctival hyperaemia, corneal verticillata, and reticular corneal epithelial oedema, we also highlight other effects, such as corneal haemorrhages, changes in corneal contour, anterior subcapsular opacities, contact dermatitis, punctal stenosis, and eyelid wound dehiscence, which have been described in case series and case reports. Finally, we evaluated studies describing potential novel applications of ROCK inhibition for treating disorders affecting the cornea, the retina, and the optic nerve, finding strong evidence in support of a beneficial effect of ROCK inhibitors on corneal oedema due to corneal endothelial cell dysfunction. The other potential applications require further research.

针对Rho相关蛋白激酶(ROCK)信号传导的局部疗法, 包括奈塔舒地尔(Rhopressa®) 和利帕舒地尔 (Glanatec®), 已被广泛用于临床实践作为标准的一部分, 以降低高眼压症或青光眼患者的眼内压 (IOP)。鉴于 ROCK 信号传导的多能作用, ROCK 抑制剂除了降低眼内压以及作用于眼部其它结构以外, 还可能导致意想不到的眼部副作用, 这些副作用可能有益, 也可能有害。对接受此类药物治疗的患者的额外经验和观察揭示了最初的临床试验中未报导的新副作用, 也激发了非标签使用的潜在益处, 并且这些益处已成为众多临床研究、病例系列、病例汇报和转化研究所关注的方向。在本文中, 我们确定了168项描述ROCK抑制剂对眼部影响的研究并进行了系统分析。除了描述与 ROCK 信号传导抑制相关的已明确的眼部效应, 如结膜充血、角膜轮状化和网状角膜上皮水肿外, 我们还强调了其它作用, 如角膜出血、角膜轮廓变化、前囊下混浊、接触性皮炎、泪点狭窄和眼睑伤口裂开, 这些副作用均在在病例系列和病例汇报中进行了描述。最后, 我们评估了ROCK抑制剂在治疗角膜、视网膜和视神经的等疾病方面的潜在新应用的研究, 发现有强有力的证据支持ROCK抑制剂对角膜内皮细胞功能障碍所致角膜水肿会产生有益的作用。其他潜在应用需要进一步研究。

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JBL was supported by the VitreoRetinal Surgery Foundation and the Gragoudas-Folkman Award. JMH was supported by the Gragoudas-Folkman Award. MAM was supported by NIH/NEI R01EY035312, the Glaucoma Research Foundation Catalyst for a Cure Award, the Melza M. and Frank Theodore Barr Foundation, the Research to Prevent Blindness Career Development Award, the Alcon Research Institute Young Investigator Award, the Massachusetts Lions Eye Research Fund, the Robert M. Sinskey Foundation, the Ruettgers Family Charitable Foundation, and the B.L. Manger Foundation. The funders played no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The sponsor or funding organization had no role in the design or conduct of this research.

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Jonathan B. Lin, James M. Harris, George Baldwin, Deborah Goss & Milica A. Margeta

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Conceptualization: MAM. Methodology: MAM, JBL, and DG. Investigation: JBL, JMH, GB, and DG. Writing—original draft: JBL, JMH, and GB. Writing—review & editing: JBL, JMH, GB, DG, and MAM. Supervision: MAM and JBL. Funding acquisition: MAM.

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Lin, J.B., Harris, J.M., Baldwin, G. et al. Ocular effects of Rho kinase (ROCK) inhibition: a systematic review. Eye (2024). https://doi.org/10.1038/s41433-024-03342-4

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Management of Infected Tibial Nonunion: Combining Synthetic Bone Grafting with Continuous Local Antibiotic Perfusion (CLAP)

Kenichi sawauchi.

1 Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Tomoaki Fukui

Ryosuke kuroda, takahiro niikura.

