Antidepressants/antidepressant therapy action mechanisms

With the preceding issues in mind, the clinician can begin to formulate a logical and systematic approach to antidepressant therapy. At present, several classes of antidepressants are available as defined by the presumed mechanism of action underlying their antidepressant efficacy ( Table 7-16). 

Kozisek ME, Middlemas D, Bylund DB Brain-derived neurotrophic factor and its receptor tropomyosin-related kinase in the mechanism of action of antidepressant therapies. Pharmacol Ther 2008 117(1) 30. [PMID 17949819]... 

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

Each antidepressant has a response rate of approximately 60% to 80%, and no antidepressant medication or class has been reliably shown to be more efficacious than another 22 MAOIs may be the most effective therapy for atypical depression, but MAOI use continues to wane because of problematic adverse effects, dietary restrictions, and possibility of fatal drug interactions.22,28 There is some evidence that dual-action antidepressants, such as TCAs and SNRIs, may be more effective for inpatients with severe depression than are the single-action drugs such as SSRIs,22,28 but the more general assertion that multiple mechanisms of action confer efficacy advantages is quite controversial.33... 

Grahame-Smith DG, Green AR, Costain DW Mechanism of the antidepressant action of electroconvulsive therapy. Lancet 1 254-256, 1978... 

Psychopharmacol Bull 30 501-521, 1994b Sackeim HA, Decina P, Prohovnik 1, et al Anticonvulsant and antidepressant properties of electroconvulsive therapy a proposed mechanism of action. Biol Psychiatry 18 1301-10, 1983... 

Electroconvulsive therapy is especially useful when rapid onset of clinical effect is desired and when patients are refractory to a number of antidepressant drugs. It is also very helpful in psychotic and bipolar depression and in postpartum psychosis. If the mechanism of the therapeutic action of ECT could be unraveled, it might lead to a new antidepressant drug capable of rapid onset of antidepressant effects or with special value for refractory patients. Until then, ECT will remain a valuable member of the therapeutic armamentarium for depression. 

In addition to locomotor activity, delta opioid agonists produce convulsions in mice [41,43], rats [34,35], and monkeys [44 46], In the past, chemical-induced convulsions induced by camphor or pentylenetetrazol (Metrazol) were used as treatments for depression today, however, ECT is the only convulsant therapy used because the treatment-induced effects are less unpleasant than those produced by chemical convulsants [47]. ECS was demonstrated to have antidepressant-like effects in the forced swim test in rats [3], and ECT is a very effective treatment for depression in humans. Based on these observations, it was proposed that delta opioid agonists produce antidepressant-like effects tough a convulsive- or electroconvulsive shock (ECS)-like mechanism of action [41]. 

Although the pathophysiology of major depression remains elusive, the clinician can now select from multiple drug therapies with different mechanisms of action. Failure to respond to one antidepressant class or one antidepressant drug within a class does not predict a failed response to another drug class or another drug within the class. 

Chamey DS, Menkes DB, Heninger GR. Receptor sensitivity and the mechanism of action of antidepressant treatment implications for the etiology and therapy of depression. Arch Gen Psychiatry 1981 38 1160... 

Lithium, the mainstay for bipolar disorder treatment, often needs supplementation with antidepressant j and/or sedative drugs. The uses, mechanisms of action, and adverse effects of lithium therapy as well j as back-up drugs used for treatment of bipolar disorder are considered. I... 

Irrespective of the mechanism of action of tricyclic antidepressants, antagonists of a2 autoreceptors per se might have a beneficial effect in depressive illness, since they facilitate noradrenergic neurotransmission. Phenoxybenzamine, dihydroergotamine and yohimbine, but not the selective ai adrenoceptor antagonist prazosin, have been shown to be synergistic with several antidepressants in decreasing B-adrenoceptor density in rat cerebral cortex.Thus combined administration of an a2 adrenoceptor blocker with other antidepressants may provide a rapid onset therapy.RS 21361 produces a more rapid onset of B-adrenoceptor desensitization by itself than desipramine. 

Of these, the low level of SERTs in depressed patients has received the most attention in the development and synthesis of the SSRIs. The precise antidepressant mechanism of action for the SSRIs eludes neuroscientists, but the SSRIs have been shown to alleviate depression and are the most commonly used drugs in the therapy for depression. Claims of decreased adverse effects (adverse drug reactions) and less toxicity in overdose than both the MAOIs and the TCAs, together with increased safety, have led to their extensive use, and several are ranked in the Top 50 prescription drugs dispensed in the United States during the year 2005. 

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