Amitriptyline use

Figure 1.29. LC separation of (1) norephedrine, (2) nortriptyline, (3) toluene, (4) imipnamine, and (5) amitriptyline using columns with various bonded phases [all-ACE column 250mmx4.6mm, 5 pm mobile phase 80/20 (v/v) methanol-25 mM phosphate buffer usually, phosphate buffers are not preferred for MS applications], (Reprinted with permission from Dolan, 2007.)...

Smith, C.S. Abramson, R.K. Morgan, S.L. An investigation of the metabolism of amitriptyline using high performance liquid chromatography. J.Liq.Chromatogr., 1986, 9, 1727-1745 [rat metabolites tissue liver]... 

Two recently introduced antidepressants are notable m that they are selective serotonin uptake inhibitors Citalopram (19) is reported to be as effective as amitriptyline m the treatment of endogenous depression [75, 16] Fluoxetine (20) as the hydrochlonde is approved for major depressive disorders mcludmg those with concomitant anxiety Interestmgly, it also appears useful m the treatment of obesity [17]... 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Tricyclic antidepressants (TCAs) such as amitriptyline and doxepin have been used with some success in the treatment of IBS-related pain (Table 18-5). They modulate pain principally through their effect on neurotransmitter reuptake, especially norepinephrine and serotonin. Their helpfulness in functional gastrointestinal disorders seems independent of mood-altering effects normally associated with these agents. Low-dose TCAs (e.g., amitriptyline, desipramine, or doxepin 10 to 25 mg daily) may help patients with IBS who predominantly experience diarrhea or pain. 

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. 

Amitriptyline appears to be the tricyclic antidepressant (TCA) of choice, but imipramine, doxepin, nortriptyline, and protriptyline have also been used. 

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%. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Solid phase extraction (SPE) has been used to efficiently extract several types of antidepressants, which can then be conveniently analyzed on GC-NPD. One assay extracted and analyzed viloxazine, venlafaxine, imipramine, desipramine, sertraline, and amoxapine from whole blood in one procedure (Martinez et al., 2002). The same laboratory analyzed fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiUne, clomipramine, and trazodone in whole blood in one assay (Martinez et al., 2003). SPE has also been used for the simultaneous analysis of TCAs and their metabolites by de la Torre et al. (1998). 

Certain prototypic drug substrates have been used to characterize enzyme activity in the human brain tissue. Amitriptyline, for example, was shown to be demethylated to nortriptyline by both rat and human... 

In the stationary phase test discussed here, we use naphthalene and acenaphthene as our hydrophobic reference compounds, propranolol and amitriptyline as the compounds with basic functional groups, and dipropylphthalate and butylparaben for the determination of other polar selectivities of a packing. The mobile phase is a pH 7.00 phosphate buffer (35.0%) mixed with methanol (65.0%). The details of the test procedure are discussed in References 34, 38 and 39. 

Tricyclic Antidepressants (TCAs). Because of their effectiveness not only for depression but for anxiety disorders such as panic disorder as well, TCAs were the first medications formally tested in the treatment of PTSD. Three TCAs, amitriptyline, imipramine, and desipramine, have been studied in small trials, producing modest benefit for reexperiencing and hyperarousal symptoms, without any relief of avoidance/numbing symptoms. Given this limited benefit in conjunction with the side effect burden and potential for toxicity in a suicide prone population, TCAs are infrequently used in the treatment of PTSD. Please refer to Chapter 3 for more information regarding TCAs. 

Despite limited success with amitriptyline in some anorexia patients, using this class of antidepressants can be problematic in AN patients and therefore cannot be routinely recommended. TCAs slow gastrointestinal function and can therefore worsen the constipation and bloating that commonly plague AN patients during refeeding. In addition, TCAs can increase the likelihood of seizure or cardiac arrhythmia in patients already at risk due to electrolyte disturbances. Moreover, they are often lethal after overdose. 

Tricyclic Antidepressants (TCAs). The TCAs have been nsed to treat ADHD for 30 or more years. Most often used are imipramine (Tofranil) and desipramine (Norpramin), mainly becanse they are the TCAs that most specihcally increase norepinephrine activity. Remember, boosting norepinephrine activity in the brain shonld improve attention. Other TCAs, namely, amitriptyline (Elavil, Endep) and nortriptyline (Pamelor), have been used, though they also increase norepinephrine activity. TCAs do offer a modest benefit for both the inattention and the hyperactivity of ADHD. In addition, they are often effective at doses mnch lower than those required to treat depression. However, their effectiveness nsnally falls short of the stimulant medications. In addition, TCAs have considerable side effects including dry mouth, constipation, drowsiness, weight gain, and adverse cardiac effects. 

Antidepressants. For three apparent reasons, antidepressants have long been used to treat insomnia. First, some of them are quite sedating. In particular, doxepin (Sinequan), amitriptyline (Elavil), and trazodone (Desyrel) have been used to treat... 

Ergotamine is an ergot derivative indicated for the treatment of migraine. Amitriptyline and propranolol can be used for the prophylaxis of migraine. 

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