2 Department of Orthopaedic Surgery, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan

Hirotsugu Muratsu

3 Department of Orthopaedic Surgery, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji, Hyogo, Japan

Akihiro Maruo

Patient: Female, 31-year-old

Final Diagnosis: Infected nonunion

Symptoms: Infection • nonunion

Clinical Procedure: —

Specialty: Orthopedics and Traumatology

Unusual or unexpected effect of treatment

Background:

Infection control and reconstruction of bone and soft tissue are essential for treating infected nonunion. Continuous local antibiotic perfusion (CLAP) is a drug delivery system that continuously delivers antibiotics at the required concentration, area, and duration. This case report describes the instance of infected nonunion in which infection eradication and bone union were achieved using CLAP and synthetic bone grafting while retaining the implant.

Case Report:

The case was a 31-year-old woman with an infected nonunion. After she underwent osteosynthesis using nail for open fractures of tibia and fibula, bone union remained unachieved, and she exhibited skin defects and draining of pus. Following the removal of the infected granulation tissue from the bone defects, 2 bone marrow needles, serving as intramedullary antibiotic perfusion (iMAP) pins, were inserted into the medullary cavity tibia. A double-lumen tube was placed in the subcutaneous pocket as the intra-soft tissue antibiotic perfusion (iSAP) tube. No bone mobility was observed around the bone defect and nail, and replacement of the implant was not necessary. Beta-tricalcium phosphate was transplanted to the bone defect, and negative pressure wound therapy was applied. Gentamicin was injected continuously through iMAP and iSAP. Finally, the infection was eradicated, and cortical bone bridging was observed without additional surgery or adverse effects.

Conclusions:

CLAP emerges as a viable treatment option for infected nonunion, as it enables the delivery of antibiotics at a concentration sufficient for infection control while providing the surgeon with flexibility to design the area, dosage, and duration of antibiotic delivery.

Introduction

The treatment of an infected nonunion requires infection control and the reconstruction of bone and soft tissue. Despite advancements in treatment methods, infected nonunions persist as difficult-to-treat orthopedic problems. Generally, standard treatment involves complete resection around the infected lesion, followed by soft tissue and skeletal reconstruction [ 1 ]. This requires multiple surgical procedures and an extended treatment duration, imposing a heavy burden on patients [ 2 ].

We recently introduced a case series in which fracture-related infections were treated with continuous local antibiotic perfusion (CLAP) [ 3 , 4 ]. CLAP is an antibiotic delivery system consisting of intramedullary antibiotic perfusion (iMAP) and intra-soft tissue antibiotic perfusion (iSAP), which continuously delivers antibiotics at the required concentration, area, and duration, with negative pressure assistance. This system facilitates infection control while retaining the implants and tissues affected by the bacteria. In this report, we describe the case of an infected nonunion in which infection eradication and bone union were achieved using CLAP and synthetic bone grafting, while retaining the implant. Retaining the nail prevents the infection from spreading to healthy tissue, including the knee joint. Since this technique does not require autologous bone grafting, it is much less invasive than standard treatments.

Case Report

The patient, a 31-year-old woman, presented with a medical history of eating disorders and depression and had been taking aripiprazole, nitrazepam, topiramate, clonazepam, and sodium valproate. She had no history of alcohol intake or smoking. At the age of 29 years, she sustained injuries to her left tibia and fibula, resulting in open fractures classified as Gustilo-Anderson type IIIA ( Figure 1A ). Within 3 h of the injury, she underwent debridement and osteosynthesis using an intramedullary nail ( Figure 1B ). Subsequently, she began walking with a patellar tendon-bearing brace and was discharged without signs of infection. However, she continued to experience walking pain 12 months after surgery. At 15 months after injury, she exhibited skin defects and pus drainage near the wound without bone union ( Figure 2A, 2B ). The infection was not controlled even after several weeks of intravenous antibiotic treatment. Following a period of treatment interruption owing to mental issues, the 2 screws around the skin defect were removed 21 months after surgery; however, the symptoms persisted. At 27 months after surgery, the patient consented to surgical intervention to address the infected nonunion.

( A ) Radiographs of anteroposterior view and lateral view at the time of injury. Open fractures of the left tibia and fibula were observed. ( B ) Radiographs after osteosynthesis using an intramedullary nail on the day of the injury.

