A review of Cochrane reviews on pharmacological treatment for attention deficit hyperactivity disorder / Revisão de revisões Cochrane sobre o tratamento farmacológico para transtorno do déficit de atenção e hiperatividade

ABSTRACT. Attention deficit hyperactivity disorder (ADHD) is one of the most frequent childhood psychiatric problems. Objective: The objective of this study was to identify, synthesize the results, and critically evaluate all Cochrane systematic reviews (SRs) on the pharmacological interventions for children and adolescents (up to age 18) diagnosed with ADHD. Methods: The search was performed in the Cochrane Database of Systematic Reviews (via Wiley) in July 2020. Results: The search strategy resulted in four SRs of high methodological quality, analyzing 51 randomized clinical trials (9,013 participants). Compared to placebo, treatment with tricyclic antidepressants (TCAs) (desipramine), amphetamine, and methylphenidate showed improvement in symptoms such as difficulty concentrating, impulsivity, and hyperactivity in the short term (up to 6 months). There was an increase in the occurrence of adverse events, such as reduced appetite, difficulty sleeping, and abdominal pain. Insufficient evidence was found to support the effects of supplementation with polyunsaturated fatty acids. Conclusions: The use of TCAs, amphetamine, and methylphenidate in children and adolescents with ADHD seems to present positive effects and higher rates of minor adverse events when compared to placebo.

RESUMO. Déficit de atenção e hiperatividade (TDAH) é uma das mais frequentes condições psiquiátricas da infância. Objetivo: O objetivo deste artigo foi identificar, sintetizar os resultados e avaliar criticamente todas as revisões sistemáticas (RS) da Cochrane sobre as intervenções farmacológicas para crianças e adolescentes (até 18 anos de idade) diagnosticados com transtorno do déficit de atenção com hiperatividade. Métodos: A pesquisa foi realizada na base de dados Cochrane de Revisões Sistemáticas — CDSR (via Wiley) em julho de 2020. Resultados: A estratégia de busca resultou em quatro RS de alta qualidade metodológica, que analisavam 51 ensaios clínicos randomizados (9.013 participantes). Comparado ao placebo, o tratamento com antidepressivos tricíclicos (desipramina), anfetamina e metilfenidato apresentou melhora nos sintomas, como dificuldade de concentração, impulsividade e hiperatividade no curto prazo (até seis meses). Houve aumento na ocorr≖ncia de eventos adversos, como redução do apetite, dificuldade para dormir e dor abdominal. Foram encontradas evid≖ncias insuficientes para apoiar os efeitos da suplementação com ácidos graxos poli-insaturados. Conclusões: Com base nos resultados de revisões sistemáticas Cochrane, o uso de antidepressivos tricíclicos, anfetamina e metilfenidato em crianças e adolescentes com TDAH parece apresentar efeitos positivos e taxas mais elevadas de eventos adversos menores quando comparado ao placebo. Dado o alto risco de viés nos estudos primários incluídos nessas RS, ainda são necessários novos ensaios clínicos randomizados com rigor metodológico para apoiar esses achados.

Effect of desipramine on apoptosis and endoplasmic reticulum stress in atherosclerotic plaque of rabbits / 中国药理学通报

Aim: To investigate the effect of desipramine (DES) on apoptosis and endoplasmic reticulum stress(ERS) in atherosclerotic model of rabbits. Methods: The rabbit model of atherosclerosis (AS) was established through abdominal aorta balloon injury and high fat diets for 12 weeks. They were divided into high-fat diet(HFD) group and HFD + DES group randomly. The same numbers of healthy rabbits with chow diet were divided randomly into normal control (NC) group and DES group. All interventions were given for the last 4 weeks. At the end of week 12, serum lipid was tested by conventional method. Plasma ox-LDL was measured by ELISA. Plasma and arterial acid sphingomyelinase(ASM) activity and ceramide levels were detected by UPLC analysis. Cell apoptosis in abdominal aorta was measured by TUNEL staining. Expression of GRP78 and CHOP proteins were detected by Western blot. Results: On the one hand, DES had no effect on serum lipid profiles including TG, TC, HDL-C.LDL-C and ox-LDL levels compared with either healthy or atherosclerosis rabbits. On the other hand, DES inhibited ASM and ceramide levels both in plasma and aorta, and decreased apoptotic cells and proteins of GRP78 and CHOP expression in abdominal aorta. Conclusions: DES attenuates AS via inhibition of ASM, down-regulating ceramide, attenuating ERS and thus reducing the apoptosis of AS plaques.

