Effect of lemborexant on pharmacokinetics of clozapine: A potential drug-drug interaction mediated by time-dependent inhibition of CYP3A4.

Clozapine (CLZ) is extensively used for treatment-resistant schizophrenia (TRS) with caution to avoid serious adverse events such as agranulocytosis and drug-drug interactions (DDIs). In the current report, we present a case of a 35-year-old male non-smoking TRS patient whose steady-state plasma trough concentrations (Ctrough ) of CLZ and its active metabolite, N-desmethylclozapine (NDMC), were significantly increased after initiating oral administration of lemborexant (LEM), a dual orexin receptor antagonist, for the treatment of insomnia. The patient experienced oversedation with sleepiness and fatigue while maintaining high levels of Ctrough of CLZ. The increased concentrations of CLZ returned to normal ranges after the discontinuation of LEM dosing, implying a pharmacokinetic DDI between CLZ and LEM. To gain insight into possible mechanisms, we performed in vitro assays of CYP1A2- and CYP3A4-mediated CLZ metabolism by measuring the formations of NDMC and clozapine N-oxide (CNO). In accordance with previous studies, the incubation of CLZ with each enzyme resulted in the production of both metabolites. LEM had only a weak inhibitory effect on CYP1A2- and CYP3A4-mediated CLZ metabolism. However, the preincubation of LEM with CYP3A4 in the presence of NADPH showed a significant enhancement of inhibitory effects on CLZ metabolism with IC50 values for the formations of CNO and NDMC of 2.8 µM and 4.1 µM, respectively, suggesting that LEM exerts as a potent time-dependent inhibitor for CYP3A4. Taken together, the results of the current study indicate that co-medication of CLZ with LEM may lead to increase in exposure to CLZ and risks of CLZ-related adverse events.

Lurasidone for the Treatment of Schizophrenia: Design, Development, and Place in Therapy.

This review aims to provide a comprehensive overview of the current literature on the drug design, development, and therapy of lurasidone for the treatment of schizophrenia. Lurasidone has antagonistic effects on the dopamine D2, 5-hydroxytryptamine (5-HT)2A, and 5-HT7 receptors and a partial agonistic effect on the 5-HT1A receptor with low affinities for muscarinic M1, histamine H1, and a1 adrenergic receptors. The receptor-binding profile of lurasidone is thought to be associated with fewer side effects such as anticholinergic effects, lipid abnormalities, hyperglycemia, and weight gain. Behavioral pharmacological studies have demonstrated that lurasidone exerts anxiolytic and antidepressive effects and improves cognitive function, which are associated with the modulation of 5-HT7 and 5-HT1A receptors. Literature search using PubMed was performed to find published studies of randomized controlled trials and recent meta-analyses regarding efficacy and safety, particularly metabolic side effects of lurasidone in schizophrenia. In short-term studies, the results of randomized placebo-controlled trials and meta-analyses have suggested that lurasidone was superior to placebo in improving total psychopathology, positive symptoms, negative symptoms, and general psychopathology in patients with acute schizophrenia. Regarding safety, lurasidone had minimal metabolic side effects, and was identified as one of the drugs with the most benign profiles for metabolic side effects. Long-term trials revealed that lurasidone had the preventive effects on relapse, with minimal effects on weight gain and other metabolic side effects. Furthermore, lurasidone improves cognitive and functional performance of patients with schizophrenia, especially in long-term treatment. Patients with schizophrenia require long-term treatment with antipsychotics for relapse prevention; thus, minimizing weight gain and other side effects is crucial. Lurasidone is suitable as one of the first-line antipsychotic drugs in the acute phase, and a switching strategy should be considered during the maintenance phase, to balance efficacy and adverse effects and achieve favorable outcomes in the long-term course of schizophrenia.

Switching to lemborexant for the management of insomnia in mental disorders: the SLIM study.