( A ) Photographs 15 months after osteosynthesis using an intramedullary nail. The patient began exhibiting skin defects and draining of pus proximal to the wound. ( B ) Radiographs and computed tomography scans 27 months after the first surgery. The fracture was not united, and bone defects were observed at the anterior and medial parts of the fracture site.

Under general anesthesia, a Z-shaped skin incision was made around the fistula, extending 4 cm both proximally and distally on the medial side of the left lower leg. The fistula communicated with the bone defect through the subcutaneous pocket, with pus and infectious tissue filling the bone defect ( Figure 3A ). The bone defects measured 2.5×1 cm, mainly in the anterior and medial aspects of the distal tibia ( Figure 3B ). Despite the removal of the distal screws, no bone mobility was observed around the bone defect and nail. After assessing the nonunion stability, we concluded that implant exchange or additional plate fixation to improve fixation was not necessary. We also determined to retain the nail because there was a risk that the infection, which was thought to be localized in the distal tibia, might spread to healthy tissue, including the knee joint, by removing the nail.

Photographs taken during surgery. ( A ) The fistula communicated with the bone defect through the subcutaneous pocket, with pus and infectious tissue filling the bone defect. ( B ) The bone defect measured 2.5×1 cm, mainly in the anterior and medial aspects of the distal tibia.

Following the removal of the infected granulation tissue from the bone defects, 2 bone marrow needles (Senko Medical, Tokyo, Japan) with a diameter of 3 mm, serving as iMAP pins, were inserted percutaneously into the medullary cavity of the proximal and distal tibia. Sclerotic changes were observed on the surface of the bone defect, prompting the creation of multiple drill holes using a 1.0 mm Kirschner wire to intersect the normal medullary canal and infected region. A 22 Fr double-lumen tube (Salem sump tube; Covidien, Japan) was placed in the subcutaneous pocket as an iSAP tube. Upon injection of saline through the iMAP pins, the contaminated yellow tissue containing pus flowed out of the medullary canal. This irrigation continued until the discharge became clear. Beta-tricalcium phosphate (β-TCP) was transplanted to the bone defect. Following skin closure, a 1×1-cm skin defect remained, and negative-pressure wound therapy was applied over the subcutaneous pocket and skin defect. Fluid infused through the iMAP pins and iSAP tubes was aspirated through the negative-pressure wound therapy and iSAP tubes, confirming fluid perfusion throughout the infected area ( Figure 4A, 4B ).

( A ) Photograph during the surgery, using continuous local antibiotic perfusion (CLAP). There were 2 intramedullary-antibiotic perfusion (iMAP) pins and an intra-soft tissue antibiotic perfusion (iSAP) tube. Beta-tricalcium phosphate (β-TCP) was transplanted to the bone defect. ( B ) Radiograph after the CLAP surgery shows that iMAP pins were placed at the proximal anterior and distal anterior tibia and an iSAP tube was placed in the subcutaneous pocket.

Gentamicin was injected continuously at a concentration of 1200 µg/mL at a rate of 2.0 mL/h via iMAP pins and iSAP tubes immediately after surgery. Six days postoperatively, the serum concentration of gentamicin was above 2.0 µg/mL, prompting a reduction in injection concentration to 600 µg/mL. Subsequently, serum concentrations remained below 1.0 µg/mL. The effluent concentrations of gentamicin measured at 2 and 6 days postoperatively were 680 µg/mL and 780 µg/mL, respectively. All the pins and tubes were removed on postoperative day 20.

The skin defects gradually reduced as swelling decreased, finally healing without additional surgery 1 month after the procedure ( Figure 5 ). The patient regained the ability to walk without weight-bearing limitations. Tissue cultures revealed the presence of 2 microorganisms: Streptococcus agalactiae and Citrobacter freundii , which are resistant to gentamicin. Intravenous antibacterial treatment with 6.0 g/day of ampicillin/sulbactam was administered until 1 month postoperatively, followed by a switch to oral antibiotics, which continued until 3 months postoperatively. C-reactive protein levels normalized 9 days postoperatively and remained within the reference range thereafter ( Figure 6 ). No adverse effects were observed during these treatments, and the patient was discharged 46 days after surgery, without the need for additional surgery. Unexpectedly, bone remodeling progressed at the β-TCP transplant site, and cortical bone bridging and new bone formation in the medullary cavity were observed 15 months after CLAP surgery ( Figure 7A, 7B ). Nail removal was performed 3 years after surgery, and the patient had not experienced a recurrence of infection at 3.5 years after surgery. The patient was able to walk with a patellar tendon-bearing brace before nonunion surgery, walk with a cane 1 month after surgery, and walk unassisted at the final follow-up, with visual analog scale scores of 4, 2, and 0, respectively.

