Novel Off-label Use of Desipramine in Infantile Neuroaxonal Dystrophy: Targeting the Sphingolipid Metabolism Pathway to Reduce Accumulation of Ceramide.

This is a research study to find out if clinically prescribed desipramine is effective at improving the symptoms and slowing the progression of Infantile Neuroaxonal Dystrophy (INAD) in affected children.
Participants will receive an initial oral dose of study drug once a day. This dose may be changed depending on response to study drug Clinically collected data will be recorded for up to 5 years. Investigators will also ask for participant permission to obtain a sample of child's skin biopsy from unused clinical sample previously collected for standard of care.

Start Date14 Jan 2019

Sponsor / Collaborator

Duke University

NCT03548454 / RecruitingPhase 4IIT

Comparing Effectiveness of Duloxetine and Desipramine in Patients With Chronic Pain: A Pragmatic Trial Using Point of Care Randomization

Over 100 million Americans suffer from chronic pain resulting in annual cost of roughly $635 billion. Limited treatments are available for this widespread disease. The data supporting these treatments lack generalizability to patients with more serious medical and psychological comorbidities who are often excluded from explanatory efficacy trials. Our work aims to integrate randomized comparative effectiveness research with patient care. The investigators will randomize the patients and collect data using an open-source learning healthcare system already in use in our department to monitor patients' progress: Collaborative Health Outcomes Information Registry (CHOIR). Collaborative Health Outcomes Information Registry uses the National Institute of Health Patient Reported Outcomes Measurement Information System item banks for comparative metrics through computer adaptive testing. The investigators will leverage the advantage of this novel system to compare effectiveness of duloxetine and desipramine in decreasing pain in patients with chronic pain. The investigators will also compare adherence of patients to these two commonly used medications over a period of six months. This will evaluate feasibility of integrating randomized comparative effectiveness research with patient care in subspecialty clinics. Collaborative Health Outcomes Information Registry can then be applied for numerous future trials to advance our knowledge in perioperative and pain medicine.

Start Date20 Sep 2018

Sponsor / Collaborator

Stanford University

IRCT20160813029315N2 / CompletedPhase 2/3IIT

Placebo-controlled randomized clinical trial testing the efficacy of desipramine in reducing craving in patients with methamphetamine use disorder

Start Date03 Jun 2016

Sponsor / Collaborator-

100 Clinical Results associated with Desipramine Hydrochloride

100 Translational Medicine associated with Desipramine Hydrochloride

100 Patents (Medical) associated with Desipramine Hydrochloride

7,251

Literatures (Medical) associated with Desipramine Hydrochloride

01 Feb 2024·International journal of biological macromolecules

Chitosan functionalized doxorubicin loaded poly(methacrylamide) based copolymeric nanoparticles for enhanced cellular internalization and in vitro anticancer evaluation

Article

Author: Sharma, Deepika ; Sharma, Rohit K ; Wangoo, Nishima ; Manhas, Priya ; Sharma, Rohit ; Peneva, Kalina ; Cokca, Ceren

Doxorubicin (Dox), a chemotherapeutic agent, encounters challenges such as a short half-life, dose-dependent toxicity, and low solubility. In this context, the present study involved the fabrication of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-aminopropyl)methacrylamide (APMA) bearing P(HPMA-s-APMA) copolymeric nanoparticles (P(HPMA-s-APMA) NPs) and their investigation for efficient delivery of Dox. Furthermore, the synthesized nanoparticles (NPs) were coated with chitosan (Cht) to generate positively charged nanoformulations. The prepared formulations were evaluated for particle size, morphology, surface charge analysis, percentage encapsulation efficiency (EE%), and drug release studies. The anticancer activity of Cht-P(HPMA-s-APMA)-Dox NPs was assessed in the HeLa cancer cell line. The prepared P(HPMA-s-APMA)-Dox NPs exhibited an average particle size of 240-250 nm. Chitosan decorated P(HPMA-s-APMA)-Dox NPs displayed a significant increase in particle size, and the zeta potential shifted from negative to positive. The EE% for Cht-P(HPMA-s-APMA)-Dox NPs was calculated to be 68.06 %. The drug release studies revealed a rapid release of drug from Cht-P(HPMA-s-APMA)-Dox NPs at pH 4.8 than pH 7.4, demonstrating the pH-responsiveness of nanoformulation. Furthermore, the cell viability assay and internalization studies revealed that Cht-P(HPMA-s-APMA)-Dox NPs had a high cytotoxic response and significant cellular uptake. Hence, the Cht-P(HPMA-s-APMA)-Dox NPs appeared to be a suitable nanocarrier for effective, and safe chemotherapy.