STUDY OBJECTIVES: We conducted a retrospective study to investigate the efficacy and safety of switching from other hypnotics, including benzodiazepines and Z-drugs, suvorexant, ramelteon, mirtazapine, trazodone, and antipsychotics, to lemborexant, a dual orexin receptor antagonist, for 3 months. METHODS: Clinical data obtained from the medical records of 61 patients treated at the Horikoshi Psychosomatic Clinic between December 2020 and February 2022 were analyzed, including the Athens Insomnia Scale, Epworth Sleepiness Scale, and Perceived Deficits Questionnaire-5. The primary outcome was the mean change in Athens Insomnia Scale score after 3 months. Secondary outcomes were the mean changes in the Epworth Sleepiness Scale and Perceived Deficits Questionnaire-5 scores over 3 months. We also compared pre- and post-diazepam equivalents. RESULTS: The mean Athens Insomnia Scale score decreased over 3 months after switching to lemborexant (1 mo: -2.98 ± 5.19, P < .001; 2 mo: -3.20 ± 5.64, P < .001; 3 mo: -3.38 ± 5.61, P < .001). Mean Epworth Sleepiness Scale score did not change from baseline to 1 month (-0.49 ± 3.41, P = 0.27), 2 months (0.082 ± 4.62, P = .89), or 3 months (-0.64 ± 4.80, P = .30). Mean Perceived Deficits Questionnaire-5 score did improve from baseline to 1 month (-1.17 ± 2.47, P = .004), 2 months (-1.05 ± 2.97, P = .029), and 3 months (-1.24 ± 3.06, P = .013). There was also a reduction in the total diazepam equivalent (baseline vs 3 mo: 14.0 ± 20.2 vs 11.3 ± 20.6, P < .001). CONCLUSIONS: Our study showed that, by switching to lemborexant from other hypnotics, the risks associated with benzodiazepines and Z-drugs may be reduced. CITATION: Horikoshi S, Miura I, Suzuki Y, et al. Switching to lemborexant for the management of insomnia in mental disorders: the SLIM study. J Clin Sleep Med. 2023;19(10):1753-1758.

Alterations in prefrontal cortical neuregulin-1 levels in post-pubertal rats with neonatal ventral hippocampal lesions.

Genetic studies in humans have implicated the gene encoding neuregulin-1 (NRG-1) as a candidate susceptibility gene for schizophrenia. Furthermore, it has been suggested that NRG-1 is involved in regulating the expression and function of the N-methyl-D-aspartate receptor and the GABAA receptor in several brain areas, including the prefrontal cortex (PFC), the hippocampus, and the cerebellum. Neonatal ventral hippocampal lesioned (NVHL) rats have been considered as a putative model for schizophrenia with characteristic post-pubertal alteration in response to stress and neuroleptics. In this study, we examined NRG-1, erb-b2 receptor tyrosine kinase 4 (erbB4), and phospho-erbB4 (p-erbB4) levels in the PFC and the distribution of NRG-1 in the NVHL rats by using immunoblotting and immunohistochemical analyses. Neonatal lesions were induced by bilateral injection of ibotenic acid in the ventral hippocampus of postnatal day 7 Sprague-Dawley (SD)-rats. NVHL rats showed significantly decreased levels of NRG-1 and p-erbB4 in the PFC compared to sham controls at post-pubertal period, while the level of erbB4 did not differ between sham and NVHL rats. Moreover, microinjection of NRG-1 into the mPFC improved NVHL-induced prepulse inhibition deficits. Our study suggests PFC NRG-1 alteration as a potential mechanism in schizophrenia-like behaviors in the NVHL model.

Subacute hemorrhagic cyst of the ligamentum flavum occurred in the lumbosacral transitional vertebra presenting as progressive lumbar nerve root compression: a case report.

The lumbosacral transitional vertebrae (LSVT) has been reported to be a cause of lumbar disc herniation as a result of mechanical stress, however there were no reports about relationship between LSTV and hemorrhagic intervertebral cystic lesion. We report a rare case of a hemorrhagic intravertebral cystic lesion that occurred in the LSVT of a 42-year-old man and had a subacute course of lumbar nerve root compression. He presented our hospital with complain of increasing left leg pain for one week. Contrast-enhanced MRI (Gd-T1WI) showed a heterogenous contrast-enhanced effect on the nodule at the entrance of the left pedicle root of L6. The LSTV was classified as Type IIIA using the Castellvi's classification, and the nodule was found on the ipsilateral of the lumbarization. From the imaging findings, disc cysts, ganglion cysts, synovial cysts, disc sequestration and Schwannomas were differentials of the intravertebral canal cystic lesions; however, it was suspected to be a hemorrhagic cystic lesion because of their acute progression of his symptoms, his relatively young age and imaging findings. His symptoms improved shortly after the resection of the cyst and he was diagnosed as intracystic hemorrhage of a ganglion in the ligamentum flavum. There were no features suggestive of recurrence of the cystic lesion in the follow-up MRI on 6 months after the surgery. It was speculated that in the LSTV, twisting movements act on the upper part adjacent to the transitional vertebra, causing microtrauma around the facet joint that leads to the forming a hemorrhagic cyst following damage around the joint capsule. It is difficult to make a diagnosis of hemorrhagic cyst from imaging alone. It must be suspected from the aspect of age (relatively young), gender (male), clinical course (acute to subacute) and MR imaging (various signal intensity patterns on T2WI and contrast effect on Gd enhancement).