Photographs of skin-defect area. Negative pressure wound therapy was applied over the subcutaneous pocket and skin defect. Skin defects gradually reduced as swelling decreased, finally healing without additional surgery 1 month after the continuous local antibiotic perfusion surgery.

Graph of blood test data and locally/intravenously administered antibiotics. WBC – white blood cells; CRP – C-reactive protein; conc – concentration; GM – gentamicin; ABPC/SBT – ampicillin/sulbactam.

Radiographs of the nonunion site until 15 months after surgery ( Above: anteroposterior view, Below: lateral view). Bone remodeling continued to progress at the β-TCP transplant site, and cortical bone bridging and new bone formation in the medullary cavity were observed 15 months after continuous local antibiotic perfusion surgery.

Advantages of CLAP

This is the report of an infected nonunion that was treated by retaining the implant and performing one-stage synthetic bone grafting for the bone defect in combination with CLAP. The advantage of CLAP lies in its ability to deliver a high concentration of gentamicin, which can destroy biofilms, even those formed by drug-resistant microbes. In the present case, implants believed to be coated with biofilms of gentamicin-resistant microbes developed during long-term infection were successfully retained. In addition, fracture healing was achieved using a synthetic bone graft.

Comparison with Previous CLAP Cases

According to the literature, there are 16 case reports or case series papers related to CLAP, 6 of which are about fracture-related infection. Of these, 2 of the studies included cases in which infection occurred more than 10 weeks after the fracture, and, as in our case, the infection was successfully treated with CLAP, while retaining the implant [ 4 , 5 ]. In these studies, autologous bone grafting was performed in cases with bone defects, while no cases of healing using synthetic bone grafting were reported. In the present case, we planned additional surgery to exchange or compensate for the bone defect after the synthetic bone graft; however, unexpectedly, bone union was achieved without an additional surgery. Treatment with synthetic bone graft alone might be a good option, without loss of autologous bone.

Comparison with Traditional Methods

One of the standard treatments for infected nonunion is the Masquelet technique [ 6 ]. The treatment principle involves the complete removal of tissues with poor vascularity, including sclerotic bone and metal implants. Subsequently, bone cement is placed in the bone defect [ 7 ]. This can reduce the risk of recurrent infection but can also increase the risk of bone instability and re-fracture. Other treatment options include fixation with an antibiotic-coated nail, which has been reported to control infection but presents challenges such as nail breakage and difficulty in removal [ 8 , 9 ]. In both treatments, the antibiotics eluted from the bone cement remain at high concentrations for the first few days and then rapidly decrease to sub-therapeutic levels [ 10 ]. After this period, biofilm can form on the cement surface, necessitating surgical removal. In contrast, CLAP allows the administration of high supratherapeutic concentrations of antibiotics for the required duration without increasing the risk of re-fracture or implant fracture and without the need for additional surgery for removal.

Efficacy of Gentamicin in CLAP

Gentamicin is known for its efficacy against bacterial biofilms in postoperative orthopedic infections, and high concentrations have sufficient antibacterial activity regardless of susceptibility [ 11 ]. In the present case, the effluent gentamicin concentrations at 2 and 6 days after surgery were 680 µg/mL and 780 µg/mL, respectively, and were estimated to exceed a minimal inhibitory concentration of gentamicin-resistant microbes.