Reversal effects of desipramine on resistance of U251/TR cells to temozolomide / 中国药理学与毒理学杂志

OBJECTIVE To examine the reversal effect of desipramine (DMI) on resistance to temozolomide(TMZ) in U251/TR cells and explore its mechanism. METHODS U251/TR cells were exposed to DMI (20-80μmol · L-1) or TMZ (0.5-10 mmol · L-1) for 24 h, cell viability was determined by cell counting kit-8 assay with IC50 calculated. The cytotoxicity of U251/TR cells treated with TMZ (1 or 2 mmol·L-1) in combination with DMI (20, 30 or 40 μmol · L-1) for 24 h was detected using CCK-8 assay. Synergism between DMI and TMZ was analyzed by the JIN Zheng-jun method. Apoptosis of U251/TR cells induced by TMZ 1 mmol · L-1, DMI 30 μmol · L-1,or their combination was examined by Hoechst33258 stains and caspase 3 activity was detected by luminescence analysis. Expression of C/EBP homologous protein (CHOP) was measured using quantitative real-time PCR and Western blotting. The survival rate of U251/TR cells treated with TMZ 1 mmol·L-1 and/or DMI 30μmol·L-1 was also assessed after silencing CHOP expression by small interference RNA (siRNA). RESULTS DMI or TMZ alone inhibited the growth of U251/TR cells significantly in a concentration-dependent manner (r 2=0.983,0.982,P1.15), ie, compared with TMZ alone, TMZ (1 mmol·L-1) com?bined with DMI (30 μmol · L-1) produced significant nuclear fragmentation and condensation (P< 0.05). In addition, DMI and TMZ in combination activated caspase 3 activity in U251/TR cells (P<0.05). Knock?down of CHOP by specific siRNA attenuated the synergistic effect of DMI in the presence of TMZ, the survival rate of the combined drug group raised from 51.8%to 62.2%(P<0.05). CONCLUSION The results suggest that DMI reverse resistance of U251/TR cells to TMZ through activation of the CHOP-depend?ently apoptosis pathway.

Influence of desipramine on lipopolysaccharide-induced acute lung injury in mice / 中国药理学通报

Aim To investigate the potential role of desipramine(DP) on lipoplysaccharide（LPS）-induced acute lung injury(ALI)and the mechanism of its action.Methods Kunming mice were divided into four groups randomly:NS group(NS),DP control group(DP),LPS group(LPS)and DP treatment group(DP+LPS).The model of ALI in mice was induced by lipoplysaccharidel(LPS,10 mg·kg~(-1),ip).Six hours after LPS challenged,the lung samples were taken for determination of lung wet-to-dry weight ratio(W/D),myeloperoxidase(MPO)activity,and malondialdehyde(MDA)content.The bronchoalveolar lavage fluid(BALF)samples were analyzed for total protein concentrateion and white blood cell(WBC)count.The levels of tumor necrosis factor-α(TNF-α)in lung were measured by ELISA.Results LPS could significantly increase the total protein concentration and WBC number in BALF.The lung W/D ration,MPO activity,MDA content and the levels of TNF-α in lungs all increased after ip injection of LPS.Pretreatment with DP decreased all the changes induced by the LPS.Conclusion Pretreatment with DP protects lung from LPS-induced lung injury in mice,which is,at least in part,through inhibiting the level of TNF-α and decreasing the sequestration of neutrophils and lipid peroxidation.

Effects of antidepressant agents on the neuropathic pain induced by oxaliplatin / 中国癌症杂志

Background and purpose:Oxaliplatin is a new cytotoxic platinum compound widely used in antineoplastic treatments.Peripheral neuropathy characterized by allodynia remains the most common way to limit the usage of oxaliplatin.Oxaliplatin-associated neuropathic pain is often resistant to standard analgesics.The effects of antidepressant agents such as desipramine and fluoxetine on chemotherapy-induced neuropathic pain were investigated so as to provide experimental evidence for clinical treatment.Methods:A single injection of oxaliplatin(30 mg/kg)intraperitoneal was injected into a test subject,a mouse that had chronic neuropathic pain.Using the von Frey filament as a touch stimulator,the mechanical withdrawal threshold(MWT)was measured when observing allodynia.The MWT was measured before and 1 h after the administration of desipramin and fluoxetine.Results:Desipramine and fluoxetine both have the potential to increase the MWT in mice with oxaliplatin-induced neuropathic pain.Pretreatment with antagonists such as an opioid receptor like naloxone could deepen their effects.Furthermore,when desipramine is combined with an opioid analgesic as buprenorphine,it causes an augmentation in the MWT.Conclusion:Antidepressants desipramine and fluoxetine antagonize oxaliplatin-induced neuropathic pain by inhibiting allodynia.Furthermore,the tricyclic antidepressing agent desipramine could enhance the effects of buprenorphine in subjects with oxaliplatin-induced pain,suggesting a synergistic effect for opioid analgesic.