Effect of Switching to Brexpiprazole on Plasma Homovanillic Acid Levels and Antipsychotic-Related Side Effects in Patients with Schizophrenia or Schizoaffective Disorder.

OBJECTIVE: Although switching antipsychotics is a common strategy in the treatment of schizophrenia, caution is needed because of the risk of worsening of psychosis, particularly when switching to a dopamine D2 partial agonist. Homovanillic acid (HVA), a dopamine metabolite, is thought to be a possible indicator of the response to antipsychotics. We examined the effects of switching to brexpiprazole monotherapy from other antipsychotics on plasma HVA levels and side effects during maintenance treatment of schizophrenia. METHODS: The antipsychotics of 37 Japanese patients with schizophrenia or schizoaffective disorder were switched to brexpiprazole for the improvement of side effects. We evaluated clinical symptoms and extrapyramidal symptoms (EPS) and took fasting blood samples at baseline and endpoint (eight weeks after completing the switch) to measure plasma levels of HVA, prolactin, and metabolic parameters. RESULTS: Switching to brexpiprazole significantly decreased the Drug-Induced Extrapyramidal Symptoms Scale total score (p=0.008), prolactin levels (p<0.001), body weight (p=0.046), and body-mass index (p=0.034), and increased HDL cholesterol (p=0.008). On the other hand, switching to brexpiprazole did not change plasma levels of HVA or Positive and Negative Syndrome Scale scores. CONCLUSION: Switching to brexpiprazole significantly improved EPS, high prolactin levels, and metabolic side effects without elevating plasma HVA levels. Brexpiprazole may stabilize dopaminergic neural transmission and could be a useful strategy to decrease the burden in patients with schizophrenia during the maintenance phase. Because of the small sample size, further studies with larger sample sizes are needed to confirm and extend our results.

Role of prefrontal cortical 5-HT2A receptors and serotonin transporter in the behavioral deficits in post-pubertal rats following neonatal lesion of the ventral hippocampus.

Neonatal ventral hippocampal-lesioned (NVHL) rats have been shown to display neurochemical and behavioral abnormalities at adulthood, analogous to some of those seen in schizophrenia. Serotonergic neurotransmission is implicated the pathophysiology and treatment of schizophrenia. In this study, we evaluated possible role of serotonergic transmission is the behaviors of NVHL-lesioned rats. Bilateral lesions to the ventral hippocampus (VH) in rat pups were made using the excitotoxin ibotenic acid. We investigated 5-HT2A-receptor and SERT binding sites in cortical and subcortical areas in post-pubertal NVHL and sham-lesioned rats, using quantitative receptor autoradiography. We compared a 5-HT-dependent behavior in NVHL and sham animals, the wet-dog shake response (WDSr) to a 5-HT2A receptor agonist DOI. In addition, we studied prepulse inhibition (PPI) of startle responses in NVHL and Sham-lesioned animals treated with antipsychotic drugs haloperidol, risperidone and clozapine and 5-HT2A antagonists ketanserin or MDL100907. The WDSr elicited by DOI was enhanced in post-pubertal NVHL rats compared to sham-lesioned controls. Moreover, post-pubertal NVHL rats exhibited PPI deficits which was reversed by atypical antipsychotics, ketanserin and MDL100907. A significant increase in 5-HT2A-like receptor binding was observed in the medial prefrontal cortex (mPFC) in post-pubertal NVHL rats without any significant change in the striatum and ventral pallidum. A significant increase in SERT-like binding was also observed in the mPFC and striatum of NVHL rats at pre-pubertal period; however, at post-pubertal age, the binding remained elevated in mPFC only. These data suggest that increased prefrontal cortical 5-HT transmission may play a role in the behavioral deficits observed in this neurodevelopmental model of schizophrenia.

Low- and high-dose aripiprazole augmentation and plasma levels of homovanillic acid in major depressive disorder: A randomized, open-label study.

