Any disruption in the synthesis, metabolism or uptake of this neurotransmitter has been found to be partly responsible for certain manifestations of schizophrenia, depression, compulsive disorders and learning problems.
Serotonin originates in neurons deep in the midline of the brainstem. Because these neurons profile diffusely throughout the brain, serotonin can affect various brain functions. It also interacts with many other neurotransmitters, either directly through neurons that use both serotonin and another neurotransmitter, or by serotonin neurons influencing neurons that primarily use these other transmitters.
The diffuse connections of serotonin allow it to affect many basic psychological functions such as anxiety mechanisms and the regulation of mood, thoughts, aggression, appetite, sex drive and the sleep/wake cycle. Multiple observations suggest that serotonin, one of the most abundant neurotransmitters, plays an important role in the regulation of mood and a key role in the treatment of depression.
Data suggest that serotonin is associated with reduced serotonin function. Studies of cerebrospinal fluid, whole blood, and plasma have shown that serotonin levels are reduced in depressed patients.
Serotonin reuptake inhibitors such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) have become part of the medical armamentarium for the treatment of depression. They have joined other drugs that are used to treat depression, including monoamine oxidase inhibitors (MAOIs), lithium, methylphenidate (Ritalin), trazodone (Desyrel), bupropion (Wellbutrin), and the tricyclic antidepressants.
Selective serotonin uptake inhibitors (SSRIs) are no more effective than traditional agents, but their side-effects profiles often present important clinical advantages, such as the low incidence of side effects compared with standard tricyclic and tetracyclic antidepressant drugs. The mildness of their side effects makes then particularly well suited for treating moderately depressed outpatients or the elderly. It has been estimated that 75 to 80 percent of patients taking tricyclic antidepressants receive subtherapeutic doses because of the intolerable side effects associated with higher dosages. Thus, side effects may limit the clinical effectiveness of traditional antidepressant medications.
The SSRIs are also used to treat conditions other than depression, including bulimia nervosa, personality disorders, and obsessive-compulsive disorder. Treatment of these conditions requires higher dosages than the dosages used to treat depression.
Unlike the SSRIs, nefazodone - which exerts significant inhibitory effects on serotonin uptake - does not seem to cause an adverse effect on sexual drive and function.
The precise mechanism of action of antidepressants is largely unknown. In depression, the principal biochemical abnormality appears to be impaired metabolism of one or more central amines or peptide neurotransmitters and their receptor sites. SSRIs inhibit the reuptake of serotonin and, thus, increase the concentration of this neurotransmitter in the central nervous system.
The mechanism of action for the SSRIs is the blocking of the uptake pump action on the presynaptic neuron. This increases the amount of serotonin in the synaptic cleft and at the postsynaptic serotonin receptor site, resulting in greater postsynaptic serotonin stimulation.
In contrast, tricyclic antidepressants and MAOIs not only increase the concentration of serotonin in the central nervous system, but they also increase the levels of norepinephrine and dopamine.