Insomnia tryptophan

Many studies have tested tryptophan as a hypnotic agent. While the results have been variable, the consensus of reviews is that under certain conditions tryptophan can be an effective hypnotic.54-57 Although in severe insomnia tryptophan is not as effective as standard hypnotics, in mild insomnia it is able to decrease sleep latency by about one half. It can be useful at low doses (<4 g) without altering sleep architecture.58... 

Uses Obesity Action Blocks uptake of norepinephrine, serotonin, dopamine Dose 10 mg/d PO, may to 5 mg after 4 wk Caution [C, -] w/ SSRIs, Li, dextromethorphan, opioids Contra MAOI w/in 14 d, uncontrolled HTN, arrhythmias Disp Caps SE HA, insomnia, xerostomia, constipation, rhinitis, tach, HTN Interactions T Risk of serotonin synd W/ dextromethorphan, ergots, fentanyl, Li, meperidine, MAOIs, naratriptan, pentazocine, rizatriptan, sumatriptan, SSRIs, tryptophan, zolmitriptan, St. John s wort effects W/ cimetidine, erythromycin, ketoconazole T CNS depression W/ EtOH EMS Use fentanyl w/ caution, may T risk of serotonin synd concurrent EtOH use can T CNS depression OD May cause tach, HTN, diaphoresis, HA, fever, agitation, muscle tremors, and Szs symptomatic and supportive... 

Because it was known by 1960 that the pontine brain stem was crucial to REM sleep generation, it was natural to assume that the newly discovered modulatory elements played an important role in its generation. It was even reasonable, on an a priori basis, that each of the elements had responsibility for one state, viz, dopamine controls waking, serotonin controls slow wave sleep, and norepinephrine controls REM. Early lesion and parenteral pharmacological studies—some even armed with measures of amine concentrations in the brain—gave initial support to this concept. For example, Michel Jouvet produced insomnia in cats by blocking the enzyme that is essential to convert tryptophane into serotonin. He interpreted this result to mean that serotonin was a sleep mediator. 

The possibility that mental illness may be alleviated by biogenic amine precursors is an appealing one (SEDA-4, 18). Tryptophan is a naturally-occurring essential amino acid, which has been advocated as an innocuous health food for the treatment of depression, insomnia, stress, behavioral disorders, and premenstrual syndrome. The availability of amino acids in health food stores and a contemporary interest in natural remedies led to reported widespread use of tryptophan to treat depression. It was estimated in 1976 that up to that time several hundred patients with affective disorders had been studied, with results reported in at least 21 papers (1). However, the results of clinical trials with L-tryptophan in the treatment of depressive disorders are inconsistent (2). 

The amino acid L-tryptophan (19), used as a food supplement and in insomnia, is manufactured in Japan by a novel biotechnological process that leads to the contaminant bisindole 50 (peak E) 126), for which earlier an aminal structure was proposed 127). An outbreak of an eosinophilia... 

L-Tryptophan usage was widespread in the United States in 1989. In Oregon and Minnesota, 2% of the household members surveyed had used tryptophan at some time between 1980 and 1989. The most common reasons for tryptophan use were insomnia, premenstrual syndrome, and depression other reasons included anxiety, headaches, behavior disorders, obesity, and smoking cessation. Although most consumers purchased tryptophan for therapeutic use, it was marketed as a food supplement and widely available in the United States without a prescription. This product was not approved or regulated by the FDA. 

The use of L-tryptophan as a therapeutic agent probably began in the 1970s and early 1980s when reports in the medical literature suggested that it might be useful for the treatment of depression.13 Since then, its efficacy for a variety of other conditions has been examined these include chronic pain, insomnia, premenstrual syndrome, schizophrenia, affective disorders, and behavioral disorders.4 16 The rationale for its therapeutic use in treatment of psychiatric and behavioral disorders came mainly from the observation that brain serotonin content could be altered by changes in plasma tryptophan levels.17... 

Hartmann, E., Lindsley, J. G., and Spinweber, C., Chronic insomnia Effects of tryptophan, flurazepam, secobarbital, and placebo, Psychopharmacology, 80, 138, 1983. 

Demisch, K., Bauer, J., Georgi, K., and Demisch, L., Treatment of severe chronic insomnia with L-tryptophan Results of a double-blind cross-over study, Pharmacopsychiatry, 20, 242, 1987. 

Initially, a predominance of female patients was reported.20 However, other later studies have not established that the female sex was an independent factor for the development of EMS.23 The increased rate of EMS reported for women may have been due to greater use of L-tryptophan.20 Furthermore, only women used L-tryptophan for treatment of premenstrual syndrome, a frequently cited indication for usage. Also, women used benzodiazepines more than men to treat anxiety and/or insomnia. 

Fluoxetine is absorbed well from the GI tract, is bound to plasma proteins to the extent of 95%, is metabolized in the Uver to norfluoxetine, and is excreted in the urine. Tryptophan is used as an antidepressant. However, the combined use of tryptophan, which increases the level of serotonin, and fluoxetine, which inhibits the neuronal uptake of serotonin, enhances the side effects of fluoxetine such as GI disturbances, anxiety, and insomnia (see Figure 86). 

Tryptophan Essential amino acid Insomnia, depression Eosinophilia-myalgia syndrome was reported in 1989, possibly due to contaminants in production of tryptophan. Similar contaminants have been found in 5-hydroxy-l-tryptophan. 

Drugs can be found sometimes in foods and can participate in the metabolism. However, these substances are not normally exposed in humans at the dose at which they exert their beneficial effect. Some dietary supplements are drug-like when ingested in amounts that could never be achieved in the diet, even though they are essential nutrients when ingested in smaller quantities, for example, tryptophan is an essential amino acid required for metabolism and incorporation into proteins at low dose in humans. At high dose, it increases 5-hydroxytryptamine levels in brain and thus acts as a drug to treat insomnia. 

Inhibition of serotonin reuptake from the neuronal synapse and the subsequent increase in its functionality is one of the mainstays of the pharmacological treatment of depression. Like many amino acids, tryptophan is commercially available as a nutritional supplement or as a so-called smart drug, claiming to reduce symptoms of depression, anxiety, obsessive-compulsive disorders, insomnia, fibromyalgia, alcohol withdrawal, and migraine. However, no convincing clinical data are available to support these... 

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