Antidepressants drug administration

Goddard AW, Mason GF, Almai A, Rothman DL, Behar KL, Petroff OA, Charney DS, Krystal JH (2001) Reductions in occipital cortex GABA levels in panic disorder detected with Ih-magnetic resonance spectroscopy. Arch Gen Psychiatry 58 556-561 Grant MM, Weiss JM (2001) Effects of chronic antidepressant drug administration electroconvulsive shock on locus coeruleus electrophysiologic activity. Biol Psychiatry 49 117-129... 

The ethologically relevant models include the resident intruder and social hierarchy paradigms (Mitchell and Red-fern, 2005). These models are relatively recent, and have the relative advantage of relying on more naturalistic stressor, compared to shock or sw im. Also, they respond to chronic, but not acute antidepressant drug administration. 

However, these neurochemical effects are acute. That is to say, biogenic amine reuptake is blocked within minutes of drug administration. The therapeutic effects, on the other hand, in ameliorating or reversing the symptoms of major depression, require repeated antidepressant drug administration. Though some improvement in symptoms is often noted during the... 

In the learned helpless model, animals (usually rats) are subjected to a brief (l-2h) inescapable shock. Subsequently, they are tested in a task in which they can terminate the shock by an operant response. Animals with prior inescapable shock exposure do not perform as well in the test (Maier and Watkins, 2005). Advantages of the learned helplessness model include its use in studies of neurochemical changes, and that it responds to repeated, rather than acute, antidepressant drug administration. Disadvantages of the model include its dependence on acute stress administration, suggesting it may better model posttrau-matic stress disorder than major depressive disorder. 

We have shown that the increase in aggressiveness with chronic antidepressant drug administration can be blocked by lithium. Thus it may be that 5-HT plays a role in inhibiting both the... 

Table 20.7 Neurochemical changes generally found after chronic administration of antidepressant drugs or repeated electroconvulsive shock...

Moore and Blair T. Johnson, Initial Severity and Antidepressant Benefits A Meta-Analysis of Data Submitted to the Food and Drug Administration , PLoS Medicine, no. 2 (2008) http //medicine. plosjournals.org/perlserv/ request=get-document doi=io.i37i /joumal.pmed.0050045... 

Laughren, Thomas P., Approvable Action on Forrest Laboratories, Inc. Nda 20-822 Celexa (Citalopram Hbr) for the Management of Depression , in Memorandum to the Department of Health and Human Services, Public Health Service, Pood and Drug Administration, Center for Drug Evaluation and Research, Washington, DC, 26 March 1998 Laurance, Jeremy, Antidepressant Drugs Don t Work- Official Study , The Independent, 26 February 2008... 

Ultrasonic vocalizations are emitted by rat pups (under the age of 14 days) when they are isolated from their mother, and are thought to reflect anxiety. This measure has proven sensitive to both anxiolytic and anxiogenic manipulation of GABA neurotransmission. However, the early developmental window used is problematic, in that chronic drug administration probably results in a variety of compensatory changes not seen in adulthood, and may alter development of relevant brain systems. Indeed, in contrast to the clinical situation, the antidepressant clomipramine has acute, but not chronic, anxiolytic efficacy in this model. 

Jones RS, OIpe HR. (1984). An increase in sensitivity of rat cingulate cortical neurones to substance P occurs following withdrawal of chronic administration of antidepressant drugs. Br J Pharmacol. 81(4) 659-64. 

Antidepressant drugs, by contrast, require long-term administration for their therapeutic effects to become evident. Thus, it is clear that the acute actions of these drugs, which are most often to enhance synaptic levels of monoamines, are not sufficient in themselves to mediate their therapeutic effects. Neither is the effect of increased monoamines on postsynaptic second messenger systems, which occurs relatively quickly as well, adequate to account for the therapeutic actions of antidepressants. The most obvious explanation, then, is that molecular adaptations in response to chronic exposure to these drugs are what underlie their therapeutic effects. Consistent with this idea, several hypotheses as to the nature of the relevant molecular adaptations have been proposed. Two models focus on adaptations of the 5-HTia receptor. One theory proposes that desensitization of presynaptic somatodendritic 5-HTia autoreceptors is responsible for the therapeutic action... 

Blier, P. and Bouchard, C. (1994). Modulation of 5-HT release in the guinea-pig brain following long-term administration of antidepressant drugs. Br J Pharmacol 113 485 95. 

The prototypical serotonin reuptake inhibitor (SRI) medication is the non-selective agent clomipramine, a tricyclic antidepressant (TCA). The Selective SRIs (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalo-pram (Celexa). The Food and Drug Administration (FDA) approved clinical indications for these medications are described in Table 22.1. 

Khan, A., Warner, H.A., and Brown, W.A. (2000) Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials an analysis of the Food and Drug Administration database. Arch Gen Psychiatry 57 311-317. 

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