OBJECTIVE: This randomized controlled study evaluated the efficacy of low-dose (LD) and high-dose (HD) aripiprazole augmentation in major depressive disorder. Additionally, we examined the relationship between clinical response and changes in plasma homovanillic acid (pHVA) levels during aripiprazole augmentation. METHODS: Thirty-one patients with inadequate response to antidepressants were randomized to receive adjunctive treatment with LD (3 mg/day, n = 17) or HD (up to 12 mg/day, n = 14) aripiprazole for 6 weeks. We evaluated the Montgomery-Åsberg Depression Rating Scale (MADRS) and measured pHVA at baseline, Week 2, and end point. RESULTS: Both LD and HD aripiprazole significantly decreased MADRS score after 6 weeks, and the response rate was higher in HD aripiprazole group at end point. HD aripiprazole significantly decreased MADRS score at Week 2 compared with LD aripiprazole (p = .015). There was a significant difference in changes in pHVA between responders and nonresponders, showing pHVA decreased significantly in responders at Week 2 (p = .044). CONCLUSIONS: Increasing aripiprazole from the early period appeared useful for immediate response, although caution is needed when increasing the dose >6 mg/day. pHVA may be a possible indicator of the response to aripiprazole augmentation. Caution is needed in interpreting these findings because of the small sample size.

An increase in the risk of excessive femoral anteversion for relatively younger age and types of femoral morphology in total hip arthroplasty with direct anterior approach.

BACKGROUND: Direct anterior approach (DAA) is known to diminish a dislocation risk and widely used for total hip arthroplasty (THA). On the other hand, anterior dislocation due to increasing stem anteversion and cup anteversion is an important complication. METHODS: A retrospective analysis of 140 (male/female: 10/130) consecutive patients with 149 hips who had undergone primary THA in the period between 2011 and 2015 was conducted. Factors including age, gender, body mass index (BMI), and primary diagnosis were examined. Radiographic parameters including the Dorr proximal femoral types, cortical thickness index (CTI), canal flare index (CFI), and canal to calcar index were measured. To investigate relationships of combined anteversion (CA) with other factors, a stepwise regression analysis was performed. RESULTS: The mean age, BMI, and the follow-up period were 69.5 ± 10.3 years old, 23.4 ± 3.4 kg/m2, and 48.2 ± 13.6 months, respectively. The proximal femurs of the 149 hips were categorized as Dorr type A ( n = 33), type B ( n = 110), and type C ( n = 6). The mean CTI, CFI, and canal to calcar index were 0.56 ± 0.08, 4.15 ± 0.83, and 0.46 ± 0.09, respectively. The mean stem varus angle, radiographic inclination, and radiographic anteversion of the cup were 0.19 ± 1.63, 40.9 ± 6.0°, and 12.7 ± 3.5°, respectively. Stem anteversion measured by computed tomography (CT) axial image was 17.7 ± 12.0°. The mean radiographic inclination, radiographic anteversion (CTRA), and anatomical anteversion analyzed by Kyocera 3-D template were 40.8 ± 7.2°, 19.8 ± 6.6°, and 28.8 ± 10.0°, respectively. Mean CA defined as the sum of stem anteversion and CTRA was 37.5 ± 14.5°. To investigate relationships of CA with other factors, a stepwise regression analysis was performed and resulted in a model with age ( p < 0.001). In the same way, stem anteversion and CTRA were analyzed; only for the stem anteversion, the stepwise selection process resulted in a model with age ( p < 0.001) and the Dorr types ( p = 0.047). CONCLUSION: The risk of excessive femoral anteversion increases for relatively younger age and for types of femoral morphology according to the Dorr classification, moreover with an increase of CA in DAA-THA with cementless tapered-wedge stem.

Tarsal Tunnel Syndrome Caused by a Schwannoma of the Posterior Tibial Nerve.

Schwannoma is the most common tumor of the peripheral nerve sheath. However, there have been few reports on schwannoma of the posterior tibial nerve causing tarsal tunnel syndrome. We report on a 60-year-old man with tarsal tunnel syndrome caused by a schwannoma of the posterior tibial nerve, which was first diagnosed as a ganglion cyst. After enucleation of this tumor, the patient was asymptomatic and had no related sequelae except for minor numbness in the plantar aspects of his digits. Although schwannoma of the posterior tibial nerve is rare, it should be considered even if a ganglion is clinically suspected.

