Antidepressants, tetracyclic

GG is used extensively for analysis of antidepressants (Orsulak et al, 1989), but HPLC assays and enzyme immunoassays have become more popular in recent years. However, GC has advantages such as economy and ready availability. LCD and NPD generally are the detectors of choice (Coutts and Baker, 1982). NPD is relatively efficient for the analysis of tricyclic antidepressants (TCAs) as derivatization is not necessary, although the secondary, demethylated amines are sometimes derivatized to improve resolution and peak shape (Coutts and Baker, 1982). Acetylation, under aqueous or anhydrous conditions, followed by GC-NPD, has been used extensively for analysis of TCAs and the tetracyclic antidepressant maprotiline in plasma samples (Drebit et al., 1988). O Table 1-1 summarizes GC assays for some commonly prescribed antidepressants and their metabolites. 

Studies have shown that most of the tricyclic and tetracyclic antidepressants can be determined by RP-HPLC with UV/VIS detection. Presented here are some examples of HPLC determination of TCAs. 

Maprotiline is frequently referred to as a tetracyclic antidepressant. This hybrid drug, containing both elements of classic tricyclic antidepressants and protriptyline elements, is pharmacologically and clinically more similar to imipramine. 

They are classified into two main categories e.g. MAO inhibitors and tricyclic/tetracyclic antidepressants as in table 2.5.3. 

Many chromatographic separations of isotopologues of various amines that are biologically active or have drug properties have been achieved. Among these are perdeuteronucleosides 137 a tetracyclic 3,3,4,4-c/4-piperazine with antimigraine activity 138 the tetracyclic antidepressant mianserin with 2H or 3H in the A-methyl 139 A-CH3-tritiated chlorpromazine... 

Maprotiline, a tetracyclic antidepressant, repeatedly induced hypoglycemia in a 39-year-old woman with type 1 diabetes, even when the insulin dosage was reduced from 20 U/day to 4-10 U/day. Maprotiline seems to prolong the half-life of insulin. A glucagon... 

Jabbari B, Bryan GE, Marsh EE, Gunderson CH. Incidence of seizures with tricychc and tetracyclic antidepressants. Arch Neurol 1985 42(5) 480-1. 

The authors recognized that mirtazapine alone could have caused the hypertensive event. In postmarketing surveillance of mirtazapine, hypertension occurred in at least 1% of patients. However, it is likely that the patient lost antihypertensive control because mirtazapine antagonized the antihypertensive effect of clonidine. Mirtazapine, a tetracyclic antidepressant, stimulates the noradrenergic system through antagonism at central alpha2 inhibitory receptors, which is precisely opposite to the effect of clonidine. 

Mirtazapine is a tetracyclic antidepressant, similar to mianserin, and is a potent 5-HT2a/2c receptor antagonist. It has been successfully used to treat akathisia. In a doubleblind, placebo-controlled study in 26 patients with schizophrenia who were receiving neuroleptic drugs, mirtazapine 15 mg/day for 5 days was associated with less akathisia (227). 

Preference of some prescribers for amitriptyline over other tricyclic/tetracyclic antidepressants for the treatment of chronic pain syndromes is based more upon art and anecdote rather than controlled clinical trials, since many TCAs/tetracylics may be effective for chronic pain syndromes... 

For fhe expert only although generally prohibited, a heroic but potentially dangerous treatment for severely treatment-resistant patients is to give a tricyclic/tetracyclic antidepressant other than clomipramine simultaneously with an MAO inhibitor for patients who fail to respond to numerous other antidepressants... 

If this option is elected, start the MAOl with the tricyclic/tetracyclic antidepressant simultaneously at low doses after appropriate drug washout, then alternately increase doses of these agents every few days to a week as tolerated... 

Since tricyclic/tetracyclic antidepressants are substrates for CYP450 2D6, and 7% of the population (especially Caucasians) may have a genetic variant leading to reduced activity of 2D6, such patients may not safely tolerate normal doses of tricyclic/tetracyclic antidepressants and may require dose reduction... 

Phenotypic testing may be necessary to detect this genetic variant prior to dosing with a tricyclic/tetracyclic antidepressant, especially in vulnerable populations such as children, elderly, cardiac populations, and those on concomitant medications... 

Tricyclic antidepressant (TCA), sometimes classified as a tetracyclic antidepressant... 

Tricyclic/tetracyclic antidepressants are no longer generally considered a first-line treatment option for depression because of fheirside effect profile... 

Tricyclic/tetracyclic antidepressants continue to be useful for severe or treatment-resistant depression... 

Since tricyclic and tetracyclic antidepressants are frequently associated with weight gain, before starting treatment, weigh all patients and determine it the patient is already overweight (BMI 25.0-29.9) or obese (BMI >30)... 

Since SSRIs may improve (increase) heart rate variability in patients following a myocardial infarct and may improve survival as well as mood in patients with acute angina or following a myocardial infarction, these are more appropriate agents for cardiac population than tricyclic/tetracyclic antidepressants... 

Although very strict dietary and concomitant drug restrictions must be observed to prevent hypertensive crises and serotonin syndrome, the most common side effects of MAOl and tricyclic/tetracyclic antidepressant combinations may be weight gain and orthostatic hypotension... 

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