Doxepin adverse 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. 

Topical doxepin in the form of cream is used in the treatment of pruritus associated with atopic dermatitis or lichen chronicus. Adverse effects include marked burning and stinging at the treatment site. 

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. 

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. 

Doxepin is a tricyclic antidepressant that has also been used topically in the treatment of atopic dermatitis and other forms of eczematous dermatitis. It causes the adverse effects that one would expect, and systemic effects can result from absorption after topical administration. 

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). 

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). 

AMOXAPINE, CLOMIPRAMINE, DOXEPIN, IMIPRAMINE, NORTRIPTYLINE, TRIMIPRAMINE PROTEASE INHIBITORS Possibly t adverse effects of amoxapine with atazanavir and ritonavir Inhibition of CYP3A4-mediated metabolism of amoxapine, clomipramine and doxepin inhibition of CYP3A4-, CYP2D6-and CYP2C9-mediated metabolism of imipramine inhibition of CYP2D6-mediated metabolism of nortriptyline and trimipramine Monitor closely... 

Thiothixene levels are usually increased by TCAs (doxepin and nortriptyline). Additive adverse effects have also been reported when co-administered with ciomipramine (rapid development of tardive dyskinesia). Marked extrapyramidal side-effects have been reported (a few cases only) with suipiride or thiothixene when fluoxetine is added to the regimen. Unlike the established interactions between most phenothiazines and TCAs, in which serum levels of both agents could increase, no apparent interaction is evident to date between fiupenthixoi and imipramine or any other TCA. 

The SSRIs are reported to have fewer side effects than the TCAs, which have strong anticholinergic and cardiotoxic properties (50). Among the SSRIs, there are few differences in adverse effects. The adverse effects observed for the SSRIs include nausea, diarrhea, anxiety, agitation, insomnia, and sexual dysfunction. Fewer patients have discontinued SSRIs than TCAs (amitriptyline and imipramine, and not nortriptyline, desipramine, doxepin, and clomipramine). 

Because doxepin is administered as an 85 15 mixture of geometric isomers, its mechanism of action and antidepressant properties refiects this ratio. Therefore, dioxepin s seiectivity for inhibiting presynaptic NE reuptake is most iikeiy caused by the 85% presence of the E-isomer in the geometric mixture. Its antidepressant activity is similar to amitriptyline. Data suggest NE reuptake inhibitory potency comparable to imipramine and clomipramine the fact that doxepin is an 85 15 mixture of - and Z-geometric isomers clouds its true efficacy for SERT or NET. The formation of N-desmethyIdoxepin results in inhibition of NE reuptake with enhanced noradrenergic activity. As a result of these mixed effects on the 5-HT and NE transporters, doxepin shares the pharmacological and adverse-effect profile of the other TCAs. 

In a double-blind study 3 patients given a phenothiazine and benzatropine for the parkinsonian adverse effects, developed an intermittent toxic confusional state (marked disturbance of short-term memory, impaired attention, disorientation, anxiety, visual and auditory hallucinations) with peripheral antimusearinies signs. Similar reactions occurred in 3 elderly patients given imipramine or desipramine, with trihexyphenidyl, and in another man given chlorpromazine, benzatropine and doxepin. ... 

A study in 14 treatment-resistant depressed patients aged between 61 and 82 found that 7 showed eomplete improvement and 3 showed partial improvement, 3 to 21 days after lithium was added to treatment with the tricyclic or related antidepressants. Lithium adverse effects occurred in 6 patients 4 of whom stopped lithium as a result. One of them was successfully restarted at a lower dose. Tremor was the most frequent adverse effect, and reversible neurotoxicity with a stroke-like syndrome was the most severe. The antidepressants used were amitriptyline, doxepin, maprotiline and trazodone. A meta-analysis of 9 studies on the acute treatment of unipolar or bipolar depression indicated that the combined use of a mood stabiliser (lithium in 6 studies) and a tricyclic antidepressant was associated with an increased risk of switches into (hypo)mania, when compared with a mood stabiliser alone. It was suggested that monotherapy with a mood stabiliser should be tried to see if it is effective, before adding an antidepressant. Tricyclics were considered to be second-line antidepressants, with SSRIs the preferred choice. ... 

In another study cimetidine 600 mg twice daily was found to double the steady-state plasma levels of doxepin 50 mg daily, whereas ranitidine 300 mg daily had no effect. A patient taking doxepin complained that the normally mild adverse effects (urinary hesitancy, dry mouth and decreased visual acuity) became incapacitating when he also took cimetidine. His serum doxepin levels were found to be elevated. ... 

The interactions with cimetidine are well established, well documented and of clinical importance. The incidence is uncertain hut most patients could be affected. Those taking amitriptyline, desipramine, doxepin, imi-pramine or nortriptyline who are given cimetidine should be warned that adverse effects such as mouth dryness, urine retention, blurred vision, constipation, tachycardia, postural hypotension may be more likely to occur. Other tricyclic antidepressants would be expected to be similarly affected. If symptoms are troublesome reduce the dosage of the antidepressant (33 to 50% has been suggested) or replace the cimetidine with ranitidine, which does not appear to interact. Other H2-ieceptor antagonists that do not cause enzyme inhibition (e.g. famotidine and nizatidine) would also not be expected to interact. 

Plasma levels of doxepin similar to those achieved during oral therapy may be obtained with topical application the usual drug interactions associated with tricyclic antidepressants may occur. Therefore, monoamine oxidase inhibitors must be discontinued at least 2 weeks prior to the initiation of doxepin cream. Topical application of the cream should be performed four times daily for up to 8 days of therapy. The safety and efficacy of chronic dosing has not been established. Adverse local effects include marked burning and stinging of the treatment site which may necessitate discontinuation of the cream in some patients. Allergic contact dermatitis appears to be frequent, and patients should be monitored for symptoms of hypersensitivity. 

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