01 Feb 2024·Drug metabolism and disposition: the biological fate of chemicals

Novel Independent Trans- and Cis-Genetic Variants Associated with CYP2D6 Expression and Activity in Human Livers

Article

Author: Smith, Dylan ; Shi, Jian ; Zhu, Hao-Jie ; He, Bing ; Wang, Xinwen

Cytochrome P450 2D6 (CYP2D6) is a critical hepatic drug-metabolizing enzyme in humans, responsible for metabolizing approximately 20%-25% of commonly used medications such as codeine, desipramine, fluvoxamine, paroxetine, and tamoxifen. The CYP2D6 gene is highly polymorphic, resulting in substantial interindividual variability in its catalytic function and the pharmacokinetics and therapeutic outcomes of its substrate drugs. Although many functional CYP2D6 variants have been discovered and validated, a significant portion of the variability in the expression and activity of CYP2D6 remains unexplained. In this study, we performed a genome-wide association study (GWAS) to identify novel variants associated with CYP2D6 protein expression in individual human livers, followed by a conditional analysis to control for the effect of functional CYP2D6 star alleles. We also examined their impact on hepatic CYP2D6 activity. Genotyping on a genome-wide scale was achieved using the Illumina Multi-Ethnic Genotyping Array (MEGA). A data-independent acquisition (DIA)-based proteomics method was used to quantify CYP2D6 protein concentrations. CYP2D6 activity was determined by measuring the dextromethorphan O-demethylation in individual human liver s9 fractions. The GWAS identified 44 single nuclear polymorphisms (SNPs) that are significantly associated with CYP2D6 protein expressions with a P value threshold of 5.0 × 10^-7 After the conditional analysis, five SNPs, including the cis-variants rs1807493 and rs1062753 and the trans-variants rs4073010, rs729559, and rs80274432, emerged as independent variants significantly correlated with hepatic CYP2D6 protein expressions. Notably, four of these SNPs, except for rs80274432, also exhibited a significant association with CYP2D6 activities in human livers, suggesting their potential as novel and independent cis- and trans-variants regulating CYP2D6. SIGNIFICANT STATEMENT: Using individual human livers, we identified four novel cis- and trans-pQTLs/aQTLs (protein quantitative trait loci/activity quantitative trait loci) of Cytochrome P450 2D6 (CYP2D6) that are independent from known functional CYP2D6 star alleles. This study connects the CYP2D6 gene expression and activity, enhancing our understanding of the genetic variants associated with CYP2D6 protein expression and activity, potentially advancing our insight into the interindividual variability in CYP2D6 substrate medication response.

01 Feb 2024·Inflammation

Anti-Necroptotic Effects of Itaconate and its Derivatives

Article

Author: Shi, Fu-Li ; Xu, Rong ; Zhou, Zhi-Ya ; Wong, Tak-Sui ; Li, Qing ; Hu, Bo ; Lu, Na ; Gan, Ying-Qing ; Li, Ya-Ping ; He, Xian-Hui ; Yuan, Li-Sha ; Xu, Li-Hui ; Ni, Si-Tao ; Chen, Ying ; Ouyang, Dong-Yun

Itaconate is an unsaturated dicarboxylic acid that is derived from the decarboxylation of the Krebs cycle intermediate cis-aconitate and has been shown to exhibit anti-inflammatory and anti-bacterial/viral properties. But the mechanisms underlying itaconate's anti-inflammatory activities are not fully understood. Necroptosis, a lytic form of regulated cell death (RCD), is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) signaling. It has been involved in the pathogenesis of organ injury in many inflammatory diseases. In this study, we aimed to explore whether itaconate and its derivatives can inhibit necroptosis in murine macrophages, a mouse MPC-5 cell line and a human HT-29 cell line in response to different necroptotic activators. Our results showed that itaconate and its derivatives dose-dependently inhibited necroptosis, among which dimethyl itaconate (DMI) was the most effective one. Mechanistically, itaconate and its derivatives inhibited necroptosis by suppressing the RIPK1/RIPK3/MLKL signaling and the oligomerization of MLKL. Furthermore, DMI promoted the nuclear translocation of Nrf2 that is a critical regulator of intracellular redox homeostasis, and reduced the levels of intracellular reactive oxygen species (ROS) and mitochondrial superoxide (mtROS) that were induced by necroptotic activators. Consistently, DMI prevented the loss of mitochondrial membrane potential induced by the necroptotic activators. In addition, DMI mitigated caerulein-induced acute pancreatitis in mice accompanied by reduced activation of the necroptotic signaling in vivo. Collectively, our study demonstrates that itaconate and its derivatives can inhibit necroptosis by suppressing the RIPK1/RIPK3/MLKL signaling, highlighting their potential applications for treating necroptosis-associated diseases.