Evaluation of Antidepressant Drug Effect in a Depressive Animal Model by Proton MR Spectroscopy / 의학물리

In this study, we observed the alteration of choline signal intensity in hippocampus region of the depressive rat model induced by forced swimming test (FST). The purpose of this study was to evaluate the antidepressant efficacy in the depressive animal model using MR spectroscopy. Fourteen experimentally naive male Sprague-Dawley rats weighting 160~180 g were used as subjects. Drug injection group was exposed to the FST except for control group. The drugs were administered subcutaneously (SC) in a volume equivalent to 2 ml/kg. And three injections were administered 23, 5, and 1 h before beginning the given test. 1H MR spectra were obtained with use of a point resolved spectroscopy (PRESS) localization sequence performed according to the following parameters: repetition time, 2500 ms; echo time, 144 ms; 512 average; 2048 complex data points; voxel dimensions, 1.5x2.5x2.5 mm3; acquisition time, 25 min. There were no differences in NAA/Cr and Cho/Cr ratio between the right and the left hippocampus both normal control rats and antidepressant-injected rats. Also, no differences were observed in NAA/Cr and Cho/Cr ratio between the normal control rats and the antidepressant-injected rats both the right and the left hippocampus. In this study, we found the recovery of choline signals in the depressive animal model similar to normal control groups as injecting desipramine-HCl which was antidepressant causing anti-immobility effects. Thus, we demonstrated that MR spectroscopy was able to aid in evaluating the antidepressant effect of desipramine-HCl.

Amitriptyline, Desipramine, and Paroxetine Inhibit Nitric Oxide Production in Primary Schwann Cell Cultures of Rats / 대한마취과학회지

BACKGROUND: Antidepressants are being used as supplemental therapy in neuropathic and inflammatory pain. The mechanism of their inhibitory effect on experimental animal inflammation is not clear. Studies during the past few years clearly indicate an important role for nitric oxide (NO) in the inflammation and pain-processing system. We evaluated the effects of amitriptyline, desipramine and paroxetine on NO production in primary Schwann cell cultures. METHODS: Primary cultures of the Schwann cell were prepared from dorsal root ganglia of 1- to 3-day old Spraque-Dawley rats. Schwann cells were cultured in the presence or absence of interferon-gamma (500 ng/ml) plus tumor necrosis factor-alpha (500 ng/ml), amitriptyline, desipramine or paroxetine. Production of NO was determined in the supernatant of the culture media. RESULTS: Amitriptyline (10ng/ml), desipramine (10ng/ml) and paroxetine (10ng/ml) inhibited NO release by 29.8%, 51.4%, and 66.8%, respectively. No drug had a toxic effect on cultured cells, which was determined by an LDH assay. CONCLUSIONS: Inhibition of NO production by Schwann cells may be a mechanism by which some antidepressant medications affect inflammatory and neuropathic pain.

Effect of desipramine on proliferation inhibition and apoptosis induction in rat glioma C6 cells / 中国药理学通报

AIM To study the effect of desipramine (DMI ) on proliferation inhibition and apoptosis induction of rat glioma C6 cells. METH ODS Cell proliferation was measured by MTT col- orimetric assay and cells undergoing apoptosis were determined by electron microscope and flow cytometry. The expression of hcf-2 was evaluated by immunohistochemistry. RESULTS DMI could result in the concentration- dependent inhibition of C6 cell proliferation and lead to arrest in GO - G1 phase of cell cycle. The value of Ica and 95% confidence limits were 20.7(17 .3~24 .2) ?mol?L~ 1. DMI(40 ?mol? L-l )-induced apoptosis showed classical apoptotic morphology and the hypodiploid peak appeared on the histogram of FCM in a concentration- dependent man ner, which could be abrogated by cycloheximide(1. 8 ?mol? L- １ ). Meanwhile, DMI (10 ?mol? L- 1 ) could down-regulate the expression of apoptosis associated gene hcl-2. CONCLUSION DMI could inhibit cell proliferation in a concentration dependent manner and induce typical apoptosis of C6 cells.