Second Generation Antidepressants

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Second-Generation Antidepressants. The frequency of adverse effects associated with first-generation antidepressants and the lack of patient compliance arising from such adverse effects led to the development of a number of second-generation antidepressants. 

The second-generation antidepressants, particularly RIMAs and SSRJs, are much less toxic ia overdose than the older TCAs and irreversible MAO inhibitors. However, similar to first-generation antidepressants, the therapeutic effect only becomes manifest after several weeks. Up to one-third of depressed patients are nonresponders. Ideally, an antidepressant would combine a more rapid onset of action with greater clinical efficacy and a higher responder rate, as well as even better tolerability. 

SGAs = second-generation antipsychotics (SGAs) FM03 = flavin-containing monooxygenase TCAs = tricyclic antidepressants Adapted from de Leon et al., 2005b... 

Laura C. Morgan, Janelle A. Shumate, Loraine G. Monroe and Kathleen N. Lohr, Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative Effectiveness Review No. 7. (Prepared by Rti International-University of North Carolina Evidence-Based Practice Center under Contract No. 290-02-0016.) Rockville, Md Agency for Healthcare Research and Quality (2007) www.effective-healthcare.ahrq.gov/reports/final.cfm... 

Hansen, Richard A., Gerald Gartlehner, Kathleen N. Lohr, Bradley N. Gaynes and Timothy S. Carey, Efficacy and Safety of Second-Generation Antidepressants in the Treatment of Major Depressive Disorder , Annals of Internal Medicine 143 (2005) 415-26... 

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... 

The first second-generation antidepressant an alpha-2 adrenoceptor antagonist with some affinity for S-HT a/ 5-HT2a arid 5-HT3, alpha-1 adrenoceptors and HI receptors... 

Mianserin was the first of the second-generation antidepressants to be developed. It lacked the amine reuptake inhibitory and MAOI actions of the first-generation drugs and also lacked the cardiotoxicity and anticholinergic activity of the TCAs. However, it was sedative (antihistaminic), caused postural hypotension (alpha-1 blockade) and also caused blood dyscrasias and agranulocytosis in a small number of patients. This has limited the use of mianserin in recent years. 

These include trazodone and a derivative of its metabolite nefazodone, both of which are strongly sedative, an effect which has been attributed to their potent alpha-1 receptor antagonism rather than to any antihistaminic effects. A main advantage of these drugs in the treatment of depression is that they appear to improve the sleep profile of the depressed patient. Their antidepressant activity is associated with their weak 5-HT reuptake inhibition and also a weak alpha-2 antagonism. However, unlike most of the second-generation antidepressants, neither drug is effective in the treatment of severely depressed patients. Furthermore, there is some evidence that trazodone can cause arrythmias, and priapism, in elderly patients. 

Treatment of choice - second-generation antidepressants such as a SSRI,... 

Switching - alternative second-generation antidepressant, usually from... 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

Goodnick, P.J. (1991) Pharmacokinetics of second generation antidepressants bupropion. Psychopharmacol Bull 27 513—519. 

Masand PS, Anand VS, Tanquary JF Psychostimulant augmentation of second generation antidepressants a case series. Depress Anxiety 7 89—91, 1998... 

TABLE 7-6. First versus second generation standard antidepressants acute treatment... 

Serotonin syndrome SSRIs, second generation antidepressants, MAOIs, linezolid, tramadol, meperidine, fentanyl, ondansetron, sumatriptan, MDMA, LSD, St. John s wort, ginseng Hypertension, hyperreflexia, tremor, clonus, hyperthermia, hyperactive bowel sounds, diarrhea, mydriasis, agitation, coma onset within hours Sedation (benzodiazepines), paralysis, intubation and ventilation consider 5-HT2 block with cyproheptadine or chlorpromazine... 

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