News (Medical) associated with Desipramine Hydrochloride

06 May 2024

·www.biospace.com

Boehringer Ingelheim shares positive results from the first study worldwide in diabetic macular ischemia

Boehringer Ingelheim today presented positive data from the HORNBILL Phase I/IIa study of BI 764524, the first ever study exploring a potential treatment for people living with diabetic macular ischemia (DMI). The study found that BI 764524 was well tolerated following intravitreal administration of single and multiple doses, meeting its primary safety endpoints and showed early signs of potential efficacy.1 DMI is a common, irreversible complication of diabetic retinopathy (DR) that may lead to blindness.12,3,4 It can develop when the light sensitive tissues of the central retina do not receive adequate blood supply over a longer time. There are currently no approved treatments for DMI. The current standard of care for advanced DR includes intravitreal anti-VEGF treatment or invasive laser treatment. However, some patients’ conditions progress despite this treatment.5 BI 764524 uses a novel mode of action by inhibiting the Sema3A pathway to re-vascularize ischemic areas and potentially overcome the limitations of anti-VEGF and laser treatments.1 “The results from the HORNBILL study are really encouraging. They suggest there may be a pathway for earlier intervention that could decrease the risk of, and maybe even prevent, people with diabetic retinopathy from developing irreversible and vision-threatening complications, such as DMI,” said Quan Dong Nguyen, MD, MSc, FARVO, FASRS, Professor of Ophthalmology at the Byers Eye Institute, Professor of Medicine and of Pediatrics at Stanford School of Medicine, and Principal and Coordinating Investigator of the trial. “Retinal non-perfusion is a key driver of vision loss in people living with diabetic retinopathy. However, until the HORNBILL study, retinal non-perfusion has not been explored as a potential treatment target.” “Vision loss associated with retinal conditions such as diabetic retinopathy and DMI has a devastating impact on quality of life. Today’s results are an important step towards achieving our aspiration of developing precision therapies delivering the right treatment for the right patient at the right time to prevent vision loss before irreversible damage occurs,” said Ulrike Graefe-Mody, Ph.D., Head of Retinal Health at Boehringer Ingelheim. “We’re looking forward to start a Phase IIb study to further explore the safety and efficacy of BI 764524.” HORNBILL is one of 23 abstracts being presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual meeting 2024, spanning Boehringer Ingelheim’s retinal health portfolio, including other studies of retinal non-perfusion and diabetic retinopathy, geographic atrophy and neovascular age-related macular degeneration. About the HORNBILL study The HORNBILL study consisted of two parts (single rising dose (SRD), N=12 and multiple dose (MD), N=31) both of which met the primary safety endpoints of number of patients with dose-limiting adverse events (SRD) and treatment-related adverse events(MD).1 The study also met its pre-specified criterion for early efficacy of foveal avascular zone area stabilization versus sham at week 16 (p<0.2).1 This suggests that BI 764524 may positively impact retinal non-perfusion and potentially halt the progression of capillary loss.1 The upcoming CRIMSON trial, a Phase IIb trial, will assess safety and efficacy of BI 764524 in patients with DR further and start recruiting later this year. Notes to Editors: About the trial (NCT04424290) This Phase I/IIa trial assessed the tolerability of BI 764524 in people with diabetic retinopathy (DR) with diabetic macular ischemia (DMI) who have previously been treated with panretinal photocoagulation.1 The trial consisted of a single rising dose (SRD) part followed by a multiple dosing (MD) part, with BI 764524 administered via intravitreal injection.1 Single rising dose part In the non-randomized, open-label, SRD part, 12 patients received intravitreal BI 764524 doses: 0.5 (n=3), 1.0 (n=3), or 2.5 mg (n=6).1 The primary endpoint was the number of patients with dose-limiting events (DLEs); secondary endpoints were the number of patients with drug-related adverse events (AEs) and any ocular AEs.1 Patients in the SRD part had a mean age of 61.8 years.1 No DLEs were reported in the SRD part.1 There were five ocular AEs in four patients in the study eye, none related to the study drug. The highest tested dose (BI 764524 2.5 mg) was considered safe and applied in the MD part.1 Multiple dosing part In the randomized, masked, sham-controlled, MD part, 31 patients received three intravitreal doses of BI 764524 2.5 mg (n=21) or sham injection procedures (n=10) at 4-week intervals (baseline, week 4, and week 8), followed by 14 weeks of follow-up until the end of study at week 22.1 The primary endpoint was the number of patients with drug-related AEs; secondary endpoints included number of patients with ocular AEs, change from baseline in foveal avascular zone (FAZ) area, best corrected visual acuity (BCVA) and central retinal thickness (CRT).1 Patients in the MD part had a mean age of 59.5 years.1 There were seven patients with ocular AEs (study eye; three patients with four AEs for BI 764524, four patients with six AEs for sham), one of which was reported as related to the study drug (vitreous floater).1 In addition, there was one systemic AE (increase deemed related to the study drug by the investigator). There were no cases of intraocular inflammation or occlusive retinal vasculitis.1 At baseline, mean BCVA was 65.2 letters, mean FAZ area was 0.65 mm, and mean CRT was 252 mm.1 The HORNBILL study met its pre-specified criterion for early efficacy of FAZ area stabilization versus sham at week 16 (p<0.2). Over the short trial period, other secondary efficacy endpoints showed no relevant change. About BI 764524 BI 764524 is a humanized monoclonal anti-Sema3A antibody intended to re-vascularize ischemic areas and reduce leakage in the retina, offering the potential to address retinal non-perfusion in retinal diseases. The compound was discovered and developed by Boehringer Ingelheim and is part of its research and development portfolio in retinal conditions. About diabetic retinopathy and diabetic macular ischemia Diabetic retinopathy affects 1 in 3 people with diabetes and is the leading cause of vision loss in adults of working age. It is a growing epidemic that is expected to increase as the incidence of diabetes escalates across the globe. Diabetic macular ischemia (DMI) is a complication of diabetic retinopathy which can lead to slowly progressing, irreversible vision loss. About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at Boehringer Ingelheim’s Intended Audiences Notice This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. References 1 Nguyen QD, Jhaveri C, Habib MS. Oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2024. Abstract number: 959 2 Marques IP, et al. Diabetes 2019;68:648–653 3 Sim DA, et al. Invest Ophthalmol Vis Sci 2013;54:2353–2360 4 Tey KY, et al. Eye Vis (Lond) 2019;6:37 5 Ip MS, et al. Ophthalmology 2014;122:367–374

