Eating disorders serotonin

Neurotransmitters are chemicals that carry messages, or signals, from a nerve cell to a target cell, which may be another nerve cell or a muscle cell. They may be inhibitory or excitatory and all are nitrogen-containing compounds. The catecholamines include dopamine, norepinephrine, and epinephrine. Too little dopamine results in Rarkinson s disease. Too much is associated with schizophrenia. Dopamine is also associated with addictive behavior. A deficiency of serotonin is associated with depression and eating disorders. Serotonin is involved in pain perception, regulation of body temperature, and sleep. Histamine contributes to al-... 

The newest appetite suppressant, sibutramine (Meridia), works by blocking the reuptake of both serotonin and norepinephrine. It does not stimulate nerve cells to release serotonin, as do fenfluramine and dexfenfluramine. Administered at 20 mg/ day, sibutramine effectively reduces weight in obese patients, but its use has not been assessed in eating disorder patients. The most common side effects of this medication are insomnia, dry mouth, and constipation. It has not been associated with the more serious heart and lung complications observed with fenfluramine and dexfenfluramine. Because sibutramine acts in part through modulation of norepinephrine, there is no rational basis for coadministering phentermine, which acts via this same mechanism. 

The most compelling evidence for a disturbance of serotonin and/or norepinephrine in eating disorders is that people with BN (Walsh, 1991 (Mitchell et ah, 1993) and AN (Kaye et ah, 2001) respond to antidepressants in placebo-controlled trials. Numerous studies have also shown alterations in these monoamines in the ill state. While less well studied, monoamine disturbances appear to persist after recovery. 

The selective serotonin reuptake inhibitors (SSRI) have been used in adults for a wide variety of disorders, including major depression, social anxiety (social phobia), generalized anxiety disorder (GAD), eating disorders, premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), panic, obsessive-compulsive disorder (OCD), trichotillomania, and migraine headaches. Some of the specific SSRI agents have an approved indication in adults for some of these disorders, as reviewed later in this chapter. The SSRIs have also been tried in children and in adults for symptomatic treatment of pain syndromes, aggressive or irritable ( short fuse ) behavior, and for self-injurious and repetitive behaviors. This chapter will review general aspects of the SSRIs and discuss their approved indications in children and adolescents. 

Ferguson, C., Lavia, M., Crossan, P., and Kaye, W. (1999) Are serotonin selective reuptake inhibitors effective in undetweight anorexia nervosa Int J Eat Disord 25 11-17. 

Fluoxetine Highly selective blockade of serotonin transporter (SERT) little effect on norepinephrine transporter (NET) Acute increase of serotonergic synaptic activity slower changes in several signaling pathways and neurotrophic activity Major depression, anxiety disorders panic disorder obsessive-compulsive disorder post-traumatic stress disorder perimenopausal vasomotor symptoms eating disorder (bulimia) Half-lives from 15-75 h oral activity Toxicity Well tolerated but cause sexual dysfunction Interactions Some CYP inhibition (fluoxetine 2D6, 3A4 fluvoxamine 1A2 paroxetine 2D6)... 

In terms of antidepressant actions, evidence points to the projection of serotonin neurons from the midbrain raphe to frontal cortex as the substrate of this therapeutic action (Fig. 5—51). Therapeutic actions in bulimia, binge eating, and various other eating disorders may be mediated by serotonin s pathway from raphe to hypothalamic feeding and appetite centers (Fig. 5-55). 

Tecott LH, Sun LM, Akana SF, et al. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 1995 374(6522) 542-546. 

Some studies have reported associations of serotonin receptor variants with clinical phenotypes. Cys23Ser and Gly22Ser 5-HTiA receptor variants, for example, have been associated with phenotypes such as intractable suicidal ideation [98], ADHD [100], bipolar disorder, and schizophrenia [98, 99, 109-116] and the -1348 A/G polymorphism of the 5-HT receptor has been associated with schizophrenia, eating disorders, and psychotic symptoms in Alzheimer s patients [94, 100, 117, 118], although these associations are not consistent across different studies. 

Serotonin is found in various cells within the central ner- yjl vous system, where it inhibits feeding. Serotonin has been implicated in human eating disorders such as anorexia nervosa, bulimia, and the carbohydrate craving associated with seasonal affective disorder (SAD). SAD is a clinical depression triggered... 

Introduced in 1988, Prozac is the oldest in the SSRI class and is still the most commonly prescribed (Morris, 1999). Prozac is a highly successful antidepressant that has revolutionized the treatment of depression because of its ability to raise serotonin levels in the brain. Increased availability of this neurochemical has been directly related to addressing effectively the symptoms prevalent in depression, and Prozac was recently approved to treat obsessive-compulsive disorder and the eating disorder bulimia. Prozac and the other SSRIs are also considered the medication of choice for working with depressed older individuals because of fewer side effects than the tricyclic medications (Haider Miller, 1993). In 1999 Prozac was endorsed by the FDA as being especially effective for geriatric depression (Hussar, 2000). 

Antidepressants cover a wide range of indications and include depression, obsessive-compulsive disorders, anxiety, pain, panic, eating disorders or social phobia. The monoamine hypothesis of depression is an often-used term that describes a concept that arose over 50 years ago when a direct link was observed between major depression and imbalance/deficiency of available monoamines such as serotonin and catecholamines. 

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