Amitriptyline adverse effects

The answer is a. (Katzung, p 499.) Of the listed a n tide press ants, only amitriptyline, a tricyclic, causes adverse effects related to blockade of muscarinic acetylcholine receptors. Both trazodone and amitriptyline cause adverse effects related to a-adrenoreceptor blockade... 

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. 

Although most physicians avoid the combination of an MAOl with most other antidepressants, a number of reports indicate that MAOIs combined with a TCA can be effective and safe in treatment-resistant patients. This combination should be used only by a physician skilled in their use and familiar with their potential adverse effects and drug interactions. Generally, tertiary amine TCAs have been used in combination with MAOIs. Once the dose of the TCA is established, the MAOl should be slowly added. Never attempt the reverse order without a 2-week delay. It may also be prudent to lower the TCA dose slightly before starting the MAOl. An example might be the addition of phenelzine to amitriptyline, starting with an initial dose of 15 mg and subsequent dose increments weekly as needed. The total dose of an MAOl, used in combination with TCA, is usually lower than when used alone (e.g., 30 to 60 mg per day). When the combination is discontinued, the MAOl should be stopped first. 

Sedative antidepressants, such as amitriptyline, doxepin, or trazodone, in low doses, have hypnotic efficacy and may be less likely to evoke the adverse effects associated with higher doses. 

The primary adverse effects of TCAs have been described in the previous text. Anticholinergic effects are perhaps the most common. These effects result in dry mouth, constipation, urinary retention, blurred vision, and confusion. They are more common with tertiary amine TCAs such as amitriptyline and imipramine than with the secondary amine TCAs desipramine and nortriptyline. The potent a-blocking property of TCAs often results in orthostatic hypotension. Hi... 

Oral contraceptives reduce the clearance of imipramine, probably by reducing hepatic oxidation, and thus increase its half-life. Hydroxylation of amitriptyline is inhibited by contraceptive steroids. The clinical significance is uncertain, but there is at least anecdotal evidence of an increase in antidepressant adverse effects (360). Caution should be exercised when tricyclic antidepressants are used long term in women taking oral contraceptives. 

Adverse effects of various antidepressants are summarized in Table 30-5. Most common unwanted effects are minor, but they may seriously affect patient compliance the more seriously depressed the patient is, the more likely it is that unwanted effects will be tolerated. Most normal persons find that even moderate doses of many antidepressants cause disagreeable symptoms, especially the classic tertiary amine tricyclics amitriptyline, imipramine, clomipramine, and doxepin. With the SSRIs, transient nausea is the most frequent complaint, and decreased libido and sexual dysfunction create the greatest concerns during maintenance treatment. 

The barbiturates and meprobamate have been entirely superseded by the benzodiazepines and because of their low benefit-to-risk ratio (dependence producing, lethality in overdose, potent sedative effects) they should never be used as anxiolytics. Despite their popularity as short-term sedatives, antihistamines are ineffective anxiolytics, while the use of sedative antidepressants such as amitriptyline should be limited to the treatment of patients with symptoms of both anxiety and depression due to their limited efficacy and the poor patient compliance associated with their adverse effects. However, patients with panic disorder do appear to show a beneficial response to antidepressants (see Chapter 6). A similar argument... 

Amitriptylinoxide, a metabolite of amitriptyline, has been compared with the parent drug (1). The antidepressant effects were comparable, but the metabolite was thought to have fewer adverse effects, especially cardiotoxic ones. This conclusion was based on the absence of cardio-graphic abnormalities in 15 patients, but this is a very small series on which to base such a conclusion. 

Butriptyline is the isobutyl side-chain homologue of amitriptyline. Its adverse effects, reported in two open studies, were no different from those of other tricyclic antidepressants (1,2). 

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. 

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). 

Sexual disturbance has also been associated with sertraline (14), and a high frequency of such adverse effects has been reported in studies in which high doses were used. In a double-blind, placebo-controlled study of sertraline and amitriptyline in patients with major depression, male sexual dysfunction, mainly ejaculatory disturbance, was reported significantly more often with sertraline (in 21% of the patients) (15). Male sexual dysfunction in 15% of sertraline-treated patients has also been reported (16). 

In a multicenter comparison of moclobemide, amitriptyline, and placebo, gastrointestinal discomfort, headache, and dizziness occurred in over 20% of moclobemide-treated patients insomnia was also common (10). In healthy volunteers there were no effects of moclobemide on psychomotor performance. Acute confusion and agitation was reported in one patient who dropped out of a clinical trial owing to this adverse effect (SEDA-16, 7). Hypomania was attributed to moclobemide in two cases (SEDA-17, 16). Aggressive behavior and mild manic symptoms were described in severely depressed patients, refractory to other treatments, who took moclobemide (SEDA-18, 15). 

There have been several comparisons of maprotiline with other antidepressants. There was no significant difference in adverse effects compared with doxepin (5), amitriptyline (6), or imipramine (7). 

One of the putative benefits of mianserin is its alleged safety in overdose, which may be related to a reduced risk of cardiovascular adverse effects and convulsions. Data from the UK Committee on Safety of Medicines suggest that mianserin accounts for 11% of reported convulsions and 5.8% of use, putting it intermediate between amitriptyline and maprotiline (15). On the other hand, in the London Poisons Unit survey, involving 84 patients who took mianserin alone (up to 1000 mg), there were no deaths and no patients with convulsions, although this could represent a frequency of up to 3.6% (12). 

AMITRIPTYLINE PROTEASE INHIBITORS t adverse effects when amitriptyline is co-administered with ritonavir (with or without lopinavir) and possibly atazanavir Inhibition of CYP3A4-mediated metabolism. Note that SSRIs are metabolized by a number of enzymes, including CYP2C9, CYP2C19, CYP2D6 as well as CYP3A4 therefore the effect of protease inhibitors is variable Monitor closely... 

Note. When SSRIs are compared with TCAs for patients who discontinue therapy (a surrogate endpoint for tolerability), most meta-analyses show a slight benefit in favour of SSRIs. Comparisons which exclude TCAs with the most prominent anti-muscarinic effects (amitriptyline and imipramine) show either marginal benefits in favour of SSRIs or no difference between the groups. It is noteworthy that despite their pronounced adverse effects, amitriptyline and imipramine tend to be selected as standard TCAs against which SSRIs are compared. Lofepramine, the second most prescribed TCA in the UK and the one TCA which causes little sedation, has few antimuscarinic effects and is as safe as SSRIs in overdose is it under-represented in meta-analyses... 

Melitracen is structurally and pharmacologically related to imipramine, with two methyl groups attached to the central ring. It has similar efficacy to amitriptyline, with a somewhat more rapid effect and similar adverse effects (1). 

---