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Antidepressant Medications
Selective Serotonin Reuptake Inhibitors (SSRIs)


In a controlled clinical study, melatonin levels were reduced significantly in study participants treated with fluoxetine (20 mg/day) for six weeks (Childs et al. 1995). The decrease in melatonin levels associated with this drug may be explained by down-regulation of b-adrenoreceptors, reduction in cAMP accumulation, or interference with suprachiasmatic nucleus output.

Significance of Depletion

Alterations in melatonin levels have been associated with disturbances in the sleep-wake cycle and jet lag (Avery et al. 1998).

Replacement Therapy

Optimal doses for melatonin therapy have not been established (Avery et al. 1998). Commonly available doses range from 0.3 to 5 mg. Physiological blood levels are achieved with doses of 0.3 mg; higher doses (1 mg) result in supraphysiological levels of melatonin in the blood. The efficacy of melatonin supplementation is dependent upon the time of administration, as effects are related to circadian rhythms.

Protein & Amino Acids

Fluoxetine reduces leucine absorption by 37% in vitro and 30% in vivo; it may affect the nutritional status of patients by reducing absorption of neutral amino acids (Urdaneta et al. 1998). More research is needed to confirm these effects.

Significance of Depletion

Deficiencies of protein are characterized by compromised immune status, generalized decreases in function and strength, apathy, weight loss, increased susceptibility to infection, impaired wound healing, and growth retardation in children (Covington 1999). Severe depletion may be characterized by muscle wasting, deterioration in skin and hair, decreased heart rate, blood pressure, and body temperature.

Replacement Therapy

Nutritional repletion through dietary means is the preferred treatment approach in cases of protein depletion or deficiency (Covington 1999). Adopting a balanced diet consisting of high levels of calories, protein, vitamins, and minerals is one option available for the treatment of patients with depleted levels of protein. Oral or parenteral supplementation offers another therapeutic approach to restore nutritional status, maintain caloric intake, and achieve recommended dietary allowances for protein (generally 600 to 800 mg/kg protein) (Reeds and Beckett 1996).

Editorial Note

This information is intended to serve as a concise reference for healthcare professionals to identify substances that may be depleted by many commonly prescribed medications. Depletion of these substances depends upon a number of factors including medical history, lifestyle, dietary habits, and duration of treatment with a particular medication. The signs and symptoms associated with deficiency may be nonspecific and could be indicative of clinical conditions other than deficiency. The material presented in these monographs should not in any event be construed as specific instructions for individual patients.


Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med. 1998;30:122-130.

Childs PA, Rodin I, Martin NJ, et al. Effect of fluoxetine on melatonin in patients with seasonal affective disorder and matched controls. Br J Psychiatry. 1995;166:196-198.

Covington T, ed. Nonprescription Drug Therapy Guiding Patient Self-Care. St Louis, MO: Facts and Comparisons; 1999:467-545.

Reeds P, Beckett P. Protein and amino acids. In: Ziegler E, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington, DC: International Life Sciences Institute; 1996:67-86.

Urdaneta E, Idonte I, Larraldo J. Drug-nutrient interactions: inhibition of amino acid intestinal absorption by fluoxetine. Br J Nutr. 1998;79(5):439-446.

Copyright © 2000 Integrative Medicine Communications

This publication contains information relating to general principles of medical care that should not in any event be construed as specific instructions for individual patients. The publisher does not accept any responsibility for the accuracy of the information or the consequences arising from the application, use, or misuse of any of the information contained herein, including any injury and/or damage to any person or property as a matter of product liability, negligence, or otherwise. No warranty, expressed or implied, is made in regard to the contents of this material. No claims or endorsements are made for any drugs or compounds currently marketed or in investigative use. The reader is advised to check product information (including package inserts) for changes and new information regarding dosage, precautions, warnings, interactions, and contraindications before administering any drug, herb, or supplement discussed herein.