Tuberculosis of the Wrist Accompanied with Calcium Pyrophosphate.

This is a rare case of tuberculosis (TB) complicated with pseudogout of the wrist joint in a non-immunocompromised 84-year-old female with a history of pulmonary tuberculosis. She was diagnosed with extrapulmonary tuberculosis of the wrist based on a polymerase chain reaction (PCR) study and synovial fluid aspiration in which the cytology was positive for acid-fast bacilli. Calcium pyrophosphate was also positive. We must be careful not to miss articular tuberculosis as it may mimic common inflammatory arthritis, such as pseudogout of the wrist. Even if the patient is positive for calcium pyrophosphate, this does not exclude the possibility of articular tuberculosis.

Successful Closed Reduction of a Lateral Elbow Dislocation.

In this report, we present a case of lateral elbow dislocation treated with closed reduction. Lateral elbow dislocation is rare, and a closed reduction is reported with even less frequency. The reduction can be hindered by swelling and soft tissue interposition, and we describe the use of a nonoperative reduction technique performed under mild sedation with early physiotherapy to avoid joint stiffness. No additional complication was observed, and the normal range of elbow movement and function was obtained by early physiotherapy.

Associations between five-factor model of the Positive and Negative Syndrome Scale and plasma levels of monoamine metabolite in patients with schizophrenia.

The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms is the most common multiple-factor model used in analyses; its use may improve evaluation of symptoms in schizophrenia patients. Plasma monoamine metabolite levels are possible indicators of clinical symptoms or response to antipsychotics in schizophrenia. We investigated the association between five-factor model components and plasma monoamine metabolites levels to explore the model's biological basis. Plasma levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography in 65 Japanese patients with schizophrenia. Significant negative correlation between plasma 5-HIAA levels and the depression/anxiety component was found. Furthermore, significant positive correlation was found between plasma MHPG levels and the excitement component. Plasma HVA levels were not correlated with any five-factor model component. These results suggest that the five-factor model of the PANSS may have a biological basis, and may be useful for elucidating the psychopathology of schizophrenia. Assessment using the five-factor model may enable understanding of monoaminergic dysfunction, possibly allowing more appropriate medication selection. Further studies of a larger number of first-episode schizophrenia patients are needed to confirm and extend these results.

Impacts of age on plasma monoamine metabolite concentrations in a large cohort of healthy individuals.

The measurement of plasma concentrations of monoamine metabolites is a useful method for inferring the dynamics of monoamine metabolites in the brain. To clarify effects of age and sex on plasma monoamine metabolites levels, we used high-performance liquid chromatography to measure plasma levels of homovanillic acid (HVA), free and total 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) in healthy men and women of various ages (n=214). In all plasma monoamine metabolites, there were significant differences across the age groups, and multiple comparisons revealed that older subjects had higher levels than younger subjects. Moreover, significant positive correlations were found between age and plasma levels of HVA, free MHPG, total MHPG, and 5-HIAA. On the other hand, plasma concentrations of monoamine metabolites were not influenced by sex, except for total MHPG for which the plasma levels were significantly higher in men than in women. Age-related changes in monoamine oxidase and renal function might affect our results. This large cohort survey provides further evidence to be cautiously aware of age effects when regarding plasma monoamine metabolites levels as reflections of central activity.

Effect of switching to risperidone after unsuccessful treatment with aripiprazole on plasma monoamine metabolites level in the treatment of acute schizophrenia.

OBJECTIVE: In the treatment of acute schizophrenia, risperidone and aripiprazole are both placed the first line antipsychotics. These two antipsychotics have different pharmacological effects. We investigated the effects of risperidone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4hydroxyphenylglycol after unsuccessful aripiprazole treatment in acute schizophrenia. METHODS: Ten Japanese patients with acute schizophrenia were enrolled to this study. Plasma levels of monoamine metabolites were analyzed with high-performance liquid chromatography with electrochemical detection. RESULTS: Risperidone improved the symptoms and 4 of 10 patients were responders. Risperidone showed a tendency to decrease plasma HVA (pHVA) levels in responders (p = 0.068), but not in non-responders (p = 1.0). At baseline, pHVA levels of responders were significantly higher than that of non-responders (p = 0.033). A trend for negative correlation was found between pHVA at baseline and the changes in Positive and Negative Syndrome Scale-Total (p = 0.061, r = -0.61). CONCLUSION: Our results suggest that high pHVA level before switching may predict good response to the second line antipsychotics after unsuccessful first antipsychotic treatment. If aripiprazole is not effective in acute schizophrenia, switching to risperidone may be effective and reasonable strategy for improving symptoms.

