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Evidence Report/technology Assessment... Nov 1999To determine (a) the long-term and short-term effectiveness and safety of pharmacological and nonpharmacological interventions for attention-deficit/hyperactivity... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
To determine (a) the long-term and short-term effectiveness and safety of pharmacological and nonpharmacological interventions for attention-deficit/hyperactivity disorder (ADHD) in children and adults and (b) whether combined interventions are more effective than individual interventions.
SEARCH STRATEGY
MEDLINE (from 1966), CINAHL (from 1982), HEALTHStar (from 1975), PsycINFO (from 1984), EMBASE (from 1984), and the Cochrane Library searches were completed in November 1997. Reference lists of eligible studies and files of members of the research team and partner organizations were also searched.
SELECTION CRITERIA
Studies were selected if they focused on the treatment of ADHD in humans and were published in any language as a full report in peer-reviewed journals. Studies including conditions other than ADHD were reported if separate subgroup analyses for patients with ADHD were provided.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data for 41 variables on general characteristics, along with detailed information on interventions, outcomes, and tests. Differences were resolved by consensus or by a third researcher. Studies were not combined quantitatively because the quality of reporting was low and heterogeneity existed across outcome measures and tests.
MAIN RESULTS
Seventy-eight studies (77 randomized controlled trials) met the inclusion criteria. Twenty-three studies compared drugs and showed few, if any, differences among methylphenidate (MPH), dextroamphetamine (DEX), and pemoline; studies comparing stimulants with tricyclic antidepressants (2) were inconclusive. Six studies compared drugs with nondrug interventions and showed consistently that stimulants, particularly MPH, may be more effective than nonpharmacological interventions. Twenty studies compared combination therapies with a stimulant or a nondrug intervention alone; no additional beneficial effects for combination therapies were shown. Nine studies compared tricyclic antidepressants with placebo and showed that desipramine may be more effective than placebo; no consistent effect was shown for imipramine. Fourteen studies (13 in school children and 1 in adults) evaluated long-term therapy (> or = 12 weeks) and showed a trend to general improvement regardless of treatment, but the length of followup was inadequate. MPH may reduce behavioral disturbance in children with ADHD while it is taken. Academic performance does not appear to be improved with stimulants. Twelve studies evaluated treatment in adults with ADHD. For MPH vs. placebo, the results were contradictory. Antidepressants may be effective in adults, but no beneficial effect was seen with pemoline, nicotine, or phenylalanine compared with placebo. Thirty-two reports (29 studies) evaluated adverse effects of drug therapy; many of the side effects associated with stimulant use appear to be relatively mild and of short duration and to respond to dosing or timing adjustments. Data are inadequate on the long-term effects and severity of adverse effects of most interventions.
CONCLUSIONS
This report describes rigorous systematic reviews on the treatment of ADHD, ready for incorporation into evidence-based clinical practice guidelines or performance measures. The report also provides a detailed description of the many limitations of the evidence available and provides recommendations to fill existing knowledge gaps. Studies on ADHD have low reporting quality, methodological flaws, and heterogeneity across outcome measures and tests. A detailed description is included of the many limitations of the available evidence plus recommendations to fill existing knowledge gaps. Fulfilling such knowledge gaps will not be easy and will require genuine collaboration among decisionmakers.
Topics: Adrenergic Uptake Inhibitors; Adult; Antidepressive Agents, Tricyclic; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child Behavior; Combined Modality Therapy; Desipramine; Dextroamphetamine; Evidence-Based Medicine; Follow-Up Studies; Humans; Imipramine; Methylphenidate; Nicotine; Nicotinic Agonists; Pemoline; Phenylalanine; Placebos; Randomized Controlled Trials as Topic; Safety; Treatment Outcome
PubMed: 10790990
DOI: No ID Found -
The New England Journal of Medicine May 1992Amitriptyline reduces the pain caused by peripheral-nerve disease, but treatment is often limited by side effects related to the drug's many pharmacologic actions.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Amitriptyline reduces the pain caused by peripheral-nerve disease, but treatment is often limited by side effects related to the drug's many pharmacologic actions. Selective agents might be safer and more effective.
