Antidepressant drugs antidepressants behavioral effects

In my admittedly biased view, the most coherent approach is that of a profoundly disturbed stress system that under specific conditions paves the way to development of mood disorders. These stress-system alterations can be genetic or acquired through trauma in early life or even in utero. Consistent with this neuroendocrine hypothesis are findings that centrally released neuropeptides that drive the HPA system also have behavioral effects that are similar to affective symptoms. This view is further supported by the documented ability of various antidepressants to enhance corticosteroid receptor synthesis and efficacy. Moreover, the stress system, particularly the corticosteroids and their receptors, interferes with all of the neurotransmitter receptor systems, including intracellular signaling, that have been considered in the context of mood disorders. New drugs targeted directly to various elements of the stress system will constitute a major step forward. 

Muth EA, Moyer JA, Haskins JT, et al. Husbands GEM. Biochemical, neurophysiological, and behavioral effects of Wy-45,233 and other identified metabolites of the antidepressant venlafaxine. Drug Dev Res 1991 23 191-199. 

Saarelainen, T., Hendolin, P., Lucas, G., Koponen, E., Sairanen, M., MacDonald, E., Agerman, K., Haapasalo, A., Nawa, H., Aloyz, R., Ernfors, P., Castren, E. (2003). Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci, 23, 349-57. 

Lucid I, O Leary OF. Distinguishing roles for norepinephrine and serotonin in the behavioral effects of antidepressant drugs. J Clin Psychiatry. 2004 65(suppl 4) 11-24. 

Other classes of antidepressant drugs can sometimes cause somnambulism, and it seems likely that paroxetine provoked this rare adverse effect. Sleep-walking is thought to be initiated during slow-wave sleep, after which partial arousals activate motor behaviors in the absence of full consciousness. The disrupting effects of antidepressants on sleep architecture might lead to somnambulism in pre-disposed individuals. 

Interestingly, in the learned helplessness animal model of depression, reversal of helpless behavior may be obtained acutely by direct intracerebral drug administration into frontal cortex, though reversal of helpless behavior by systemic drug administration requires several days (Sherman and Petty, 1980). This suggests that the reversal of depressive symptoms by antidepressant drugs may involve pharmacokinetic as well as pharmacodynamic effects (Petty et al., 1982). 

In addition to antidepressant drugs, some forms of psychological treatments have been shown effec tive for treatment of major depressive disorder. These include cognitive behavioral psychotherapy and interpersonal psychotherapy (Weissman, 1979). These therapies differ from traditional psychoanalytically oriented methods in that the therapist takes an active role, the patient is expected to do homework, and the treatment is time limited, usually for about six months. Little data are available regarding whether the combination of medications and psychotherapy is more effective than either treatment alone, but data are suggestive of an additive effect. 

Aminocyclopropyl compounds 630 (Lilly 51641) and 631 (Encyprat) have also been tested clinically as antidepressant drugs 630 turned out to be a fairly selective inhibitor for type A MAO, e.g. Refs 637, 638, 658, 669, 670, 675, 676 a similar behavior was found for the corresponding iodo compound (630, I instead of Cl). Derivatives 632 (AB 15) " 633 and 53468 -690 further examples for compounds with remarkable inhibitory effects for MAO. 

When they occur, depressive symptoms should be treated actively using a combination of cognitive-behavioral therapy and an antidepressant drug. Of the available antidepressants, selective serotonin reuptake inhibitors (SSRIs) have the most favourable combination of efficacy and side-effect profile for the elderly, regardless of the presence of medical co-morbidities. Although the dual agent venlafaxine has been proposed as an alternative agent for older patients who are either non-responders or partial responders to SSRIs, the frail elderly may be particularly vulnerable to its side effects (Hayes 2004). 

The behavioral despair of mice forced to swim without escape is measured by their immobility during a retest under the same conditions. Immobility in the forced swim test (FST) is reversed by antidepressant drugs (137), whereas PCP enhances the immobility. Pretreatment with clozapine and risperidone, as well as the 5-HT, antagonists, mianserin and ketanserin, attenuated the PCP-induced increase in immobility, whereas haloperidol and antidepressants have no effect (138,139). The PCP enhancement of the FST may provide a more selective animal model for the negative symptoms of schizophrenia. 

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