Retaining Nail

In the present case, we considered that there were many benefits to not exchanging the implant. Since the radiographic images did not show any loosening around the proximal nail, we judged that the infection was localized in the distal tibia. In the exchange of the implant, the existing nail, which was previously inserted antegradely, must have been removed through the knee joint, which could have caused infection to spread to the proximal tibia and knee joint. Treatment using CLAP allowed us to administer antibiotics at local concentrations that could control the biofilm; therefore, we thought there was a chance of eradicating the infection. In addition, we thought the patient would not be able to tolerate prolonged and highly invasive surgery because of her mental health status. Therefore, we chose these less invasive and shorter treatments first. However, if we had failed to control the infection, we might have switched to standard treatments, such as exchanging the nail.

Synthetic Bone Remodeling

One-stage treatment of infected cases with bone defects using antimicrobial-containing calcium sulfate or antimicrobial-impregnated allograft has been reported to result in infection control and subsequent bone formation in the bone defect, contrary to the conventional treatment principle advocating for the removal of material with poor blood flow [ 12 , 13 ]. In the present case, we used β-TCP, a synthetic bone, as a scaffold. Autologous bone grafting is common for bone defects, and we planned it as the next surgery. However, β-TCP remodeling had already progressed unexpectedly. We inferred that multiple drill holes with Kirschner wires, a standard technique in CLAP to perfuse antibiotics to infected but biologically active areas, allowed us to avoid unnecessary extensive curettage. Additionally, this induced osteogenic cells and growth factors from the normal bone marrow into the β-TCP, which acts as the osteoconductive scaffold, resulting in bone healing.

Future Directions

When treating with CLAP, there is a possibility that antibiotics will not reach the required concentration and area, necessitating careful observation, especially in cases of minimal curettage and implant preservation. The identification of synthetic bone remodeling subsequent to the eradication of the infection was a novel discovery in the present case. However, we considered that complete bone union may not be achieved in all cases using synthetic bone, and such cases require second-stage reconstruction planning. In the future, it will be necessary to investigate this issue with multiple cases.

Conclusions

We encountered a case of a patient with an infected nonunion for which infection control and bone union were achieved without implant replacement or autologous bone grafting, using CLAP. CLAP emerges as a viable treatment option for infected nonunion, as it enables the delivery of antibiotics at a concentration sufficient for infection control while providing the surgeon with flexibility to design the area, dosage, and duration of antibiotic delivery. An individualized treatment plan is important, as a thorough evaluation of the nonunion stability and the infection area can provide less invasive treatment options.

Acknowledgments

We would like to thank Editage ( www.editage.jp ) for English language editing.

Abbreviations:

Publisher’s note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher

Department and Institution Where Work Was Done

Department of Orthopaedic Surgery, Steel Memorial Hirohata Hospital, Himeji, Hyogo, Japan.

Declaration of Figures’ Authenticity

All figures submitted have been created by the authors who confirm that the images are original with no duplication and have not been previously published in whole or in part.

References:

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Aripiprazole-induced Diplopia: A Rare Case Report Aripiprazole-induced Diplopia: A Rare Case Report -->

Manaswini Mullapudi, R Madan, Vishnu Vardhan, M Vidhyavathi

Keywords : Adverse effects, Aripiprazole, Diplopia dialogue , Eurocentrism -->

DOI: 10.5005/jp-journals-10045-00122

License: CC BY-NC 4.0

Published Online: 15-07-2020

Copyright Statement:  Copyright © 2019; The Author(s).

