Nortriptyline dosing

Although you see many patients on meds, Harry s side effects seem extreme, and you place a call to his physician later in the day. She is appreciative of your call and agrees with your concerns. She decides to lower Harry s nortriptyline dose until she receives pending lab results of his nortriptyline level. She also shares with you information that indicates certain Asian populations may be unable to effectively metabolize tricyclic antidepressants and antipsychotics, necessitating lower than average doses. She promises to call you after further evaluation (Shimoda et al. 1993). 

Note Derivatization with this reagent sequence in combination with extraction and TLC separation is speciftc for amitriptyline and nortriptyline in the analysis of plasma furthermore its high sensitivity allows its employment in pharmacokinetic studies, e. g. after the oral administration of a single dose of 25 mg amitriptyline. 

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

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

Nortriptyline 0 Second-line Titrate up to 75-100 mg orally daily 6-12 months Dry mouth, blurred vision, and constipation are dose-dependent adverse effects. B2... 

Nortriptyline is initiated 10 to 28 days before the quit date. The dose is initiated at 25 mg/day, gradually increasing to 75 to 100 mg/day. Treatment duration is commonly 12 weeks in trials, and common side effects were sedation, dry mouth, blurred vision, urinary retention, and lightheadedness. 

The common side effects of TCAs frequently limit their usefulness, particularly in older patients. Side effects can be minimized by starting at low doses that are slowly titrated upward or by choosing one of the so-called secondary amine TCAs, nortriptyline and desipramine, with less potent side effects. In addition, it should be remembered that some of the troublesome side effects, such as sedation, tend to disappear over time. 

The TCAs are the only antidepressant class in which effectiveness is dependent on serum level. Attainment of the minimal therapeutic level is typically required for effectiveness. Exceeding the maximum treatment level usually provides no additional benefit and risks toxicity. Unique in this regard is nortriptyline, which is the only TCA with a therapeutic window. This means that beyond the maximum therapeutic level of 150ng/mL nortriptyline not only risks toxicity but is actually less effective at treating depression. Please refer to Table 3.9 for a summary of dosing guidelines and therapeutic levels. 

Tricyclic Antidepressants (TCAs). The TCAs, particularly imipramine (Tofranil), were also discovered soon after their introduction to be effective in the treatment of panic attacks. Imipramine, the best-studied TCA in the treatment of panic disorder, is most often helpful at daily doses of 150-250 mg, though it must be started at 10-25 mg, usually at bedtime, and gradually increased over 2-4 weeks. Although they are not as well studied, many clinicians prefer to use the secondary amine TCAs, desipramine (Norpramin) and nortriptyline (Pamelor), because they have milder side effects than imipramine. Clomipramine (Anafranil), though probably the TCA with the greatest side effect burden, is often said to be most effective in patients with refractory disease. 

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. 

One particular variant of the post-TBl behavioral disturbances, nighttime agitation, can be managed successfully with low bedtime doses of sedating antidepressants such as trazodone (25-50mg) or nortriptyline (10mg). These antidepressants may calm the patient and help him/her to sleep while avoiding the potential for confusion or disinhibition posed by other commonly used sleep medicines. 

Braithwaite et al. (B20) treated fifteen patients with a fixed daily dose of 150 mg of amitriptyline by mouth for 6 weeks. Plasma amitriptyline and nortriptyline levels were measured, by GLC, in venous blood collected 19 hours ( SD 4.3 hours) after the last dose of the drug. Steady-state blood levels were achieved within 2 weeks, on average, but there were large between patient differences. 

For some psychotropic drugs (e.g., lithium and some antidepressants) a good correlation exists between plasma levels and therapeutic or toxic effects. Optimum steady-state levels can now be predicted from single-dose blood level data of some drugs (lithium, nortriptyline, desipramine). Altered PK behavior in children has to be taken into consideration in using psychotropic drugs. With development of suitable drug... 

Geller, B. Cooper, T.B., Chestnut, E.C., Anker, J.A., Price D.T., and Yates, E. (1985b) Child and adolescent nortriptyline single dose kinetics predict steady state plasma levels and suggested dose preliminary data. / Clin Psychopharmacol 5 154—158. 

Dose adjusted according to serum levels (therapeutic window for nortriptyline)... 

In a prospective placebo-controlled discontinuation trial, we recently demonstrated the efficacy of nortriptyline in doses of up to 2 mg/kg daily in 35 school-aged youth with ADHD (Prince et al., 2000). In that study, 80% of youth responded by week 6 in the open phase. During the discontinuation phase, subjects randomized to placebo lost the anti-ADHD effect. There... 

Biederman et al. (1989a,b) also found desipramine (at the relatively high mean dose of 4.6 mg/kg/day) to be safe and effective for treatment of ADD. Despite these positive results, however, concerns about prolonged cardiac conduction times and the reports of several sudden deaths of children on desipramine have left many clinicians and parents reluctant to use the drug (Riddle, et ah, 1993). Another less well-studied tricyclic, nortriptyline, which some believe to have less potential cardiotoxicity, has shown promise in a retrospective study in children with ADHD plus tic disorder (Spencer et al., 1993b). 

Nortriptyline therapy should be initiated at 25 mg/day, and the dose should be increased to 75 mg/day over 1-2 weeks depending on tolerability and clinical response. Some patients require doses of up to 150 mg/day. Amoxapine therapy should be started at 50 mg/ day, and the dose should be titrated to 400 mg/day amoxapine has a short half-life and should be given in divided doses. Treatment with protriptyline can be started at 10 mg/day, and the dose can be increased to up to 60 mg/day. Maprotiline therapy should be started at 50 mg/day, and that dose should be maintained for 2 weeks the risk of seizure is increased if the dose is raised too quickly. The dose can be increased over 4 weeks to 225 mg/day. 

Clinically meaningful plasma levels are available for imipramine, desipramine, and nortriptyline. For imipramine, the sum of the plasma levels of imipramine and the desmethyl metabolite (desipramine) should be greater than 200-250 ng/mL. Desipramine levels should be greater than 125 ng/mL. A therapeutic window has been noted for nortriptyline, with optimal response between 50 and 150 ng/mL. These therapeutic levels are based on steady-state concentrations, which are reached after 5-7 days of administration of these medications. Blood should be drawn approximately 10-14 hours after the last dose of medication. 

In a double-blind, parallel-group study, Bondareff et id. (2000) compared the SSRI sertraline and the tricyclic compound nortriptyline with regard to their efficacy and safety in a group of 210 outpatients 60 years and older. The patients met the DSM-DI-R criteria for major depressive episode and had a minimum score of 18 on the Hamilton Rating Scale for Depression. Their mean age was about 68 years, most patients were white and about 60% were female the severity of depression was rated as moderate in more than 70% and as severe in more than 20% of the cases. The daily doses of sertraline were between 50 and 150 mg, and those of nortriptyline were 25 100 mg the treatment lasted 12 weeks. In addition to clinical rating scales and self-assessment instruments, patients took the following tests of cognitive performance ... 

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. 

---