Amitriptyline side effects

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]. 

Amitriptyline, doxepin, and nortriptyline are effective, but side effects include anticholinergic effects, adrenergic blockade, and cardiac conduction prolongation. 

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. 

Pharmaceutical Comparison. At least 8 studies to date have examined the effectiveness of hypericum compared to the pharmaceutical antidepressants imipramine, amitriptyline, and maprotiline. Preliminary results indicate that hypericum is equivalent to standard antidepressants in effectiveness (Linde et al. 1996 Vorbach 1997). Similar to the pharmaceutical antidepressants, there is a 10-14 day lag for therapeutic effects of hypericum (Harrer et al. 1994). Indeed, the differences seen between hypericum and placebo groups becomes apparent between 2 and 4 weeks (Sommer and Harrer 1994). Hypericum has been reported to have a more favorable side-effect profile than several pharmaceutical antidepressants as well (Vorbach et al. 1994 Harrer et al. 1994). In double-blind studies, subjects have reported fewer and less-severe side effects. Although these initial results are promising, Linde and colleagues (1996) have concluded that the present evidence is inadequate to establish... 

The true tricyclics are often subdivided into tertiary and secondary amine groups. Structurally, the difference lies in the length of side chains branching off the basic three-ringed hub of the molecule. Clinically, side effects are most common and most severe with the tertiary amine medications such as amitriptyline, imipramine, and doxepin. The secondary amines are generally better tolerated. It should be added that two of the tertiary amine TCAs, amitriptyline and imipramine, are metabolized... 

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. 

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. 

When treating insomnia without depression, doxepin and amitriptyline (both tricyclic antidepressants) can be administered in low doses (25-100 mg) at bedtime. These antidepressants, however, do have troublesome anticholinergic side effects (dry mouth, constipation, blurred vision, dizziness) and adverse effects on the heart, and they can be lethal if taken in overdose. Because of their effect on heart function, these antidepressants should be avoided in patients with heart problems and administered cautiously, if at all, to those who are already receiving one of any number of newer antidepressants that inhibit the metabolism of the TCAs. 

The metabolism and elimination of TCAs takes several days to occur, the elimination half-life ranging from 20 hours for amitriptyline to 80 hours for protriptyline. The half-life values for the desmethylated metabolites such as desmethylimipramine and nortriptyline are approximately twice those of the parent compounds imipramine and amitriptyline. It is also well established that the half-life values of the TCAs are considerably greater in the elderly, which predisposes such patients to a greater possibility of severe side effects. 

Selective serotonin re-uptake inhibitors such as paroxetine tend to cause less antimuscarinic side-effects and are less toxic in overdose than the tricylic antidepressants, such as amitriptyline. However, selective serotonin re-uptake inhibitors are more likely to cause gastrointestinal disturbances, such as nausea and vomiting, than tricylic antidepressants. Selective serotonin re-uptake inhibitors and tricylic antidepressants are equally effective. 

One of the main side-effects of opioid analgesics, such as codeine and tramadol, is constipation. Amitriptyline (tricyclic antidepressant) and orphenadrine tend to have antimuscarinic properties, resulting in side-effects such as constipation. Senna is a stimulant laxative indicated in constipation. 

Amitriptyline is a tricylic antidepressant and these have antimuscarinic side-effects, such as urinary retention, blurred vision, dry mouth and sweating. They also tend to cause drowsiness. 

Tricylic antidepressants such as amitriptyline cause antimuscarinic side-effects, such as dry mouth and constipation. These antidepressants also tend to exhibit... 

The antidepressant action of amoxapine is comparable to that of imipramine and amitriptyline. It exhibits antagonistic activity on dopamine (D2) receptors. Amoxapine is intended more for relieving symptoms in patients with neurotic or situational depression. It has a number of serious side effects. Synonyms of this drug are asendin, amoxan, moxadil, and others. 

This group includes compounds with actions on a range of neurotransmitter systems. Their antidepressant efficacy is mediated by reuptake inhibition of serotonin and noradrenaline, although side-effects such as sedation may also be useful. Their use in anxiety disorders is supported by a long history of clinical experience and a reasonable evidence base from controlled trials. Studies support the use of clomipramine (a potent serotonin reuptake inhibitor) in panic disorder and OCD (Lecrubier et al. 1997 Clomipramine Collaborative Study Group 1991), of imipramine in panic disorder and GAD (Cross-National Collaborative Panic Study 1992 Rickels et al. 1993), and of amitriptyline in PTSD (Davidson et al. 1993a). No controlled studies support the use of TCAs in social anxiety disorder. 

