Doxepin side effects

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

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... 

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. 

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. 

Antidepressants as analgesics are almost a closed book as far as preclinical and clinical development is concerned. TCAs are an old drug class, and because of the rather problematic side-effect profile, interest in developing new drugs from this class is small. BL-1834 (Bioglan Lab.) is an intranasal formulation of doxepine that is in clinical development (phase II) for the treatment of severe pain. In patents on novel monoamine reuptake inhibitors, pain is usually claimed as a possible indication, but depression and anxiety are mentioned as the primary indications in most cases, and we are not aware of novel... 

Side-effects of TCA were compared in double-blind trials in healthy subjects. Marked inhibitory effects on salivary flow declined from amitriptyline through doxepin, Imipramine, nortriptyline to desipramine, paralleling subjective reports of anticholinergic side-effects and reported affinities for muscarinic receptors.74 Similar rankings for sedation and decrements in psychometric performance were obtained in another study ... 

Histamine-1 receptor antagonists (e.g., diphenhydramine) and antidepressants with high histamine-1 blockade (e.g., doxepin and amitriptyline) have been used for acute sleep disturbances but may cause anticholinergic side effects, daytime sedation, and weight gain. Trazodone, a serotonin-2A and ai -adrenergic antagonist, has sedative properties at lower doses and may be useful to promote sleep. The chronic use of benzodiazepines is not recommended for insomnia... 

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. 

Antidepressants with sedation as a side effect often are used to treat insomnia. The antidepressants most frequently associated with sedation as a side effect are the tricyclics (amitryptyline, imipramine, nortriptyline, trimipramine, doxepin, amoxapine, and protriptyline), nontricyclics (maprotiline and mirtazepine), trazodone, and nefazodone (55), which are discussed in greater detail in Chapter 21. Of these drugs, trazodone, doxepin, and mirtazepine have been shown to be effective in the treatment of insomnia in patients with depression (1). The effectiveness of these drugs to treat insomnia in nondepressed patients, however, has not been proven. The mechanism by which this occurs is unknown, but most of these drugs have some activity as H2 antagonists that may contribute to the effect (56). 

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). 

Commonly prescribed medications to prevent migraines are amitriptyline, divaproex sodium, propranol, timolol, topiramate, bupropion, cyproheptadine, diltiazem, doxepin, fluvoxamine, ibuprofen, imipramine, and methysergide. Methysergide is particularly effective. However, there are side effects that might make this dmg less tolerable. 

Doxepin (Ila) was marketed this year as a mixture of cis and trans isomers (acid catalyzed equilibration in the final step of the synthesis gave a cis to trans ratio of approximately 15 85), This drug was compared with eimitriptyline eind found to be clinically similar in its properties. Side effects were due to its anticholinergic properties. Several clinical studies with doxepin showed that the drug was a good antidepressant. One report stated that there was noticeable sedation while others claimed only mild side effects. ... 

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 ... 

---