Doxepin dosing

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. 

Tricyclic antidepressants Nortriptyline Doxepin Given by mouth once daily or in two divided doses 75-150 mg/day 150-250 mg/day... 

Doxepin is a tricyclic antidepressant that inhibits histamine receptors. It may be helpful in atopic patients who have a component of depression. Doses of 10 to 75 mg at night and up to 75 mg twice daily in adults have been used. 

Molander L, LuneU E, Andersson SB, Kuylenstiema F (1996) Dose released and absolute bioavaU-abUity of nicotine from a nicotine vapor inhaler. CUn Pharmacol Ther 59 394 00 Murphy JK, Edwards NB, Downs AD, Ackerman BJ, Rosenthal TL (1990) Effects of doxepin on withdrawal symptoms in smoking cessation. Am J Psychiatry 147 1353-1357 Nabi Biopharmaceuticals (2007). Nabi biopharmaceuticals announces positive results of phase Ilb trial of NicVAX. Medical News Today, 3 May 2007. See http //www.medicalnewstoday.com/ articles/69666.php, accessed October 11, 2007... 

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. 

Short-term Rx pruritus (atopic dermatitis or lichen simplex chronicus) Action Antipruritic Hi- H2-receptor antagonism Dose Apply thin coating qid, 8 d max Caution [C, /-] Contra Component sensitivity Disp Cream SE X BP, tach, drowsiness EMS Widespread use can lead to systemic absorption see Doxepin, earlier OD Unlikely... 

Tapering off doxepin and Klonopin was not fun. For the first few weeks I did pretty well. Although I noticed an increase in my usual morning anxiety, it was nothing especially alarming. But when I finally reached one-fourth of my normal dose, I got very sick. My sleeping, always the barometer of my emotional well-being, eroded badly. I documented this process in my Doxepin Diary ... 

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. 

HCA is the term is used to refer to both TCAs and analogues of these agents, such as maprotiline and amoxapine. TCAs are by far the most commonly used HCAs and include tertiary amines such as amitriptyline, doxepin, and imipramine and secondary amines such as desipramine and nortriptyline. Most secondary amines could also be viewed as NE-selective antidepressants, while the hallmark of tertiary amine TCAs is their effects on multiple neurotransmitters over their clinically relevant dosing range. 

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. 

To manage withdrawal insomnia, we recommend the supplemental use of hypnotics such as zolpidem or a sedating antidepressant such as trazodone. Rickels et al. recommend the supplemental use of hypnotics such as diphenhydramine, doxylamine, or chloral hydrate or a sedating TCA such as doxepin ( 259). These investigators also recommend that chronic BZD users with evidence of depression or panic be treated with adequate doses of an appropriate antidepressant, a management technique that may help patients succeed in discontinuation. 

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. 

Tricyclics and the second- and third-generation agents differ mainly in the degree of sedation they produce (greatest with amitriptyline, doxepin, trazodone, and mirtazapine) and their antimuscarinic effects (greatest with amitriptyline and doxepin Table 30-3). SSRIs are generally free of sedative effects and remarkably safe in overdose. Combined with the ease of once-a-day dosing, these qualities may explain why they have become the most widely prescribed antidepressants. 

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. 

There is compelling evidence for a withdrawal syndrome due to abrupt discontinuation of tricyclic antidepressants (SEDA-5,16), and the literature has been reviewed (121). Reports have involved both imipramine and doxepin (122). Symptoms occur as early as the morning after a missed dose (123), but more often after 48 hours and up to 2 weeks after withdrawal. They include anxiety, restlessness, sweating, diarrhea, hot or cold flushes, and piloerec-tion. Amitriptyline withdrawal was followed by similar physical symptoms 36 hours after the last dose, followed by severe depressive illness (SEDA-17,18). 

A 66-year-old woman was treated for a skin allergy with doxepin cream in large doses. Withdrawal of this treatment led to two complex partial seizures. 

TCAs DRUG DEPENDENCE THERAPIES-BUPROPION 1. t risk of seizures This risk is marked in elderly people, in patients with a history of seizures, addiction to opiates/cocaine/ stimulants, and in diabetics treated with oral hypoglycaemics or insulin 2. t plasma concentrations of amitriptyline, clomipramine, desipramine, doxepin and imipramine, with risk of toxic effects 1. Bupropion is associated with a dose-related risk of seizures. TCAs lower the seizure threshold. Additive effects when combined 2. Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 1. Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in those with severe hepatic cirrhosis) 2. Initiate therapy of these drugs at the lowest effective dose... 

Daily oral doses of 75 to 200 mg given to 5 subjects, produced steady-state plasma concentrations of 0.05 to 0.15 pg/ml of doxepin in two of these subjects plasma concentrations for monodesmethyldoxepin of 0.09 and O.lOpg/ml were reported (J. E. O Brien and O. N. Hinsvark, J. pharm. Sci., 1976,65, 1068-1069). 

Much of the study of interethnic differences in the pharmacokinetics and pharmacodynamics of psychotropic medications has involved TCAs and differences between Asians and Caucasians (Pi et al. 1993a). As with antipsychotics, there are clinical reports that Asians require lower doses of TCAs (Pi and Gray 1998 Pi et al. 1993a). It has also been suggested that Asians show a therapeutic response at lower blood levels of TCAs (Yamashita and Asano 1979), suggesting pharmacodynamic differences. Other studies of prescribing patterns have failed to confirm this and found that the daily doses of amitriptyline, imipramine, doxepin, and nortriptyline prescribed by psychiatrists at 29 medical schools in 9 Asian countries were the same as those used in the United States (Pi et al. 1985). It was also reported that Asians and whites need similar doses of at least 150 mg/day to attain recommended therapeutic blood concentrations (Kinzie et al. 1987). 

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