This chapter describes the structure and neurochemical function of TCAs, metabolism and significant interactions with other medications, side effects, and specific recommendations for monitoring of side effects in children and adolescents. Because of the recent concern regarding the sudden deaths of children stabilized on TCAs, particular attention will be paid to the potential cardiovascular effects of these medications. The chapter will focus on the five TCA medications that have been most widely used in children amitriptyline (AMI), nortriptyline (NT), imipramine (IMI), desipratnine (DMI), and clomipramine (CMI). 

Doxepin 0.1 mg/kg/day 1-2 h before bedtime. Titrate to 0.5-2 mg/kg/day over 2-3 weeks Instead of amitriptyline if anticholinergic side effects are not well tolerated Shannon and Berde, 1989 (G)... 

Imipramine, amitriptyline, clomipramine, trimipramine, and doxepin are tertiary amine TCAs. Desipramine, nortriptyline, and protriptyline are secondary amine TCAs. Tertiary amine tricyclics have more potent serotonin reuptake inhibition, and secondary amine tricyclics have more potent noradrenergic reuptake inhibition. Tertiary amine TCAs tend to have more side effects than do... 

Imipramine, amitriptyline, doxepin, desipramine, clomipramine, and trimipramine therapy can be initiated at 25-50 mg/day. Divided dosing may be used at first to minimize side effects, but eventually the entire dose can be given at bedtime. The dose can be increased to 150 mg/day the second week, 225 mg/day the third week, and 300 mg/ day the fourth week. The dose of clomipramine should not exceed 250 mg/day because of an increased risk of seizures at higher doses. 

Paykel ES, Mueller PS, De la Vergne PM. Amitriptyline, weight gain and carbohydrate craving a side effect. Br J Psychiatry 1973 123(576) 501-7. 

In the past, tricyclic drugs such as amitriptyline and nortriptyline were the most commonly used antidepressants and were the standard against which other antidepressants were measured.30 The use of tricyclic drugs as the initial treatment of depression has diminished somewhat in favor of some of the newer second-generation drugs, which may have more favorable side-effect profiles. Tricyclic agents, nonetheless, remain an important component in the management of depressive disorders, especially in more severe forms of depression that fail to respond to other antidepressants.6,53... 

Tricyclic antidepressants (TCAs) are the oldest antidepressants. TCAs consist of a seven-membered ring both fused with two benzenes and bearing a tethered amine. Examples include imipramine (A.53) and amitriptyline (A.54) (Figure A.16). TCAs primarily act by blocking the reuptake of NE from the synaptic junction and prolonging the time of action of NE. TCAs, however, also affect the action of 5-HT and DA and therefore have more side effects than most antidepressants. 

Q9 What are the possible side effects associated with the use of amitriptyline hydrochloride ... 

ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, FLUCONAZOLE, VORICONAZOLE TCAs Possible t plasma concentrations of TCAs All TCAs are metabolized primarily by CYP2D6. Other pathways include CYP1A2 (e.g. amitriptyline, clomipramine, imipramine), CYP2C9 and CYP2C19(e.g. clomipramine, imipramine). Ketoconazole and voriconazole are documented inhibitors of CYP2C19. Fluconazole and voriconazole are reported to inhibit CYP2C9 Warn patients to report t side-effects of TCAs such as dry mouth, blurred vision and constipation, which may be an early sign of t TCA levels. In this case, consider 1 dose of TCA... 

Broom 2. Ginkgo biloba 3. Scopolia 4. Yohimbine 1. TCAs (e.g. amitriptyline, nortriptyline, clomipramine) 2. SSRIs (e.g. fluvoxamine fluoxetine, paroxetine) 3. Venlafaxine 4. Trazodone May develop cardiac arrhythmias and side-effects such as dryness of the mouth, retention of urine and tachycardia, t sedation Broom contains cardioactive alkalamines such as sparteine Inhibits metabolizing enzymes Anticholinergic properties (hyoscine present in scopolia may worsen side-effects of TCAs-additive antimuscarinic effects) Yohimbine alone can cause hypertension, but lower doses cause hypertension when combined with TCAs Unknown mechanism (ginkgo t sedative effects of trazodone) St John s wort inhibits the uptake of serotonin and thereby t serotonin levels Avoid concomitant use. An SSRI may be a better alternative to be used with broom... 

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