Antidepressants effectiveness

Selected for clinical trials as a compound to calm agitated patients, imipramine was relatively ineffective. However, it was observed to be effective in the treatment of certain depressed patients (38). Early studies on the mechanism of action showed that imipramine potentiates the effects of the catecholamines, primarily norepinephrine. This finding, along with other evidence, led to the hypothesis that the compound exerts its antidepressant effects by elevating norepinephrine levels at central adrenergic synapses. Subsequent studies have shown that the compound is a potent inhibitor of norepinephrine reuptake and, to a lesser extent, the uptake of serotonin, thus fitting the hypothesis that had been developed to explain the antidepressant actions ofMAOIs. 

Landgrebe J, Welzl G, Metz T et al (2002) Molecular characterisation of antidepressant effects in the mouse brain using gene expression profiling. J Psychiatr Res 36 119-129... 

Cocaine and desipramine inhibit the reuptake of monoamine neurotransmitters whereas amphetamine, which is a phenylalkylamine - similar in structure to the catecholamines, see Fig. 4 - competes for uptake and more importantly, evokes efflux of the monoamine neurotransmitters. All of them exert antidepressant effects. Cocaine and amphetamine are addictive whereas tricyclic antidepressants and their modern successors are not. The corollaty of the addictive properties is interference with DAT activity. Blockade of DAT by cocaine or efflux elicited by amphetamine produces a psychostimulant effect despite the different mechanisms even the experienced individual can hardly discern their actions. Because of the risk associated with inhibiting DAT mediated dopamine clearance the antidepressant effects of psychostimulants has not been exploited. 

Stimulants induce both tolerance and sensitization to their behavioral effects. Tolerance develops to the anorectic and euphoric effects of stimulants (Schuster 1981) however, chronic intermittent use of low doses of stimulants delays the development of tolerance. With the doses commonly used in clinical practice, patients treated for narcolepsy or for depressive or apathetic states find that the stimulant properties usually persist without development of tolerance however, the persistence of antidepressant effects remains a matter of controversy. Sensitization has been linked to the development of amphetamine-induced psychosis (Yui et al. 1999). Sensitization to the induction of psychosis is suggested because psychosis is induced by progressively lower doses and shorter periods of consumption of amphetamine following repeated use over time (Sato 1986). Sensitization for amphetamine-induced psychosis may persist despite long periods of abstinence. 

The use of animal models for depression has two main objectives. One is to provide a behavioural model that can be used to screen potential antidepressant treatments. For this, the behaviour does not have to be an animal analogue of depression all that is needed is for it to be consistently prevented by established antidepressant agents (i.e. no false negatives) but not by drugs which have no antidepressant effect in humans (i.e. no false positives). 

A second objective is to produce behavioural changes in animals that are analogous to depression so that the model can be used to discover its neurobiological cause(s). This is a far more demanding problem and its success rests on satisfying at least three criteria (see Willner 1984) face validity (i.e. the behaviour looks like depression), construct validity (i.e. the causes and consequences of the behavioural change are the same as in depression) and predictive validity (i.e. the behaviour is reliably prevented only by drugs which have antidepressant effects in humans). 

Set against this background is the finding that the inhibition of [ H]noradrenaline uptake by the neuroleptic, chlorpromazine, is even greater than that of imipramine and yet chlorpromazine has no apparent antidepressant effects. This serves as a testimony... 

MAOI Phenelzine 15 45-90 Antidepressant effects Dietary restrictions drug... 

One aspect of the labeling deserves special mention. The Clinical Efficacy Trials subsection within the Clinical Pharmacology section not only describes the clinical trials providing evidence of citalopram s antidepressant effects, but makes mention of adequate and well controlled clinical studies that fail to do so. I... 

It is important to note that claims for the effectiveness of iproniazid and imipramine were not based on placebo-controlled clinical trials. Instead, they were based on clinical impressions.6 In discovering the antidepressant effects of imipramine, Kuhn did not even use precise measurement, rating scales or statistics. His claim was that precise measurement led to stagnation rather than progress in medicine, and he preferred to rely on his extensive medical experience and artistic imagination instead.7... 

I disagree strongly with the Don t ask don t tell policy. Without accurate knowledge, patients and physicians cannot make informed treatment decisions, researchers will ask the wrong questions and policymakers will implement misinformed policies. If the antidepressant effect is largely or entirely a placebo effect, it is important that we know this. If placebos can make people better, then depression can be ameliorated without reliance on drugs that have potentially serious side effects and that foster dependency. 

Thase, Michael E., Antidepressant Effects The Suit May Be Small, but the Fabric Is Real , Prevention ir Treatment, no. 32 (2002) http / / www.joumals.apa.org/prevention/volumes/preoo50032c.html... 

Sousa FCF, Melo CTV, Monteiro AP, et al. Antianxiety and antidepressant effects of riparin III from Aniba riparia (Nees) Mez (Lauraceae) in mice. Pharmacol Biochem Behav 2004 78 27-33. 

Tranylcypromine sulfate is an antidepressant drug and an inhibitor of MAO. Its antidepressant effect is probably due to the accumulation of NE in the brain as a consequence of inhibition of the enzyme. The other MAO I currently used as an antidepressant is phenelzine sulfate. 

It has been known for over 25 years that many of the tricyclic antidepressants (TCAs), e.g. imipramine and amitriptyline, are potent inhibitors of both norepinephrine and 5-HT reuptake. Some tricyclic antidepressants, e.g. desipramine, inhibit the uptake of norepinephrine much more potently than the uptake of 5-HT. Thus, it was unclear for some time whether the inhibition of 5-HT uptake played any role in the antidepressant action of those TCAs that possessed this pharmacological property. Recently, however, effective antidepressants such as fluoxetine, paroxetine and sertraline have been marketed and these SSRIs are much more potent inhibitors of the uptake of 5-HT than that of norepinephrine (Fig. 13-8). Thus, selective inhibition of the uptake of either norepinephrine or 5-HT can result in an antidepressant effect (Ch. 55). 

The antidepressant effects reported for some drugs that antagonize NMDA receptors suggest a role for the glutamatergic system in depressive disorders 892... 

Postsynaptic changes in receptor sensitivity. Studies of many antidepressants have demonstrated that desensitization or downregulation of NE or 5-HT1A receptors may relate to onset of antidepressant effects. 

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