Tricyclic antidepressants dosages

A comparative study of 99 patients taking amitriptyline or nortriptyline alone, and 60 other patients also taking perphenazine 10 mg daily, found that although the tricyclic antidepressant dosages were the same, the plasma tricyclic antidepressant levels of the perphenazine group were up to 70% higher. ... 

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. 

The answer is a. (Hardman, p 436J The most common side effects associated with tricyclic antidepressants are their anti muscarinic effects, which may be evident in over 50% of patients. Clinically, the anti muscarinic effects may manifest as dry mouth, blurred vision, constipation, tachycardia, dizziness, and urinary retention. At therapeutic plasma concentrations, these drugs usually do not cause changes in the EKG Direct cardiac effects of the tricyclic antidepressants are important in over dosage. 

Sodium bicarbonate administration for cardiac arrest is controversial because there are few clinical data supporting its use, and it may have some detrimental effects. Sodium bicarbonate can be used in special circumstances (i.e., underlying metabolic acidosis, hyperkalemia, salicylate overdose, or tricyclic antidepressant overdose). The dosage should be guided by laboratory analysis if possible. 

In general, the SSRIs have a more tolerable side effect profile than the tricyclic antidepressants with their anticholinergic effects. Review of the rate that subjects in the controlled studies discontinued a SSRI because of adverse effects provides some perspective on how well tolerated the medications are, although the specifics may vary according to dosage and design (e.g., forced titration) and are not directly comparable. The rate of discontinuation was reported to be 12% (4/48) for fluoxetine (Emslie et ah, 1997), 9.7% for paroxetine (Keller et ah, 2001), 13% (12/92) for sertraline (March et ah, 1998), and 33% (19/57) (Riddle et ah, 2001) and 7.9% (5/63) for fluvoxamine (Walkup et ah, 2001). 

When a patient has not responded to a tricyclic antidepressant for an adequate trial period and with an appropriate dosage... 

J. E. Kountourellis and C. K. Markopoulou, A simultaneous analysis by HPLC of bamipine combined with tricyclic antidepressants and/or antipsychotics in dosage forms, J. Liquid Chromatogr., 14 2969 (1991). 

Ayd, F. J. (1974). Once-a-day dosage of tricyclic antidepressant drug therapy A survey. Diseases of the Nervous System, 35, 475-480. 

The tricyclic antidepressants increase bladder sphincter tone and the volume of fluid necessary to trigger detrusor contraction (80). Such effects may account for their efficacy in nocturnal enuresis, in which the benefit occurs early and at a low dosage, consistent with anticholinergic activity. However, this pharmacological action can cause hesitancy and urinary retention, especially in predisposed men who have prostatic hyperplasia. 

There is a more clear-cut cause-and-effect relation in the parkinsonian symptoms that occasionally occur with high-dosage tricyclic therapy in susceptible individuals (particularly elderly women). Because of its piperazine side-chain and structural resemblance to the phenothia-zines, amoxapine has antidopaminergic properties that appear to produce typical dystonic reactions (88), but other tricyclic antidepressants may also be implicated in producing the full range of so-called extrapyramidal syndromes, including akathisia, dystonic reactions, parkinsonism, and tardive dyskinesia. Case reports have been described before (SEDA-16, 9 SEDA-17, 18 SEDA-18, 18). In the reports of tardive dyskinesia the problem is often that these patients have taken many different drugs. 

Two Scandinavian patients taking combinations of neuroleptic drugs and tricyclic antidepressants developed epileptic seizures (194). The risk of seizures is greater in patients with brain damage or epilepsy and with high dosages, sudden increases in dosage, or shortly after the introduction of a second compound. 

Of all the tricyclic antidepressants, amineptine appears to be the most likely to cause liver damage. More than 26 cases of toxic hepatitis have been reported in France (6). In most cases, hepatitis occurred within the usual dosage range and recurred on rechallenge. However, in several instances it was reported after overdosage. There are other reports of hepatotoxicity associated with amineptine (7,8). 

Amoxapine is less potent than other tricyclic antidepressants, with a therapeutic dosage range of 75-600 mg/day (usually 200-400 mg/day). Clinical effects have not been consistently correlated with plasma concentrations, but amoxapine has similar efficacy to other tricyclic antidepressants in heterogeneous populations of depressed patients. Controlled comparisons have shown that its clinical profile is very similar to that of imipra-mine (3) and that it is somewhat less sedative than amitriptyline (4-6). In two of these studies (4,6) the... 

May inhibit metabolism of SSRIs, anticonvulsants (phenobarbital, phenytoin, primidone), tricyclic antidepressants, and coumarin anticoagulants, requiring downward dosage adjustments of these drugs... 

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