METHODS
We carried out two randomized, double-blind, crossover studies in patients with painful diabetic neuropathy, comparing amitriptyline with the relatively selective blocker of norepinephrine reuptake desipramine in 38 patients, and comparing the selective blocker of serotonin reuptake fluoxetine with placebo in 46 patients. Fifty-seven patients were randomly assigned to a study as well as to the order of treatment, permitting comparison among all three drugs and placebo as the first treatment. The patients rated the degree of pain present each day using verbal descriptors, and they also assessed the extent of pain relief globally at the end of each treatment period.
RESULTS
After individual dose titration, the mean daily doses of the drugs were as follows: amitriptyline, 105 mg; desipramine, 111 mg; and fluoxetine, 40 mg. There was moderate or greater relief of pain in 28 of the 38 patients (74 percent) who received amitriptyline, 23 of the 38 patients (61 percent) who received desipramine, 22 of the 46 patients (48 percent) who received fluoxetine, and 19 of the 46 patients (41 percent) who received placebo. The differences in responses between amitriptyline and desipramine and between fluoxetine and placebo were not statistically significant, but both amitriptyline and desipramine were superior to placebo. Amitriptyline and desipramine were as effective in patients who were not depressed as in depressed patients, but fluoxetine was effective only in depressed patients.
CONCLUSIONS
Desipramine relieves pain caused by diabetic neuropathy with efficacy similar to that of amitriptyline, offering an alternative for patients unable to tolerate the latter. Blockade of norepinephrine reuptake is likely to mediate the analgesic effect of these antidepressant drugs in diabetic neuropathy. Fluoxetine, which blocks serotonin uptake, is no more effective than placebo for the relief of pain.
Topics: Adult; Aged; Aged, 80 and over; Amitriptyline; Analgesics; Depression; Desipramine; Diabetic Neuropathies; Double-Blind Method; Female; Fluoxetine; Humans; Infant, Newborn; Male; Middle Aged; Pain
PubMed: 1560801
DOI: 10.1056/NEJM199205073261904 -
The Journal of Pharmacology and... Jan 2017Depression is a major public health concern with symptoms that are often poorly controlled by treatment with common antidepressants. This problem is compounded in...
Depression is a major public health concern with symptoms that are often poorly controlled by treatment with common antidepressants. This problem is compounded in juveniles and adolescents, because therapeutic options are limited to selective serotonin reuptake inhibitors (SSRIs). Moreover, therapeutic benefits of SSRIs are often especially limited in certain subpopulations of depressed patients, including children and carriers of low-expressing serotonin transporter (SERT) gene variants. Tricyclic antidepressants (TCAs) offer an alternative to SSRIs; however, how age and SERT expression influence antidepressant response to TCAs is not understood. We investigated the relation between antidepressant-like response to the TCA desipramine using the tail suspension test and saturation binding of [H]nisoxetine to the norepinephrine transporter (NET), the primary target of desipramine, in juvenile (21 days postnatal [P21]), adolescent (P28), and adult (P90) wild-type (SERT+/+) mice. To model carriers of low-expressing SERT gene variants, we used mice with reduced SERT expression (SERT+/-) or lacking SERT (SERT-/-). The potency and maximal antidepressant-like effect of desipramine was greater in P21 mice than in P90 mice and was SERT genotype independent. NET expression decreased with age in the locus coeruleus and increased with age in several terminal regions (e.g., the cornu ammonis CA1 and CA3 regions of the hippocampus). Binding affinity of [H]nisoxetine did not vary as a function of age or SERT genotype. These data show age-dependent shifts for desipramine to produce antidepressant-like effects that correlate with NET expression in the locus coeruleus and suggest that drugs with NET-blocking activity may be an effective alternative to SSRIs in juveniles.
Topics: Aging; Animals; Antidepressive Agents; Desipramine; Female; Gene Expression Regulation; Genotype; Hindlimb Suspension; Hippocampus; Immobility Response, Tonic; Locus Coeruleus; Male; Mice; Mutation; Norepinephrine Plasma Membrane Transport Proteins; Serotonin Plasma Membrane Transport Proteins
PubMed: 27831486
DOI: 10.1124/jpet.116.237305 -
Brain, Behavior, and Immunity May 2017Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the...
Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the tricyclic norepinephrine/serotonin reuptake inhibitor desipramine (Desip), were developed under the premise that increasing extracellular neurotransmitter level was the sole mechanism by which they alleviate depressive symptomologies. However, evidence suggests that anti-depressants have additional actions that contribute to their therapeutic potential. The Kynurenine Pathway produces tryptophan metabolites that modulate neurotransmitter activity. This recognition identified another putative pathway for anti-depressant targeting. Considering a recognized role of the Kynurenine Pathway in depression, we investigated the potential for Desip to alter expression of rate-limiting enzymes of this pathway: indoleamine-2,3-dioxygenases (Ido1 and Ido2). Mice were administered lipopolysaccharide (LPS) or synthetic glucocorticoid dexamethasone (Dex) with Desip to determine if Desip alters indoleamine-dioxygenase (DO) expression in vivo following a modeled immune and stress response. This work was followed by treating murine and human peripheral blood mononuclear cells (PBMCs) with interferon-gamma (IFNγ) and Desip. In vivo: Desip blocked LPS-induced Ido1 expression in hippocampi, astrocytes, microglia and PBMCs and Ido2 expression by PBMCs. Ex vivo: Desip decreased IFNγ-induced Ido1 and Ido2 expression in murine PBMCs. This effect was directly translatable to the human system as Desip decreased IDO1 and IDO2 expression by human PBMCs. These data demonstrate for the first time that an anti-depressant alters expression of Ido1 and Ido2, identifying a possible new mechanism behind anti-depressant activity. Furthermore, we propose the assessment of PBMCs for anti-depressant responsiveness using IDO expression as a biomarker.
Topics: Adrenergic Uptake Inhibitors; Animals; Desipramine; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interferon-gamma; Leukocytes, Mononuclear; Male; Mice; Young Adult
PubMed: 28212884
DOI: 10.1016/j.bbi.2017.02.010 -
Acta Bio-medica : Atenei Parmensis Apr 2023Background and aim Crocin is a pharmacologically active chemical found in the spice saffron from Crocus sativus L. It possesses antioxidant and anti-radical properties...
UNLABELLED
Background and aim Crocin is a pharmacologically active chemical found in the spice saffron from Crocus sativus L. It possesses antioxidant and anti-radical properties that can minimize the hepatic phospholipidosis triggered using the tricyclic antidepressant desipramine. The aim of this study was to examine the effect of crocin on desipramine-induced hepatic phospholipidosis targeting the oxidative stress-related PI3K/Akt/mTOR signaling pathways.
METHODS
Forty adult male rats were divided into 4 groups (n =10): control group, a group receiving intraperitoneal (IP) crocin (50 mg/kg/day), a group receiving IP desipramine (10 mg/kg/day), and a group receiving both IP crocin and desipramine.
RESULTS
After 3 weeks of treatment, the combined treatment group showed diminished desipramine-induced hepatic phospholipidosis, along with significant reductions in total oxidant status (TOS) , the levels of inflammatory markers including interleukin 6 (IL6) and tumor necrosis factor α (TNF-α) and apoptotic markers including caspase3 and Bcl2 (B-cell lymphoma 2) while other markers including total antioxidant capacity (TAC), superoxide dismutase (SOD), phosphoinositide 3-kinases (PI3K), and mammalian target of rapamycin (mTOR) were increased. The gene expression of lysosomal enzymes including ELOVL6, SCD1 and HMGR was notably downregulated, while AP1S1 was upregulated in the combined treatment group compared to the desipramine group. No ultrastructural signs of hepatic phospholipidosis, in the form of multilamellar bodies, were apparent in the combined treatment group.
CONCLUSIONS
These data collectively suggest that crocin has a protective effect against desipramine-induced phospholipidosis. (www.actabiomedica.it).
