Lofepramine 70mg/5ml oral suspension

BackgroundDose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the present study is to examine dose equivalence of antidepressants by a less arbitrary and more systematic method.MethodsWe used data from all randomized, double-blind, flexible-dose trials comparing fluoxetine or paroxetine as standard drugs with any other active antidepressants as monotherapy in the acute phase treatment of unipolar depression. We calculated the ratio of the mean doses for each study and weighted it by the total sample size to find the weighted mean ratio for each drug, which was then used to define the drug׳s dosage equivalent to fluoxetine 40mg/d.ResultsWe included 83 studies (14 131 participants). In the primary analysis, fluoxetine 40mg/day was equivalent to paroxetine dosage of 34.0mg/day, agomelatine 53.2mg/day, amitriptyline, 122.3mg/day, bupropion 348.5mg/day, clomipramine 116.1mg/day, desipramine 196.3mg/day, dothiepin 154.8mg/day, doxepin 140.1mg/day, escitalopram 18.0mg/day, fluvoxamine 143.3mg/day, imipramine 137.2mg/day, lofepramine 250.2mg/day, maprotiline 118.0mg/day, mianserin, 101.1mg/day, mirtazapine 50.9mg/day, moclobemide 575.2mg/day, nefazodone 535.2mg/day, nortriptyline 100.9mg/day, reboxetine 11.5mg/day, sertraline 98.5mg/day, trazodone 401.4mg/day, and venlafaxine 149.4mg/day. Sensitivity analyses corroborated the results except for doxepin.LimitationsThe number of studies for some drugs was small. The current method assumes dose response relationship of antidepressants.ConclusionsOur findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research.

Abstract licence: CC BY-NC-ND

ObjectiveTo assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression.DesignCohort study.SettingUK general practices contributing to the QResearch primary care database.Participants238,963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011.ExposuresAntidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs.Main outcome measuresFirst diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years' follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables.ResultsDuring five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years' follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years' follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses ≥ 40 mg/day).ConclusionsThis study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine.

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Patients with a diagnosis of multiple sclerosis (MS) or major depressive disorder (MDD) share a wide array of biological abnormalities which are increasingly considered to play a contributory role in the pathogenesis and pathophysiology of both illnesses. Shared abnormalities include peripheral inflammation, neuroinflammation, chronic oxidative and nitrosative stress, mitochondrial dysfunction, gut dysbiosis, increased intestinal barrier permeability with bacterial translocation into the systemic circulation, neuroendocrine abnormalities and microglial pathology. Patients with MS and MDD also display a wide range of neuroimaging abnormalities and patients with MS who display symptoms of depression present with different neuroimaging profiles compared with MS patients who are depression-free. The precise details of such pathology are markedly different however. The recruitment of activated encephalitogenic Th17 T cells and subsequent bidirectional interaction leading to classically activated microglia is now considered to lie at the core of MS-specific pathology. The presence of activated microglia is common to both illnesses although the pattern of such action throughout the brain appears to be different. Upregulation of miRNAs also appears to be involved in microglial neurotoxicity and indeed T cell pathology in MS but does not appear to play a major role in MDD. It is suggested that the antidepressant lofepramine, and in particular its active metabolite desipramine, may be beneficial not only for depressive symptomatology but also for the neurological symptoms of MS. One clinical trial has been carried out thus far with, in particular, promising MRI findings.

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