Serotonin/serotonergic system treatment

Serotonergic systems are also affected by adolescent treatment in a sexually dimorphic manner. During adolescence, at doses that produce plasma nicotine doses similar to levels found in smokers, nicotine decreases serotonin receptors specifically in the cortex, in female rats. However, in the midbrain, there was an increase in males (Xu et al. 2002). 

Vetulani J, Lebrecht V, Pile A. Enhancement of responsiveness of the central serotonergic system and serotonin-2 receptor density in rat frontal cortex by electroconvulsive treatment. EurJ Pharmacol 1981 76 81. 

Additionally, COX-2 inhibitors influence—either directly or via CNS-immune mechanisms—the CNS serotonergic system. In a rat model, treatment with rofecoxib was followed by an increase of serotonin in the frontal and the temporo-parietal cortex (Sandrini et al., 2002). Since the lack of serotonin is one of the pinpoints in the pathophysiology of depression, a clinical antidepressant effect of COX-2 inhibitors would be expected due to this effect. A possible mechanism of the antidepressant action of COX-2 inhibitors is the inhibition of the release of IL-1 and IL-6. Moreover, COX-2 inhibitors also protect the CNS from effects of quinolinic acid (Salzberg-Brenhouse et al., 2003). 

Monoamine oxidase inhibitors, such as SSRIs, have been shown to be effective in the treatment of depression, and they have become among the most widely used prescription drugs in the United States. Prozac is used not only to treat major depressive disorders but also bulimia nervosa, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder. Multiple serotonin receptor subtypes are involved. Specific serotonin receptor subtype agonists and antagonists have been radiolabeled with positron-emitting tracers to assess the state of the serotonergic system. 

Schizophrenia is a chronic, complex psychiatric disorder affecting approximately 1% of the population worldwide. The chronic nature of the illness, in addition to the early age of onset, results in direct and indirect health care expenditures in the U.S., which amount to approximately 30 to 64 billion dollars per year [4]. It is perhaps the most devastating of psychiatric disorders, with approximately 10% of patients committing suicide. The dopamine hypothesis of schizophrenia postulates that overactivity at dopaminergic synapses in the central nervous system (CNS), particularly the mesolimbic system, causes the psychotic symptoms (hallucinations and delusions) of schizophrenia. Roth and Meltzer [5] have provided a review of the literature and have concluded a role for serotonin as well in the pathophysiology and treatment of schizophrenia. The basic premise of their work stems from the known interaction between the serotonergic and dopaminergic systems. 

SERTPR variants may also not be specifically associated with response to SSRIs but confer a more general predisposition to respond to any kind of antidepressant treatment targeting the serotonin system. The 1 allele of SERTP R has not only associated been associated with a better response to SSRIs but also a good response to total sleep deprivation (Benedetti et al. 1999). An enhancement of serotonergic transmission has been proposed as one possible mechanism of action of sleep deprivation (Gardner et al. 1997). 

Selective serotonin reuptake inhibitors. Currently available selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram. At present, expert opinion does not support the usefulness of these serotonergic compounds in the treatment of core ADHD symptoms (National Institute of Mental Health, 1996). Nevertheless, because of the high rates of comorbidity in ADHD, these compounds are frequently combined with effective anti-ADHD agents (see Combined Pharmacotherapy, below). Since many psychotropics are metabolized by the cytochrome P450 system (Nemeroff et ah, 1996), which in turn can be inhibited by the SSRIs, caution should be exercised when combining agents, such as the TCAs, with SSRIs. 

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