Topics: Animals; Male; Rats; Antioxidants; Desipramine; Liver; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 37092612
DOI: 10.23750/abm.v94i2.14442 -
British Medical Journal Apr 1968
Topics: Amitriptyline; Antidepressive Agents; Desipramine; Dibenzazepines; Enuresis; Humans; Imipramine; Nortriptyline; Opipramol
PubMed: 5646073
DOI: No ID Found -
British Journal of Pharmacology Aug 20011. The effects of desipramine (3 mg kg(-1) i.p.) and clorgyline (1 mg kg(-1) i.p.) on extracellular noradrenaline (NA) in the locus coeruleus (LC) and cingulate cortex...
Acute and chronic effects of desipramine and clorgyline on alpha(2)-adrenoceptors regulating noradrenergic transmission in the rat brain: a dual-probe microdialysis study.
1. The effects of desipramine (3 mg kg(-1) i.p.) and clorgyline (1 mg kg(-1) i.p.) on extracellular noradrenaline (NA) in the locus coeruleus (LC) and cingulate cortex were assessed in freely-moving rats by dual-probe microdialysis. Functional activities of alpha(2)-adrenoceptors regulating NA release in the LC and cingulate cortex were determined by systemic (0.3 mg kg(-1) i.p.) or local (0.1 - 100 microM) clonidine administration. 2. Extracellular NA was increased in the LC and cingulate cortex following acute desipramine but not clorgyline treatment. Systemic clonidine decreased NA similarly in desipramine-, clorgyline-, and saline-treated animals, in both brain areas. 3. Long-term (twice daily, 14 days) but not short-term (twice daily, 7 days) desipramine, and long-term clorgyline (once daily, 21 days) treatments increased NA (3 fold) in cingulate cortex but not in the LC. Following long-term treatments, responses of NA to systemic clonidine were attenuated in the LC and cingulate cortex. 4. Clonidine perfusion by reverse dialysis into the cingulate cortex decreased local NA (-55 +/- 9%). The effect was attenuated by long-term desipramine (-31 +/- 9%) and clorgyline (-10 +/- 2%) treatments. 5. Clonidine perfusion by reverse dialysis into the LC decreased NA in the LC (-89 +/- 2%) and in cingulate cortex (-52 +/- 12%). This effect was attenuated in the LC following long-term desipramine (-72 +/- 4%) and clorgyline (-62 +/- 12%) treatments but it was not modified in the cingulate cortex (-57 +/- 10% and -68 +/- 6%, respectively). 6. These findings demonstrate that chronic desipramine or clorgyline treatments increase NA in noradrenergic terminal areas and desensitize alpha(2)-adrenoceptors modulating local NA release at somatodendritic and terminal levels. However, somatodendritic alpha(2)-adrenoceptors that control LC firing activity are not desensitized.
Topics: Adrenergic Uptake Inhibitors; Adrenergic alpha-Agonists; Animals; Brain; Clonidine; Clorgyline; Desipramine; Gyrus Cinguli; Locus Coeruleus; Male; Microdialysis; Norepinephrine; Rats; Receptors, Adrenergic, alpha-2; Time Factors
PubMed: 11498523
DOI: 10.1038/sj.bjp.0704196 -
Journal of Psychiatry & Neuroscience :... Jan 1994In neurochemistry there are advantages in determining how patients are likely to react to psychoactive drugs prior to the commencement of drug therapy. Explanations of a... (Review)
Review
In neurochemistry there are advantages in determining how patients are likely to react to psychoactive drugs prior to the commencement of drug therapy. Explanations of a patient's nonresponse, or unexpected adverse reactions to drugs are required. In many instances, a knowledge of the drug metabolism status of a patient can be helpful in the selection of a drug and its dosage regimen, and in the prediction of possible drug/drug interactions when two or more drugs have to be administered concomitantly. Important information on these topics may be obtained by phenotyping patients prior to drug therapy. The metabolism of various antidepressant and neuroleptic drugs is catalyzed by CYP2D6, a cytochrome P450 isozyme (also named P450IID6), whereas the metabolism of other drugs may involve different cytochromes P450. The properties of CYP2D6 and four other isozymes (CYP1A1, CYP1A2, CYP2C8/9 and CYP3A4) are described, and substrates identified. Phenotyping of patients for CYP2D6 activity and mephenytoin hydroxylase activity is described.
