Dosulepin

Rao et al.20 demonstrated a fluorescence polarization immunoassay for evaluating serum concentrations of tricyclic antidepressants (amitriptyline, imipramine, clomipramine, and doxepin) with respect to nonresponse, compliance, therapeutic window, and influences of age, sex, substance abuse, and toxicity. Abbott Laboratories TDx/TDxFLx Toxicology Tricyclic Assay FPIA (fluorescence polarization immunoassay) was used. This assay of 50 /uL samples contained tricyclic antidepressant antibodies raised in rabbits and fluorescein-labeled tricyclic antidepressant as a tracer. The assay was calibrated with imipramine in the range of 75 to 1000 fig/L (268 to 3571 nmol/L). Intra-assay and inter-assay coefficients of variation for internal quality control samples from the manufacturer were 4.2 and 4.7%, respectively. The limits of detection were 72,71,64, and 72 nmol/L for amitriptyline, imipramine, clomipramine, and doxepin, respectively. This high-throughput immunoassay was easy to use although amitriptyline, dosulepine, desipramine, and nortriptyline showed cross-reactivities ranging from 74 to 100%. 

Imipramine, desipramine, amitriptyline, nortriptyline, trimipramine, clomipramine, lofepramine, amoxapine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipram, sulpiride, tandspirone, methylpheni-date, melitracen Amitriptyline, imipramine, trimipramine, clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, reboxetine, viloxazine, doxepin, maprotiline, mianserine, mirtazapine, moclobemide, trazodone, opipramol (and some metabolites)... 

In a prospective cohort study of over 450 patients who had attempted suicide by antidepressant ingestion the risk of seizures after venlafaxine overdose (14%) was significantly greater than that of SSRIs (1.3%) and similar to that seen with dosulepin (11%) (12). Rates of 5HT toxicity did not differ significantly between venlafaxine and SSRIs (29% versus 19%) but were greater than with tricyclic antidepressants (1.2%). Unlike SSRIs, venlafaxine was associated with significant prolongation of the QT interval tricyclic antidepressants had a similar effect. 

The majority of all deaths from antidepressant poisoning in Scotland, England, and Wales, during 1975-1984 and 1985-1989 were due to two tricyclic drugs, amitriptyline and dosulepin, and they, as well as the entire group of older tricyclic antidepressants, had a fatality index (deaths per million prescriptions) significantly higher than the mean (150). 

Dosulepin (dothiepin) is a tricyclic antidepressant that has been available in Europe for over 30 years and is particularly... 

Trimipramine is a sedating tricyclic antidepressant that has been used as a hypnotic (1) it shares this activity with other drugs of its class, notably amitriptyline, dosulepin, doxepin, and trazodone, and with the tetracyclics mianserin and mirtazapine. Trimipramine may be preferred for this purpose, since it has less effect on sleep architecture, including REM sleep (2), and has only a modest propensity to produce rebound insomnia in a subset of patients (3). Sedative antidepressants may be particularly appropriate for individuals at risk of benzodiazepine abuse and patients with chronic pain (4). The usual pattern of tricyclic adverse effects, especially antimuscarinic and hypotensive effects and weight gain, can be expected. Some authors, enthusiastic about GABA enhancers, contend that antidepressants are not useful hypnotic alternatives (5). 

Acute angle closure glaucoma has been reported in a 45-year-old woman taking venlafaxine (75 mg/day) and chlorpromazine (150 mg/day) (15). She had previously taken low-dose dosulepin (75 mg/day), chlorpromazine, and SSRIs without ophthalmic problems. 

Paclt I, Slavicek J, Dohnalova A, Kitzlerova E, Pisvejcova K. Electrocardiographic dose-dependent changes in prophylactic doses of dosulepine, lithium and citalopram. Physiol Res 2003 52 311-17. 

Hallucinations have been described after the use of morphine in various dosage forms in one series, patients experienced adequate pain relief and no further hallucinations or nightmares when changed to oxycodone (540). Delusions and hallucinations have been reported in a patient who was also taking dosulepin (541). Restlessness, vomiting, and disorientation were described in two male patients over 60 years of age taking modified-release morphine for relief of pain in advanced cancer (542). 

A 66-year-old tetraparetic man developed hallucinations while taking tramadol, paroxetine, and dosulepin for chronic pain (654). 

Amitryptiline, imipramine, clomipramine, dosulepin and doxepin are more potent CYP inhibitors, inhibiting CYP2C19 and CYP1A2. 

Overdose. Depression is a risk factor for both parasuicide and completed suicide, and TCAs are commonly taken by those who deliberately self-harm. Dothiepin (dosulepin) and amitriptyline are particularly toxic in overdose, being responsible for up to 300 deaths per year in the UK despite the many alternative antidepressants that are available. Lofepramine is at least 15 times less likely to cause death from overdose clomipramine and imipramine occupy intermediate positions. 

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