Tricyclic antidepressants Amitriptyline Clomipramine

Tricyclic antidepressants Amitriptyline Clomipramine Desipramine Doxepin Imipramine Trimipramine... 

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%. 

Frequent Drowsiness headaches gastrointestinal upset Occasional Ventricular arrhythmias peripheral edema Rare Priapism in men increased libido TRICYCLIC ANTIDEPRESSANTS (amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine)... 

Tricyclic antidepressants (TCAs) Clomipramine Doxepin Imipramine Lofepramine Nortriptyline Trimipramine (Amitriptyline, Dosulepin) Nocte See BNF See BNF See BNF For depression clomipramine used in OCD Liquids and tablets available Very toxic in overdose (amitriptyline and dosulepin no longer recommended for depression due to OD risk) Caution in CVD and many physical conditions Tolerance to side effects may develop Anticholinergic side effects ... 

Until the introduction of selective serotonin reuptake inhibitors (SSRIs) in the 1980s, tricyclic antidepressants were the most widely used drugs. The therapeutic effect of amitriptyline and imipramine are related to their ability to inhibit the presynaptic reuptake of both NA and 5-HT. They are referred to as non-selective reuptake inhibitors, whereas many of the other tricyclics are more selective thus, clomipramine is a selective reuptake inhibitor for 5-HT and desipramine and nortriptyline are selective... 

Drug therapies include tricyclic antidepressants and SSRIs. Treatment should be continued for at least 29 weeks. Nortriptyline, amitriptyline, clomipramine, desipramine, fluvoxamine, and bupropion have been used successfully. 

Tricyclic antidepressants such as imipramine (25), clomipramine (26), amitriptyline (27), and doxepine (28) were found to be weak inhibitors of GST Pl-1 in vitro. Inhibition of GST Pl-1 was enhanced with the introduction of a chloro group on the dibenzazepine ring (25 40% inhibition at 15 mM 26 70% inhibition at 10 mM). The same result was observed with the substitution of an oxygen for a carbon in the heptadiene ring (27 18% inhibition at 10 mM 28 48% inhibition at 15 mM) [35],... 

Another approach to correct neurotransmission is to inhibit the reuptake of the neurotransmitters into their presvnaptic endings. If the presynaptic reuptake mechanism of a neurotransmitter is blocked then more of the neurotransmitter will stay in the synaptic cleft and be functionally available. Many antidepressant drugs, called reuptake inhibitors , are thought to act via this mechanism. If selective for serotonin they are called selective serotonin reuptake inhibitors (SSRIs, Chapter 1), but if selective for both serotonin and noradrenaline they are called serotonin noradrenaline reuptake inhibitors (SNRIs). Most older antidepressants, such as the tricyclic compounds amitriptyline, imipramine and clomipramine, have little specificity for any of the neurotransmitters fluoxetine, paroxetine, citalopram and a few others are specific for serotonin venlafaxine is a representative of the SNRIs. A more recent mixed-uptake inhibitor is mirtazepine, and some similar compounds are about to be launched. 

Tricyclic antidepressants. Imipramine and clomipramine have been the most extensively studied of the tricyclic antidepressants and both have demonstrated efficacy in treating panic disorder. Other tricyclic antidepressants that have shown some evidence of efficacy include desipramine, doxepin, amitriptyline, and nortriptyline. 

Tricyclic antidepressants (TCAs) - first-generation antidepressants Examples - tertiary amine type imipramine, amitriptyline, dothiepin, clomipramine... 

The tricyclics, such as clomipramine (Anafranil), amitriptyline (Elavil), and imipramine (Tofranil), have been used for several decades. I have previously described their central nervous system toxic effects in some detail (Breggin, 1983b see also Breggin, 1991b). This section will therefore be abbreviated. A list of some of the older antidepressants can be found in the appendix. 

In a controlled comparison between clomipramine and amitriptyline, the former caused adverse effects more often, especially drowsiness (3). Overdose toxicity is the same as with other tricyclic antidepressants (4) fatal interactions with monoamine oxidase (MAO) inhibitors have been reported (SEDA-18, 16 5). Altogether, toxic effects are not substantially different. 

The interactions of tricyclic antidepressants with MAO inhibitors are so dangerous that they constitute a formidable barrier to their combined clinical use. The temptation to treat refractory patients with this combination is great, but considerable care should be taken (169,170), and it should be remembered that there is no firm proof of the superiority of such combinations. Several reviewers (171-173) have concluded that the dangers of these interactions have been overstated and the potential therapeutic advantages underestimated. On the other hand, reports of serious and fatal complications continue to appear (174,175). Specialists have advised that the combination of an MAO inhibitor with trimipramine or amitriptyline is usually safe, but that imipramine and clomipramine must be avoided. 

