Tricyclic antidepressants second-generation effects

The answer is c. (Hardman, p 436.) The tricyclics and second-generation antidepressants act by blocking serotonin or norepinephrine uptake into the presynaptic terminal. Fluoxetine selectively inhibits serotonin uptake with minimal effects on norepinephrine uptake. Protriptyline, maprotiline, desipramine, and amoxapine have greater effect on norepinephrine uptake... 

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... 

The cardiac toxicity of tricyclic antidepressants in overdose has been a source of continued concern. Undesirable cardiovascular effects, besides representing a major therapeutic limitation for this category of drugs, delineate an area in which tricyclic compounds with novel structures, as well as second-generation antidepressants, may have significant advantages. The cardiovascular effects of tricyclic antidepressants and the new generation of antidepressants have been reviewed (SEDA-18,16) (16). 

Second-generation antidepressants Have fewer side effects than tricyclic and do not cause hypotension, sedation, anticholinergic effects, or cardiotoxicity. Types of second-generation antidepressants are ... 

Thus there appear to be significant mechanistic differences the hydrazines inhibit MAO, the tertiary amine tricyclics seem to inhibit the serotonin amine pump, whereas the secondary amine ones seem better in switching off the NE reuptake mechanism. Table 12-18, however, shows that there is some overlap. Nevertheless, there is a thread of commonality—the net increase of amine neurotransmitters in the synaptic area—yet all these drugs require several weeks of treatment before objective results are noted. The biogenic amine hypothesis does not satisfactorily explain this. It is even more difficult to explain the antidepressant action of some of the second-generation drugs, such as mianserin (Fig. 12-26), that seem to have no significant effect on amine reuptake mechanism of either... 

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. 

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