A case of peripheral T-cell lymphoma presenting with acute liver failure.

A 68-year-old woman was evaluated by her primary physician for swelling and pain in the right neck. Treatment with antibiotics failed to achieve any improvement. Two weeks later, she was hospitalized to the gastroenterology department because of liver dysfunction and pneumonia. Disseminated intravascular coagulation (DIC) was diagnosed, and protease inhibitor and steroid pulse therapy were started. She was transferred to our department for further evaluation the following day. Bone marrow examination revealed hemophagocytosis and infiltration of CD3-positive cells. Multiple masses were identified in the liver. Her prothrombin time was 35.7% of the standard value 17 days from disease onset, despite improvement of DIC. She was diagnosed with acute liver failure based on the Japanese diagnostic criteria. Her general condition worsened quickly, which prevented use of chemotherapy, and she died after a total course of 19 days. Autopsy revealed atypical lymphocytes in the liver. The diagnosis was peripheral T-cell lymphoma.

[An example of metastasis to the iliopsoas muscle from sigmoid colon cancer].

Even though skeletal muscle, making up about 40% of body weight, is the largest organ in the human body, metastasis from malignant lesions is rare. Among reports of metastasis, those involving the iliopsoas muscle are numerous but few reports involve resection. Reported here is one example we experienced where metastasis developed in the iliopsoas muscle following colectomy, resection was then made possible by radiotherapy and chemotherapy. The case involved a 71-year- old male in which a Hartmann procedure was performed for sigmoid colon cancer. The pathology was Type 3 (8 × 7 cm, adenocarcinoma( mod), ss or more, ly1, v1, n0, ow(-), aw or ew(+), stage II). Upon additional sampling, thermal degredation of neoplastic cells was shown and outpatient oral UFT was performed. Five years following surgery, lymphoadenopathy was noted in the area of the left iliac artery upon US and CT. PET showed a probable metastasis to the left iliopsoas muscle. Early esophageal and stomach cancer were diagnosed by GFT. The esophageal cancer was located 30-32 cm from the incisors, unstained, Borrmann type 1, penetrating deeper than the muscularis propria. Biopsy revealed a diagnosis of tubular adenocarcinoma. ESD was performed for the esophageal cancer and one month later, a total gastrectomy D1+ß was performed. During surgery, the iliopsoas muscle tumor was determined to be large and impossible to resect. Radiotherapy of 10MV X-ray, 8 fields, 65-70 Gy/26 times for 6 . 5 weeks was performed for residual tumor but had no effect on tumor size. Fifteen courses of FOLFOX+bevacizumab were then performed. The tumor was markedly reduced in size, unidentifiable upon CT but showed slight uptake on PET and resection of the suspected residual tumor was performed. Histologically, atypical cells were shown in scarred muscle and connective tissue, however, degradation by chemotherapy was high. Residual tumor at resection margins was found, findings consistent with metastasis form sigmoid colon cancer. Taking into account the age and condition of the patient following surgery, chemotherapy was changed to S-1. Currently, 5 months after resection, there has been no recurrence.

[Effects of anticoagulant therapy for rapidly progressive interstitial pneumonias].

To clarify the effects of anticoagulant therapy, we investigated patients with rapidly progressive interstitial pneumonias, retrospectively. We defined rapidly progressive pneumonia as idiopathic or secondary interstitial pneumonia with acute exacerbation of respiratory symptoms within 2 months, without infection or heart failure. A total of 20 cases admitted to our hospital between April 1999 and January 2010 met our criteria. Of those 20 cases, 6 were non-idiopathic pulmonary fibrosis (non-IPF), 3 were IPF, 6 were amyopathic dermatomyositis (ADM), 2 were DM, 2 were rheumatoid arthritis, and 1 was mixed connective-tissue disease. We divided the 20 cases into two groups according to whether they were treated with anticoagulant therapy (dalteparin and/or warfarin) (group A, n = 11) or not (group B, n = 9), and compared their outcomes. They were all given standard therapy. There was significantly better survival time in group A than in group B by the Kaplan-Meier survival curve (p = 0.0389). Anticoagulant therapy may improve the survival of patients with rapidly progressive interstitial pneumonias.