Clinically important, potentially hazardous interactions with amiodarone, amitriptyline, amoxapine, benzodiazepines, bepridil, clomipramine, clonazepam, clorazepate, delavirdine, desipramine, diazepam, dihydroergotamine, doxepin, ergotamine, fentanyl, flurazepam, imipramine, ixabepilone, lidocaine, lorazepam, methysergide, midazolam, nortriptyline, oxazepam, phenytoin, protriptyline, quazepam, quinidine, rifampin, ritonavir, sildenafil, St John s wort, temazepam, tricyclic antidepressants, trimipramine, vitamin E... 

Clinically important, potentially hazardous interactions with acebutolol, amitriptyline, amoxapine, atenolol, betaxolol, carteolol, clomipramine, desipramine, dexmethylphenidate, doxepin, esmolol, imipramine, insulin detemir, insulin glulisine, metoprolol, nadolol, nortriptyline, oxprenolol, penbutolol, pindolol, propranolol, protriptyline, sulpiride, timolol, tricyclic antidepressants, trimipramine, verapamil... 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, amphetamines, bupropion, citalopram, clomipramine, cyproheptadine, desipramine, dextroamphetamine, dextromethorphan, diethylpropion, dopamine, doxepin, entacapone, ephedra, ephedrine, epinephrine, fluoxetine, fluvoxamine, ginseng, imipramine, levodopa, mazindol, meperidine, methamphetamine, nefazodone, nortriptyline, paroxetine, phendimetrazine, phentermine, phenylephrine, pizotifen, propoxyphene, protriptyline, pseudoephedrine, rizatriptan, sertraline, sibutramine, sumatriptan, sympathomimetics, tramadol, tricyclic antidepressants, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

Clinically important, potentially hazardous interactions with amiodarone, amisulpride, amitriptyline, amoxapine, arsenic, bepridil, bretylium, calcium, chlorpromazine, clomipramine, desipramine, disopyramide, doxepin, erythromycin, fluphenazine, imipramine, iron salts, magnesium, mesoridazine, nortriptyline, pentamidine, perphenazine, phenothiazines, pimozide, procainamide, prochlorperazine, promazine, promethazine, protriptyline, quinidine, sotalol, sucralfate, thioridazine, tricyclic antidepressants, trifluoperazine, trimipramine, zinc salts... 

Doxepin [1668-19-5] (38), unlike other commercially available tricyclics, has an oxygen atom in the bridge between the two aromatic rings. It is marketed as a cis—trans mixture (1 5) of isomers, both of which are active. This close relative of amitriptyline (33) has both sedative and anxiolytic properties associated with its antidepressant profile. Maprotiline [10262-69-8] (39) and amoxapine [14028-44-5] (40) are pharmacologically, although not chemically, similar to the tricyclic secondary amines. Clomipramine [303-49-1] (41) has similar pharmacological and antidepressant efficacy. However, clomipramine is approved by the U.S. FDA only for the treatment of obsessive—compulsive disorder. Representative brands of tricyclic antidepressants marketed in the United States are Us ted in Table 2. 

Chronic abuse of alcohol can lead to enhanced activity of cytochrome P450 enzymes and a consequent decrease in tricyclic antidepressant (TCA) serum levels. Central receptor interactions between alcohol and TCAs can cause impaired motor abilities (evident with amitriptyline, clomipramine, doxepin, and nortriptyline). 

Addition of citalopram does not significantly affect the plasma concentration of tricyclic antidepressants (TCAs) such as amitriptyline, clomipramine, or imipramine. However, citalopram may increase desipramine plasma concentrations by up to 50%... 

Fluvoxamine inhibits the cytochrome P450 liver catabolic enzymes (predominantly this is inhibition of N-demethylation), leading to an increase in tricyclic antidepressant (TCA) serum levels. Plasma levels of several antidepressant drugs (e.g. amitriptyline, clomipramine, desipramine, imipramine, maprotiline, and nortriptyline) have been reported to increase by up to 4-fold during co-administration with fluvoxamine. Fluvoxamine at a daily dose of 50-100 mg causes a 3-4-fold increase in the plasma concentration of mirtazapine. 

Most antipsychotic drugs as well as tricyclic antidepressants (TCAs) are inhibitors of the chytochrome P450 liver catabolic enzymes, thus potentially increasing each other s serum levels. Chlorpromazine increases imipramine serum levels. Levomepromazine can cause a significant increase in clomipramine serum levels. Perphenazine has been reported to increase the serum levels of amitriptyline, desipramine, imipramine, and nortriptyline. Thioridazine has also been shown to increase TCA serum levels (mainly desipramine). Marked extrapyramidal side-effects have been reported in a few cases with fluphenazine or perphenazine when fluoxetine was added to the regimen. The mechanism is not known. A mutual increase in serum levels of both thioridazine and paroxetine is evident when these agents are... 

The treatment of MDD corresponds to three stages acute phase, continuation phase, and maintenance phase. The gross treatment options should follow the strategies listed in Scheme 9.3. The following are only suggestions, which are based mainly on specific data from accumulated research. The selective serotonin reuptake inhibitors (SSRIs) and venlafaxine are usually considered as first-line treatments. Amitriptyline and clomipramine are second-line treatments. Other tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs) are third-line treatments. 

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