Clinical ResultPhase 2

22 Nov 2023

·www.prnewswire.com

Novel MRI Reveals Brain Changes in Long-COVID Patients

CHICAGO, Nov. 22, 2023 /PRNewswire/ -- People with long COVID exhibit patterns of changes in the brain that are different from fully recovered COVID-19 patients, according to research being presented next week at the annual meeting of the Radiological Society of North America (RSNA). "To the best of our knowledge, this is the first study comparing patients with long COVID to both a group without history of COVID-19 and a group that went through a COVID-19 infection but is subjectively unimpaired," said one of the study's lead authors, Alexander Rau, M.D., resident in the Departments of Neuroradiology and Diagnostic and Interventional Radiology at University Hospital Freiburg in Freiburg, Germany. After infection with COVID-19, as many as 10-25% of patients may develop a post-COVID condition commonly referred to as "long COVID." People with long COVID may experience a wide variety of symptoms, including difficulty concentrating ("brain fog"), change in sense of smell or taste, fatigue, joint or muscle pain, shortness of breath, digestive symptoms, and more. These symptoms may persist for weeks, months, or—as is only now becoming apparent—years after COVID-19 infection. However, the basis of this condition is poorly understood. Diffusion microstructure imaging (DMI), a novel MRI technique, is a promising approach to fill this gap. DMI looks at the movement of water molecules in tissues. By studying how water molecules move in different directions and at various speeds, DMI can provide detailed information on the microstructure of the brain. It can detect even very small changes in the brain, not detectable with conventional MRI. For this prospective, cross-sectional study, Dr. Rau and colleagues compared MRI brain scans of three groups: 89 patients with long COVID, 38 patients that had contracted COVID-19 but did not report any subjective long-term symptoms, and 46 healthy controls with no history of COVID-19. The researchers first compared the cerebral macrostructure of these three groups to test for atrophy or any other abnormalities. Next, they used DMI to gain a deeper insight into the brain. The three groups were compared to reveal group differences in the brain's microstructure. DMI parameters were read for the gray matter in the brain. Additionally, whole brain analyses were employed to reveal the spatial distribution of alterations and associations with clinical data, including long-COVID symptoms like fatigue, cognitive impairment or impaired sense of smell. The results showed no brain volume loss or any other lesions that might explain the symptoms of long COVID. However, COVID-19 infection induced a specific pattern of microstructural changes in various brain regions, and this pattern differed between those who had long COVID and those who did not. "This study allows for an in vivo insight on the impact of COVID-19 on the brain," Dr. Rau said. "Here, we noted gray matter alterations in both patients with long-COVID and those unimpaired after a COVID-19 infection. Interestingly, we not only noted widespread microstructural alterations in patients with long COVID, but also in those unimpaired after having contracted COVID-19." The findings also revealed a correlation between microstructural changes and symptom-specific brain networks associated with impaired cognition, sense of smell and fatigue. "Expression of post-COVID symptoms was associated with specific affected cerebral networks, suggesting a pathophysiological basis of this syndrome" Dr. Rau said. The researchers hope to reexamine the patients in the future, recording both clinical symptoms and changes to the brain's microstructure. Despite these brain imaging findings, it remains unclear why some people develop long COVID while others do not, although previous studies have identified risk factors including female sex, older age, higher body mass index, smoking, preexisting comorbidities, and previous hospitalization or intensive care