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Background: Aripiprazole is a second-generation antipsychotic (SGA) drug. The commonly reported side effects of aripiprazole are headache, nausea, constipation, somnolence, or insomnia. However, ocular side effects are rarely reported with aripiprazole, with myopia being the most commonly reported. Eight cases of aripiprazole-induced myopia were reported and only two cases of diplopia secondary to aripiprazole use were reported in literature. Aim: We aim to report a case of aripiprazole-induced diplopia in a 28-year-old woman who was treated for depression with psychotic symptoms. Case description: A 28-year-old woman who was a known case of depression with psychotic symptoms was treated with 3 mg oral risperidone but had to be switched to aripiprazole due to hyperprolactinemia. Within 10 days of starting oral aripiprazole at a dose of 10 mg, the patient reported symptoms of double vision and blurring of vision in both eyes. On ophthalmologic evaluation, the patient did not have any refractory error. She did not have signs of any extrapyramidal symptoms, and preliminary neurological examination did not reveal any other abnormalities. Keeping in mind the possibility of the rare side effect of diplopia, she was advised to discontinue aripiprazole. On stopping the drug, the patient reported reduction in symptoms within 5 days with complete resolution in 10 days of stopping aripiprazole. The acute onset of diplopia and resolution of symptoms after stopping the drug correlates strongly with aripiprazole-induced diplopia. Till date, only two such cases were reported. Conclusion: Both the treating psychiatrists and ophthalmologists should be well aware that though rare, diplopia is a possible adverse effect of aripiprazole. Prompt discontinuation can reverse the condition.

• Taylor DM. Aripiprazole: a review of its pharmacology and clinical use. Int J Clin Pract 2003;57(1):49–54.
• Fleischhacker WW. Aripiprazole. Expert Opin Pharmacother 2005;6(12):2091–2101. DOI: 10.1517/14656566.6.12.2091.
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• Gupta S, Lakshmanan DAM, Khastgir U, et al. Management of antipsychotic-induced hyperprolactinaemia. B J Psych Adv 2017;23(4):278–286. DOI: 10.1192/apt.bp.115.014928.
• Abreu T, Pinheiro J. Aripiprazole induced myopia–case report and literature review: Aripiprazole induced myopia. Clin Schizophr Relat Psychoses 2019. DOI: 10.3371/CSRP.TAJP.121218.
• Selvi Y, Atli A, Aydin A, et al. Aripiprazole-related acute transient myopia and diplopia: a case report. J Clin Psychopharmacol 2011;31(2):249–250. DOI: 10.1097/JCP.0b013e3182103493.
• Atli A, Selvi Y, Yildiz A, et al. Aripiprazole-induced diplopia: a case report. Klinik Psikofarmakol Büteni 2013;23(4):353–356. DOI: 10.5455/bcp.20130303114826.

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Persistent hiccups due to aripiprazole: a case report and review of the literature

Affiliations.

• 1 Department of Psychosomatics, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
• 2 Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, China.
• 3 Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
• PMID: 38249349
• PMCID: PMC10797005
• DOI: 10.3389/fphar.2023.1284510

Introduction: Aripiprazole, a commonly prescribed antipsychotic, has been rarely associated with the onset of hiccups. This study aims to elucidate the prevalence, risk factors, and management of aripiprazole-induced hiccups. Methods: We report a case of aripiprazole-induced hiccups in a 32-year-old male diagnosed with Somatic Symptom Disorder per DSM-5 criteria.A comprehensive literature review was conducted, identifying 29 case reports of aripiprazole-induced hiccups. Patient demographics, dosage, onset and duration of hiccups, and management strategies were analyzed. Results: Aripiprazole-induced hiccups predominantly affected adolescents and middle-aged male patients (86.7%). The majority of hiccups developed within 1-2 days post-prescription (90.9%) and resolved within 1-4 days after discontinuation of aripiprazole. Discontinuation of aripiprazole was the most effective management strategy (51.7%). Co-administration with benzodiazepines was identified as a significant risk factor. Discussion: The findings suggest that clinicians should be vigilant for the onset of hiccups during the early stages of aripiprazole treatment, especially in male patients and those co-administered with benzodiazepines. Conclusion: Clinicians should be vigilant for hiccups during early aripiprazole treatment. Considering personality and psychological factors is crucial in managing hiccups in psychiatric patients.

Keywords: adverse effects; aripiprazole; hiccup; management; psychosocial factor.

Copyright © 2024 Zhang, Chen, Chen, Li, Huang and Min.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

DA:Dopamine D2 receptors; 5HT1A:serotonin 5-HT1A…

DA:Dopamine D2 receptors; 5HT1A:serotonin 5-HT1A receptors; 5HT2A:serotonin 5-HT2A receptors; GABAA (β-1):Gamma-aminobutyric acid A…

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