Topics: Clomipramine; Cytochromes; Dealkylation; Depressive Disorder; Desipramine; Dextromethorphan; Drug Interactions; Female; Humans; Hydroxylation; Imipramine; Isoenzymes; Male; Mephenytoin; Nortriptyline; Phenotype; Polymorphism, Genetic
PubMed: 8148364
DOI: No ID Found -
Journal of Chromatographic Science Apr 2016A rapid and sensitive ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometric (UHPLC-Q-TOF-MS) method was developed for quantification...
A Simple, Rapid and Reliable Method to Determine Imipramine and Desipramine in Mouse Serum Using Ultra-High-Performance Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry.
A rapid and sensitive ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometric (UHPLC-Q-TOF-MS) method was developed for quantification of imipramine, one of the most widely used tricyclic antidepressants, and desipramine, an active metabolite of imipramine, in mouse serum. The developed method included a simple protein precipitation with acetonitrile in 50 μL of serum and analyte separation on an Acquity UPLC BEH C18 column using a gradient elution of acetonitrile with 0.1% formic acid and 20 mM ammonium formate. As a result, the entire analysis time was <20 min including the sample preparation and the LC-MS analysis. The limit of quantification was 5.0 ng mL(-1) for both imipramine and desipramine, and calibration curves were linear over the concentration range of 5.0-1,000.0 and 5.0-250.0 ng mL(-1) for imipramine and desipramine, respectively. Intraday precisions at three levels were 2.2-3.6 and 1.7-4.2% for imipramine and desipramine, respectively, whereas interday precisions were 2.6-5.0 and 2.0-8.4% for imipramine and desipramine, respectively. Accuracy ranged between 93.6 and 106.6% for imipramine and 94.1 and 106.4% for desipramine. Absolute recovery was 96.0-97.6% for imipramine and 87.0-99.5% for desipramine. Finally, the described method was applied to mice administered with imipramine, demonstrating the suitability for quantification of imipramine and desipramine for therapeutic drug monitoring or bioequivalence studies.
Topics: Animals; Antidepressive Agents, Tricyclic; Chromatography, High Pressure Liquid; Desipramine; Imipramine; Limit of Detection; Male; Mass Spectrometry; Mice; Mice, Inbred ICR; Reproducibility of Results
PubMed: 26688563
DOI: 10.1093/chromsci/bmv187 -
Behavioural Pharmacology Aug 2018The forced swim test in rodents allows rapid detection of substances with antidepressant-like activity, evidenced as a decreased duration of immobility that is produced...
The forced swim test in rodents allows rapid detection of substances with antidepressant-like activity, evidenced as a decreased duration of immobility that is produced by the majority of clinically used antidepressants. Antidepressants also increase the latency to immobility, and this additional measure reportedly can increase the sensitivity of the forced swim test in mice. Extending these findings, the present study examined the effects of desipramine and fluvoxamine in a forced swim test in C57BL/6J mice, a strain commonly used as background for genetic modifications, analyzing results with a method (i.e. survival analysis) that can model the skewed distribution of latencies and that can deal with censored data (i.e. when immobility does not occur during the test), in comparison with the more traditional Student's t-test. Desipramine increased the latency to immobility at 32 mg/kg, but not at lower doses. Fluvoxamine also did not affect latency at lower doses, but in contrast to desipramine, fluvoxamine decreased the latency to immobility at the highest dose (i.e. 32 mg/kg). At doses affecting latency to immobility, neither desipramine nor fluvoxamine significantly affected duration of immobility. Together, these results are generally consistent with the suggestion that inclusion of the latency measure can increase the sensitivity of the forced swim test to detect antidepressant-like effects in mice.
Topics: Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic; Behavior, Animal; Depression; Desipramine; Disease Models, Animal; Fluoxetine; Fluvoxamine; Immobilization; Male; Mice; Mice, Inbred C57BL; Motor Activity; Swimming
PubMed: 29200003
DOI: 10.1097/FBP.0000000000000371