unit admission. Co-authors are Jonas A. Hosp, M.D., Nils Schroter, M.D., Marco Reisert, Ph.D., Horst Urbach, M.D., Cornelius Weiller, M.D., and Elias Kellner, Ph.D. Note: Copies of RSNA 2023 news releases and electronic images will be available online at RSNA.org/press23. RSNA is an association of radiologists, radiation oncologists, medical physicists and related scientists promoting excellence in patient care and health care delivery through education, research and technologic innovation. The Society is based in Oak Brook, Illinois. (RSNA.org) Editor's note: The data in these releases may differ from those in the published abstract and those actually presented at the meeting, as researchers continue to update their data right up until the meeting. To ensure you are using the most up-to-date information, please call the RSNA Newsroom at 1-312-791-6610. For patient-friendly information on brain MRI, visit RadiologyInfo.org. SOURCE Radiological Society of North America (RSNA)

Clinical Result

04 Apr 2023

·www.sciencedaily.com

DMI allows magnon-magnon coupling in hybrid perovskites

An international group of researchers has created a mixed magnon state in an organic hybrid perovskite material by utilizing the Dzyaloshinskii--Moriya-Interaction (DMI). The resulting material has potential for processing and storing quantum computing information. An international group of researchers has created a mixed magnon state in an organic hybrid perovskite material by utilizing the Dzyaloshinskii-Moriya-Interaction (DMI). The resulting material has potential for processing and storing quantum computing information. The work also expands the number of potential materials that can be used to create hybrid magnonic systems. In magnetic materials, quasi-particles called magnons direct the electron spin within the material. There are two types of magnons -- optical and acoustic -- which refer to the direction of their spin. "Both optical and acoustic magnons propagate spin waves in antiferromagnets," says Dali Sun, associate professor of physics and member of the Organic and Carbon Electronics Lab (ORaCEL) at North Carolina State University. "But in order to use spin waves to process quantum information, you need a mixed spin wave state." "Normally two magnon modes cannot generate a mixed spin state due to their different symmetries," Sun says. "But by harnessing the DMI we discovered a hybrid perovskite with a mixed magnon state." Sun is also a corresponding author of the research. The researchers accomplished this by adding an organic cation to the material, which created a particular interaction called the DMI. In short, the DMI breaks the symmetry of the material, allowing the spins to mix. The team utilized a copper based magnetic hybrid organic-inorganic perovskite, which has a unique octahedral structure. These octahedrons can tilt and deform in different ways. Adding an organic cation to the material breaks the symmetry, creating angles within the material that allow the different magnon modes to couple and the spins to mix. "Beyond the quantum implications, this is the first time we've observed broken symmetry in a hybrid organic-inorganic perovskite," says Andrew Comstock, NC State graduate research assistant and first author of the research. "We found that the DMI allows magnon coupling in copper-based hybrid perovskite materials with the correct symmetry requirements," Comstock says. "Adding different cations creates different effects. This work really opens up ways to create magnon coupling from a lot of different materials -- and studying the dynamic effects of this material can teach us new physics as well." The work appears in Nature Communications and was primarily supported by the U.S. Department of Energy's Center for Hybrid Organic Inorganic Semiconductors for Energy (CHOISE). Chung-Tao Chou of the Massachusetts Institute of Technology is co-first author of the work. Luqiao Liu of MIT, and Matthew Beard and Haipeng Lu of the National Renewable Energy Laboratory are co-corresponding authors of the research.

