Antidepressant agents amitriptyline

Maprotiline (Ludiomil) and amoxapine (Asendin) are heterocyclic antidepressant agents that are not members of the tricyclic family. However, their pharmacology is so similar to that of the tricyclic amines that they are included for discussion purposes with this class of agents. Desipramine and nortriptyline are major metabolites of imipramine and amitriptyline, respectively. 

For chronic abdominal pain, low doses of tricyclic antidepressants (eg, amitriptyline or desipramine, 10-50 mg/d) appear to be helpful (see Chapter 30). At these doses, these agents have no effect on mood but may alter central processing of visceral afferent information. The anticholinergic properties of these agents also may have effects on gastrointestinal motility and secretion, reducing stool frequency and liquidity. Finally, tricyclic antidepressants may alter receptors for enteric neurotransmitters such as serotonin, affecting visceral afferent sensation. 

Tricyclic antidepressants (eg, amitriptyline, desipramine, doxepin, many others see Chapter 30 Antidepressant Agents) are among the most common prescription drugs involved in life-threatening drug overdose. Ingestion of more than 1 g of a tricyclic (or about 15-20 mg/kg) is considered potentially lethal. 

Of the systemic antihistamines, the ethanolamines, including diphenhydramine, have significant antimuscarinic activity. In addition, the antipsychotic agents, particularly the phenothiazines such as thioridazine (Mellaril), have well-dociunented anticholinergic properties. Therapeutic doses of tricyclic antidepressants, like amitriptyline hydrochloride (Elavil) and imipramine (Tofranil), produce significant anticholinergic actions and thus have the potential for ocular side effects. 

Side Effects of Antidepressant Drugs - Recent publications pertaining to the clinical side effects of antidepressant agents are by Hollister, Kahr et al. 5, Tschen et al. 6, Blair and Simpson and Simpson et al. 8. The toxicology of amitriptyline has been described by Myers et al. 9. 

Clinically, protriptyline is a purer type of antidepressant agent, in that it lacks the sedative properties of amitriptyline and nortriptyline. It is said to be the more potent of the three agents and useful also in the treatment of anxiety depressions. However, until further clinical work is published, it will be difficult to assess the therapeutic spectrum of this most recent agent. 

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. 

Agents Acetaminophen or NSAID combinations with opioids Adjuncts Tricyclic antidepressants Anticonvulsants Radiopharmaceuticals (Bone pain) Acetamnophen (See above) Opioids Titrate Amitriptyline 10-50 mg Imipramine 10-50 mg NSAIDs (See above) Gabapentin (Neurontin) 3.6 g... 

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. 

In the past, tricyclic drugs such as amitriptyline and nortriptyline were the most commonly used antidepressants and were the standard against which other antidepressants were measured.30 The use of tricyclic drugs as the initial treatment of depression has diminished somewhat in favor of some of the newer second-generation drugs, which may have more favorable side-effect profiles. Tricyclic agents, nonetheless, remain an important component in the management of depressive disorders, especially in more severe forms of depression that fail to respond to other antidepressants.6,53... 

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. 

In a systematic review of 32 randomized trials in which 1389 patients took lithium and 2069 took another agent (carbamazepine, divalproex, lamotrigine, or the antidepressants amitriptyline, fluvoxamine, mianserin, and maprotiline), among the seven studies that reported suicides, lithium-treated patients had significantly fewer completed events (242). These included two suicides on lithium (out of 503, 0.4%) and 11 suicides on other agents (two placebo, two amitriptyline, six carbamazepine, and one lamotrigine, out of a total of 601,1.8%) (OR = 0.26 95% Cl = 0.09, 0.77). 

The first TCAs (imipramine and amitriptyline) and MAOIs appeared between 1957 and 1961 (Fig. 19.1). The MAOIs were developed from antituberculosis agents which had been noted to elevate mood. Independently, imipramine was synthesised from the antipsychotic drug chlorpro-mazine and found to have antidepressant rather than antipsychotic properties. Over the next 25... 

Chronic pain patients tend to have concurrent depression however, the antidepressants chosen may not have any pain-relieving properties. Antidepressants that affect one neurotransmitter in the brain, such as selective serotonin reuptake inhibitors have not appeared to be effective in the management of pain in clinical trials. Antidepressants that affect multiple neurotransmitters— namely, serotonin and norepinephrine—have been shown to be effective pain relievers.Two published metaanalyses have shown that tricyclic antidepressants amitriptyline, desipramine, imipramine, and nortriptyline are the most effective treatment for the management of neuropathic pain. ° These publications review the published clinical trial data for all agents available for the management of neuropathic pain. 

---