Tricyclic antidepressants dosing

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

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... 

Peripheral neuropathy is the most common complication reported in type 2 DM. This complication generally presents as pain, tingling, or numbness in the extremities. The feet are affected more often than the hands and fingers. A number of treatment options have been tried with mixed success. Current options include pregabalin, gabapentin, low-dose tricyclic antidepressants, duloxetine, venlafaxine, topiramate, non-steroidal anti-inflammatory drugs, and topical capsaicin. 

The tricyclic antidepressant clomipramine also has been studied for PMDD. In placebo-controlled trials, both continuous daily dosing and luteal phase administration proved effective.17 Compared with the SSRIs, however, clomipramine has a less desirable side-effect profile with low tolerability. 

Dizziness, vertigo, nausea, vomiting, constipation, and lethargy are all relatively common adverse events. These effects are more pronounced for several days after initiation and following upward dose titration. Seizures have been reported rarely the risk is dose-related and appears to increase with concomitant use of antidepressants, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. Tramadol should be avoided in patients receiving monoamine oxidase (MAO) inhibitors because tramadol inhibits the uptake of norepinephrine and serotonin. 

Non-compliance issues appear more prevalent in some non-Western cultures. One study in South Africa revealed non-compliance rates to oral neuroleptics in two-thirds of Black patients and one-half of colored patients compared to only one-quarter of Caucasians (Gillis.Trollip, Jakoet etal., 1987). Cultural and communication factors were considered to be significant barriers apart from those related to cost and social factors. Kinzie et al. (1987) reported that despite prescribing adequate doses of tricyclic antidepressants (TCAs) to depressed Asian refugees,... 

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). 

Some studies compare dietary supplements to sub-therapeutic dosages of prescription medicine. For example, St. John s wort is compared to some of the tricyclic antidepressants. However, the given doses of amitriptyline and imipramine were below the recommended antidepressant doses. 

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. 

IR, immediate-release LA, long-acting TCAs, tricyclic antidepressants TDS, transdermal system XL, extended-release, investigational. Doses provided are those best supported by clinical trials to date. 

Desipramine has been used to facilitate withdrawal from chronic PCP use. The rationale is that PCP depletes norepinephrine concentrations in brain, and that this tricyclic antidepressant is the most selective blocker of norepinephrine uptake. Consequently, some of the deficiency of the neurotransmitter could be remedied. A dose of 25 to 50 mg was said to reduce craving for several hours. Six of eight patients treated with this drug were successfully withdrawn, while none of the eight offered other types of programs were successful (45). 

In 1985, 1 finally took the county public health psychiatrist s recommendation to try Desipramine, an ostensibly mild tricyclic antidepressant. I took tiny dot doses, and for a month or so I felt encouraged except for intense muscle tension and clenching. The psychiatrist said it was not remotely possible that this response was related to the medication. I took a low dose for four more months before throwing them out. The side effects had escalated horribly, and become what I later learned are called tardive dyskinesia and tardive dystonia. Subsequently, chemical and electromagnetic field exposures, feeling compromised or ashamed, or stress can trigger uncontrollable movement, hyperactivity, rigid posture and then, frequently, paralysis. 

TABLE 3.9. Doses and Serum Levels of Tricyclic Antidepressants... 

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. 

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. 

Tricyclic Antidepressants (TCAs). TCAs were introduced in the 1950s and over the years have become the mainstay of treatment for cataplexy and the other REM-related symptoms. The doses used are usually less than the doses required in the treatment of depression. Imipramine (Tofranil) is the most widely used TCA for narcolepsy and is usually effective at doses from 10 to 75 mg given once a day. Some doctors prefer the TCA protriptyline (Vivactil) because it has mild stimulant effects, but it has not been as widely used or as thoroughly studied in narcolepsy. The common side effects of TCAs are drowsiness, dry mouth, and constipation, but these are usually not a problem at the lower doses used for narcolepsy. Patients should receive a baseline electrocardiograph (EKG) before starting a TCA and should have blood levels of the medication checked periodically. 

Medications that enhance norepinephrine activity can do so in one of several ways. First, they can block the reuptake of norepinephrine back into the nerve cell once it has been released. This keeps the norepinephrine in the synapse longer and therefore makes it more active. The tricyclic antidepressants (TCAs), duloxetine (Cymbalta), and venlafaxine (Effexor) act in this manner, as does paroxetine (Paxil) at higher doses. Atomoxetine (Strattera), a treatment for ADHD, also works in this way. 

The excellent clinical efficacy of the TCAs has been well documented and the pharmacokinetic profiles are favourable. The most serious disadvantage of the TCAs lies in their cardiotoxicity. Thus, with the exception of lofepramine, all the tricyclic antidepressants, including maprotiline, block the fast sodium channels in the heart which can lead to heart block and death. Approximately 15% of all patients with major depression die by suicide and a high proportion of these (up to 25%) do so by taking an overdose of TCAs. Such a dose can be as low as 5-10 times the recommended daily dose. 

Nomifensine and bupropion are examples of non-tricyclic antidepressants that facilitate catecholaminergic function. These drugs have the advantage over the TCAs of being non-sedative in therapeutic doses. The... 

Tricyclic antidepressants are cardiotoxic, inducing tachycardias and an increased tendency for ventricular arrhythmias with high doses. This dose dependent cardiotoxicity gives these agents a low therapeutic index. Overdoses are characterized by cardiac conduction disturbances, hyperpyrexia, hypertension, confusion, hallucinations, seizures and coma and there is a high mortality rate in suicide attempts. Depressed patients should therefore not be given more than one week supply of these drugs. 

Tricyclic antidepressants are used for treatment of chronic pain. The mechanism of action supposedly is related to their activity at the sodium channel. It also is hypothesized that tricyclic antidepressants affect norepinephrine release and, possibly, serotonin release, thereby altering spinothalamic transmission of pain. However patients who require higher doses often find that the pain relief obtained is not adequate to justify the adverse effects. 

Supportive care is important, especially in unconscious patients. If the airway is protected (gag reflex or cuffed endotracheal tube present), then activated charcoal can be given. Repeated doses of oral activated charcoal increase the rate of elimination of several tricyclic antidepressants, but may not influence outcome. 

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