100 Deals associated with Desipramine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00812	Desipramine Hydrochloride	N06AA01	DB01151

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Depressive Disorder	US	Validus Pharmaceuticals LLC	20 Nov 1964

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01899326 (CTgov)	Not Applicable	Plasma cell myeloma refractory	10	Laboratory Biomarker Analysis+Filgrastim+Desipramine Hydrochloride	ksbizdmbex(wafiogamjy) = pfebgvgfjd hewkgkvaks (tyojaxsebz, gpxqxkcoox - dsvrfxftck) View more	-	28 Mar 2023
ISTH2021	Not Applicable	-	-	Desipramine	qblikwubcy(pudvcixjhw) = bkouhkpqgx wwlfadgufm (wxftnzruev )	-	17 Jul 2021
				PRP pre-incubated with 10μM desipramine	qblikwubcy(pudvcixjhw) = lxjkjclxpw wwlfadgufm (wxftnzruev )
NCT03726996 (CTgov)	Phase 4	Neuroaxonal Dystrophies	4	Desipramine	timygbnujj(cthgaoeizi) = ixrbgutohs bpubhyeyez (vaozdvayud, xqkbuatsvm - cxbvbqafzs) View more	-	14 Oct 2020
NCT01411085 (CTgov)	Phase 2	Alcoholism \| Schizophrenia	12	Risperidone+Desipramine	kkosfbxesw(iaowkjzhdh) = quwkitnjvu mowjzojaox (umecqqvqgf, ebxjmofgvh - fkucpyrvuq) View more	-	23 Mar 2018
NCT00990691 (Pubmed \| Ann Clin Transl Neurol)	Phase 2	Rett Syndrome	36	high Desipramine	zfxtywdget(hrujjvkmzl) = ckiuenyfjt ysrnrnkikf (cpezcknjfn, -37 to -11)	Negative	01 Feb 2018
				low Desipramine	zfxtywdget(hrujjvkmzl) = edhpnsiwdf ysrnrnkikf (cpezcknjfn, -31 to 13)
NCT00338962 (CTgov)	Phase 3	Alcoholism \| Depressive Disorder \| Stress Disorders, Post-Traumatic ... View more	88	paroxetine+Naltrexone (Paroxetine and Naltrexone)	hvwtcaoibs(kfvizfwrkl) = zxzgsonfee ykmucviafh (ofcfbkvpbs, zibkpqrpyk - rnflcrmzvl) View more	-	05 Feb 2016
				Placebo+paroxetine (Paroxetine and Placebo)	hvwtcaoibs(kfvizfwrkl) = jrhgjceptd ykmucviafh (ofcfbkvpbs, ysilhcgrxq - pgnstvlend) View more
NCT00166114 (CTgov)	Phase 4	Depressive Disorder, Major \| Depression	40	Escitalopram (Escitalopram)	ajmcfzuhyj(vqwezktkmq) = yiiamywiek eyzzkcqami (mhxomsqrws, pzdpjopmvm - ljdmzbslca) View more	-	23 Jul 2015
				Desipramine (Desipramine)	ajmcfzuhyj(vqwezktkmq) = leyxjylmbv eyzzkcqami (mhxomsqrws, ytqlftcomm - eyoygstajc) View more
NCT00000271 (Pubmed \| Drug Alcohol Depend)	Phase 2	Depressive Disorder	111	Desipramine	hvztcmmcad(mlhwllnprh) = hwyvwgsvke hdrjsbourr (xuslwcztjd )	-	01 Nov 2005
				Placebo	hvztcmmcad(mlhwllnprh) = nwsgcqctmd hdrjsbourr (xuslwcztjd )

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