Antidepressant agents clinical effects

The significance of the effects of the TCAs on receptor sensitivity and subsequent antidepressant effects remains unclear. Other agents that possess similar receptor interactions to TCAs (such as cocaine and the tti receptor) are devoid of antidepressant activity. In addition, receptor blockade is seen with initial doses of medication, while changes in mood symptoms have considerable lag time. The lag phase of clinical effectiveness appears to be due to changes in receptor density and postsynaptic activity associated with chronic administration of TCAs (Sugrue, 1983). 

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. 

Toxic Effects of Acute Overdoses Acute poisoning with tricyclic antidepressants or MAO inhibitors is potentially hfe-threatening. Fatalities are much less common since modern antidepressants have widely replaced these drugs however, suicide rates have not declined consistently as clinical usage of modern antidepressants has increased. Deaths have been reported with acute doses of 2 g of imipramine, and severe intoxication can be expected at doses >1 g, or about a week s supply. If a patient is severely depressed, potentially suicidal, impulsive, or has a history of substance abuse, prescribing a relatively safe antidepressant agent with close clinical follow-up is appropriate. If a potentially lethal agent is prescribed, it is best dispensed in small, sublethal quantities, with the risk that sustained adherence to recommended treatment may be compromised. 

Testing Procedures - The difficulties in devising a reliable test, or a series of tests, that can predict antidepressive activity become apparent frcxn an examination of the extensive effort thus exerted. The ability of a compound to suppress the behavioral effects of yohimbine in the dog has been proposed as an indication of its potential clinical effectiveness as an antidepressive agent.34,35 study of 15 centrally... 

Administration of therapeutic doses of a tricyclic antidepressant to depressed patients results in an elevation of the mood. About 2-3 weeks should be allowed for the antidepressant to exert its effect. For this reason, the tricyclic antidepressants cannot be prescribed on an as-needed basis. With some antidepressants, sedative or antianxiety effects may appear within a few days of treatment. The manner in which these agents relieve the signs of depression is not clear. However, manic excitement as well as euphoria and insomnia can be induced in some patients, contributing to the conclusion that antidepressant agents have clinically important mood-elevating actions. 

A number of new MAO inhibitors were described in 1971 however, because of the limited clinical utility of these agents in the treatment of depression, they will not be reviewed in detail. Nonetheless, several of these substances are noteworthy. Sydnophene ( ) was Included in a series of sydnonimines examined for MAO-inhibitory activity. It demonstrated mild stimulant and antidepressive actions in extensive clinical studies in Russia. Another MAO-inhibitor, clorgiline (32. M B 9302) had antidepressive activity its clinical effects were similar to those of imipramine. Proportions of two forms of MAO (Type A, B) were found to vary in different areas of rat brain. The type A enzyme, predominant in sympathetic nerves, acted on both 5-HT and tyramlne and was Inhibited by 32. whereas type B-MAO was insensitive to and acted on tyramine, but not 5-HT. In humans, tranylcypromine and isocarboxazid Increased 5HT, NE and dopamine levels in various brain areas however, the effect of tranylcypromine was significantly greater than that of the other two on dopamine in the caudate nucleus and hypothalamus. In vitro. Lilly 516 1 ( ), like harmaline, preferentially blocked MAO oxidation of 5-HT, whereas tranylcypromine and pargyline selectively inhibited the oxidation of tyramine. ... 

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